All-endoscopic approach for distal biceps tendon pathology: analysis of long-term outcomes in partial and complete ruptures.

BACKGROUND: Distal biceps tendon (DBT) pathology is a spectrum that ranges from tendinopathy to complete retracted ruptures, and surgical treatment is usually performed via open approaches. The purpose of this study was to analyze safety and long-term outcomes of all-endoscopic surgery for entire spectrum of primary DBT pathology. The hypothesis was that at an all-endoscopic technique would result in satisfactory clinical outcomes and a low complication rate. METHODS: Consecutive patients who underwent all-endoscopic surgery for primary isolated DBT pathology (bursitis, partial and acute/chronic complete tears) between January 2013 and December 2021 were assessed and analyzed retrospectively. Refractory bursitis and low-grade partial tears underwent endoscopic débridement, and high-grade partial tears and complete ruptures underwent all-endoscopic repair or graft reconstruction. Preoperative and follow-up assessment included functional assessment using Mayo Elbow Performance Score and a Patient-Reported Distal Biceps Score, and radiological assessment was performed using plain biplanar radiographs and sonography. Pre- and postoperative scores for the overall group, and for partial and complete tears, were compared using a paired t test. RESULTS: Overall, 26 male patients underwent an all-endoscopic surgery for DBT tears; the pathology was classified by endoscopic findings into 6 types, and follow-up period ranged from 21 to 125 months (mean 79.4 months). Nine chronic partial tears (35%) included predominantly bursitis (type I, n = 2) and predominantly partial tears (type IIA and B, n = 7). The complete tear group (65%) included isolated short or long head tears (type IIIA and IIIB, n = 2) and complete tendon ruptures (types IV, V, and VIA-C, n = 15). Endoscopic débridement of the bursitis/low-grade tears and repair of the high-grade and complete ruptures resulted in complete resolution of symptoms and significant improvement in both Mayo Elbow Performance Score and Patient-Reported Distal Biceps Score (P < .001). Autografts were necessary in 35% (6/17) of complete tears, and no significant difference was found in functional scores in this group as compared to those where primary repairs were possible. There were 2 minor complications (7.6%) that involved transient lateral antebrachial cutaneous nerve neuropraxia. Follow-up sonography and radiographs showed an intact tendon and absence of heterotopic ossification or synostosis. CONCLUSIONS: An all-endoscopic approach for treating DBT pathology was safe and reliable and was associated with significant improvement in subjective and functional outcomes in the long-term. The dual-anchor onlay repair technique showed long-term radiologically demonstrable structural integrity of the tendon and was associated with a low minor complication rate and absence of heterotopic ossification.

How does dynamic arthroscopic tracking compare with radiologic glenoid track for identification of on- and off-track lesions in anterior shoulder instability?

BACKGROUND: Current treatment paradigms for anterior shoulder instability are based on radiologic measurements of glenohumeral bone defects, and mathematical calculation of the glenoid track (GT) is used to classify lesions into on-track and off-track morphology. However, radiologic measurements have shown high variability, and GT widths under dynamic conditions have been reported to be significantly smaller than those under static radiologic conditions. The purpose of this study was to assess the reliability, reproducibility, and diagnostic validity of dynamic arthroscopic standardized tracking (DAST) in comparison to the gold-standard radiologic track measurement method for the identification of on- and off-track bony lesions in patients with anteroinferior shoulder instability. METHODS: Between January 2018 and August 2022, 114 patients with traumatic anterior shoulder instability were evaluated using 3-T magnetic resonance imaging or computed tomography scans; glenoid bone loss, Hill-Sachs interval, GT, and Hill-Sachs occupancy ratio (HSO) were measured, and defects were classified as on-track or off-track defects and peripheral-track defects (based on HSO percentage) by 2 independent researchers. During arthroscopy, a standardized method (DAST method) was used by 2 independent observers to classify defects into on-track defects (central and peripheral) and off-track defects. Interobserver reliability of the DAST and radiologic methods was calculated using the κ statistic and reported as percentage agreement. Diagnostic validity (sensitivity, specificity, positive predictive value, and negative predictive value) of the DAST method was calculated using the radiologic track (HSO percentage) as the gold standard. RESULTS: The radiologically measured mean glenoid bone loss percentage, Hill-Sachs interval, and HSO in off-track lesions were lower with the arthroscopic method (DAST) as compared with the radiologic method. The DAST method showed nearly perfect agreement between the 2 observers for the on-track/off-track classification (κ = 0.96, P < .001) and the on-track central or peripheral /off-track classification (κ = 0.88, P < .001). The radiologic method showed greater interobserver variability (κ = 0.31 and κ = 0.24, respectively) with only fair agreement for both classifications. Inter-method agreement varied between 71% and 79% (95% confidence interval, 62%-86%) between the 2 observers, and reliability was assessed as slight (κ = 0.16) to fair (κ = 0.38). Overall, for identification of an off-track lesion, the DAST method showed maximum specificity (81% and 78%) when radiologic peripheral-track lesions (HSO percentage of 75%-100%) were considered off-track and showed maximum sensitivity when arthroscopic peripheral-track lesions were classified as off-track. CONCLUSION: Although inter-method agreement was low, a standardized arthroscopic tracking method (DAST method) showed superior interobserver agreement and reliability for lesion classification in comparison to the radiologic track method. Incorporating DAST into current algorithms may help reduce variability in surgical decision making.

How does anterior glenoid bone loss affect shoulder stability? A cadaveric analysis of glenoid concavity and bony shoulder stability ratio.

BACKGROUND: Concavity compression is an important glenohumeral stabilizing factor, and recent studies have suggested that peripheral glenoid bone loss creates the most relevant change in stability. This study analyzed changes in the bony shoulder stability ratio (BSSR) with sequential anterior glenoid bone loss (0%-40% width) and with reconstructive bone graft procedures. The aim was to quantify the critical bone defect size that would significantly alter the BSSR and determine restoration of the BSSR with the Latarjet procedure. METHODS: Anterior glenoid defects were created with sequential osteotomies (10%-40%), and defects were reconstructed using 2 Latarjet modifications (classic Latarjet procedure and congruent-arc Latarjet [CAL] procedure). We obtained 108 computed tomography scans of (1) intact scapulae (n = 12), (2) after each bone defect (n = 48), and (3) after each reconstruction (n = 48). The glenoid concavity depth and concavity radius were measured, and the BSSR was determined using a validated mathematical formula. Statistical analysis was performed to determine significant differences between the intact state and each of the deficient and reconstructed glenoids. RESULTS: The glenoid concavity radius increased by approximately 30% (14 mm) and the glenoid concavity depth decreased by 50% (1.5 mm) from the 0% to 40% defect. The maximal sequential change in depth (1.2 mm, 44%; P < .001) and radius (6 mm, 12%; P < .001) occurred at the 10% glenoid defect. The overall BSSR decreased by approximately 40% (0.15) from the intact glenoid to the 40% defect. This change in the BSSR was most profound (0.11, 30%; P < .001) at the 10% glenoid defect and was only marginal thereafter between the 20% and 40% defects (0.24, 0.22, and 0.21). The Latarjet procedure adequately restored glenoid concavity; however, the CAL procedure significantly overcorrected all 3 parameters at 10% defect. CONCLUSION: The glenoid concavity depth and BSSR undergo progressive deformation with sequential bone loss, and 90% of this change occurs with a 10% glenoid defect. Articular concavity and the BSSR are adequately restored with the Latarjet procedure, and the CAL procedure significantly overcorrects concavity in mild (0%-10%) defects.

Endoscopic anatomy of distal biceps tendon insertion and bicipitoradial bursa: a cadaveric study.

BACKGROUND: Distal biceps endoscopy has emerged as a minimally invasive alternative to open procedures for distal biceps tendon (DBT) pathology. The purpose of this study was to systematically describe the static and dynamic appearance and variations of the DBT insertional region using a standardized endoscopic technique and dissection in healthy cadaveric elbows. METHODS: Endoscopic assessment of the DBT insertional region was performed using a standard proximal parabiceps portal in 20 fresh frozen cadaveric upper extremities. A 6-point endoscopic evaluation of the DBT and bicipitoradial bursa was performed in a static supination position and with dynamic rotation. Anatomic variations in the DBT insertional characteristics, as well as the extent and appearance of the intrabursal space, were documented. Each cadaver was then dissected to correlate endoscopic findings with gross anatomic structures. RESULTS: A bare oval tuberosity area (n = 20) bounded by the supinator and DBT was observed. The DBT inserted ulnar to the bare area (n = 16) and the presence of an intervening wide (n = 1) or narrow (n = 3) tuberosity sulcus were documented. The dorsoradial DBT surface was consistently intrabursal and was differentiated into 2-5 fiber bundles (n = 15). The volar-ulnar DBT surface was always extrabursal and was associated with endoscopically identifiable proximal and distal fat pads. The bicipitoradial bursa formed a bursal sac that was attached to the dorsoradial (n = 13) or volar (n = 7) aspect of the tuberosity and extended proximally along the DBT for 3-5 cm (parabiceps space). A distinct ligament-like band (transverse radioulnar ligament) extended transversely across the proximal radioulnar space and appeared to form a sling that provided ulnar support to the DBT during dynamic rotation. The intact DBT surface was robust and could not be breached, even with firm pressure using a probe. CONCLUSIONS: The bare tuberosity area, the bursal sac, and the parabiceps space are consistent anatomic landmarks that can be used during DBT endoscopy. An insertional tuberosity sulcus and DBT surface differentiation are normal anatomic variations. The transverse radioulnar ligament provides ulnar support for the DBT during pronation and forms a pulley mechanism for smooth tendon gliding motion.

Nanodelivery of Resveratrol-Loaded PLGA Nanoparticles for Age-Related Macular Degeneration.

Age-related macular degeneration, precisely neovascular form, is the leading cause of vision loss and the key treatment includes intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. A method to increase local concentration of drug at posterior segment of the eye and to reduce the frequency of intravitreal injections is an unmet need. Resveratrol, a naturally occurring antioxidant and anti-inflammatory polyphenol, was loaded in PLGA polymeric nanoparticles to study their sustained release property and effectiveness in reducing expression of VEGF protein in vitro. Nanoparticles were characterized using FTIR, DSC, size, encapsulation efficiency, TEM, and in vitro drug release studies. Using MTT assay, the cytotoxicity of formulation was evaluated on ARPE-19 cells. The cellular uptake and VEGF expression levels were also evaluated in in vitro settings. The optimized formulation had a particle size of 102.7 nm with - 47.30 mV of zeta potential. Entrapment efficiency was found to be 65.21%. The cell viability results suggested compatibility of developed formulation. Cellular uptake and VEGF expression levels for the formulated nanoparticles specified that the developed formulation showed potential cellular uptake and had displayed anti-angiogenic property by inhibiting VEGF expression in vitro. The results showed successful development of resveratrol-loaded nanoparticles which may be used for neovascular AMD treatment alone or in combination with anti-VEGF agents.

Jaundice outbreak likely caused by HEV in Amritsar, Punjab, India, 2013.

BACKGROUND: Hepatitis-E Virus (HEV) infection is endemic in Punjab, India. On 4th April 2013, public officials of Labour Colony, Amritsar reported > 20 jaundice cases occurring within several days. METHODS: We performed a case-control study to identify the cause and prevent additional cases of jaundice cases in Amritsar, Punjab, India in 2013. RESULTS: A total of 159 cases (attack rate 3.6%) and 1 death were identified in Labour and 5 adjoining colonies from January 1 to June 5, 2013. Persons with jaundice were more likely to report foul-smelling piped water (adjusted odds ratio [AOR], 4.0, 95% confidence interval [CI], 2.2-7.2) and used piped water for drinking (AOR, 5.1; 95% CI, 2.2-11.4) than persons without jaundice. Among 14 cases tested, all had anti-hepatitis E virus IgM, and none had anti-hepatitis A virus IgM. Additionally, 21/23 tap water samples from affected households had detectable fecal coliforms. An environmental investigation found that water pipelines were damaged during sewer construction and likely led to contamination of drinking water with hepatitis E virus. CONCLUSIONS: Hepatitis E outbreaks are common in India, to curb future outbreaks of hepatitis E; measures to ensure safe drinking water are urgently needed.

Bone defect-induced alteration in glenoid articular surface geometry and restoration with coracoid transfer procedures: a cadaveric study.

BACKGROUND: This study analyzed the alteration in glenoid articular geometry with increasing anterior bone loss, as well as its subsequent correction with 2 modifications of the Latarjet procedure. METHODS: Anterior defects were simulated by creating glenoid osteotomies (10%, 20%, 30%, and 40%), and defects were reconstructed using 2 Latarjet modifications (classic and congruent arc). A total of 108 computed tomography scans were performed (1) on intact scapulae (n = 12), (2) after each bone defect (n = 48), and (3) after each reconstruction (n = 48). Glenoid parameters (width, area, arc length, and version) were analyzed on computed tomography scans. Statistical analysis was used to determine significant differences between intact, deficient, and reconstructed glenoids. RESULTS: All parameters were reduced with every 10% defect increment (mean change in width, 2.5 mm; area, 64 mm2; version, 2.2°; and arc length, 2.2 mm). Width correction with the classic Latarjet procedure was not statistically significant in 30% and 40% defects. Area correction in 30% defects was not significant with the classic Latarjet procedure and was significantly undercorrected in 40% defects. Version correction was not significant after the classic Latarjet procedure in 20%, 30%, and 40% defects. Arc-length correction was not significant in 20% and 30% defects with the classic Latarjet procedure and was significantly undercorrected in 40% defects. The congruent-arc Latarjet procedure overcorrected glenoid parameters in all defects; however, area and arc length were not significantly different from intact glenoids in 40% defects (P < .05). CONCLUSION: Glenoid articular geometry is progressively altered with a sequential increase in anterior bone defects from 0% to 40%. The classic Latarjet procedure provided significant correction in bone defects of 10% and 20%. The congruent-arc Latarjet procedure restored and overcorrected most parameters even in 40% glenoid defects.

Toward the Synthesis and Improved Biopotential of an N-methylated Analog of a Proline-Rich Cyclic Tetrapeptide from Marine Bacteria.

An N-methylated analog of a marine bacteria-derived natural proline-rich tetracyclopeptide was synthesized by coupling the deprotected dipeptide fragments Boc-l-prolyl-l-N-methylleucine-OH and l-prolyl-l-N-methylphenylalanine-OMe. A coupling reaction was accomplished utilizing N,N'-Dicyclohexylcarbodidimde (DCC) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC·HCl) as coupling agents and Triethylamine (TEA) or N-methylmorpholine (NMM) as the base in the presence of the racemization suppressing agent. This was followed by the cyclization of the linear tetrapeptide fragment under alkaline conditions. The structure of the synthesized cyclooligopeptide was confirmed using quantitative elemental analysis, FTIR (Fourier-transform infrared spectroscopy), ¹H NMR (Nuclear magnetic resonance spectroscopy), 13C NMR, and mass spectrometry. From the bioactivity results, it was clear that the newly synthesized proline-rich tetracyclopeptide exhibited better anthelmintic potential against Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus eugeniae at a concentration of 2 mg/mL as well as improved antifungal activity against pathogenic dermatophytes Trichophyton mentagrophytes and Microsporum audouinii at a concentration of 6 µg/mL, as compared to non-methylated tetracyclopeptide. Moreover, N-methylated tetracyclopeptide displayed significant activity against pathogenic Candida albicans.

Analysis of technical feasibility and neurovascular safety of endoscopic distal biceps repair: a cadaveric study.

BACKGROUND: This cadaveric study was designed to analyze the safety of endoscopic repair of distal biceps tendon (DBT) tears using 2 reattachment techniques. We evaluated the proximity of neurovascular structures to endoscopy portals; iatrogenic injury to neurovascular, musculotendinous, and osseous structures; and changes in compartment pressures. We hypothesized that an all-endoscopic repair of the ruptured DBT would be technically safe and the risk of iatrogenic injury would be low. METHODS: A 2-portal endoscopic tendon repair was performed in 28 fresh-frozen cadaveric elbows with button devices (with or without interference screws) (n = 17) and suture anchors (n = 11). Dissection was performed, and neurovascular, musculotendinous, and osseous structures were assessed for iatrogenic injury. The repair construct (tendon-tuberosity contact area and implant placement site) was evaluated, and compartment pressures were measured. Statistical analysis was performed to determine significant differences in iatrogenic injury, compartment pressure changes, and tendon-bone contact area between different devices. RESULTS: The lateral cutaneous nerve, cephalic vein, and radial artery were in close proximity to the portals. The button group showed a significantly higher number of iatrogenic injuries than the anchor group (P = .036). All-suture anchor repair showed a significantly higher contact area (mean, 85 mm2) than repairs with all other devices (P < .001). Compartment pressures increased by 2-4 mm in each of the 3 compartments tested (P < .001). CONCLUSION: Endoscopic DBT repair was technically feasible with both fixation techniques. Button devices were associated with a significantly higher number of iatrogenic injuries. Endoscopic repair with dual suture anchors was safe in cadavers; however, further clinical results are necessary to establish the clinical safety of this technique.

Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations.

The physicochemical and biological properties of active pharmaceutical ingredients (APIs) are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development. This review summarizes several criteria for choosing the appropriate salt forms, along with the effects of salt forms on the pharmaceutical properties of APIs. In addition to a comprehensive review of the selection criteria, this review also gives a brief historic perspective of the salt selection processes.

Cadaveric Study of Insertional Anatomy of Distal Biceps Tendon and its Relationship to the Dynamic Proximal Radioulnar Space.

PURPOSE: To quantify and assess the relationship between the insertional dimensions of the distal biceps tendon (DBT) and radioulnar space (RUS) in 3 rotational positions. We hypothesized that in all positions RUS would be adequate for the DBT and would remain adequate even after an incremental increase (1 to 3 mm) in tendon thickness. METHODS: Eleven fresh-frozen cadaveric elbows were dissected; DBT dimensions and bicipital tuberosity measurements were performed and insertional footprints were quantified using a distal biceps footprint index. The RUS was measured at 3 levels of the bicipital tuberosity and in 3 positions of forearm rotation. We performed statistical analysis to analyze differences in RUS (positional and inter-level). In addition, significant differences between DBT thickness (native and incremental) and RUS were analyzed to identify potential sites of radioulnar impingement. RESULTS: The DBT had a mean length of 92 mm; thickness ranged from 2.9 to 6.1 mm. Three variations in DBT insertional footprint were observed and quantified. The RUS linear distance reduced significantly from a supinated to a pronated position at each of 3 bicipital tuberosity levels; the reduction was statistically significant at the lower tuberosity level (45%). Pronation RUS distance was adequate for native DBT thickness and was significantly less when DBT thickness increased by 2 and 3 mm. CONCLUSIONS: Radioulnar space reduces significantly from the supinated to the pronated position and is most evident in the lower aspect of the tuberosity. In addition, the RUS in pronation is inadequate for incremental increases in DBT thickness. CLINICAL RELEVANCE: Postoperative DBT impingement in the RUS may be prevented by avoiding techniques that increase the thickness of the tendon and by using a reattachment site at the proximal aspect of the tuberosity.

Risk factors for death during a resurgence of influenza-A (H1N1) pdm09 in Punjab State in 2013.

BACKGROUND: In 2013, high mortality from influenza-A (H1N1) pdm09 (pH1N1) was observed in Punjab, India. OBJECTIVES: To describe cases and deaths of 2013 pH1N1 positives, to evaluate the high case fatality ratio and risk factors for pH1N1-associated mortality among the hospitalized cases in Punjab for 2013. METHODS: A case-control study was conducted and compared those who died from confirmed pH1N1 with those who survived in the hospital between January 1, 2013, and April 30, 2013. Sociodemographic and clinical details were extracted from hospital records and from telephone interviews with controls and next of kin of cases using pretested questionnaires. Logistic regression analysis was performed. RESULTS: A total of 182 laboratory-confirmed pH1N1 cases (99 males and 83 females) were hospitalized in 30 hospitals in Punjab; 42 (23%) patients died. Those who died were significantly more likely to be younger than 50 years of age (adjusted odds ratio [AOR] =10.6, 95% confidence interval [CI] =1.8-21.1), be obese (AOR = 16.7, 95% CI = 1.6-170.7), and have visited more than two health-care facilities before laboratory confirmation (AOR = 25.8, 95% CI = 5.4-121.6). CONCLUSIONS: The health-care community should have a high index of suspicion for influenza, and general community should be sensitized about risk factors and to seek medical advice early in the illness.

Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2-5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer.

Endoscopic Repair of Acute and Chronic Retracted Distal Biceps Ruptures.

Distal biceps tendon (DBT) ruptures are infrequent injuries that result in pain, weakness, and cosmetic deformity. Severe retraction of the ruptured DBT can occur at the time of injury, or in chronic neglected ruptures, and surgical exposure is performed using a single incision or a 2-incision technique. The technique presented here describes an endoscopic approach using 3 portals that provide access to the retracted DBT, biceps sheath, and radial tuberosity. Preoperative sonographic localization of the retracted DBT and neurovascular structures is used to guide portal placement. The parabiceps portal is used for visualization of the biceps sheath remnant, and the midbiceps portal is used to visualize and retrieve the retracted tendon in the arm. The retracted DBT is shuttled through the biceps sheath into the upper forearm, and 2 suture anchors are passed into the radial tuberosity under direct endoscopic vision. The DBT is whipstitched via the distal anterior portal, and nonsliding knots are tied to securely reattach the DBT to the prepared radial tuberosity.

Cadaveric study of anterior and posterior elbow endoscopy portals for endoscopic distal biceps repair: comparative anatomy-at-risk.

PURPOSE: The purpose of this study was to describe neurovascular structures-at-risk during establishment of five portals for access to distal biceps tendon (DBT) in cubital fossa, and to establish relative safety of these portal sites for such access. We hypothesized that all five portals are safe for endoscopic DBT exploration. METHODS: Ten fresh frozen cadaveric elbows were dissected after placement of portals at five potential sites (four anterior, one posterior). Nine neurovascular structures (CV, cephalic vein; LCN, lateral cutaneous nerve; LV, leash of vessels; RN, radial nerve; SRN, superficial radial nerve; PIN, posterior interosseous nerve; RA, radial artery; BA, brachial artery; MN, median nerve) were dissected, and their distances from portal sites were measured. Statistical analysis was performed to determine relative portal safety, and risk of injury to neurovascular structures in relation to each portal was analyzed. RESULTS: Structures that were significantly "at risk" were RA (p = 0.006), SRN (p = 0.002), and PIN (p = 0.004). RA was significantly "at risk" of injury from portal 4 (p = 0.009). Similarly, SRN was "at risk" from portal 3 (p = 0.036), and the PIN was "at risk" from portal 2 (p = 0.003). CONCLUSIONS: Portal 1 (parabiceps portal) was safe for all neurovascular structures, however, portals 2-4 were significantly closer to neurovascular structures. RA, SRN, and PIN were significantly "at risk" as compared to other structures amongst the portals studied. Portal 5 was relatively safe for SRN and PIN. CLINICAL RELEVANCE: Portals 1 (parabiceps portal) and 5 (distal posterior) can be safely placed for endoscopic access to the DBT. Portal 4 (open distal anterior) may be used after careful open dissection and under direct vision. Portals 2 and 3 are not recommended for elbow endoscopy.

Suppression of inflammatory cascade is implicated in methyl amooranin-mediated inhibition of experimental mammary carcinogenesis.

Breast cancer represents the second leading cause of cancer-related deaths among women worldwide and preventive therapy could reverse or delay the devastating impact of this disease. Methyl-amooranin (methyl-25-hydroxy-3-oxoolean-12-en-28-oate, AMR-Me), a novel synthetic oleanane triterpenoid, reduced the incidence and burden of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats through antiproliferative and proapoptotic effects. Since chronic inflammation plays an important role in the pathogenesis of breast cancer and several synthetic oleanane compounds are known potent anti-inflammatory agents, we aim to investigate anti-inflammatory mechanisms of AMR-Me by monitoring various proinflammatory and stress markers, such as cyclooxygenase-2 (COX-2) and heat shock protein 90 (HSP90), and nuclear factor-κB (NF-κB) signaling during DMBA mammary tumorigenesis in rats. Mammary tumors were harvested from a chemopreventive study in which AMR-Me (0.8-1.6 mg/kg) was found to inhibit mammary carcinogenesis in a dose-response manner. The expressions of COX-2, HSP90, NF-κB, and inhibitory κB-α (IκB-α) were determined by immunohistochemistry and reverse transcription-polymerase chain reaction. AMR-Me downregulated the expression of intratumor COX-2 and HSP90, suppressed the degradation of IκB-α, and reduced the translocation of NF-κB from cytosol to nucleus. Our present study provides the first in vivo evidence that NF-κB-evoked inflammatory cascade is a major target of AMR-Me in breast cancer. Our current results together with our previous findings suggest that disruption of NF-κB signaling contributes to anti-inflammatory, antiproliferative, and apoptosis-inducing mechanisms involved in AMR-Me-mediated chemoprevention of rat mammary carcinogenesis. These encouraging mechanistic results coupled with a safety profile should facilitate the clinical development of AMR-Me as breast cancer chemopreventive drug.

Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives.

Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented.

Endoscopic anterior capsulectomy for severe elbow contractures.

Elbow stiffness secondary to trauma or surgical reconstruction can sometimes result in a severe contracture with restricted joint space, and arthroscopic access to the joint is difficult. Previous surgery and severe stiffness can also alter the position of neurovascular structures and iatrogenic injury is possible with an inside-out arthroscopic approach. To overcome these technical difficulties, an endoscopic approach to the anterior capsule can be performed as an alternative to open approach. The endoscopic approach utilises the sub-brachialis space for an outside-in capsular resection under vision. Identification of standard anatomic landmarks is useful as a guide for safe resection in a central to peripheral direction.

Chemopreventive effect of a novel oleanane triterpenoid in a chemically induced rodent model of breast cancer.

Breast cancer represents one of the most frequently diagnosed cancers and predominant causes of death in women worldwide. The value of preventive therapy to limit the devastating impact of breast cancer is well established. Various plant triterpenoids and their synthetic analogs have shown significant promise as potent chemopreventive agents in breast cancer. The current study was initiated to investigate mechanism-based chemopreventive potential of a novel synthetic oleanane triterpenoid (methyl-25-hydroxy-3-oxoolean-12-en-28-oate, AMR-Me) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis, an experimental rodent tumor model that closely resembles human mammary cancer. Rats were orally administered with AMR-Me (0.8, 1.2 and 1.6 mg/kg) three times per week for 18 weeks. Following two weeks of AMR-Me treatment, mammary carcinogenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks following DMBA exposure), AMR-Me exhibited a striking inhibition of DMBA-induced mammary tumor incidence, total tumor burden, average tumor weight and reversed histopathological alterations without toxicity. AMR-Me dose-dependently suppressed abnormal cell proliferation, induced apoptosis, up-regulated pro-apoptotic protein Bax and down-regulated antiapoptotic protein Bcl-2 in mammary tumors. AMR-Me upregulated the transcriptional levels of Bax, Bad, caspase-3, caspase-7 and poly(ADP-ribose) polymerase and down-regulated Bcl-2. These results clearly demonstrate for the first time that novel triterpenoid AMR-Me exerts chemopreventive efficacy in the classical DMBA model of breast cancer by suppressing abnormal cell proliferation and inducing apoptosis mediated through mitochondrial pro-apoptotic mechanisms. AMR-Me could be developed as a chemopreventive drug to reduce the risk of human breast cancer that remains a devastating disease.

Black currant phytoconstituents exert chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis by suppression of the inflammatory response.

Black currant fruits containing high amounts of anthocyanins are known to possess potent antioxidant and anti-inflammatory properties. We have previously reported that anthocyanin-rich black currant skin extract (BCSE) inhibits diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats although the underlying mechanisms are not fully understood. Our present study investigates the anti-inflammatory mechanisms of BCSE during DENA rat liver carcinogenesis. Dietary BCSE (100 or 500 mg/kg) treatment for 22 wk afforded a striking inhibition of DENA-induced hepatic gamma-glutamyl transpeptidase-positive preneoplastic foci in a dose-responsive fashion. There was a significant increase in hepatic expression of heat shock proteins (HSP70 and HSP90), cyclooxygenase-2, and nuclear factor-κB (NF-κB) in DENA-exposed rat livers. Dietary BCSE dose-dependently abrogated all these elevated inflammatory markers. The possible cardiotoxicity of BCSE was assessed by monitoring cardiac functions using transthoracic echocardiography. BCSE-mediated anti-inflammatory effects during rat liver carcinogenesis have been achieved without any cardiotoxicity. Our results provide convincing evidence, for the very first time, that suppression of the inflammatory cascade through modulation of the NF-κB signaling pathway could be implicated, at least in part, in the chemopreventive effects of black currant bioactive phytoconstituents against experimental hepatocarcinogenesis. These results coupled with an excellent safety profile of BCSE support the development of black currant phytochemicals for the chemoprevention of inflammation-driven hepatocellular cancer.