Amalgamation of Toll-Like Receptor and Hypoxic Signaling in Etiology of Preeclampsia.

Inflammation and oxidative stress are involved in the pathogenesis of preeclampsia. Therefore, the aim of this study was to investigate the expression of Toll-like receptor (TLR) (TLR-4, HMGB1, NFκB, IκBα) and hypoxic (HIF-1α, HIF-1ß, PHD, pVHL) pathway proteins in the placenta of preeclamptic pregnant women after 28 weeks of gestational period. A possible association between these 2 pathways was also explored. A total of 194 placental tissues of preeclamptic as well as healthy pregnant women were analyzed by immunohistochemistry. On the basis of gestational age, the samples were divided into 2 groups, I (28-36 wk) and II (36 wk onwards), with 55 and 139 samples in the respective groups. The expression of both TLR (TLR-4, HMGB1, NFκB, IκBα) and hypoxic (HIF-1α, HIF-1ß, PHD, pVHL) pathway proteins were significantly modulated in the placental tissues of preeclampsia as compared with control. The 2 pathways were interlinked in preeclampsia. This study highlights the intercorrelation of both TLR and hypoxic signalling pathways that may be a causative factor for the pathophysiology of preeclampsia.

Author Correction: Cyclin D1 protein affecting global women's health by regulating HPV mediated adenocarcinoma of the uterine cervix.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

≤ Cyclin D1 protein affecting global women's health by regulating HPV mediated adenocarcinoma of the uterine cervix.

Adenocarcinoma (ADC) of the uterine cervix (UC) is a rare form of cervical cancer (CC) caused due to the infection of Human Papilloma Virus (HPV). Cyclin D1 is one of the downstream targets of aberrantly activated Notch signaling, contribute to the etiology of CC. However, little is known about the role of Cyclin D1 in the modulation of cervical ADC and is controversial. The purpose of this study is to determine the role of Cyclin D1 protein and to elucidate the combined analysis with Notch signaling proteins in HPV associated ADCs of CC. A total of 60 biopsy samples (40 normal and 20 ADCs of CC) were analyzed for the expression of Cyclin D1 in HPV associated ADCs via immunohistochemistry and by immunoblotting. HPV-16 positive ADC patients showed a strong association with the Cyclin D1 expression (p = 0.007). The significant mean difference (p = 0.0001) and the pairwise comparison between Cyclin D1/JAG1 (p = 0.0001), and Cyclin D1/Notch-3 (p = 0.0001) were observed. The above Notch signaling proteins showed their synergistic role in modulating Cyclin D1 which in-turn regulates HPV-16 associated ADC of the uterine cervix (UC), affecting women's global health.

Association of pro- and anti-inflammatory cytokines in preeclampsia.

INTRODUCTION: The pro- and anti-inflammatory cytokines play crucial role in the development and functions of placenta. Any changes in these cytokines may be associated with many pregnancy-related disorders like preeclampsia. Therefore, the present study is aimed to study the expression of pro-inflammatory (TNF-α, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines in placenta and serum of preeclamptic pregnant women. MATERIAL AND METHODS: For this study, a total of 194 cases of preeclamptic and control cases were enrolled in two Groups as per the gestational age that is, Group I (28-36 weeks) and II (37 weeks onwards). The number of samples was 55 in Group I and 139 in Group II. The immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were conducted on placenta and serum of both preeclamptic and normal samples, respectively. IHC results were revalidated by reverse transcriptase PCR (RT-PCR). RESULTS: Both Groups (I, II) of preeclampsia showed amended levels of pro- and anti-inflammatory cytokines in placental tissues and serum samples. The levels of TNF-α and IL-6 were significantly increased in preeclamptic cases (P = 0.0001, P = 0.0001) while the IL-4 and IL-10 were downregulated (P = 0.0001, P = 0.0001) in comparison to control. In addition, a negative correlation was also observed between the two in preeclampsia (P = 0.0001). CONCLUSION: The balanced ratio of pro- and anti-inflammatory cytokines is essential to regulate the maternal inflammation system throughout pregnancy. Therefore, the gradual cytokine profiling of the pregnant women may be useful for the management of preeclampsia.

HES1 Protein Modulates Human Papillomavirus-Mediated Carcinoma of the Uterine Cervix.

PURPOSE: Cervical cancer (CC) is the most common cancer affecting women worldwide. Human papillomavirus (HPV) infection is a major contributing factor for the development of CC. The development of CC occurs progressively from precancer stages to cancerous stages (ie, invasive squamous cell carcinoma [ISCC] and adenocarcinoma [ADC]). ADC is a rare form of CC that develops from the mucinous endocervical epithelium. It is believed that the downstream targets of Notch signaling contribute to the etiology of CC. One such target is HES1, whose role in the modulation of ADC is unknown. The purpose of this study is to determine the role of HES1 protein in HPV-associated ADC subtype of CC and also to compare its expression in histologic subtypes of precancer and ISCC. PATIENTS AND METHODS: A total of 148 patients (30 with precancers, 98 with ISCC, and 20 with ADC) and 40 normal control participants were analyzed for the expression of HES1 via immunohistochemistry, with results validated by immunoblotting. RESULTS: The comparison between HPV-16 and HES1 expression was significant in precancer (cervical intraepithelial neoplasia grades 1 to 3; P = .013), ISCC (International Federation of Gynecology and Obstetrics stages I to IV; P = .001), and ADC ( P = .007). An overall significant mean difference was observed between HES1, JAG1, and Notch-3 proteins in precancer ( P = .001), ISCC ( P = .001), and ADC ( P = .001). Pairwise comparisons between HES1 and JAG1 and HES1 and Notch-3 were also found to be significant. CONCLUSION: This study showed that among all HPV-16-positive precancers, the major HES1 positivity signal arises from cervical intraepithelial neoplasia grades 2 and 3 that develops into ISCC. Moreover, HPV-16-positive ADC also showed an association with HES1. The HES1, JAG1, and Notch-3 proteins showed their synergistic role in modulating HPV associated ADC along with histologic subtypes of precancer and ISCC of CC.

Jagged-1 induced molecular alterations in HPV associated invasive squamous cell and adenocarcinoma of the human uterine cervix.

The majority of cervical cancer (CC) cases are attributable to HPV infection. Altered Notch pathway signals and HPV are believed to modify clinicopathogenesis of CC, however, the involvement of each molecular player and its mechanism is still not known. Jagged-1 (JAG1) is one of the ligands that induce Notch pathway. The involvement of JAG1 in the modulation of a disease condition is not very clear. Hence, this study aims to study the role of JAG1 in HPV-16/18 associated different histological sub-types of CC, especially ADC. 40 non-neoplastic cervical tissues, 30 precancer and 118 tumor specimens (total 188 tissue biopsies) were studied for the expression of the JAG1 protein through immunohistochemistry, immunoblotting and for HPV infection. Two folds increase of cytoplasmic (Mean ± S.E, 3.67 ± 0.33; p = 0.0001) and nuclear (3.70 ± 0.38, p = 0.0001) JAG1 expression was identified in normal (N) vs precancer and three folds cytoplasmic (4.44 ± 0.17, p = 0.0001) and nuclear (4.64 ± 0.17; p = 0.0001) in N vs. ISCC. Total 85% of ADC patients were found to be infected with HPV, which were 100% infected with HPV-16. These findings suggest the complex synergistic interplay between JAG1 and HPV in regulating clinicopathological progression of CC through its deregulation.

Augmented Activity of Cyclooxygenase-2 in Tissue and Serum of Patients With Cervical Cancer.

BACKGROUND: Cyclooxygenase-2 (Cox-2) is frequently overexpressed in cervical carcinoma, but little is known about its altered serum concentration. Hence, this study evaluates clinical utility of cellular and serum level of Cox-2 enzyme in cervical cancer. METHODS: The expression of Cox-2 was evaluated in cervical tissues and serum samples collected from normal controls (n = 100; n = 68), cervical intraepithelial neoplasia patients (CIN, n = 67; n = 12), and invasive squamous cell carcinoma patients (SCCs; n = 153; n = 127) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses. RESULTS: The significant cytoplasmic overexpression of Cox-2 was noted in 50.7% of CIN and 69.9% of SCCs as compared with normal (P = 0.0001). Serum level of Cox-2 was also found to be elevated both in CIN (median 4.35 ng/ml) and in SCCs (median 19.39 ng/ml) with respect to normal (median 0.44 ng/ml; P = 0.0001), respectively. The ROC analysis revealed the potential of serum Cox-2 over its cellular expression to distinguish CIN and SCCs from normal. CONCLUSION: Augmented Cox-2 activity is implicated in the pathogenesis of cervical cancer, and its serum level could serve a potential to distinguish this malignancy. Therefore, it is suggested that serum Cox-2 may be useful in monitoring the diagnosis and treatment outcome of patients.

HIF-1 Alpha and Placental Growth Factor in Pregnancies Complicated With Preeclampsia: A Qualitative and Quantitative Analysis.

BACKGROUND: The pathophysiology of preeclampsia is not clearly understood worldwide. Hypoxia inducible factor 1α (HIF-1α) is thought to be the preliminary factor for the hypoxic conditions prevailing in preeclampsia, which causes imbalance in the expression of angiogenic proteins. A proangiogenic protein, placental growth factor (PIGF), is reported to be dysregulated in preeclampsia. Therefore, this study focuses on the investigation of HIF-1α and PIGF in preeclamptic conditions and a possible molecular association between them. METHODS: Placental tissue (n = 45 + 45) and serum samples (n = 80 + 80) of preeclamptic patients and healthy control were collected and processed for the analysis of HIF-1α and PIGF by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). RESULTS: In preeclamptic group, the significant nuclear and cytoplasmic expression of HIF-1α was noticed in syncytiotrophoblast (P = 0.0001) but in control placenta, it was localized to cytoplasm (P = 0.0001). The intensity of PIGF expression was lower in syncytiotrophoblast cytoplasm (P = 0.0001) in preeclamptic cases as compared with control. Also, the significant upregulated concentration of HIF-1α and downregulated PIGF was observed in serum samples of preeclamptic woman (P = 0.0001). Thus, there was a significant direct negative correlation between HIF-1α and PIGF both at tissue and serum level (P < 0.01). CONCLUSION: The direct inverse association between HIF-1α and PIGF in serum and placental tissues may be responsible for the low oxidative stress and endothelial dysfunction, leading to the pathogenesis of preeclampsia.

Anatomical Description and Clinical Relevance of a Rare Variation in the Mesenteric Arterial Arcade Pattern.

Solitary vascular variations of the mesenteric arteries are extremely rare and have been seldom reported in the past. The aim of this study is to emphasize the anatomical and clinical relevance of one such rare variation of inferior mesenteric artery (IMA). The current case anomaly was incidentally observed while guiding the undergraduate medical students in the dissection of the mesenteric region of the abdomen in an Indian cadaver. An Accessory left colic artery was seen to be branching off from the Inferior Mesenteric artery and further dividing into two transverse branches which took part in the formation of arterial arc for the perfusion of the transverse and the descending colon. Awareness of such aberrant branches of Inferior Mesenteric artery helps in optimal selection of the mode of treatment or operative planning. Additionally, this knowledge minimizes possible iatrogenic injuries resulting from surgeries. Moreover, surgical anatomy of anomalous branches of Inferior Mesenteric artery is extremely essential for planning and successfully executing reconstructive procedures using these branches as pedicles for the transposed part of the colon.

Aberrant pancreatic ductal organisation: a case report.

Anomalous pancreatic ductal system has always enthralled the anatomists, surgeons, gastroenterologists and radiologists alike. With the growing use of MRCP, ERCP and endoscopic and surgical procedures, the knowledge of anatomical aberrations of pancreaticobiliary tract becomes extremely important. Moreover, the anomalous pancreatic duct morphology may be responsible for atypical gastrointestinal complains. We report an exceptionally rare case of two accessory ventral pancreatic ducts opening separately into the common bile duct proximal to the hepato pancreatic ampulla. Concomitant occurrence of an ectopic major duodenal papilla, 3.8 cm distal to the pyloric end of stomach was also seen. Moreover, the accessory pancreatic duct and the minor duodenal papilla were absent. Clinical implications and embryological description of these rare anomalies are discussed. Awareness of such rare morphological variants can go a long way in assisting effective patient management.

Peripheral communications of intercostobrachial nerve Peripheral communications of the intercostobrachial nerve in relation to the alar thoracic artery.

The intercostobrachial nerve (ICBN) is often encountered during axillary dissection for axillary lymph node dissection (ALND) for diagnostic and therapeutic surgery for mastectomy. The present report is a case observed in the Department of Anatomy at Vardhman Mahavir Medical College, Delhi during routine dissection of the upper extremity of a male cadaver for first year undergraduate medical students. On the right side, the medial cord of brachial plexus gave two medial cutaneous nerves of arm. Both the nerves were seen communicating with the branches of the ICBN. The ICBN and one of its branches were surrounding the termination of an alar thoracic artery. These peripheral neural connections of the ICBN with the branches of the medial cord can be a cause of sensory impairment during axillary procedures done for mastectomy or exploration of long thoracic nerves. The alar thoracic artery found in relation to the ICBN could further be a cause of vascular complications during such procedures.

Unduly extensive uncinate process of pancreas in conjunction with pancreatico-duodenal fold.

Anatomical variations of pancreatic head and uncinate process are rarely encountered in clinical practice. These variations are primarily attributed to the complex development of the pancreas. An unduly enlarged uncinate process of the pancreas overlapping the third part of duodenum was discovered during dissection. This malformation of the pancreatic uncinate process was considered to be due to excessive fusion between the ventral and dorsal buds during embryonic development. On further dissection, an avascular pancreatico-duodenal fold guarding the pancreatico-duodenal recess was observed. The enlarged uncinate process can cause compression of neurovascular structures and also cause compression of adjoining viscera. The pancreatico-duodenal recess becomes a potential site for internal herniation. This case is of particular interest to the gastroenterologists and surgeons performing surgical resections. Precise knowledge of embryogenesis of such pancreatic anomalies is necessary for understanding and thus treating many diseases of the pancreas.

Unusual disposition of lateral circumflex femoral artery: Anatomical description and clinical implications.

The anatomical knowledge of arterial variations of lower limb is of utmost significance for the present day surgeons and interventional radiologists for minimizing complications during vascular reconstructive procedures, catheterization procedures and surgical intervention for embolism. Lateral Circumflex Femoral Artery (LCFA) is an important branch of Profunda Femoris artery and precise knowledge of its variations can be of great relevance during surgical and radiological procedures in femoral region. The present study reports a unique case of anomalous route taken by LCFA posterior to femoral nerve associated with a prominent muscular branch from Femoral artery mimicking the course of LCFA. Documentation of such variations is highly significant. It may serve as guideline for surgeons in reducing the incidence of postoperative complications where LCFA is used as a long vascular pedicle in anterolateral perforator thigh flap and in breast reconstruction after mastectomy. Ignorance of such variations can lead to fatal intraoperative haemorrhage and incapacitating sensory and motor deficit due to injury to femoral nerve branches which are closely related to these vessels.

Clinical significance of inactivated glycogen synthase kinase 3ß in HPV-associated cervical cancer: Relationship with Wnt/ß-catenin pathway activation.

PROBLEM: To determine the role of inactivated GSK3ß with respect to Wnt/ß-catenin pathway activation in HPV-16/18-associated cervical cancer. METHOD OF STUDY: The expression of active (pGSK3ß-Try(216)), inactive (pGSK3ß-Ser(9)), and c-Myc as well as HPV-16/18 infection was analyzed in cervical intra-epithelial neoplasia (CIN), squamous cell carcinoma (SCCs) and normal by immunohistochemistry and multiplex PCR. The proteins level was also compared with ß-catenin and APC expression. RESULTS: The dramatic decrease of pGSK3ß-Try(216) expression but ectopic overexpression of pGSK3ß-Ser(9) and c-Myc was observed both in CIN and SCCs samples compared to normal tissues. 57/67 CIN and 132/153 SCCs showed HPV-16 infection, while 3/67 CIN and 4/153 SCCs were harbored with HPV-18 infection. Both the proteins were significantly upregulated in HPV-16 infected cases (P = 0.0001; P = 0.001) and also positively correlated with nuclear ß-catenin (P = 0.0001; P = 0.0001). CONCLUSION: The process of generation of HPV-16-associated cervical tumorigenesis is synergized with GSK3ß inactivation and overactivation of Wnt/ß-catenin pathway.

Clinical impact of de-regulated Notch-1 and Notch-3 in the development and progression of HPV-associated different histological subtypes of precancerous and cancerous lesions of human uterine cervix.

BACKGROUND: Cervical cancer is the leading cause of cancer related deaths among women in India. Limited reports are available for Notch-1 and Notch-3 protein in cervical carcinoma, which play crucial role in cell proliferation, differentiation, and apoptosis. METHODS: This study was designed to evaluate the role of Notch-1 and Notch-3 with context to HPV infection in cervical carcinoma. A total of 168 tissue biopsy samples comprising of tumor specimens (n = 98), precancer (n = 30) and non-neoplastic cervical tissues (n = 40) were screened for HPV infection by PCR and expression of Notch-1 and Notch-3 protein by Immunohistochemistry and Immunoblotting. RESULTS: 80% (24/30) were found to be positive for HPV in precancer and 86.7% (85/98) in cancer patients. Notch-1 expression of precancer and cancer cases was found to be significantly down-regulated with severity of disease in nuclear (3.43±0.29; 2.04±0.19, p = 0.0001, p = 0.0001) and cytoplasm (3.07±0.29; 2.29±0.17, p = 0.0001, p = 0.0001) obtained from different stages as compared to normal cervix tissue (5.40±0.19, 4.97±0.15; p<0.001; p<0.001). However, Notch-3 expression of above cases was significantly up-regulated with severity of disease and showed intense nuclear (4.17±0.39; 4.74±0.18, p = 0.0001, p = 0.0001) and cytoplasm (3.67±0.36; 4.48±0.18, p = 0.0001, p = 0.0001) of different stages as compared to normal cervix tissue (0.95±0.20, 0.70±0.20; p<0.001; p<0.001) respectively. CONCLUSIONS: These findings suggest that Notch-1 and Notch-3 may play an important role with synergistic effect of HPV in regulating development and proliferation of cervical cancer through the deregulation of Notch signalling. This study also shows the clinical utility of both proteins which may be used as predictable biomarkers in diagnosing different histological sub-types of HPV associated cervical cancer. Nevertheless, abnormal activation of this pathway may provide legitimate targets for cervical cancer therapy.

Peptidyl-prolyl isomerase Pin1-mediated abrogation of APC-ß-catenin interaction in squamous cell carcinoma of cervix.

OBJECTIVE: The present study was aimed to investigate the importance of Pin1 expression in Squamous Cell Carcinoma (SCC) of cervix and to assess its level with ß-catenin and APC to understand the possible involvement of Pin1 in the regulation of these proteins and subsequent activation of Wnt/ß-catenin signaling. MATERIALS AND METHODS: Expression of Pin1, ß-catenin and APC was examined in 153 SCC patients by immunohistochemistry and revalidated by western blotting. RESULTS: Of the 153 SCC analyzed, Pin1 was overexpressed in 73 (47.71%) cases. Loss of membranous ß-catenin was noticed in 117 (76.47%) SCCs, whereas 66/153 (43.13%) and 93/153 (60.78%) cases showed its distinct cytoplasmic as well as nuclear accumulation respectively. Down regulation/loss of APC was observed in 69 (45.09%) cases, suggesting the activation of Wnt/ß-catenin pathway in SCCs. Pin1 showed the significant association with nuclear ß-catenin (r=.349, p<0.0001) and cytoplasmic loss of APC (r=-.287, p<0.0001). Both Pin1 as well as nuclear ß-catenin were found to be associated with tumor stage (p=0.004, p=0.031) and tumor size (p=0.022, p=0.003). The Pin1 overexpression showed the significant association with disease free survival (p=0.002) but not with overall survival (p=0.421) of SCC patients. CONCLUSION: Current results explore the expressional relationship between Pin1, ß-catenin and APC suggesting that Pin1 regulates the activation of Wnt/ß-catenin pathway in SCCs via modulating the interaction between ß-catenin and APC. Furthermore, the significant association of Pin1 and ß-catenin with tumor variables underscores the clinical utility of these proteins in cervical cancer.

Human tibial torsion--morphometric assessment and clinical relevance.

BACKGROUND: Tibial torsion is an important anatomical parameter in clinical practice and displays variability among individuals. These variations are extremely significant in view of alignment guides such as those related to rotational landmarks of tibia in total knee arthroplasty. Further, precise knowledge and information pertaining to angle of tibial torsion also helps in correction of traumatic malunion or congenital maltorsion of tibia. METHODS: The present study was carried out to determine the angle of tibial torsion in 100 adult dry tibia bones in the Department of Anatomy, Government Medical College, Amritsar. The study group comprised 50 males and 50 females with equal number of right- and left-sided bones. The measurements were meticulously recorded and the data were subjected to statistical analysis. The results were analyzed and discussed in the light of existing literature. RESULTS: On the right side, it was found to be 29.84° ± 4.86°° (range = 22.00° -38.00°) in males and 28.92° ± 5.10°° (range = 15.00°-38.00°) in females. On the left side, it was found to be 28.00° ± 4.94°° (range = 20.00°-40.00°°) in males and 28.12° ± 4.28°° (range = 20.00°-37.00°°) in females. CONCLUSION: The present study is an endeavor to provide baseline data with reference to the angle of tibial torsion in the Indian population. The results of the study assume special importance in view of the technical advancements in reconstructive surgical procedures in orthopedic practice.

Quadrifurcation of the hepatic artery proper in conjunction with double right gastric arteries.

Descriptions of the variant hepatic arterial pattern are common and frequently reported in anatomy archives. We describe a noteworthy deviation from the usual branching pattern in a single cadaver. There was a unique division of the hepatic artery proper into two right gastric arteries (RGAs), apart from the usual branches. Furthermore, an arterial loop was formed by these two RGAs, giving off another RGA, which we termed 'right gastric proper'. This report attempts to evaluate the embryological basis of the anomaly. The significance of this anomalous hepatic arterial pattern is appreciated while performing liver transplantations, hepatic artery infusion of chemotherapeutic drugs and Doppler angiographic procedures. We advocate meticulous familiarisation with the anatomy of the coeliac trunk and its topographic relationship to vital viscera for the operating hepatobiliary surgeon and radiologist.

Anomalous composition of musculature of the first dorsal fibro-osseous compartment of the wrist.

The anomalous orientation of musculature of the first dorsal fibro-osseous compartment of the wrist is clinically relevant to De Quervian's stenosing tenosynovitis and reconstructive surgeries. Split insertion of the abductor pollicis longus (APL) is commonly found in chimpanzees, gorillas and gibbons. A comparable identical pattern of anomalous slips in humans is of anthropological and phylogenetic importance and could be a result of atavism. This case report describes an unusual fused muscle belly of the APL and extensor pollicis brevis (EPB), which split into three slips--medial, intermediate and lateral. Further, the medial slip was seen to divide into two tendons, inserting on the base of the first metacarpal along with the intermediate slip. The lateral slip divided into three tendons, inserting into the base of the proximal phalanx, base of the first metacarpal and abductor pollicis brevis muscle. The fusion and unusual insertion pattern of the APL and EPB merits documentation for reconstructive procedures such as tendon transfer and interposition arthroplasty.

Unusual topography of posterior antebrachial musculature in the first osseofibrous compartment of wrist: clinicomorphological appraisal / Topografía inusual de la musculatura antebraquial posterior en el primer compartimento osteofibroso de la muñeca: valoración clínico-morfológica

Anatomical variations of abductor pollicis longus and extensor pollicis brevis are important in clinical assessment of diseased and traumatized hand. The present case reports an unusual fusion of muscle bellies of abductor pollicis longus and extensor pollicis brevis with two separate tendons of insertion, the medial tendon inserted into the base of first metacarpal and the lateral tendon into the abductor pollicis brevis muscle. Knowledge of such anatomical variations is of utmost importance in the management of De Quervain's disease and reconstructive surgeries of hand.

Las variaciones anatómicas de los músculos abductor largo del pulgar y extensor corto del pulgar son importantes en la evaluación clínica de la mano enferma y traumatizada. El presente caso informa una inusual fusión de los vientres musculares de los Mm. abductor largo del pulgar y extensor corto del pulgar con dos tendones de inserción separados, el tendón medial se insertó en la base del primer metacarpiano y el tendón lateral en el músculo abductor corto del pulgar. El conocimiento de estas variaciones anatómicas es de importancia en el manejo de la enfermedad de De Quervain y cirugía reconstructiva de la mano.