N-Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.     

Primary hydatid cyst of the retroperitoneum

Retroperitoneal contamination may occur during the natural history of hydatid disease. Primary hydatid cyst of the retroperitoneum is extremely rare. The authors report a case of a giant retroperitoneal hydatid cyst. Clinicians and surgeons must be aware of this possibility and follow a policy of nonsystematic puncture of an abdominal cyst and avoid spillage during surgery. Symptoms are related to the size, location, or ensuing complications of a cyst. Its occurrence should be strongly suspected ahead of any abdominal cyst, especially in an endemic area, where it may act as a parasite. Total and careful surgical excision is the gold-standard therapy.     

Abdominal wall abscess following laparoscopic cholecystectomy: an unusual late complication of lost gallstones

Laparoscopic cholecystectomy (LC) is associated with a significant risk of gallbladder perforation with spillage of bile and stones into the peritoneal cavity. The retrieval of the spilled stones is not always possible by laparoscopic technique. Majority of these cases do not have any problem in future but sometimes the lost stones lead to serious complications. The authors present a case of lost gallstones, which resulted into an abdominal wall abscess and discharging sinus 9 years after LC. This late presentation is among the very few reports after LC. Risk factors for gallbladder perforation, various techniques to avoid spillage of stones, possible complications and their management is discussed.     

Nociceptor-derived brain-derived neurotrophic factor regulates acute and inflammatory but not neuropathic pain

Conditional mouse knock-outs provide an informative approach to drug target validation where no pharmacological blockers exist or global knock-outs are lethal. Here, we used the Cre-loxP system to delete BDNF in most nociceptive sensory neurons. Conditional null animals were healthy with no sensory neuron loss. However, pain-related behavior was substantially altered. Baseline thermal thresholds were reduced. Carrageenan-induced thermal hyperalgesia was inhibited. Formalin-induced pain behavior was attenuated in the second phase, and this correlated with abolition of NMDA receptor NR1 Ser896/897 phosphorylation and ERK1 and ERK2 activation in the dorsal horn; AMPA receptor phosphorylation (GluR1/Ser831) was unaffected. NGF-induced thermal hyperalgesia was halved, and mechanical secondary hyperalgesia caused by intramuscular NGF was abolished. By contrast, neuropathic pain behavior developed normally. Nociceptor-derived BDNF thus plays an important role in regulating inflammatory pain thresholds and secondary hyperalgesia, but BDNF released only from nociceptors plays no role in the development of neuropathic pain.     

Autologous chondrocyte implantation drives early chondrogenesis and organized repair in extensive full‐ and partial‐thickness cartilage defects in an equine model

Autologous chondrocyte implantation (ACI) has been used clinically for over 15 years and yet definitive evidence of chondrocyte persistence and direct impact on cartilage repair in full‐thickness lesions is scant and no data are available on ACI in partial‐thickness defects in any animal model. This study assessed the effect of chondrocytes secured using periosteal overlay in partial‐ and full‐thickness cartilage defects in the equine model. Paired cartilage defects 15 mm in diameter were made in the patellofemoral joint of 16 horse and repaired with ACI or periosteal flap alone. Response was assessed at 8 weeks by clinical, microradiographic, and histologic appearance, and by collagen type II immunohistochemistry, and proteoglycan and DNA quantification. ACI improved histologic scores in partial‐ and full‐thickness cartilage defects, including defect filling, attachment to the underlying subchondral bone, and presence of residual chondrocyte accumulations. For partial‐thickness defects chondrocyte predominance, collagen type II content, and toluidine stained matrix were enhanced, and attachment to the surrounding cartilage improved. DNA and PG content of grafted partial‐thickness defects was improved by chondrocyte implantation. Periosteal patches alone did not induce cartilage repair. This study indicated implantation of chondrocytes to cartilage defects improved healing with a combination of persisting chondrocyte regions, enhanced collagen type II formation, and better overall cartilage healing scores. Use of ACI in the more challenging partial‐thickness defects also improved histologic indices and biochemical content. The equine model of cartilage healing closely resembles cartilage repair in man, and results of this study confirm cell persistence and improved early cartilage healing events after ACI. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1121–1130, 2011     

Determinants of serum sclerostin in healthy pre‐ and postmenopausal women

Sclerostin is a secreted Wnt antagonist produced almost exclusively by osteocytes that regulates bone mass. However, there is currently limited information on the determinants of sclerostin in a large population‐based study. The main objectives of the present study were to: (1) establish reference normative interval values for serum sclerostin in randomly selected healthy premenopausal women; (2) study the changes in serum sclerostin in relation to age in premenopausal and postmenopausal women and the factors that may influence bone turnover; and (3) determine the effect of menopausal status on serum sclerostin. A total of 1803 women were studied (including [n = 1235] premenopausal, and [n = 568] postmenopausal women, respectively, aged 20 to 79 years). A total of 443 healthy premenopausal women (aged 35 to 45 years) were used to establish reference normative intervals for serum sclerostin. All women studied were medically examined and had their bone mineral density values obtained for the lumbar spine (L₁–L₄) and femoral neck according to a detailed inclusion criteria. In all women, values of serum sclerostin increased with increasing age up to the age of 45 years, and remained increased in postmenopausal women. Significant increases were evident in serum sclerostin in postmenopausal women with increasing years since menopause. Using stepwise multiple linear regression analysis, several variables were identified as determinants of serum sclerostin, including age, parathyroid hormone, estradiol (E₂), and follicle‐stimulating hormone (FSH) for premenopausal women; age, FSH, and E₂ for postmenopausal women; and age, serum osteocalcin, FSH, and E₂ in the entire sample studied. Further studies are needed to establish the potential role of this increase in mediating the known age‐related impairment in bone formation. © 2011 American Society for Bone and Mineral Research     

Review of a single contemporary femoral neck fracture fixation method in young patients

An intracapsular femoral neck fracture in a young patient is a rare and difficult injury to manage. The occurrence of complications following fixation is multifactorial. Initial displacement and timing and accuracy of reduction are the key factors affecting outcome. The severities of the trauma to the hip and the impact of the intracapsular hematoma also play a role, the importance of which remains poorly understood. The purpose of this study was to evaluate the high incidence of femoral neck fractures treated in our institution over a 7-month period, to record the long-term outcome of these patients, all of whom were treated with contemporary methods of internal fixation, and to highlight the reasons for this injury being termed an "orthopedic emergency" and its differences from the same injury in the elderly population. We performed a retrospective analysis of 12 cases of intracapsular femur neck fracture in patients younger than 50 years treated over 7 months in a regional trauma center. All patients underwent satisfactory reduction and fixation. Nine of the 12 patients had a good outcome at a mean follow-up of 29 months. One patient developed a nonunion of the femoral head requiring total hip arthroplasty, one developed avascular necrosis of the femoral head, and one developed partial avascular necrosis. This compares favorably with other studies.     

Toilet seat injury of the Achilles tendon a series of twelve cases

Lacerations of the Achilles tendon are caused by a number of mechanisms. The toilet seat as a cause of Achilles tendon injury is rare. We report on this rare mechanism of laceration of the tendo Achilles. The injury can be avoided with the use of western toilets and the additional devascularisation caused by extending the wound should be avoided while repairing the tendon in such situations.     

Reamed intramedullary nailing versus unreamed intramedullary nailing for shaft fracture of femur: a systematic literature review

Introduction  

Fractures of femoral fracture are among the most common fractures encountered in orthopedic practice. Intramedullary nailing is the treatment choice for femoral shaft fractures in adults. The objective of this article is to determine the effects of reamed intramedullary nailing versus unreamed intramedullary nailing for fracture of femoral shaft in adults.