Unstable intertrochanteric versus displaced femoral neck fractures treated with cementless bipolar hemiarthroplasty in elderly patients; a comparison of 80 matched patients.

BACKGROUND: While hemiarthroplasty (HA) is considered the treatment of choice for displaced femoral neck (FN) fractures in elderly patients, HA has been partly performed as an alternative treatment option for unstable intertrochanteric (IT) fractures. However, there is a paucity of data regarding the risk and availability of HA for unstable IT fractures compared to HA for displaced FN fractures in elderly patients. Therefore, we performed this case-control study to determine whether HA for unstable IT fractures provides clinical results and survival comparable to HA for displaced FN fractures in elderly patients. HYPOTHESIS: HA for unstable IT fractures in elderly patients provides clinical results and 1-year survival comparable to HA for displaced FN fractures in the same aging group. MATERIALS AND METHODS: We identified 80 patients aged 75years or older, who underwent cementless bipolar HA for unstable IT fracture (AO/OTA type 31-A2.2/3 and A3.3). Their clinical results and 1-year survival were compared to the matched control group of 80 patients with displaced FN fractures (Garden type 3 and 4) treated with the same procedure. Perioperative results, postoperative complications, and 1-year survival were investigated between the two groups. Functional outcome was assessed by walking status and Harris hip score (HHS) 6months after surgery. RESULTS: Operating time was significantly longer in the IT group than the FN group (97.3min [50 to 255] vs. 79.3min [40 to 175], P=0.016). However, the two groups did not significantly differ regarding perioperative results, such as total blood loss, transfusion, intraoperative fracture, length of hospital stay, and postoperative complication. No statistically significant differences in walking status and HHS were observed between the groups. No significant difference in cumulative survival was observed between the two groups (P=0.836), with a 1-year survival rate of 80% (95% confidence interval [CI], 71.8 to 87.5) in the IT group and 82% (95% CI, 73.1 to 89.4) in the FN group. CONCLUSION: HA for unstable IT fractures in elderly patients showed clinical results and 1-year survival comparable to HA as the treatment of choice for displaced FN fractures in the same aging group. LEVEL OF EVIDENCE: Level III, case-control study.

Meta-analysis of the risk of small bowel obstruction following open or laparoscopic colorectal surgery.

BACKGROUND: One of the potential advantages of laparoscopic compared with open colorectal surgery is a reduction in postoperative bowel obstruction events. Early reports support this proposal, but accumulated evidence is lacking. METHODS: A systematic review and meta-analysis was performed of randomized clinical trials and observational studies by searching the PubMed and Cochrane Library databases from 1990 to August 2015. The primary outcomes were early and late postoperative bowel obstruction following laparoscopic and open colorectal surgery. Both ileus and bowel obstruction were defined as a postoperative bowel obstruction. Subgroup and sensitivity analyses were performed, and a random-effects model was used to account for the heterogeneity among the studies. RESULTS: Twenty-four randomized clinical trials and 88 observational studies were included in the meta-analysis; 106 studies reported early outcome and 12 late outcome. Collectively, these studies reported on the outcomes of 148 392 patients, of whom 58 133 had laparoscopic surgery and 90 259 open surgery. Compared with open surgery, laparoscopic surgery was associated with reduced rates of early (odds ratio 0·62, 95 per cent c.i. 0·54 to 0·72; P < 0·001) and late (odds ratio 0·61, 0·41 to 0·92; P = 0·019) postoperative bowel obstruction. Weighted mean values for early postoperative bowel obstruction were 8 (95 per cent c.i. 6 to 10) and 5 (3 to 7) per cent for open and laparoscopic surgery respectively, and for late bowel obstruction were 4 (2 to 6) and 3 (1 to 5) per cent respectively. CONCLUSION: The reduction in postoperative bowel obstruction demonstrates an advantage of laparoscopic surgery in patients with colorectal disease.

Optogenetic activation of intracellular adenosine A2A receptor signaling in the hippocampus is sufficient to trigger CREB phosphorylation and impair memory.

Human and animal studies have converged to suggest that caffeine consumption prevents memory deficits in aging and Alzheimer's disease through the antagonism of adenosine A2A receptors (A2ARs). To test if A2AR activation in the hippocampus is actually sufficient to impair memory function and to begin elucidating the intracellular pathways operated by A2AR, we have developed a chimeric rhodopsin-A2AR protein (optoA2AR), which retains the extracellular and transmembrane domains of rhodopsin (conferring light responsiveness and eliminating adenosine-binding pockets) fused to the intracellular loop of A2AR to confer specific A2AR signaling. The specificity of the optoA2AR signaling was confirmed by light-induced selective enhancement of cAMP and phospho-mitogen-activated protein kinase (p-MAPK) (but not cGMP) levels in human embryonic kidney 293 (HEK293) cells, which was abolished by a point mutation at the C terminal of A2AR. Supporting its physiological relevance, optoA2AR activation and the A2AR agonist CGS21680 produced similar activation of cAMP and p-MAPK signaling in HEK293 cells, of p-MAPK in the nucleus accumbens and of c-Fos/phosphorylated-CREB (p-CREB) in the hippocampus, and similarly enhanced long-term potentiation in the hippocampus. Remarkably, optoA2AR activation triggered a preferential p-CREB signaling in the hippocampus and impaired spatial memory performance, while optoA2AR activation in the nucleus accumbens triggered MAPK signaling and modulated locomotor activity. This shows that the recruitment of intracellular A2AR signaling in the hippocampus is sufficient to trigger memory dysfunction. Furthermore, the demonstration that the biased A2AR signaling and functions depend on intracellular A2AR loops prompts the possibility of targeting the intracellular A2AR-interacting partners to selectively control different neuropsychiatric behaviors.

The effect of horse simulator riding on visual analogue scale, body composition and trunk strength in the patients with chronic low back pain.

BACKGROUND: Chronic low back pain (CLBP) is one of the most common musculoskeletal disorders, and thus effective treatments are required. Recently, real horseback riding has been reported to be beneficial for the patients. However, it has some limitations, such as limited approaches and safety issues. OBJECTIVE: The purpose of this study was to investigate the effect of horse simulator riding on back pain, body composition and trunk strength in the patients with CLBP. PARTICIPANTS: Forty-seven men with CLBP (mean age 20.55 ± 1.38 years) were randomly divided into a control group (n = 23) and a horse simulator riding group (n = 24), and visual analogue scale (VAS), body composition and isokinetic trunk strength were measured after 8 weeks for which subjects in a horse simulator riding group had performed the horse simulator exercise (HSE). RESULTS: Horse simulator exercise significantly reduced pain scores of VAS and enhanced isokinetic torques of trunk at 30 and 90°/s. There were also significantly increased muscle mass and decreased fat mass in horse simulator riding group. CONCLUSION: It can be inferred that HSE may be helpful in relief of back pain and recovery of back function through developing trunk strength and balancing the ratio of trunk flexor/extensor muscles.

Clinical characterization and molecular classification of 12 Korean patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism.

CONTEXT: Pseudohypoparathyroidism (PHP) is defined as resistance toward parathyroid hormones. PHP and pseudopseudohypoparathyroidism (PPHP) are rare disorders resulting from genetic and epigenetic aberrations within or upstream of the GNAS locus. This study investigated the clinical characteristics and performed a molecular analysis of PHP and PPHP. METHODS: A total of 12 patients with (P)PHP from 11 unrelated families (4 with PHP-Ia, 6 with PHP-Ib, and 2 with PPHP) were characterized using both clinical and molecular methods. Clinical features included the presenting symptoms, Albright hereditary osteodystrophy features, and resistance to hormones. Comprehensive analysis of the GNAS and STX16 loci was undertaken to investigate the molecular defects underlying (P)PHP. RESULTS: All PHP-Ib patients displayed hypocalcemic symptoms. All PHP-Ia patients showed resistance toward TSH, in addition to PTH. In most patients with PHP, when the diagnosis of PHP was first established, hypocalcemia and hyperphosphatemia were associated with a significant increase in serum PTH levels. One patient with PHP-Ia was diagnosed with growth hormone deficiency and showed a good response to human recombinant growth hormone therapy. 6 patients with PHP-Ia and PPHP showed 5 different mutations in the GNAS gene. 5 patients with PHP-Ib displayed a loss of differentially methylated region (DMR) imprints of the maternal GNAS. One PHP-Ib patient showed a de novo microdeletion in STX16 and a loss of methylation of exon A/B on the maternal allele. No patients revealed paternal disomy among 4 patients with PHP-Ib. CONCLUSIONS: Identification of the molecular causes of PHP and PPHP explains their distinctive clinical features and enables confirmation of the diagnosis and exact genetic counseling.

Infectious complications following allogeneic stem cell transplantation: reduced-intensity vs. myeloablative conditioning regimens.

BACKGROUND: In allogeneic stem cell transplantation (allo-SCT), reduced-intensity conditioning (RIC) is known for producing less regimen-related toxicity. However, whether or not RIC reduces the risk for infection and infection-related mortality (IRM) remains controversial. METHODS: We retrospectively analyzed infectious episodes and IRMs after allo-SCTs by time period and by the intensity of the conditioning regimen (RIC [n = 81] vs. myeloablative conditioning, MAC [n = 150]). RESULTS: The cumulative incidence of any kind of infection was lower in the RIC group through the entire period (72% vs. 87%; P = 0.007). The onset of infections was deferred in the RIC group as compared with the MAC group (P = 0.012). Bacteremia occurred less frequently in the RIC group through the entire period (5% vs. 14%; P = 0.044). However, the incidences of cytomegalovirus reactivation and disease, herpes zoster, virus-associated hemorrhagic cystitis, and invasive fungal infection were not different between the two groups. Furthermore, there was no difference in relapse-free survival and IRM between the two conditioning regimens. CONCLUSION: Careful monitoring and appropriate preventive/therapeutic strategies for infectious complications, comparable to those for allo-SCT recipients with MAC, should also be applied to those with RIC, especially after engraftment.

The stereotypy-inducing and OCD-like effects of chronic 'binge' cocaine are modulated by distinct subtypes of nicotinic acetylcholine receptors.

BACKGROUND AND PURPOSE: High rates of cigarette smoking occur in cocaine-dependent individuals, reflecting an involvement of nicotinic acetylcholine receptors (nAChRs) in cocaine-elicited behaviour. This study was designed to assess the contribution of different nAChR subtypes to the behavioural and neurochemical effects of chronic cocaine treatment. EXPERIMENTAL APPROACH: Cocaine (15 mg·kg(-1) , i.p.) was administered to male C57BL/6J mice in a chronic 'binge' paradigm, with and without the coadministration of the α7 preferring nAChR antagonist methyllycaconitine (MLA; 5 mg·kg(-1) , i.p.) or the ß2* nAChR antagonist dihydro-ß-erythroidine (DHßE; 2 mg·kg(-1) , i.p.). Quantitative autoradiography was used to examine the effect of cocaine exposure on α7 and α4ß2* nAChRs, and on the high-affinity choline transporter. KEY RESULTS: MLA+cocaine administration induced an intense self-grooming behaviour, indicating a likely role for α7 nAChRs in modulating this anxiogenic, compulsive-like effect of cocaine. In the major island of Calleja, a key area of action for neuroleptics, MLA+cocaine reduced choline transporter binding compared with cocaine (with or without DHßE) administration. DHßE treatment prevented the induction of stereotypy sensitisation to cocaine but prolonged locomotor sensitisation, implicating heteromeric ß2* nAChRs in the neuroadaptations mediating cocaine-induced behavioural sensitisation. 'Binge' cocaine treatment region-specifically increased α4ß2* nAChR binding in the midbrain dopaminergic regions: ventral tegmental area and substantia nigra pars compacta. CONCLUSIONS AND IMPLICATIONS: We have shown a differential, subtype-selective, contribution of nAChRs to the behavioural and neurochemical sequelae of chronic cocaine administration. These data support the clinical utility of targeting specific nAChR subtypes for the alleviation of cocaine-abuse symptomatology.

Acute cytomegalovirus pneumonia and hepatitis presenting during acute HIV retroviral syndrome.

Cytomegalovirus (CMV) disease is a frequent opportunistic infection that usually occurs in the late stages of HIV infection as a result of reactivation of a latent infection. We report a case of a 23-year-old man with acute retroviral syndrome complicated by coexisting CMV pneumonia and CMV hepatitis, which were documented by histopathological examination. His CMV pneumonia and hepatitis were assumed to be primary CMV diseases owing to the absence of CMV IgG antibody. To the best of our knowledge, this is the first case of simultaneous CMV pneumonia and hepatitis occurring as primary CMV diseases during primary HIV infection. This case indicates that invasive CMV diseases such as pneumonia and hepatitis should be considered even in patients with primary HIV infection.

Population pharmacokinetics of intravenous itraconazole in patients with persistent neutropenic fever.

PURPOSE: Empirical use of intravenous (IV) itraconazole (ITZ) for febrile neutropenic patients has recently been introduced in Korea. This study was designed to investigate the population pharmacokinetics (PK) of IV-ITZ. METHODS: Sparse PK data were collected from febrile neutropenic patients undergoing empirical ITZ therapy at 200 mg/day after loading doses. NONMEM (Version. 5.1.1) was used to estimate population PK parameters. RESULTS: Forty-two patients were enrolled in the study. Mean population CL and V of IV-ITZ were 10 L/h and 1050 L, respectively. Body weight was the only contributing covariate of CL. The median simulated trough concentration of ITZ after 10 days was predicted to be about 700 ng/mL. CONCLUSIONS: In this study, we explored the population PK profile of ITZ given in IV formulation. We found that the current dosage regimen of IV-ITZ (200 mg/day) was appropriate to obtain therapeutic trough concentrations for neutropenic patients in Korea.

Infectious complications associated with alemtuzumab use for allogeneic hematopoietic stem cell transplantation: comparison with anti-thymocyte globulin.

OBJECTIVES: To evaluate the incidence of infectious complications after receiving alemtuzumab as part of a conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in Korean patients. METHODS: From November 2004 to January 2006, 12 patients who received alemtuzumab-based conditioning regimens for allogeneic HSCT were evaluated retrospectively until death or until the end of the follow-up in July 2007; they were compared with 18 patients who received rabbit anti-thymocyte globulin (ATG)-containing conditioning regimens from January 2002 to January 2006. RESULTS: Post-engraftment infections occurred more frequently in the alemtuzumab recipients than in the ATG recipients; the mean number of infections, excluding cytomegalovirus (CMV) infections, per patient during the follow-up period was 2.6+/-1.4 vs. 1.0+/-0.8 (P=0.003), respectively. Although there was no statistical difference in the cumulative incidence of CMV infection between the 2 groups (91.7% vs. 55.6%, P=0.381), the alemtuzumab recipients had a higher incidence of CMV diseases (41.6% vs. 0%, P=0.0006) and a higher recurrence rate of CMV infection (90.0% vs. 27.3%, P=0.008) than did the ATG recipients, irrespective of the dose of alemtuzumab. Hemorrhagic cystitis (HC) (66.7% vs. 16.7%, P=0.009) and BK virus-associated HC (41.7% vs. 5.6%, P=0.026) developed more frequently in the alemtuzumab recipients. The all-cause mortality rate was not significantly different between the alemtuzumab and the ATG recipients (75% vs. 55.6%, P=0.28). CONCLUSION: Alemtuzumab recipients had a high incidence of CMV disease as well as BK virus-associated HC compared with the ATG recipients. The dose of alemtuzumab should be tailored to patients' risk; in addition, the implementation of the appropriate prophylaxis for CMV and early detection strategies for BK virus are recommended.

Inhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice.

We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on N-methyl-D-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D(1) and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance.

Long-term outcome of per anum intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer.

OBJECTIVE: The authors have performed per anum intersphincteric rectal dissection. With direct coloanal anastomosis for cases of lower rectal cancer in which the distal surgical margin is difficult to secure by the double stapling technique. The aim of this study was to evaluate the long-term outcome and to clarify the surgical indications for this operation. PATIENTS AND METHODS: Between 1993 and 2002, 31 patients underwent per anum intersphincteric rectal dissection with direct coloanal anastomosis. Of these, two patients (one stage 0 and one stage IV) were excluded from the analysis of oncological outcome. The remaining 29 patients formed the basis of this study. The median follow-up was 57 months (range 6-106 months). RESULTS: Local recurrence and distant metastasis developed in 9 and 3 patients, respectively. Local recurrence rate for pT1 was significantly lower than that for pT2/T3 disease. The local recurrence rate cases with tumours less than 3 cm was significantly lower than that for tumours sized 3 cm or more. The distant metastasis rate for cases with lymph node metastasis was significantly higher than that for cases without lymph node metastasis. There was an association between distant metastasis and TNM or pT stage. The overall survival rates for stage I, II and III were 85%, 80% and 89%, respectively. No significant difference was seen in total Cleveland Clinic incontinence score between per anum intersphincteric rectal dissection with direct coloanal anastomosis and the double stapling technique. CONCLUSION: The surgical indications of this operation should be limited to patients with T1 rectal cancer or tumours less than 3 cm.

Infectious complications and outcomes after allogeneic hematopoietic stem cell transplantation in Korea.

We reviewed 242 allogeneic hematopoietic stem cell transplantation (HSCT) recipients retrospectively over a 2-year period (January 1998-December 1999) in order to analyze the characteristics and assess the outcomes of infectious complications in patients after HSCT in Korea. Bacteria were the major pathogens before engraftment, and viral and fungal infections predominated during the post-engraftment period. Varicella zoster virus was the most common viral pathogen after engraftment. Cytomegalovirus disease occurred mainly in the late-recovery phase. The frequency of mold infection was higher than that of yeast. There was a relatively high incidence of tuberculosis (3.0%) and Pneumocystis carinii pneumonia (6.5%). One case of death by measles confirmed by autopsy was also noted. Overall, cumulative mortality was 43% (104/242), and 59.6% of these deaths (62/104) were infection-related. Allogeneic HSCT recipients from unrelated donors were prone to infectious complication and higher mortality than those from matched sibling (17/39 (43.6%) vs 45/203 (22.2%), respectively; P<0.01; odd ratio 2.5; 95% confidence interval 1.2-5.1). As infection was the main post-HSCT complication in our data, more attention should be given to the management of infections in HSCT recipients.

Experimental salivary pellicles formed on the surface of self-curing resin.

The aim of this study was to identify the salivary components present in the pellicles formed on self-curing resin and to investigate the qualitative variations in adsorbed salivary pellicle compositions according to different exposure time to saliva. Experimental pellicles were formed by the incubation of polymerized resin particles with fresh human parotid or submandibular-sublingual saliva for either 20 min or 2 h. Pellicles were extracted using formic acid and lyophilized, they were then subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunoblotting to identify the adsorbed salivary components. The amino acid profiles of the 2 h-pellicles were analysed and compared with those of fresh glandular salivas. There was a difference in the 2 h-pellicle components on the self-curing resin compared with those of other dental materials as well as tooth enamel. The amino acid profiles of the 2 h-pellicles were also different from those of fresh glandular salivas. In the case of submandibular-sublingual saliva, the components of the 2 h-pellicle showed a different pattern compared with those of the 20 min-pellicle. However, there was no significant difference between the components of the 2 h- and 20 min-pellicles in the case of parotid saliva. A distinct difference was found in the surface binding affinities of immunoglobulin (IgA) from different glandular salivas. The findings of this study provide information concerning the initial bacterial adhesion on the surfaces of self-curing resin.