Norepinephrine transporter expression is inversely associated with glycaemic indices: a pilot study in metabolically diverse persons with overweight and obesity.

OBJECTIVE: The objective of this study was to examine the cross-sectional relationship between the expression of norepinephrine transporter (NET), the protein responsible for neuronal uptake-1, and indices of glycaemia and hyperinsulinaemia, in overweight and obese individuals. METHODS: Thirteen non-medicated, non-smoking subjects, aged 58 ± 1 years (mean ± standard error of the mean), body mass index (BMI) 31.4 ± 1.0 kg m-2, with wide-ranging plasma glucose and haemoglobin A1c (HbA1c, range 5.1% to 6.5%) participated. They underwent forearm vein biopsy to access sympathetic nerves for the quantification of NET by Western blot, oral glucose tolerance test (OGTT), euglycaemic hyperinsulinaemic clamp, echocardiography and assessments of whole-body norepinephrine kinetics and muscle sympathetic nerve activity. RESULTS: Norepinephrine transporter expression was inversely associated with fasting plasma glucose (r = -0.62, P = 0.02), glucose area under the curve during OGTT (AUC0-120, r = -0.65, P = 0.02) and HbA1c (r = -0.67, P = 0.01), and positively associated with steady-state glucose utilization during euglycaemic clamp (r = 0.58, P = 0.04). Moreover, NET expression was inversely related to left ventricular posterior wall dimensions (r = -0.64, P = 0.02) and heart rate (r = -0.55, P = 0.05). Indices of hyperinsulinaemia were not associated with NET expression. In stepwise linear regression analysis adjusted for age, body mass index and blood pressure, HbA1c was an independent inverse predictor of NET expression, explaining 45% of its variance. CONCLUSIONS: Hyperglycaemia is associated with reduced peripheral NET expression. Further studies are required to identify the direction of causality.

Active versus passive humidification for self-ventilating tracheostomy and laryngectomy patients: a systematic review of the literature.

OBJECTIVE: To determine whether active or passive humidification methods are more effective in preventing pulmonary complications in self-ventilating neck breather patients. DESIGN: Systematic Review adhering to PRISMA guidance (checklist sourced from www.equator-network.org/). SETTING: Review of current published relevant literature at a tertiary department of Otolaryngology and Head & Neck Surgery. PARTICIPANTS: We included all separate studies and comparison studies of active and passive humidification techniques in adult and paediatric neck breather patients. MAIN OUTCOME MEASURES: The primary outcome is the reduction in pulmonary complications. Secondary outcomes include patient compliance; carer and user satisfaction. RESULTS AND CONCLUSIONS: Seven studies were included in this review: two RCTs (133 patients), one randomised controlled cross-over trial (29 patients), three randomised prospective studies (171 patients), and one retrospective study (73 patients). Only one study was conducted on paediatric neck breathers. The overall quality of the studies was low. Five studies were at a high risk of bias. Of the remaining two studies, one study had a low risk of bias and the other had an unclear risk. Despite limited subject evidence, results show that passive methods of humidification (mainly HME) is the preferred choice of humidification in the spontaneously breathing neck breather patients group mainly due to the reduction in pulmonary complaints, and better patient compliance.

Elastin is a key regulator of outward remodeling in arteriovenous fistulas.

OBJECTIVES: Maturation failure is the major limitation of arteriovenous fistulas (AVFs) as hemodialysis access conduits. Indeed, 30-50% of AVFs fail to mature due to intimal hyperplasia and insufficient outward remodeling. Elastin has emerged as an important determinant of vascular remodeling. Here the role of elastin in AVF remodeling in elastin haplodeficient (eln(+/-)) mice undergoing AVF surgery has been studied. METHODS: Unilateral AVFs between the branch of the jugular vein and carotid artery in an end to side manner were created in wild-type (WT) C57BL/6 (n = 11) and in eln(+/-) mice (n = 9). Animals were killed at day 21 and the AVFs were analyzed histologically and at an mRNA level using real-time quantitative polymerase chain reaction. RESULTS: Before AVF surgery, a marked reduction in elastin density in the internal elastic lamina (IEL) of eln(+/-) mice was observed. AVF surgery resulted in fragmentation of the venous internal elastic lamina in both groups while the expression of the tropoelastin mRNA was 53% lower in the eln(+/-) mice than in WT mice (p < .001). At 21 days after AVF surgery, the circumference of the venous outflow tract of the AVF was 21% larger in the eln(+/-) mice than in the WT mice (p = .037), indicating enhanced outward remodeling in the eln(+/-) mice. No significant difference in intimal hyperplasia was observed. The venous lumen of the AVF in the eln(+/-) mice was 53% larger than in the WT mice, although this difference was not statistically significant (eln(+/-), 350,116 ± 45,073 µm(2); WT, 229,405 ± 40,453 µm(2); p = .064). CONCLUSIONS: In a murine model, elastin has an important role in vascular remodeling following AVF creation, in which a lower amount of elastin results in enhanced outward remodeling. Interventions targeting elastin degradation might be a viable option in order to improve AVF maturation.

Radiation therapy-induced phrenic neuropathy mimicking metastasis to the diaphragmatic crus on ¹8F-FDG PET/CT.

Benign unilateral uptake in the diaphragmatic crus is a relatively uncommon finding on (18)F-FDG PET/CT that can mimic the appearance of malignancy in patients with known cancer, as illustrated in this patient with neuroendocrine carcinoma. It is important for the PET interpreter to recognize this finding and attribute it to benign uptake based on the patient's history and symptoms at the time of the scan. Correlation with the findings of other available imaging modalities is also important to characterize focal uptake in unusual locations.

Electroacupuncture for ileus after laparoscopic colorectal surgery: a randomised sham-controlled study.

1. Electroacupuncture at acupoints of Zusanli, Sanyinjiao, Hegu, and Zhigou is more effective than no acupuncture and sham acupuncture in stimulating early return of bowel function and reducing analgesic requirement after laparoscopic colorectal surgery. 2. Electroacupuncture is more effective than no acupuncture in reducing the duration of hospital stay. 3. Receipt of electroacupuncture is an independent predictor of shorter duration of ileus and hospital stay after laparoscopic colorectal surgery.

Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

Low circulating level of CD133+KDR+cells in patients with systemic sclerosis.

BACKGROUND: Results of previous studies on the level of circulating endothelial progenitor cells (EPCs), which are involved in vascular repair, in scleroderma (SSc) patients have been controversial. OBJECTIVES: To enumerate circulating EPC subsets and to examine their relation with endothelial dysfunction, biochemical markers of endothelial injury and vascular outcome in SSc patients. METHODS: Enumeration of circulating CD34+KDR+ and CD133+ KDR+EPCs was performed by flow cytometry. Endothelium-dependent vasodilation was evaluated by changes in flow-mediated dilation (FMD%) in the brachial artery. Serum level of vascular endothelial growth factor (VEGF) was measured by enzyme linked immunosorbent assay. RESULTS: SSc patients (n=52) were found to have significantly lower CD133+KDR+EPCs (3.0 vs. 7.0/µl, p<0.001) as well as FMD% (4.8% vs. 7.8%, p<0.001) compared with age and sex-matched controls (n=52). Among patients who had no concomitant cardiovascular risk factors (n=28), CD133+KDR+ EPC level was significantly lower than controls (3.8 vs. 7.3/µl, p=0.001) and correlated modestly with FMD% (r=0.29, p=0.03). Disease duration was the only determining factor identified for circulating CD133+KDR+ EPCs (p=0.03) by logistic regression analysis. Levels of serum VEGF (p=0.92) and KDR expression were not different between patients who had early and intermediate/late disease. Circulating CD34+KDR+ EPCs was not different between SSc patients and controls and did not correlate with any clinical or biochemical parameter. CONCLUSIONS: Lower circulating CD133 +KDR+ EPC subset was found in SSc patients and correlated with impaired endothelium-dependent vasodilation in patients without cardiovascular risk factors suggesting a potential role of deficient EPC recruitment contributing to endothelial dysfunction in this disease.

Brain herniation in a neonate.

Brain herniation is generally thought to be unlikely to occur in newborns due to the presence of the patent fontanelles and cranial sutures. A review of the literature published from 1993 to 2008 via MEDLINE search revealed no reports on neonatal brain herniation from intracranial tumour. We report a preterm Malay male infant born via elective Caesarean section for antenatally diagnosed intracerebral tumour, which subsequently developed herniation. Cerebral magnetic resonance imaging showed features that were compatible with a large complex intracranial tumour causing mass effect and gross hydrocephalus. Tumour excision was scheduled when the infant was two weeks old. Unfortunately, on the morning of the surgery, he developed signs of brain herniation and had profuse tumour haemorrhage during the attempted excision. Histopathological examination revealed an embryonal tumour, possibly an atypical rhabdoid/teratoid tumour. This case illustrates that intracranial tumours in newborns can herniate and should therefore be closely monitored.

Bacille Calmette-Guérin osteomyelitis of the proximal femur.

All newborns in Hong Kong are given bacille Calmette-Guérin vaccinations. Reported complications include formation of regional and extra-regional localised abscesses, osteomyelitis, and lymphadenitis. Several cases of bacille Calmette-Guérin osteomyelitis have been reported in Europe, but there are few reports of this in Asia. To the author's knowledge, this is the first case report of bacille Calmette-Guérin osteomyelitis in Hong Kong. Bacille Calmette-Guérin osteomyelitis, although rare, should be kept in mind as a potential complication of bacille Calmette-Guérin vaccination. Clinical suspicion, early diagnosis using an image-guided tissue biopsy and polymerase chain reaction study, and early commencement of chemotherapy are key to the effective management of this problem.

Fish-oil supplement has neutral effects on vascular and metabolic function but improves renal function in patients with Type 2 diabetes mellitus.

AIMS: Increased dietary fish-oil consumption is associated with a reduced risk of coronary heart events and has pronounced effects on dyslipidaemia. However, the effects of fish-oil supplement on vascular function and metabolic profile in patients with Type 2 diabetes mellitus (DM) are unclear. METHODS: In a double-blind placebo-controlled trial, we randomized 97 Type 2 DM patients without prior cardiovascular disease to fish-oil (4 g/day, n = 49) or olive-oil (with equivalent calories, as placebo, n = 48) supplements for 12 weeks. Assessment of vascular function with brachial artery flow-mediated dilation (FMD) and circulating levels of endothelial progenitor cells (EPCs), and metabolic parameters, high-sensitivity C-reactive protein (hsCRP), oxidative stress markers and renal function were examined before and after the supplement. RESULTS: Despite a significant reduction in serum triglycerides (-0.47 mmol/l, P < 0.01), 12-week supplement of fish oil did not improve vascular function as determined by FMD (+0.16%, P = 0.83) and circulating EPC count (+4 cells/microl, P = 0.78). Furthermore, fish-oil supplement did not have any significant treatment effects on hsCRP, oxidative stress, low- and high-density lipoprotein and glycated haemoglobin (HbA(1c)) (all P > 0.05). In contrast, serum creatinine was lower (-4.5 micromol/l, P = 0.01) in fish-oil-treated patients as compared with control subjects. CONCLUSIONS: This study demonstrated that 12 weeks of fish-oil supplement had no significant beneficial effect on vascular endothelial function, but improved renal function without changes in endothelial function, metabolic profiles, blood pressure, inflammation or oxidative stress in patients with Type 2 DM.

Dural tear post mastoidectomy repaired with Dura Gen.

Dural exposure may occur during the course of thinning the tegmen tympani and tegmen mastoideum in mastoid procedure. If large area of dura is exposed or lacerated, cerebrospinal fluid and brain herniation may enter the mastoid cavity. We report a case of a patient with injured dura mater and tegmen mastoideum during mastoidectomy for chronic suppurative otitis media with cholesteatoma managed by using DuraGen. The dura mater and tegmen defect healed totally showing the success of the procedure. A collagen matrix like DuraGen is an option for repairing dural tear in mastoid region.

LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast and colorectal cancer.

Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, using both loss of heterozygosity analysis and customized microarray comparative genomic hybridization. LARG (leukemia-associated Rho guanine-nucleotide exchange factor) (also called ARHGEF12), identified from the analysed region, is frequently underexpressed in breast and colorectal carcinomas with a reduced expression observed in all breast cancer cell lines (n=11), in 12 of 38 (32%) primary breast cancers, 5 of 10 (50%) colorectal cell lines and in 20 of 37 (54%) primary colorectal cancers. Underexpression of the LARG transcript was significantly associated with genomic loss (P=0.00334). Hypermethylation of the LARG promoter was not detected in either breast or colorectal cancer, and treatment of four breast and four colorectal cancer cell lines with 5-aza-2'-deoxycytidine and/or trichostatin A did not result in a reactivation of LARG. Enforced expression of LARG in breast and colorectal cancer cells by stable transfection resulted in reduced cell proliferation and colony formation, as well as in a markedly slower cell migration rate in colorectal cancer cells, providing functional evidence for LARG as a candidate tumor suppressor gene.

Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer.

BACKGROUND: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis. METHODS: RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro. RESULTS: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar. CONCLUSION: Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy.

Residual torticollis in patients after strabismus surgery for congenital superior oblique palsy.

AIM: To study postoperative residual vertical deviation and abnormal head posture (AHP) after surgical treatment for congenital superior oblique palsy (SOP). METHOD: Children with both SOP and AHP who underwent extraocular muscle surgery for correction of AHP were recruited. The patients received complete ophthalmic and orthopaedic examinations. Residual AHP was classified according to severity of face turn, head tilt and chin elevation. RESULTS: Thirty-two children with mean age at operation of 82.6 months were recruited, with mean follow-up of 37.9 months. Of these children, 65.6% had a postoperative vertical deviation of less than three prism dioptres. In addition, 34.4% patients had resolved (0 degrees ), 34.4% had mild (1 degrees -10 degrees ), and 31.3% had significant residual torticollis (>10 degrees ). Of the patients with significant residual torticollis, 33.3% had ocular causes. The mean age at operation for the patients with residual torticollis (95.9 months) was older than those without torticollis (79.9 months) (p = 0.018). Residual torticollis was found to be related to sternocleidomastoid muscle tightness (p = 0.013). CONCLUSION: The success rate for eliminating significant AHP after strabismus surgery for patients with congenital SOP was 68.8%. Early surgery was associated with a better outcome. Association was also found between sternocleidomastoid tightness and AHP. A multidisciplinary approach is recommended in the management of torticollis as ophthalmic and orthopaedic comorbidities can coexist.

Prenatal screening for retinoblastoma in Hong Kong.

We report the first use in Hong Kong of molecular techniques to screen prenatally for retinoblastoma and review 17 cases of retinoblastoma seen at the Hong Kong Eye Hospital from 2001 to 2006. A pregnant couple whose first child had retinoblastoma requested prenatal screening for retinoblastoma during their second pregnancy in 2000. Whole RB1 coding gene sequencing was performed on peripheral blood cells taken from family members and cultured amniocytes collected from the foetus during the 14th week of gestation. No RB1 gene mutations were found in the amniocyte samples and at birth the baby had no evidence of ocular tumours. During 5 years of follow-up the child remained healthy with intact visual function. Prenatal diagnosis of retinoblastoma alleviates parental stress and improves the perinatal care of affected family members.

Changes in refraction and ocular dimensions after cataract surgery and primary intraocular lens implantation in infants.

PURPOSE: To study refraction and axial length changes after cataract extraction and primary intraocular lens (IOL) implantation in children younger than 1 year of age. SETTING: Two regional hospitals. METHODS: After determining the IOL power for emmetropia, 80% of the value was used to choose the IOL for implantation to counter anticipated myopic shift with age. The main outcome measures were changes in refraction and axial length 3 years after surgery. RESULTS: Thirty-four eyes of 20 children (mean age 6.7 months +/- 3.9 [SD]) were studied. Refraction in the immediate postoperative period was +4.53 +/- 1.45 diopters (D). Three years after surgery, the mean refraction was -2.49 +/- 3.08 D (P<.001). Twenty-two eyes (64.7%) had surgery during the first 6 months of life (group 1) and had a shorter axial length at surgery (mean 18.92 +/- 1.32 mm) compared with 12 eyes (35.3%) that received surgery between 7 and 12 months (group 2, mean 20.29 +/- 1.00 mm) (P = .007). However, the final axial length was greater in group 1 (mean 22.67 +/- 1.04 mm) than in group 2 (mean 21.23 +/- 0.26 mm) (P = .019). CONCLUSIONS: Primary IOL implantation is an option for children having cataract surgery in the first year of life. Significant myopic shifts occurred, and this seemed to be more pronounced in younger children. It appears that rethinking current strategies for IOL power calculation may be required to achieve more optimal refractive outcomes.

[Maggot therapy for treatment of severe infections in trauma surgery: "back to the future!"]. / Maden: Ein neues Konzept in der Behandlung von Infektionen in der Traumatologie -- "Back to the Future!"

The ancient method of larval therapy for treatment of acute and chronic infections has become a revival and a new dimension with introduction of the Biobag (Vitapad). With use of this therapy trauma patients suffering infectious complications can be treated very effective, which can reduce the overall time needed for treatment and can result in diminished invalidity.