Mitochondrial DNA variants as genetic risk factors for Parkinson disease.

BACKGROUND AND PURPOSE: Investigation of the relationship between mitochondrial DNA (mtDNA) variants and Parkinson disease (PD) remains an issue awaiting more supportive evidence. Moreover, an affirming cellular model study is also lacking. METHODS: The index mtDNA variants and their defining mitochondrial haplogroup were determined in 725 PD patients and 744 non-PD controls. Full-length mtDNA sequences were also conducted in 110 cases harboring various haplogroups. Cybrid cellular models, composed by fusion of mitochondria-depleted rho-zero cells and donor mitochondria, were used for a rotenone-induced PD simulation study. RESULTS: Multivariate logistic regression analysis revealed that subjects harboring the mitochondrial haplogroup B5 have resistance against PD (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002). Furthermore, a composite mtDNA variant group consisting of A10398G and G8584A at the coding region was found to have resistance against PD (odds ratio 0.50, 95% confidence interval 0.33-0.78; P = 0.001). In cellular studies, B4 and B5 cybrids were selected according to their higher resistance to rotenone, in comparison with cybrids harboring other haplogroups. The B5 cybrid, containing G8584A/A10398G variants, showed more resistance to rotenone than the B4 cybrid not harboring these variants. This is supported by findings of low reactive oxygen species generation and a low apoptosis rate in the B5 cybrid, whereas a higher expression of autophagy was observed in the B4 cybrid particularly under medium dosage and longer treatment time with rotenone. CONCLUSIONS: Our studies, offering positive results from clinical investigations and cybrid experiments, provide data supporting the role of variant mtDNA in the risk of PD.

Surveillance of avian influenza A(H7N9) virus infection in humans and detection of the first imported human case in Taiwan, 3 April to 10 May 2013.

On 3 April 2013, suspected and confirmed cases of influenza A(H7N9) virus infection became notifiable in the primary care sector in Taiwan, and detection of the virus became part of the surveillance of severe community-acquired pneumonia. On 24 April, the first imported case, reported through both surveillance systems, was confirmed in a man returning from China by sequencing from endotracheal aspirates after two negative throat swabs. Three of 139 contacts were ill and tested influenza A(H7N9)-negative.

Association between a common mitochondrial DNA D-loop polycytosine variant and alteration of mitochondrial copy number in human peripheral blood cells.

BACKGROUND: A T-to-C transition at mitochondrial DNA (mtDNA) nucleotide position 16189 can generate a variable length polycytosine tract (poly-C). This tract variance has been associated with disease. A suggested pathogenesis is that it interferes with the replication process of mtDNA, which in turn decreases the mtDNA copy number and generates disease. METHODS: In this study, 837 healthy adults' blood samples were collected and determined for their mtDNA D-loop sequence. The mtDNA copy number in the leucocytes and serum levels of oxidative thiobarbituric acid reactive substance (TBARS) and antioxidative thiols were measured. All subjects were then categorised into three groups: wild type or variant mtDNA with presence of an interrupted/uninterrupted poly-C at 16180-16195 segment. RESULTS: A step-wise multiple linear regression analysis identified factors affecting expression of mtDNA copy number including TBARS, thiols, age, body mass index and the mtDNA poly-C variant. Subjects harbouring a variant uninterrupted poly-C showed lowest mean (SD) mtDNA copy number (330 (178)), whereas an increased copy number was noted in subjects harbouring variant, interrupted poly-C (420 (273)) in comparison with wild type (358 (215)). The difference between the three groups and between the uninterrupted poly-C and the composite data from the interrupted poly-C and wild type remained consistent after adjustment for TBARS, thiols, age and body mass index (p=0.001 and p=0.011, respectively). A trend for decreased mtDNA copy number in association with increased number of continuous cytosine within the 16180-16195 segment was noted (p(trend)<0.006). CONCLUSIONS: Our results substantiate a previous suggestion that the mtDNA 16189 variant can cause alteration of mtDNA copy number in human blood cells.

Mass psychogenic illness in nationwide in-school vaccination for pandemic influenza A(H1N1) 2009, Taiwan, November 2009-January 2010.

From 16 November 2009 to 22 January 2010, Taiwan investigated 23 clusters of mass psychogenic illness after vaccination (MPIV) in the nationwide in-school vaccination programme against the 2009 pandemic influenza A(H1N1). The median age of the 350 ill students (68% female) was 13 years. Intense media coverage of these events has driven public concerns about the safety of the pandemic influenza vaccine. In the future, countries should incorporate surveillance and communication strategies for MPIV in their pandemic preparedness plans.

The significance of functioning gallbladder visualization on hepatobiliary scintigraphy in infants with persistent jaundice.

UNLABELLED: The purpose of this study was to determine whether gallbladder visualization can help exclude biliary atresia in hepatobiliary scintigraphic studies of infants with persistent jaundice. METHODS: One hundred fifty-two infants with persistent jaundice (49 patients with a final diagnosis of biliary atresia and 103 with biliary patency) were studied using both hepatobiliary scintigraphy and abdominal sonography. Food was withheld for 4 h before the examination, and the infants were fed nothing but glucose until 6 h after the initial injection of (99m)Tc-disofenin or until the gallbladder was seen. If the gallbladder was seen, the infants were fed milk, and imaging was continued to observe gallbladder contractility. RESULTS: In none of the 49 patients with biliary atresia could the gallbladder be seen with hepatobiliary scintigraphy, but abdominal sonography revealed 9 normal-sized gallbladders. Of the 103 patients with biliary patency, hepatobiliary scintigraphy detected the gallbladder more frequently (74%, 76/103) than did abdominal sonography (63%, 65/103). All visualized gallbladders contracted after the infants were fed milk. If we include visualization of both the gallbladder and bowel radioactivity as criteria, the specificity of biliary atresia on hepatobiliary scintigraphy increases to 86% (89/103). CONCLUSION: Gallbladders were usually visible on hepatobiliary scintigraphy of fasting patients with biliary patency. A functioning gallbladder, with or without visualization of bowel radioactivity, indicated biliary patency.

Population-based study of insulin, C-peptide, and blood pressure in Chinese with normal glucose tolerance.

Insulin resistance may play a role in the pathogenesis of essential hypertension. The purpose of the present study was to examine the relations of fasting serum insulin or C-peptide levels with hypertension and blood pressure (BP) in a stable homogeneous southern Chinese population with normal glucose tolerance. This community-based survey of adults aged > or = 30 years in Kin-Chen, Kinmen, was conducted by the Yang-Ming Crusade in 1992 and 1994. Data of fasting serum insulin and C-peptide from a total of 1,447 men and 1,800 women (mean age 46.7 years) were analyzed. Both continuous (by multiple regression) and categorical analyses (by analysis of covariance) were used. Fasting insulin concentrations (as independent variables) were significantly associated with log systolic BP (as outcome variables, coefficient = 0.000081, p = 0.0035) and log diastolic BP (as outcome variables, coefficient = 0.000098, p = 0.0006) after accounting for age, sex, body mass index, and waist-to-hip ratio. Similarly, fasting C-peptide concentrations were significantly associated with log systolic BP (coefficient = 0.023304, p = 0.0001) and log diastolic BP (coefficient = 0.032971, p = 0.0001). In categorical analyses, both fasting insulin and C-peptide concentrations were significantly different (insulin p = 0.01010, and C-peptide p = 0.0004) between hypertensive and normotensive subjects when the similar set of covariates were accounted for. In conclusion, both fasting serum insulin and C-peptide concentrations are significantly associated with BP in this homogeneous Chinese population with normal glucose tolerance.

A population-based epidemiological study on cardiovascular risk factors in Kin-Chen, Kinmen.

We conducted a population survey of cardiovascular risk factors in Kin-Chen, Kinmen (Quemoy), an island under military control for 40 years and the focal point of confrontation between mainland China and Taiwan. During the period 1992-1994, all residents > or = 30 years of age in Kin-Chen, the largest township in Kinmen, were invited to participate. The response rate was 60.3% (3826/6346). The prevalence of hypertension (> or = 160/95 mmHg and/or under treatment) was 25.2% in men and 17.6% in women. The rate for smoking was 41.5% in men and 2.9% in women. The prevalence of diabetes was 6.7% in men and 6.4% in women. Mean values for systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were 135.3 mmHg, 85.5 mmHg, 5.3 mmol/l, 1.1 mmol/l, 3.5 mmol/l and 1.4 mmol/l in men; and 128.0 mmHg, 79.5 mmHg, 5.2 mmol/l, 1.0 mmol/l, 3.3 mmol/l and 1.5 mmol/l in women, respectively. The unexpectedly high prevalence of hypertension in Kin-Chen male may reflect the effect of more than 40 years of military control and discipline. The high serum cholesterol level in Kin-Chen relative to mainland China and the low triglyceride level relative to Taiwan and Beijing, suggest further study of the contributions of diet and other psychosocial or environmental factors.

Prevalence of coronary heart disease in Kin-Chen, Kinmen.

We estimated the prevalence of coronary heart disease (CHD) by the Minnesota code of a 12-lead resting electrocardiogram, Rose chest pain questionnaire and self-reported previous medical history in Kin-Chen, Kinmen (Quemoy), an island under military control for 40 years and the focal point of confrontation between mainland China and Taiwan. Among the target population of 6346 who accounted for all residents aged over 30, 3826 (60.3%) responded with complete data. The prevalence of probable CHD (Minnesota code 1.1-1.2) was 4.1% (71/1732) in men and 4.0% (84/2094) in women, whereas the prevalence of possible CHD (Minnesota code 1.3, 4.1-4.4, 5.1-5.3 and 7.1.1) was significantly higher in women (21.4%) than in men (11.6%). When compared to Chinese populations elsewhere, the increased overall prevalence may suggest a link to long-term stress conditions under military control. We also found the abnormal ECG was associated with many risk factors of CHD, particularly win women. The prevalence of Rose angina and self-reported angina or myocardial infarction was, however, low and associated poorly with any cardiovascular risk factors. Long-term follow-up studies are needed to determine the predictive value of these electrocardiographic abnormalities for cardiovascular disease morbidity and mortality in this population.

Sonographic features of small-bowel intussusception in pediatric patients.

OBJECTIVE: Small-bowel intussusception (SBI) for pediatric patients is unusual and difficult to diagnose preoperatively. This study sought to determine the sonographic findings of pediatric SBI. METHODS: The sonographic features and surgical findings of 13 pediatric patients (7 boys, 6 girls; age range 4 months-15 years; average age 4 years and 2 months) with SBI encountered in the authors' hospital over a 12-year period were retrospectively reviewed. RESULTS: Most of the patients presented with nonspecific symptoms, including vomiting, abdominal pain, and/or irritable crying. Sonographic screening in the emergency department revealed a doughnut or crescent-in-doughnut sign, or a multiple-concentric-rings sign for 11 of the 13 patients, and the lesions appeared short. Eight lesions were found in the paraumbilical or left abdominal regions. Sonographic measurement of the size of the lesions from these 11 patients ranged from 2 cm to 3.7 cm (average 2.77 cm). Subsequent barium enemas were performed for these 11 patients, none of which revealed colon lesions. Surgery revealed ileoileal intussusceptions for eight cases, jejunoileal for three, and jejunojejunal for the remaining two. Bowel ischemia or necrosis and pathologic lead points were demonstrated for seven and six patients, respectively, although none were recognized preoperatively. CONCLUSIONS: Small-bowel intussusception is often over-looked due to nonspecific clinical presentations. Sonographic demonstration of a 2-3-cm sized, short, doughnut-like lesion, especially in the left abdomen or paraumbilical regions, should lead to strong suspicion of SBI.

Implication of a distant septic focus in parenteral nutrition catheter colonization.

During a 4-year period, 244 surgical patients receiving total parenteral nutrition (TPN) were studied with emphasis on the relationship between TPN catheter colonization and a preexisting distant septic focus (DSF). A colonized catheter was defined as a catheter with a positive semiquantitative culture of the catheter tip (greater than or equal to 15 colonies on the plate). Catheter-related sepsis (CRS) was defined as a catheter with either the same organisms cultured from the catheter tip and from blood or with defervescence following catheter removal. Two hundred sixty-nine catheters were inserted for TPN for a total of 4433 patient days, with a mean length of stay of 16.5 days. Forty-two of the 269 catheters (15.6%) were colonized and more than half (57.1%) of the organisms cultured were Gram-negative bacilli or enterococci. Nineteen of the 42 colonized catheters were associated with CRS with a CRS rate of 7.1% among the 269 catheters. A DSF was present in 165 of the 244 patients or in 188 of the 269 catheters (69.9%). The colonization rate of 19.1% (36/188) in those catheters with DSF was significantly higher than that of 7.4% (6/81) in those without DSF (p less than 0.05). Those patients with DSF or with a colonized catheter were associated with a high mortality (p less than 0.001). Sepsis was responsible for 33 of the 48 patients (68.8%) who died. The data stress the important contribution of DSF to the colonization of TPN catheters and to the mortality of these critically ill surgical patients.

Adverse metabolic and microbiological effects of tube feeding in experimental canine obstructive jaundice.

BACKGROUND: Inadequate oral intake and poor absorption result in malnutrition in obstructive jaundice. Both malnutrition and obstructive jaundice promote bacterial translocation from the gut. This study was designed to test the efficacy of tube feeding in preventing malnutrition and in decreasing the metabolic and microbiological adverse effects in obstructive jaundice. METHODS: Forty adult mongrel dogs were studied and were allocated into one of four groups: group I (PO-control) underwent sham ligation of the common bile duct (CBDL) and was fed ad libitum on Portagen (Mead Johnson, Evansville, IN); group II (PO-CBDL) underwent CBDL and was ad libitum fed on the same formula; group III (FEG-control) underwent sham CBDL and received forced esophagogastric feeding (FEG) with Portagen; and group IV (FEG-CBDL) underwent CBDL and received FEG. All the animals underwent insertion of a F-12 feeding tube to the stomach from an esophagotomy wound on day 1 and the tube was used for continuous enteral feeding with Portagen over 4 h/d from day 2 until day 13 in groups III and IV. Fourteen days later, blood samplings were done and a laparotomy was performed to obtain liver, mesenteric lymph nodes (MLN), and terminal ileum for quantitative bacterial culture. Bacterial translocation to MLN and liver was represented by log10 CFU/g of tissue in this study. RESULTS: Both group II and IV animals with CBDL significantly lost body weight (p = .0001) and had a lower level of prealbumin (p = .0054). A significant increase in bacterial translocation to MLN and to liver occurred in groups II and IV (p = .0017 and .0268, respectively). Intestinal bacterial population was also higher in these two groups than in the other two controls (p = 0.0028). An increase in plasma ammonia level was found in dogs with CBDL (p = .0002) and in dogs with FEG (p = .003), compared with their respective controls. Three among 13 dogs in group IV died and no mortality occurred in the other groups (p = .223). CONCLUSIONS: Tube feeding fails to improve malnutrition in obstructive jaundice and is associated with intestinal bacterial overgrowth, promoting bacterial translocation to MLN and liver, precipitating liver dysfunction and consequently a higher mortality.

Congenital bilateral cystic neuroblastoma with liver metastases and massive intracystic haemorrhage.

A case of bilateral cystic neuroblastoma with liver metastases in a newborn is reported. CT showed a 10 cm right suprarenal multicystic mass and numerous hepatic cystic masses with intracystic fluid-fluid levels. Multiple smaller cystic lesions were also present in the left adrenal gland. To our knowledge, the CT findings of neonatal bilateral cystic neuroblastoma with liver metastasis and massive acute intracystic haemorrhage has not been previously documented.

Lipoblastomatosis combined with intestinal neuronal dysplasia.

We report the case of a male infant with multifocal lipoblastomatosis and intestinal pseudo-obstruction for whom the pathologic findings of rectal biopsy were consistent with intestinal neuronal dysplasia. Lipoblastomatosis is a benign neoplasm of human fetal white adipose tissue that mainly occurs in infants and children. Intestinal neuronal dysplasia is a disorder that clinically mimics Hirschsprung's disease and that is pathologically characterized by parasympathetic hyperganglionosis of the enteric nervous system. To our knowledge, the combination of lipoblastomatosis and intestinal neuronal dysplasia has never been documented, and the gene mutations involved are completely different. In this case, therefore, we postulate that intestinal neuronal dysplasia may be secondary to either compression of the nerve tract or inhibition of bowel movement due to lipoblastomatosis.

Penoplasty for buried penis.

Buried penis is a congenitally abnormal arrangement of the foreskin relative to the penile shaft, which results in a pseudomicropenis in an otherwise healthy, nonobese child. The author proposes a penoplasty technique appropriate for correction of this disorder, based on experience with 21 patients.

Two-layer versus one-layer closure in transverse island flap repair of posterior hypospadias.

Despite its prevalence for more than two decades, one-stage repair of moderately severe hypospadias is still associated with a high complication rate. A retrospective study of 103 cases of posterior hypospadias treated exclusively with the Duckett transverse island flap procedure was conducted to analyze factors that might affect the morbidity. The latter included the age of the patients, the anatomical variants of the hypospadias, the suture materials and the technique used, the length of the urethral tube, and the methods and duration of urinary diversion. The fistula rate was 24% (25/103), and the overall complication rate was 31% (32/103). The patients in the glanular-subcoronal-penile variant had a significantly lower overall complication rate than those in the penoscrotal-scrotal variant (21% versus 39%, P < .05). The patients with a neourethra shorter than 3 cm also had significantly less complications than those with a neourethra longer than 3 cm (25% versus 47%, P < .05). The only procedural factor that makes a difference is the method of skin closure to form the neourethra. Two-layer closure resulted in a significantly lower fistula rate and overall complication rate than one-layer closure (13% versus 34% and 15% versus 45%, P < .025 and P < .005, respectively). The study confirms the value of two-layer closure in the transverse island flap repair of posterior hypospadias.

Membranous atresia of esophagus associated with pyloric stenosis.

Membranous atresia of the esophagus without tracheoesophageal fistula (TEF) is very rare, only four cases have been reported since 1928. We present a case in whom a thick membrane was present 2 cm proximal to the diaphragm. The membrane was resected and the longitudinal esophagotomy wound was closed transversely. The postoperative course was complicated with hyperbilirubinemia and hypertrophic pyloric stenosis (HPS). The problems of the feeding tube used for diagnostic evaluation of this rare esophageal anomaly are discussed. In spite of its low incidence, the potentiality of HPS as a cause of postoperative vomiting in esophageal atresia should be borne in mind in order to avoid delay in diagnosis.

Posttraumatic hepatic cyst--an unusual sequela of liver injury in the era of imaging.

Nonoperative management of blunt liver injury in children has become a generally accepted form of therapy unless vital signs deteriorate or associated injury requires emergency operation. Serial monitoring of the liver with computed tomographic (CT) scans or abdominal ultrasonography contributes much to the management of these children. A persistent intrahepatic hematoma that goes unnoticed for years and eventually results in a cyst with a thick wall that contains viscous yellowish green fluid and sludge occurred occasionally before the era of CT or ultrasound imaging, but it is unusual in modern times. We report on a 7-year-old girl who suffered blunt abdominal trauma that resulted in a grade IV liver injury. Five years later she had a large posttraumatic cyst of the liver that caused abdominal pain. She is now asymptomatic, after decortication of the cyst wall, evacuation of the contents, and filling the residual space with omentum.

Fibrosis of the omohyoid muscle--an unusual cause of torticollis.

An 11-year-old boy had a left neck mass with torticollis. On exploration, a fibrotic mass in the superior belly of the left omohyoid muscle was found, which shortened the muscle and pulled the hyoid bone downward. Resection of the fibrotic muscle was performed. The patient recovered well after the operation with resolution of his torticollis.

The efficacy of Kasai operation for biliary atresia: a single institutional experience.

To assess the efficacy of Kasai operation for biliary atresia, 60 cases during a 14-year period (1976 to 1989) at this institution were reviewed. Thirty-four (56.7%) underwent operation within 90 days of life, 11 (18.3%) between 90 and 120 days and 15 (25.0%) beyond 120 days. Fifty-six underwent hepaticoportojejunostomy and 4 underwent hepaticoportocholecystostomy. Follow-up was 1 to 14 years (mean, 7.2 years). The postoperative follow-up of these 60 patients was categorized into five groups: group A (16 patients, 26.7%) was characterized by survival greater than 3 years and without jaundice; group B (3 patients, 5.0%) was defined as survival greater than 3 years, but with jaundice; group C (11 patients, 18.3%) was defined by survival but follow-up less than 3 years, (this group was further divided into C1 [7 patients, 11.7%] if anicteric and C2 [4 patients, 6.7%] if icteric); group D (2 patients, 3.3%) was patients who underwent liver transplantation; and group E (28 patients, 46.7%) was the group of patients who died at time of review. Group A and group C1 were interpreted as success after Kasai operation; hence, the potential success rate in this series was 38.3% (23 patients). They were long-term survivers, and most of them performed normal activities appropriate for their ages. We conclude that approximately one third of patients with biliary atresia would benefit from or be cured by this operation, which should be the first attempt in the treatment of this disease entity.

Fetus in fetu: a case report and review of the literature.

A cystic tumor was first found in the abdomen of a Taiwanese girl at the age of 9 months. The tumor gradually increased in size and caused no symptoms until the girl was 7 years of age, when surgical removal was carried out. Pathological examination disclosed two "fetuses" within the fibrous sac. The pathogenesis of fetus in fetu and its differentiation from retroperitoneal teratoma are still controversial issues. Further work needs to be done to elucidate whether it is a natural progression of the twinning process to teratoma or the inclusion of a monozygotic diamniotic twin within the bearer.