NDUFA9 point mutations cause a variable mitochondrial complex I assembly defect.

Mitochondrial respiratory chain complex I consists of 44 different subunits and contains 3 functional modules: the Q-, the N- and the P-module. NDUFA9 is a Q-module subunit required for complex I assembly or stability. However, its role in complex I biogenesis has not been studied in patient fibroblasts. So far, a single patient carrying an NDUFA9 variant with a severe neonatally fatal phenotype has been reported. Via exome sequencing, we identified a novel homozygous NDUFA9 missense variant in another patient with a milder phenotype including childhood-onset progressive generalized dystonia and axonal peripheral neuropathy. We performed complex I assembly analysis using primary skin fibroblasts of both patients. Reduced complex I abundance and an accumulation of Q-module subassemblies were present in both patients but more pronounced in the severe clinical phenotype patient. The latter displayed additional accumulation of P-module subassemblies, which was not present in the milder-phenotype patient. Lentiviral complementation of both patient fibroblast cell lines with wild-type NDUFA9 rescued complex I deficiency and the assembly defects. Our report further characterizes the phenotypic spectrum of NDUFA9 deficiency and demonstrates that the severity of the clinical phenotype correlates with the severity of the effects of the different NDUFA9 variants on complex I assembly.

The Griffiths Development Scales-Chinese (GDS-C): A cross-cultural comparison of developmental trajectories between Chinese and British children.

BACKGROUND: The Griffiths Mental Development Scales (GMDS) are used in many countries to assess the development of children from birth to 8 years. There is a need for accurate and culturally appropriate developmental assessment tools for Chinese children. Here, we adapted the GMDS for use in Chinese children and compare the developmental trajectories between Chinese and British children. METHODS: Children with typical development were recruited from 7 urban cities in China between 2009 and 2013. The Griffiths Mental Development Scales-Chinese (GDS-C) were adapted and used to assess the development of urban Chinese children. Developmental curves were computed for 6 subscales using learning management system methods and compare against the British curves from the Griffiths Mental Development Scales-Extended Revised (GMDS-ER). RESULTS: The GDS-C were used to assess the developmental status of 815 Chinese children. Plots of the 1st, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 99th percentiles, and full percentile tables were obtained, which showed similar trends to data from the British GMDS-ER. CONCLUSIONS: The Chinese developmental curves obtained from the GDS-C showed similarities and differences to the developmental curves from the British GMDS-ER. The development of urban Chinese children should be assessed with the culturally appropriate GDS-C.

Influenza vaccination and hospitalisation in Elderly Health Centres.

1. A cohort of Elderly Health Centres was examined to determine whether influenza vaccination decreased hospitalisation and mortality. 2. In the influenza season, influenza vaccination reduced all-cause mortality by half and cardiorespiratory hospitalisation by a quarter. The extent to which influenza vaccination protects older people from serious morbidity and mortality needs to be confirmed in appropriately designed studies, so that scarce health care resources can be used effectively

Abrogated expression of DEC1 during oesophageal squamous cell carcinoma progression is age- and family history-related and significantly associated with lymph node metastasis.

BACKGROUND: Oesophageal squamous cell carcinoma (SCC) causes the highest number of cancer deaths in some regions of Northern China. Previously, we narrowed down a critical region at 9q33-34, identified to be associated with tumour-suppressive function of deleted in oesophageal cancer 1 (DEC1) in oesophageal SCC. METHODS: We generated DEC1 antibody and constructed tissue microarrays (TMAs) utilising tissue specimens from Henan, a high-risk region for oesophageal SCC, to investigate the importance of DEC1 expression in this cancer. RESULTS: Tissue microarray immunohistochemical staining reveals significant loss of DEC1 from hyperplasia, to tumour, and to lymph node metastasis. In addition, the loss of DEC1 in tumour is age-dependent. Interestingly, there is significant abrogation of DEC1 expression in patients with a family history of oesophageal SCC. Deleted in oesophageal cancer 1 localises to both the cytoplasm and nucleus. The vesicular pattern of DEC1 in the cytoplasm appears to localise at the Golgi and Golgi-endoplasmic reticulum intermediate compartment. CONCLUSION: This is the first TMA study to suggest a clinical association of DEC1 in lymph node metastatic oesophageal SCC, early onset oesophageal SCC and familial oesophageal SCC development. Subcellular localisation of DEC1 and its expression in oesophageal SCC tissues provide important insight for further deciphering the molecular mechanism of DEC1 in oesophageal SCC development.

Biochemical and molecular characterization of tyrosine hydroxylase deficiency in Hong Kong Chinese.

Tyrosine hydroxylase deficiency is a rare neurotransmitter disorder affecting the rate-limiting step in catecholamine biosynthesis. There are about 40 cases reported worldwide. Here, we report the biochemical and molecular findings of eight unrelated Chinese patients with tyrosine hydroxylase deficiency. We have identified eight novel mutations with 5 missense, 2 nonsense and 1 splicing mutations in the TH gene, namely p.R153X, p.R169X, p.G294R, p.G315S, p.A385V, p.I394T, p.G408R, and c.1163+5G>C. The mutations of the TH gene in Chinese are heterogeneous.

Combined use of warfarin and adjusted subcutaneous heparin during pregnancy in patients with an artificial heart valve.

Adjusted subcutaneous heparin was used for thromboembolism prophylaxis during 18 pregnancies in 16 women with an artificial heart valve. Oral warfarin was replaced by subcutaneous heparin as soon as pregnancy was confirmed. The dosage of heparin was adjusted to maintain a partial thromboplastin time at 1.5 times the control value and treatment was administered during the first trimester and the last 3 weeks of gestation. Warfarin was used between the 13th and 37th week. There were no maternal thromboembolic complications and none of the live-born infants showed congenital malformations, indicating that this regimen is effective. However, there were nine spontaneous abortions, including five that occurred in the first 12 weeks. The early abortions were probably related to warfarin exposure at the beginning of pregnancy. The preconception replacement of warfarin by heparin in these patients may be indicated.

Randomised controlled trial of qigong in the treatment of mild essential hypertension.

Exercise and relaxation decrease blood pressure. Qigong is a traditional Chinese exercise consisting of breathing and gentle movements. We conducted a randomised controlled trial to study the effect of Guolin qigong on blood pressure. In all, 88 patients with mild essential hypertension were recruited from the community and randomised to Goulin qigong or conventional exercise for 16 weeks. The main outcome measurements were blood pressure, health status (SF-36 scores), Beck Anxiety and Depression Inventory scores. In the qigong group, blood pressure decreased significantly from 146.3+/-7.8/93.0+/-4.1 mmHg at baseline to 135.5+/-10.0/87.1+/-7.7 mmHg at week 16. In the exercise group, blood pressure also decreased significantly from 140.9+/-10.9/93.1+/-3.5 mmHg to 129.7+/-11.1/86.0+/-7.0 mmHg. Heart rate, weight, BMI, waist circumference, total cholesterol, renin and 24 h urinary albumin excretion significantly decreased in both groups after 16 weeks. General health, bodily pain, social functioning and depression also improved in both groups. No significant differences between qigong and conventional exercise were found. In conclusion, Guolin qigong and conventional exercise have similar effects on blood pressure in patients with mild hypertension. While no additional benefits were identified, it is nevertheless an alternative to conventional exercise in the nondrug treatment of hypertension.

Pregnancy and Takayasu's arteritis.

Thirteen patients with Takayasu's arteritis had 30 pregnancies between 1970 and 1982. The 11 pregnancies occurring before the disease became clinically evident were uneventful. Eleven patients had 19 pregnancies after manifestation of the disease. Four ended in abortion, four in cesarean section, and 11 in uneventful vaginal delivery at term. There was no major obstetric problem apart from hypertension, and there was no maternal death directly related to the pregnancy per se. All 15 babies were born without asphyxia and congenital abnormality. The nine with some evidence of intrauterine growth retardation could be predicted by a prognostic score taking into account the timing of therapy, the severity of the hypertension, and the extent of arterial involvement.

Aerosolized fluorescent microspheres detected in the lung using confocal scanning laser microscopy.

Aerosolized fluorescent microspheres were used to study particle deposition in site-specific regions of the lung with confocal laser scanning microscopy. A nebulizer was used to aerosolize microspheres followed by passage through a heated discharging column to reduce static charge and to remove water surrounding each microsphere. Precoating of microspheres with albumin helped to minimize displacement during vascular fixation of the lungs. Confocal laser microscopy facilitated visualization of microspheres throughout the bronchial tree, ducts, and alveoli of the lungs. The use of fluorescent microspheres and confocal laser imaging provided distinct advantages compared with other methods to study lung particle deposition due to (1) the generation of single microspheres of uniform size by nebulization, (2) easy detection of microspheres in large slabs of microdissected lung tissues, (3) excellent resolution of tissue surfaces and microspheres for an infinite number of orientations and planes of section, and (4) the ability to visualize microspheres below fluid lining layers and on surfaces that could not easily be done by other methods of microscopy.

Glucose and lipid metabolism with triphasic oral contraceptives in women with history of gestational diabetes.

The glucose and lipid metabolism in a group of women with previous history of gestational diabetes were evaluated before and after 6 months treatment with a low-dose triphasic oral contraceptives pill (TP). This group was compared with a control group of women, also with history of gestational diabetes, using intrauterine devices (IUD). In the TP group, 26.7% of the women developed impaired glucose tolerance which reverted to normal in all but one after cessation of the TP. The IUD group showed no change in glucose tolerance. The integrated insulin response to a 75g OGTT in the TP group increased by 48.3% at 6 months compared with an increase of 23.4% for the same period in the IUD group. In the TP group there was a significant decrease in serum total cholesterol without changes in HDL-cholesterol and triglycerides level. We conclude that even low-dose triphasic oral contraceptive pills can cause glucose intolerance in women with previous gestational diabetes mellitus.

PIP: The glucose and lipid metabolism in a group of 20 women with a previous history of gestational diabetes were evaluated before and after 6 months of treatment with a low-dose triphasic oral contraceptive (OC). Another group of 5 women, also with a history of gestational diabetes but who were given an IUD, served as controls. 26.7% of the women in the triphasic OC group developed impaired glucose tolerance; however, values reverted to normal in all but 1 woman after OC discontinuation. The IUD group showed no change in glucose tolerance. The integrated insulin response to a 75 gm oral glucose tolerance test increased by 48.3% at 6 months in the OC group compared with an increase of 23.4% for the same period in the control group. Also recorded in the OC group but not among controls was a significant increase in serum total cholesterol without changes in high density lipoprotein-cholesterol and triglyceride levels. It was concluded that even low-dose triphasic OCs can cause glucose intolerance in women with previous gestational diabetes mellitus. Thus, the theoretical risk of precipitating permanent diabetes should be weighed against the risk of pregnancy. In cases where OCs are the only reliable method possible, careful and frequent monitoring of carbohydrate metabolism should be performed. Older, heavier women with a family history of diabetes are in particular need of close surveillance and constant monitoring of their glucose and lipid metabolism.

Clinical manifestations of neurofibromatosis-1 in Chinese children.

The complications of 50 Chinese children with neurofibromatosis-1 were found to be different from other ethnic groups. There was a predominance of scoliosis, speech problems, and blood malignancies, but brain tumors were rare. The majority had good prognosis. Clinical manifestations depend on the age of ascertainment and, therefore, the prediction of associated complications should be made accordingly.

Cortical blindness in children: a study of etiology and prognosis.

Thirty-four children (20 boys, 14 girls) with congenital and acquired cortical blindness were analyzed for visual outcome in relation to etiology, visual evoked potentials, electroencephalography, and cranial computed tomography. All 7 children with congenital cortical blindness remained blind on subsequent examination. Of the 27 children with acquired blindness, 16 (59%) had poor visual outcome. Poor visual outcome occurred in those with cardiac arrest, hypoxia, status epilepticus, intracranial hemorrhage, cerebral thrombosis, and head trauma. Good visual outcome occurred in children with hypotensive episodes after cardiac surgery. Of the 12 children with recovery of vision, the interval from acute loss of vision to partial or total recovery was 2 weeks to 5 months. Seven children had complete recovery of vision with no residual visual field defect. The majority of children (87%) had focal or multifocal spike-and-waves and slow sharp-wave discharges on electroencephalography. None had photic recruitment response or occipital spike-and-wave discharges. Flash visual evoked potential studies performed during acute episodes of cortical blindness documented 11 with absent response, 10 with bilateral increases in latency, and 6 with normal responses. There was no correlation between normal visual evoked potentials and a good visual outcome. Only 2 of 6 children with normal responses had normal vision. Abnormal or absent responses are more predictive of a poor recovery of vision because only 3 of 21 (14%) had normal vision on subsequent examination. Abnormal electroencephalographic findings with focal or multifocal spike-and-wave discharges or cerebral atrophy on cranial computed tomography are also poor prognostic signs.

Fragile X positivity in Chinese children with autistic spectrum disorder.

Chromosome analysis was performed in 105 Chinese children (96 boys, 9 girls) with autistic spectrum disorder to assess fragile X positivity. Seventy percent of these autistic children were mentally retarded. None of the children in the infantile autism group (N = 75) had fragile X positivity. Two boys in the autistic condition group (N = 30) had clinical features and chromosomal positivity for fragile X syndrome. The low (2%) prevalence rate of fragile X positivity in children with different degrees of expressivity of autistic features may be related to other factors rather than to pure autistic characteristics per se.

Basilar impression in a child with hypochondroplasia.

A 4-year-old boy with hypochondroplasia presented with delay in gross motor development. Magnetic resonance imaging demonstrated basilar impression with compression at the craniovertebral junction and mild degree of hydrocephalus. Posterior fossa decompression resulted in improvement in neurologic function and relief of hydrocephalus.

Electrophysiologic study in acute lead poisoning.

A 2-month-old girl with acute lead poisoning demonstrated electrophysiologic evidence of neurotoxicity. Motor nerve conduction studies of the median, ulnar, peroneal, and posterior tibial nerves revealed both axonal and demyelinating neuropathy. Somatosensory evoked potential studies of median and posterior tibial nerves demonstrated evidence of cortical involvement. Brainstem auditory evoked potential study disclosed the possibility of acoustic nerve involvement but no evidence of a brainstem lesion. Postmortem examination revealed cerebral edema and focal segmental demyelination of the median nerve.

Unusual case of Klüver-Bucy syndrome in a Chinese boy.

Following an encephalopathic illness, a 13-year-old Chinese boy had a partial form of Klüver-Bucy syndrome with emotional disturbance, recent memory loss, hypersexuality, and polyphagia. Other unusual features included narcolepsy, polydipsia, and polyuria. Virologic studies failed to incriminate the etiologic agent, including herpes simplex virus. Brain biopsy of the frontal lobe demonstrated Alzheimer type II astrocytosis.

Ethical considerations in safe motherhood (SM) programs in developing countries.

There are still many maternal deaths in the world each year and over 98% are in developing countries. A program of safe motherhood is needed to make certain that every woman has the right of basic maternity care.

Intrauterine death from ergotamine overdosage.

Fetal death in a primigravid patient who had taken an overdose of ergotamine tartrate is presented. Non-stress cardiotocography performed shortly after admission was technically unsatisfactory for interpretation but revealed the presence of very frequent uterine contractions. The cause of fetal death in this patient is discussed. Overdosage of ergotamine must be considered a serious threat to the well-being of the fetus in utero.

Ganglioneuroma of the spinal cord.

This report describes a 2-year-old boy who harbored an intramedullary ganglioneuroma involving almost the entire length of the spinal cord. The terminology, pathology, and neurobiological behavior of this tumor is discussed.

Developing professional responsibility in maternity care in Hong Kong.

A simple questionnaire was used to document basic information surrounding all perinatal deaths in Hong Kong. Coordinators were appointed for every maternity unit. Replies were sent by mail to the Obstetrical and Gynaecological Society. Using volunteer time and minimum budget, the data were collated and analyzed. The main causes of death were congenital anomalies, intrauterine death of unknown cause and prematurity. There was significant difference in performance when the University units were compared with the private and Government units. Changes in resource allocation and modification of clinical practice may be recommended as a result of such audit.

PIP: A pilot study was begun in Hong Kong to prove feasibility and the advantage of a low-budget surveillance program. A questionnaire was developed for reporting all perinatal deaths including a minimum gestational age of 22 completed weeks and/or a birth weight of 500 g. Coordinators were appointed for every maternity unit. Replies were sent by mail to the Obstetrical and Gynecological Society. Using volunteer time, the data were collected and analyzed. A total of 25 units participated; 4 University, 6 government, and 15 private. During the 1st study year, there were 535 perinatal deaths, which represented 90% of the total perinatal deaths for Hong Kong. The overall perinatal mortality rate (PNM) was 8.1/1000; highest in government, lowest in private units (5.1). The University units, which admitted most of the high-risk mothers, had a PNM rate of 8.6/1000. The most common causes of perinatal deaths were congenital anomalies, intrauterine death of unknown cause, and prematurity. There was a significant difference when the perinatal deaths were compared in the 3 types of units; a lower incidence in twin pregnancy in University units; a higher incidence among mothers with no prenatal care in University units, more deliveries by midwives in Government units, and the high prevalence of cesarean section in private units. Suggestions are given to decrease deaths from congenital anomalies, prematurity, and stillbirth of unknown cause. The comparison among the 3 types of hospitals is only superficial.