Merosin-deficient congenital muscular dystrophy (MDCMD): a case report with MRI, MRS and DTI findings.

Congenital muscular dystrophy (CMD) comprises a heterogeneous group of disorders present at birth with muscle weakness, hypotonia and contractures. Congenital muscular dystrophy (CMD) comprises a heterogeneous group of disorders with muscle weakness, hypotonia and contractures present at birth. A particular subset of classic CMD is characterized by a complete absence of merosin. Merosin-deficient congenital muscular dystrophy (MDCMD) is a rare genetic disease involving the central and peripheral nervous system in the childhood. High signal intensities are often observed throughout the centrum semiovale, periventricular, and sub-cortical white matters on T2-weighted images in MRI brain in children with MDCMD. Apparent diffusion coefficient (ADC) map may reveal increased signal intensity and apparent diffusion coefficient values in the periventricular and deep white matters. These white matter findings, observed in late infancy, decrease in severity with age. The pathogenesis of these changes remains uncertain at present. In this article, we outline the specific MR imaging findings seen in a patient with documented MDCMD and also suggest the causes.

Epidermal fatty-acid-binding protein: a new circulating biomarker associated with cardio-metabolic risk factors and carotid atherosclerosis.

AIMS: Epidermal fatty-acid-binding protein (E-FABP) is highly homologous to adipocyte FABP (A-FABP), which mediates obesity-related metabolic syndrome (MetS), diabetes and atherosclerosis in animals. Combined deficiency of E-FABP and A-FABP protects against the MetS and atherosclerosis in mice. This study investigated the association of serum E-FABP with cardio-metabolic risk factors and carotid atherosclerosis in humans. METHODS AND RESULTS: The presence of E-FABP in human plasma was detected by tandem mass spectrometry. Serum E-FABP levels, determined by an enzyme-linked immunosorbent assay in 479 Chinese subjects (age: 55.4 ± 13.5 years; M/F: 232/247), correlated positively (P < 0.05 to <0.001, age-adjusted) with parameters of adiposity, adverse lipid profiles, serum insulin, A-FABP, and C-reactive protein levels and were higher in subjects with the MetS (P < 0.001 vs. no MetS). The association of E-FABP with the MetS was independent of A-FABP. Furthermore, serum E-FABP correlated with carotid intima-media thickness (IMT; P < 0.001) and was independently associated with carotid IMT in men (adjusted P = 0.03). CONCLUSION: E-FABP is a new circulating biomarker associated with increased cardio-metabolic risk. It may contribute to the development of the MetS and carotid atherosclerosis in humans, independent of the effect of A-FABP.

Serum adipocyte fatty acid-binding protein levels were independently associated with carotid atherosclerosis.

OBJECTIVE: Adipocyte fatty acid-binding protein (A-FABP) has been shown to be an important player in atherosclerosis in animal models. However, the clinical relevance of these findings is still unknown. This study aims to examine the relationship between serum A-FABP level and carotid intima-media thickness (IMT), an indicator of atherosclerosis in humans. METHODS AND RESULTS: The study cohort included 479 Chinese subjects who underwent carotid IMT measurement. Serum A-FABP levels were determined by enzyme-linked immunosorbent assays. Serum A-FABP levels positively correlated with carotid IMT in both men (r=0.211, P=0.001) and women (r=0.435, P<0.001). In women, but not in men, the presence of plaques was associated with significantly higher serum A-FABP levels (P<0.001 versus women without plaques). Stepwise multiple regression analysis showed that serum A-FABP level was independently associated with carotid IMT in women (P=0.034), together with age and hypertension (both P<0.001). CONCLUSIONS: A-FABP is an independent determinant of carotid atherosclerosis in Chinese women, but not in men. This gender difference may be attributed to the lower serum A-FABP levels in men, and the effect of other risk factors, such as smoking, among our male participants. Our results have provided clinical evidence supporting the role of A-FABP in the development of atherosclerosis.

Surgical complications and outcome of pediatric liver transplantation in Hong Kong.

PURPOSE: The aim of this study was to analyze the early and late results of pediatric liver transplantation, with particular reference to complications that required surgical or radiologic intervention. METHODS: The records and code sheets of children who underwent liver transplantation in the authors' institution between September 1993 and December 2001 were reviewed. RESULTS: Twenty-nine children (16 boys and 13 girls) underwent 31 liver transplantations (23 living donor, 8 cadaveric donor) during the study period. The ages of the children ranged from 4 months to 132 months (median, 16 months). Eighteen children had complications that required surgical or radiologic interventional procedures. Complications included, among others, hepatic vein thrombosis (n = 1, 3%), hepatic vein stenosis (n = 2, 7%), portal vein thrombosis (n = 2, 7%), biliary stricture (n = 3, 10%), bile leakage (n = 2, 7%), hepatic artery pseudoaneurysm (n = 1, 3%), jejuno-jejunostomy leakage (n = 1, 3%), graft hepatitis (n = 1, 3%), and posttransplant lymphoproliferative disorder (n = 2, 7%). In addition, 6 children (21%) suffered from intraabdominal bleeding from a variety of causes. After appropriate interventions, at a median follow-up of 38 months (range, 1 to 96 months), patient and graft survival rates were 79% and 74%, respectively. The retransplantation rate was only 7%. There was no incidence of hepatic artery thrombosis. All living donors remain alive and well. CONCLUSIONS: Complications are inevitable in pediatric liver transplantation. However, with timely recognition and active intervention, a good outcome can be achieved.

The effect of pregnancy on thyroid nodule formation.

Epidemiology data have revealed a higher prevalence of nodular goiters in women than men in both iodine-sufficient and iodine-deficient areas. Increased prevalence of thyroid nodules has also been reported in women with higher gravidity. However, the association between pregnancy and thyroid nodule formation has never been studied. The aim of our study was to evaluate the incidence of thyroid nodules during pregnancy and determine whether pregnancy will induce thyroid nodule formation. Two hundred twenty-one healthy southern Chinese women in the first trimester of their pregnancy were studied prospectively. Thyroid ultrasonography, thyroid function tests, and urinary iodine excretion were measured at first, second, and third trimesters of pregnancy as well as 6 wk and 3 months postpartum. Thyroid nodules (>2 mm in any dimension on ultrasonography) were detected in 34 (15.3%) subjects at first trimester, with 12 (5.4%) subjects having more than one nodule. Eight subjects had clinically palpable nodules. Women with thyroid nodules were older (P < 0.01) and had higher gravidity (P < 0.02) than those women without thyroid nodules. The volume of the single/dominant nodules increased from 60 (14--344) mm(3), median (interquartile range) at first trimester to 65 (26-472) mm(3) at third trimester (P < 0.02). These nodules remained enlarged at 103 (25-461) mm(3) 6 wk postpartum (P < 0.005) and 73 (22-344) mm(3) at 3 months postpartum (P < 0.05). Patients with thyroid nodules had lower serum TSH values (P < 0.03) and higher Tg levels (P < 0.05) throughout pregnancy. Appearance of new nodules was detected in 25 (11.3%) women as pregnancy advanced so that by 3 months postpartum, the incidence of thyroid nodular disease was 24.4% (P < 0.02 vs. first trimester). Compared with those with no detectable nodules throughout pregnancy, subjects with new nodule formation had higher urinary iodine excretion from second trimester onward (P all < 0.05). However, no difference could be detected in their TSH and Tg levels throughout pregnancy. Fine-needle aspiration on nodules greater than 5 mm in any dimension after delivery (n = 21) confirmed the majority having histological features consistent with nodular hyperplasia. No thyroid malignancy was detected. In conclusion, pregnancy is associated with an increase in the size of preexisting thyroid nodules as well as new thyroid nodule formation. This may predispose to multinodular goiter in later life.

Colour Doppler analysis of peri-implantation utero-ovarian haemodynamics in women with excessively high oestradiol concentrations after ovarian stimulation.

BACKGROUND: Gonadotrophins are used in many assisted reproduction units to achieve a better success rate by increasing the number of replaced embryos. However, high oestradiol concentrations are associated with altered physiological functions and its complications. We investigated whether high oestradiol concentrations (> or =20 000 pmol/l) after ovarian stimulation in infertile women would affect the uterine haemodynamics at the time of embryo transfer. METHODS: Colour Doppler indices of utero-ovarian arteries and endometrial colour signals were measured. Fifty-eight women undergoing ovarian stimulation for IVF were classified according to serum oestradiol concentrations on the day of human chorionic gonadotrophin injection into moderate responders (oestradiol <20 000 pmol/l; n = 39) and high responders (oestradiol > or =20 000 pmol/l; n = 19). RESULTS: Haemodynamic parameters were significantly lower in high responders; the uterine arterial pulsatility index (PI) and resistance index (RI) were (median; range) 1.87 (0.84-2.82) and 0.79 (0.57-0.90) respectively; ovarian artery PI was 0.57 (0.40-1.12) and RI was 0.43 (0.33-0.64). In moderate responders the uterine PI and RI were 2.63 (1.46-5.92) and 0.88 (0.77-1.10) respectively. Ovarian PI was 0.81 (0.32-3.72) and RI was 0.55 (0.23-0.97). The number of women showing endometrial colour signals was significantly lower in high responders (63%) than in moderate responders (92%) (P < 0.05). A further increase in oestradiol (> or =25 000 pmol/l; n = 8) showed significantly (P = 0.03) fewer endometrial colour signals [1.5 (0-8)] compared with moderate responders [4 (0-14)]. CONCLUSION: Despite low uterine PI and RI, the endometrial blood flow in high responders appears to be impaired. This may contribute to the decline in implantation efficiency noted in high responders.

Mild iodine deficiency and thyroid disorders in Hong Kong.

OBJECTIVES: To review evidence of iodine deficiency and clinical thyroid disorders in Hong Kong. DATA SOURCES: Publications on local dietary iodine intake, the iodine content of local food items, and clinical thyroid problems in the Hong Kong population. DATA EXTRACTION: Data was extracted and evaluated independently by the authors. DATA SYNTHESIS: Iodine is an essential nutrient. Iodine deficiency can lead to goitre, hypothyroidism, mental deficiency, and impaired growth. It is now appreciated that determination of goitre incidence in children alone may grossly underestimate the problem of iodine deficiency in a population. In total, the evidence indicates that iodine deficiency exists in Hong Kong, leading to clinical problems of transient neonatal hypothyroidism, goitrogenesis, and thyroid disorders in pregnant women and neonates, as well as thyroid dysfunction in the elderly. CONCLUSION: A supplementation programme aimed at a relatively uniform iodine intake is recommended to avoid deficient or excessive iodine intake in subpopulations.

Goitrogenesis during pregnancy and neonatal hypothyroxinaemia in a borderline iodine sufficient area.

OBJECTIVE: Severe iodine deficiency disorders (IDDs) may have been eradicated in many parts of the world, but milder forms still exist and may escape detection. We evaluated the impact of pregnancy on the maternal and fetal thyroid axis in Hong Kong, a coastal city in southern China with borderline iodine intake. DESIGN: A prospective study performed in a maternity hospital. PATIENTS: Two hundred and thirty pregnant women were prospectively studied and their neonates assessed at birth. MEASUREMENTS: Urine iodine concentration, thyroid function tests and thyroid volume (TV) by ultrasound were determined in the mothers during pregnancy and up to 3 months postpartum and in the neonates. RESULTS: Increased urinary iodine concentration was seen from first trimester onwards and the proportion of women having urine iodine concentration of < 0.4 micromol/l decreased from 11.3% in the first trimester to 4.7% in the third trimester. There was progressive reduction in circulating fT4 and fT3 concentrations and free thyroxine index (FTI) with increasing gestation and the percentage of women having subnormal levels at term were 53.2%, 61.1% and 4.8%, respectively. The serum TSH concentration during pregnancy doubled towards term. In the first trimester, multiparous women had significantly larger TV than the nulliparous women (P < 0.001). By the third trimester, TV had increased by 30% (range 3-230%) so that the goitre incidence was 14.1%, 21.8%, 25.9% during the three trimesters of pregnancy, and 24.3% and 21.9% at 6 weeks and 3 months postpartum (ANOVA, P < 0.05). The change in thyroid volume during pregnancy correlated positively with the change in thyroglobulin (r = 0.225, P < 0.002) and negatively with urinary iodine concentration (r = - 0.149, P < 0.02). Fourteen women with excessive thyroidal stimulation in the second trimester (defined as those with thyroglobulin (Tg) concentrations in the highest tertile and FTI in the lowest tertile) were found to have lower urine iodine concentrations and larger TV (both P < 0.005) throughout pregnancy, and their neonates had higher cord TSH (P < 0.05), Tg (P < 0.05) and slightly larger TV (P = 0.06) as compared to the findings in 216 pregnant women without evidence of thyroid stimulation. Seven neonates (50%) born to these women had subnormal fT4 levels at birth. CONCLUSION: In a borderline iodine sufficient area, pregnancy posed an important stress resulting in higher rates of maternal goitrogenesis as well as neonatal hypothyroxinaemia and hyperthyro- trophinaemia. An adequate iodization program is necessary to eliminate iodine deficiency disorders during pregnancy.

Liver transplantation in infants.

PURPOSE: In view of the earlier reports that children below 1 year of age constitute a high-risk group for liver transplantation, the authors reviewed their experience in performing orthotopic liver transplantation in this age group. METHODS: The records of 9 children aged less than 1 year who underwent 6 living-related liver transplants and 3 reduced-size liver transplants between December 1993 and June 1997 were reviewed. RESULTS: Five reexplorations were required for 3 children who had 1 or more of the following early complications: bleeding from hepatic vein to inferior vena cava anastomosis (n = 1), right hepatic vein stump bleeding (n = 1), intraabdominal hematoma (n = 2), jejuno-jejunostomy leakage (n = 1), and colonic perforation (n = 1). Late complications include stricture at the biliary-enteric anastomosis requiring percutaneous balloon dilatation (n = 3) and hepatitis of undetermined etiology requiring retransplantation (n = 1). There was no hepatic artery thrombosis despite the small arteries available for anastomosis. Follow-up ranged from 19 to 61 months (mean, 40 months). Patient survival rate was 100%, and graft survival with good liver function was 89%. All living donors, 2 fathers and 4 mothers, are well. CONCLUSIONS: Liver transplantation in infants less than 1 year of age is technically demanding but feasible and still can be performed with a good outcome. Age alone (under 1 year) should not be considered as a contraindication for liver transplantation.

Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endothelium-dependent and independent vasodilation in patients with type 2 diabetes.

Recent studies have suggested that hypercholesterolemia is associated with endothelial dysfunction. In patients with type 2 diabetes mellitus, dyslipidemia is mainly characterized by hypertriglyceridemia, low high density lipoprotein, and a preponderance of small dense low density lipoprotein (LDL) particles. We have examined the relationships among LDL subfractions, the susceptibility of LDL to oxidation in vitro, and endothelial function in type 2 diabetes mellitus. LDL subfractions were measured by density gradient ultracentrifugation. The susceptibility of LDL to oxidation was determined by measuring the kinetics of conjugated dienes formation during copper-mediated oxidation of LDL. Endothelium-dependent and independent vasodilation of the brachial artery were assessed by high resolution vascular ultrasound. Diabetic patients had a higher concentration of small dense LDL-III than matched controls (P < 0.01). The lag phase of conjugated dienes formation was shorter in the diabetic patients (P < 0.05), and the rate of LDL oxidation was faster (P < 0.05). Both endothelium-dependent (P < 0.01) and independent dilation of the brachial artery (P < 0.01) were impaired in the diabetic patients. On multivariate analysis, the rate of oxidation and LDL-III concentration accounted for 12% and 6%, respectively, of the variation in endothelium-dependent vasodilation (adjusted r2 = 0.18; P < 0.05), whereas LDL-III concentration and the maximum amount of conjugated dienes formed accounted for 27% and 5%, respectively, of the variation in endothelium-independent vasodilation (adjusted r2 = 0.32; P < 0.01) in the diabetic patients. In conclusion, endothelial and smooth muscle cell dysfunction in type 2 diabetes were related to abnormalities in LDL subfractions and in LDL oxidation.

Ultrasound contrast agent Levovist in colour Doppler sonography of hepatocellular carcinoma in Chinese patients.

In a phase IIIb clinical trial of the ultrasound contrast agent Levovist (Schering AG, Berlin, Germany), the role of Levovist in the management of patients with clinically suspected hepatocellular carcinoma (HCC) was evaluated and its efficacy was assessed. The assessment included the duration of diagnostically usable Doppler signal enhancement, and safety and tolerance of intravenous administration. All patients with clinically suspected hepatocellular carcinoma were referred for Doppler sonographic examination over a 5-month period and lesions with absent or suboptimal Doppler signals were included in the trial. A total of 300 mg/mL in concentration (8.5 mL) of Levovist was administered through a peripheral vein while Doppler signal intensity in the lesion, based on a visual score, was recorded. Blood pressure and pulse were recorded before and after injection. Thirty-eight patients were examined, of which 29 were included in the trial. The lesions were subsequently proven histologically to be 19 HCC, one cholangiocarcinoma, two regeneration nodules and one colonic metastasis. For six patients in whom histological proof was not available, the diagnosis of HCC was suggested based on markedly elevated serum alpha-fetoprotein levels. All but one (96%) of the 25 HCC demonstrated increased Doppler signal after Levovist. There were no Doppler signals before and after Levovist injection in three non-HCC lesions (two regeneration nodules and one colonic metastasis). Two patients (6.9%) suffered minor adverse reactions of nausea and vomiting. The results show that Levovist is safe and is able to improve lesion characterization and increase diagnostic confidence of hepatocellular carcinoma by enhancing tumour vascularization Doppler signal intensity.

Sonographic evaluation of the myomectomy 'scars'.

BACKGROUND: The evolution of myomectomy 'scars' has not been reported. This prospective study was carried out to determine the evolution of the myomectomy 'scars' following conventional open myomectomy. METHODS: Ten patients admitted for myomectomy were recruited. The sizes of the leiomyomata were determined with ultrasonography. Serial sonographic examinations were performed following the open myomectomy so as to determine the morphology and volume of the scars. The volumes of the uterus were also measured to document the postoperative remodeling of the uterus. RESULTS: The myomectomy 'scars' were represented by an area with mixed echogenic echoes in the immediate postoperative period. In one month, their volumes decreased to less than 5% of the preoperative volumes and were reduced to vague areas marked by short echogenic lines at 6 months. Most of the remodeling of the uterus occurred in the first month postoperatively. CONCLUSIONS: The mixed echogenic areas probably represented the approximated myometrial walls of the leiomyomata. Detection of such in postoperative sonography should not cause undue alarm.

Sonographic localization of abdominal vessels in Chinese women: its role in laparoscopic surgery.

Trauma to abdominal wall blood vessels occurs following 0.2-2% of laparoscopic operations. This prospective observational study assessed the possible role of sonographic localization of abdominal blood vessels prior to laparoscopic surgery in Chinese women and compared the findings reported in a Western group. The inferior epigastric and superficial circumflex iliac vessels were located by color Doppler imaging. Ultrasonography was 100% and 80% successful in locating the inferior epigastric and the superficial circumflex iliac vessels, respectively. The positions of the inferior epigastric vessels were similar to those reported in the Western population whilst the superficial circumflex iliac vessels were found to be situated 1 cm more medially. In our study population, a safe area for entry of lateral ports appeared to be 7 cm from the midline and 5 cm above the pubic symphysis. Sonographic localization of abdominal blood vessels is a potentially useful clinical tool in the prevention of blood vessel trauma.

Paediatric liver transplantation: Queen Mary Hospital experience.

OBJECTIVE: To assess the results of paediatric liver transplantation in our institution. METHODS: From September 1993 to November 1996, 10 living-related liver transplants (LRLT) and 3 reduced-size liver transplants (RSLT) were performed on 12 children at our hospital. The medical records of the patients were reviewed. All patients suffered from end-stage liver disease resulting from biliary atresia with failed Kasai's operations. Their ages at initial transplantation ranged from 8 months to 11 years. Excluding the 2 older children aged 7.5 and 11 years, the remaining patients were aged 10.5 months on the average and weighed 6 to 9.5 kg (mean: 6.8 kg) at the time of initial transplantation. RESULTS: All living donors were discharged on postoperative day 4 to 8 and resumed their previous normal activities. All recipients were alive with normal liver function and growing after a follow-up period of 3-40 months (mean: 21 months). The patient survival rate was 100%. One patient with RSLT had hepatitis of undetermined aetiology and underwent retransplant with a graft from her mother. The graft survival rate was 92%. Postoperative complications included: postoperative bleeding (n = 3), hepatic vein stenosis (n = I), biliary-enteric anastomotic stenosis (n = 3), intestinal perforation (n = I) and portal vein thrombosis (n = I). They were all treated promptly. In all patients, the hepatic artery (diameter ranged from 1.5 to 2.5 mm) anastomosis was achieved by microvascular technique. There was no hepatic artery thrombosis in our patients. CONCLUSION: With technical refinements, early detection and prompt treatment of complications, and advances in immunotherapy, excellent results can be achieved in paediatric liver transplantation.

Transperineal versus transvaginal color Doppler imaging of the uterine circulation.

Transperineal sonography has been described as being useful in assessing patients in special clinical situations such as posterior placenta previa, preterm labor, stress incontinence, and vaginal atresia. We explored the feasibility of this approach in assessing the uterine circulation in 54 subjects, of whom 36 were postmenopausal. We found that visualization of the uterine artery by the transperineal approach was satisfactory in most patients. The uterine arterial Doppler indices obtained from this approach were compared with those obtained by the transvaginal route. Highly significant correlations were found (correlation coefficient tau for pulsatility index = 0.74, p < 0.0001). No significant differences in results between the two approaches were detected using the Wilcoxon Matched-Pairs Signed-Rank test. We conclude that transperineal Doppler studies of the uterine circulation are possible and may be useful in certain patient groups.

Liver transplantation in children: the experience of Queen Mary Hospital, Hong Kong.

Seven living-related liver transplants (LRLT) and two reduced-size liver transplants (RSLT) were performed on eight children who suffered from end-stage liver disease, having previously undergone one to three abdominal operations. Their ages at initial transplantation ranged from 8 months to 11 years (mean 35 months, median 12 months). Excluding the two older children aged 7 and 11 years, respectively, the rest of the children weighed 6 to 9.5 kg (mean 7.3 kg) at the time of the initial transplantation. Seven left lateral segments (S2 + 3) and two left lobes (S2 + 3 + 4) were used; of these the smallest graft had a graft-to-recipient body weight ratio of 0.9%. The volunteer living donors were four mothers, two fathers and one sister who were selected after medical and psychiatric evaluations, and their suitability was confirmed by hematological, biochemical, and radiological criteria. During a follow-up period of 3 to 30 months, all eight children are alive and well with normal liver function, one of them having undergone a retransplant LRLT because of hepatitis of undetermined etiology following a RSLT 1.5 years earlier. All seven donors had an uneventful postoperative course and were discharged on day 4 to 7 postoperatively. They have all resumed normal day-to-day activities. There were no complications in the donor group. A variety of complications occurred in the recipients, all of which were overcome. Operating microscope was used to perform all the arterial anastomoses using microvascular techniques. This method has proven to be a major factor in preventing arterial thrombosis even with the smallest of arterial anastomosis where a 1.5-mm diameter recipient artery was anastomosed to a 2.5-mm diameter donor hepatic artery.