Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.

INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

Budd-Chiari syndrome secondary to toxic pyrrolizidine alkaloid exposure.

In this report, we describe a case of pyrrolizidine alkaloid-related Budd-Chiari syndrome in Hong Kong. A 10-month-old boy presented with ascites, right pleural effusion, and hepatomegaly after consumption of herbal drinks for 3 months. His clinical (including imaging) features were compatible with Budd-Chiari syndrome. Budd-Chiari syndrome is a rare disease entity in paediatric patients. In our case, extensive workup performed to look for the underlying cause of Budd-Chiari syndrome was unrevealing, except for toxic pyrrolizidine alkaloid exposure in his herbal drinks.

Outbreak of hypoglycaemia: sexual enhancement products containing oral hypoglycaemic agent.

OBJECTIVES: To describe a cluster of Hong Kong subjects with hypoglycaemia, after they had taken various non-prescription sildenafil products containing glibenclamide. DESIGN: Retrospective study. SETTING: A tertiary referral centre for clinical toxicology analysis in Hong Kong. PATIENTS: All men referred to the laboratory for investigation of suspected drug-induced hypoglycaemia from December 2007 to September 2008. MAIN OUTCOME MEASURES: The characteristics of these patients, including their clinical presentations, outcomes, drug history, urine toxicology analysis results, and in some instances, analysis results of unused products. RESULTS: A total of 144 male patients were referred for suspected drug-induced hypoglycaemia. Sildenafil and glibenclamide, or their metabolites, were detected in the urine specimens of 68 (47%) patients, none of whom had been prescribed either drug by a registered medical practitioner. Among these subjects, 24 (35%) denied any use of sexual enhancement products despite repeated questioning. Eight patients had repeated exposure resulting in re-admission. The sources of these sexual enhancement products included pharmacies in Mainland China, friends, local pharmacies, peddlers, or were unknown. Three patients died, one remains in a vegetative state and one suffered cognitive impairment; the remaining 63 recovered fully. Twenty-five unused sexual enhancement products of seven different kinds were recovered for analysis. The median (range) of sildenafil and glibenclamide per unit dose was 64 (0.05-198) mg and 70 (0-158) mg, respectively. CONCLUSION: These illegal products pose a severe and continued threat to society and therefore deserve widespread vigilance, so that such products can be eradicated at their source.

Grayanotoxin poisoning from Rhododendron simsii in an infant.

We report a case of severe poisoning in a 57-day-old infant who presented with vomiting, convulsions, and shock after ingesting a bottle of milk containing a decoction of Rhododendron simsii. The grandmother collected this toxic plant from a cultivated area, believing it was good for the airways. Grayanotoxin was detected in both the urine and plant specimens. The infant made a good recovery after requiring ventilatory support for 2 days. Rhododendron is a common gardening shrub in Hong Kong. Some Rhododendron species are poisonous and contain grayanotoxin. Intentional or accidental ingestion of toxic plants can be severe or even life-threatening. It is therefore essential that clinicians be familiar with local toxic plant species.

Factitious thyrotoxicosis and herbal dietary supplement for weight reduction.

This article describes three patients who developed factitious thyrotoxicosis, as well as other adverse effects, after taking herbal dietary supplements for weight reduction. All products were found to contain undeclared animal thyroid tissue and western pharmaceuticals causing the adverse effects. Adulteration is concealed addition of undeclared drugs, or other substances with therapeutic effects, to a health product. Consumption of such products, and the concealed components unwittingly, is obviously dangerous. Multiple adulterants in one product are often seen. Untoward adverse effect or drug interaction could occur. Overdose subsequent to poor standardization of the adulterants is another concern. Health care professionals must therefore be aware of the potential dangers posed by adulterated dietary supplements.

Hazards posed by a banned drug--phenformin is still hanging around.

The Hospital Authority Toxicology Reference Laboratory confirmed six cases of phenformin use, with or without complications, from July 2005 to November 2006. Two of the patients presented with potentially fatal phenformin-induced lactic acidosis. Phenformin was found (or suspected to be) adulterating Chinese proprietary medicine in five of the six cases. We report these six cases to highlight the underrecognised hazards posed by phenformin, a banned drug in Hong Kong.

Analogues of erectile dysfunction drugs: an under-recognised threat.

OBJECTIVES: To investigate the problem of drug analogue adulteration in male erectile dysfunction health products. DESIGN: Survey of over-the-counter male erectile dysfunction health products available in convenience stores and pharmacies in Hong Kong. SETTING: Tertiary referral centre for clinical toxicology analysis in Hong Kong. MAIN OUTCOME MEASURES: The pattern and extent of adulteration of male erectile dysfunction health products with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues. RESULTS: Of 26 products studied, one (4%) was found to contain undeclared sildenafil, while 14 (54%) contained drug analogues of different kinds. The latter included acetildenafil, hydroxyacetildenafil, hydroxyhomosildenafil, and piperidenafil. The first three were analogues of sildenafil and the last was an analogue of vardenafil. One young patient presented with ataxia after taking an acetildenafil-containing product. CONCLUSIONS: The positive rate of concealed drug analogues in male erectile dysfunction health products is alarmingly high. Such analogues are difficult to detect by ordinary laboratory methods, and might be used in an attempt to evade regulatory inspection. Without going through the stringent drug testing process, the adverse effects of these chemicals remain largely unknown and unpredictable. Effective surveillance system and control measures are needed urgently. The medical profession and the public should be alerted to this under-recognised threat.

Adulteration of over-the-counter slimming products with pharmaceutical analogue--an emerging threat.

OBJECTIVES: To review pharmaceutical analogue adulteration of non-prescription slimming products. DESIGN: Retrospective study. SETTING: Tertiary referral centre for toxicology analysis, Hong Kong. PATIENTS: All patients known to have been hospitalised after taking slimming products adulterated with pharmaceutical analogues from September 2004 to December 2006. MAIN OUTCOME MEASURES: Age, reasons for hospital admission, major biochemical findings, and toxicology analysis results of the offending slimming products. RESULTS: N-nitrosofenfluramine, an analogue of fenfluramine with hepatotoxic effect, was found in two slimming products. Three patients were hospitalised after taking these slimming products, one of whom developed liver failure treated by liver transplantation. Another slimming product was found to contain N-desmethyl-sibutramine, an analogue of sibutramine. A patient with an unremarkable medical history developed acute psychosis after taking the latter product for 1 week. CONCLUSIONS: Analogues, created by modifying the chemical structures of pharmaceuticals, are used as adulterants in non-prescription slimming products, in an attempt to evade regulatory inspection. The imperceptible use of these analogues is very dangerous because they have not been tested formally for efficacy and safety. In view of the potential harm to the public, more effective and proactive measures are required to guard against the illicit use of pharmaceutical analogues. There is also a need for increased awareness among the public and the medical professionals about this emerging threat.

Methemoglobinemia after ingestion of Chinese herbal medicine in a 9-day-old infant.

Traditional Chinese Medicine has long been popular among Chinese people, but it is always difficult for physicians to ascertain the nature and use of different ingredients involved. We report case of a 9-day-old infant who ingested home-made herbal medicine and developed cyanosis with methemoglobinemia. He responded to a single dose of methylene blue therapy. The suspected causative agent identified in the herbal medicine was sulfamethazine. This is the first reported case of methemoglobinemia related to the use of Chinese herbal medicine in the newborn period.

Aconite poisoning in camouflage.

The Toxicology Reference Laboratory has confirmed 10 cases of aconite poisoning from March 2004 to May 2006. In four of these 10 cases, the aconite herb was not listed in the written prescription. We report these four cases to highlight the problem of 'hidden' aconite poisoning.

Drug-induced hypoglycaemia--new insight into an old problem.

OBJECTIVE: To review the causes of drug-induced hypoglycaemia in patients not taking hypoglycaemic medications. DESIGN: Retrospective study. SETTING: Regional hospitals in Hong Kong. PATIENTS: Patients with suspected drug-induced hypoglycaemia without a known history of exposure to hypoglycaemic agents, referred to the Hospital Authority Toxicology Reference Laboratory from June 2005 to March 2006 inclusive. MAIN OUTCOME MEASURES: Rate of positive cases, laboratory findings, possible causes, age distribution, and final outcomes. RESULTS: A total of 51 such patients were referred, in whom the presence of oral hypoglycaemic agents was detected (or inferred) in 23 (45%). In 12 of the 23 patients, oral hypoglycaemic agents could only be detected by target analysis, not through broad-spectrum screening. Gliclazide and glibenclamide were detected in 14 and eight patients respectively, whereas glimepiride, nateglinide and rosiglitazone were detected in the remaining patient. Possible sources of oral hypoglycaemic agents included drug administration errors in residential care homes for the elderly (n=9), mistakenly taking medication of a family member or employer (n=6), taking stock medication by mistake (n=2), taking Chinese proprietary medicine adulterated with oral hypoglycaemic agents (n=1), taking unknown pills bought from a retail pharmacy (n=1), and unknown (n=4). Regarding these 23 patients, 17 (74%) were aged 70 years or above and 21 (91%) recovered uneventfully. CONCLUSION: Hypoglycaemia due to inadvertent use of oral hypoglycaemic agents is a recognised problem, particularly in cases where family members living in the same household are taking similar medications. Possible drug administration errors in residential care homes for the elderly should be investigated, and procedures rectified if confirmed. Health care providers should be vigilant to such potential errors, especially in cases of unexplained hypoglycaemia.

Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones.

Chinese herbal medicine preparations are widely available and often regarded by the public as natural and safe remedies for a variety of medical conditions. Nephropathy caused by Chinese herbs has previously been reported, usually involving the use of aristolochic acids. We report a 23-year-old woman who developed acute renal failure following prolonged use of a proprietary Chinese herbal slimming pill that contained anthraquinone derivatives, extracted from Rhizoma Rhei (rhubarb). The renal injury was probably aggravated by the concomitant intake of a non-steroidal anti-inflammatory drug, diclofenac. Renal pathology was that of hypocellular interstitial fibrosis. Spontaneous renal recovery occurred upon cessation of the slimming pills, but mild interstitial fibrosis and tubular atrophy was still evident histologically 4 months later. Although a causal relationship between the use of an anthraquinone-containing herbal agent and renal injury remains to be proven, phytotherapy-associated interstitial nephropathy should be considered in patients who present with unexplained renal failure.

A case of tetramine poisoning: a lethal rodenticide.

We report a fatal case of suicide presenting with convulsions and subsequently multi-organ failure. Rodenticide poisoning was not suspected until the next day when tetramine was detected in the patient's blood, urine, and food residues. Tetramine is a potent rodenticide with a rapid action and high mortality. The poison has been banned worldwide but is still readily available in Mainland China. Outbreaks of poisoning are reported frequently and doctors should be alert for this lethal toxin.

Nitrite-induced methaemoglobinaemia - aetiology, diagnosis and treatment.

A 41-year-old woman presented with the clinical features of methaemoglobinaemia after drinking Chinese herbal medicine. A life threatening methaemoglobin level of 68% was measured. Both clinical and laboratory diagnostic difficulties were encountered. The pitfalls of pulse oximeter, blood gas analysis and co-oximeter interpretation during diagnosis and after methylene blue administration are discussed.

Use of hair analysis in the diagnosis of heavy metal poisoning: report of three cases.

We report three paediatric cases of suspected heavy metal poisoning that presented with non-specific symptoms. Hair samples of the three patients were sent overseas for analysis; results showed abnormal levels of many elements, including some heavy metals. A diagnosis of heavy metal poisoning was made and chelation therapy was offered to each patient. Blood levels for some heavy metals were subsequently checked and all were within the normal range. The original diagnosis of heavy metal poisoning was therefore not substantiated. The patients did not have a history of exposure to heavy metals or specific clinical features of heavy metal poisoning. The non-invasive nature of hair analysis is tempting, but the validity of such testing in diagnosing heavy metal poisoning is questionable.

Coping with failure: relationship with self-concept discrepancy and attributional style.

In the relationship of attributional style and self-concept discrepancy with coping behavior among 10th-grade Hong Kong Chinese students, 3 significant canonical variate pairs were identified. The total criterion redundancy showed that self-concept discrepancy and attributional style predicted about 20% of the variance of coping behavior. The 1st variate pair indicated that students with small self-concept discrepancy and low-depressive attributional style tended to cope with failure by planful problem solving and by positive reappraisal. The 2nd variate pair showed that students, particularly girls, with small self-concept discrepancy in verbal ability and same-sex peer relations tended to cope with failure by seeking social support. The last variate pair showed that students with great self-concept discrepancy in same-sex peer relations and parent relations tended to cope with failure by avoiding or escaping. The 3 canonical variate pairs also suggested a new taxonomy for coping behavior: mobilization of internal coping resources, mobilization of external coping resources, and the inability to mobilize any coping resources.

Neuronal generators of visual evoked potentials in humans: visual processing in the human cortex.

PURPOSE: We wished to define the localization of cortical generators of visual (pattern) evoked potentials (VEP) and the temporal sequence of activation in the occipital region. METHODS: In 4 candidates for epilepsy surgery, a large array of subdural electrodes was placed over occipital areas. Checkerboard pattern reversal stimuli were generated and the epileptogenic focus was localized and functionally mapped. Magnetic resonance imaging did not show any occipital lesions in any of the 4 patients. RESULTS: The area first activated was the lingual gyrus in the mesial occipital lobe (negative potential peaks at approximately 70 ms), followed by an area superior to the calcarine fissure (negative peaks at approximately 80 ms). Later (starting at approximately 90 ms), there were positive potentials over the occipital pole and lingual gyrus, followed by potentials at the lateral occipital lobe. CONCLUSIONS: These data support the idea that VEP are generated in the mesial and lateral occipital cortex by different circumscribed neuronal generators with different latencies of activation. The scalp-recorded N1 and P1 potential peaks most likely derive from the progressive activation of neuronal masses in different regions of the occipital lobe.