Hong Kong College of Physicians Position Statement and Recommendations on the 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension Guidelines for the Management of Arterial Hypertension.

The American College of Cardiology/American Heart Association released guidelines for the prevention, detection, evaluation, and management of high blood pressure (BP) in adults in 2017. In 2018, the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) published new guidelines for the management of arterial hypertension. Despite the many similarities between these two guidelines, there are also major differences in the guidelines in terms of diagnosis and treatment of hypertension. A working group of the Hong Kong College of Physicians (HKCP) convened and conducted a focused discussion on important issues of public interest, including classification of BP, BP measurement, thresholds for initiation of antihypertensive medications, BP treatment targets, and treatment strategies. The HKCP concurs with the 2018 ESC/ESH guideline on BP classification, which defines hypertension as office systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. The HKCP also acknowledges the growing evidence of home BP monitoring and ambulatory BP monitoring in the diagnosis and monitoring of hypertension and endorses the wider use of both methods. The HKCP also supports the direction of a risk-based approach for initiation of antihypertensive medications and the specification of a treatment target range for both systolic and diastolic BP with consideration of different age-groups and specific disease subgroups. Non-pharmacological interventions are crucial, both at the societal and individual patient levels. The recent guideline publications provide good opportunities to increase public awareness of hypertension and encourage lifestyle modifications among the local population.

Prolonged myoclonus after a single bolus dose of propofol.

Propofol is a commonly used anaesthetic agent and is rarely associated with seizure-like phenomena. This case report presents a young woman with seizure-like phenomena lasting more than 4 weeks after a single dose of propofol. The underlying pathophysiology of this condition is poorly understood but a psychological component is possible in this case.

Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kappaB activation.

The Tax protein of human T-lymphotropic virus type 1 (HTLV-1), an oncoprotein that transactivates viral and cellular genes, plays a key role in HTLV-1 replication and pathogenesis. We used cDNA microarrays to examine Tax-mediated transcriptional changes in the human Jurkat T-cell lines JPX-9 and JPX-M which express Tax and Tax-mutant protein, respectively, under the control of an inducible promoter. Approximately 300 of the over 2000 genes examined were differentially expressed in the presence of Tax. These genes were grouped according to their function and are discussed in the context of existing findings in the literature. There was strong agreement between our results and genes previously reported as being Tax-responsive. Genes that were differentially expressed in the presence of Tax included those related to apoptosis, the cell cycle and DNA repair, signaling factors, immune modulators, cytokines and growth factors, and adhesion molecules. Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax-mediated NF-kappa-B signaling. Our current results provide additional insights into Tax-mediated signaling.

The alpha-synuclein gene and Parkinson disease in a Chinese population.

OBJECTIVE: To study the Ala53Thr and Ala30Pro mutations of the alpha-synuclein gene in a large number of Chinese patients with Parkinson disease (PD) as well as controls. METHODS: We recruited 183 Chinese patients with sporadic PD, 17 with younger-onset PD (onset age <50 years), and 7 with PD and a positive family history as well as 227 unaffected Chinese control subjects from the outpatient departments of 2 major hospitals in Hong Kong. All subjects were assessed for the the diagnosis of PD by a consultant neurologist or geriatrician. Subjects were interviewed with a standard questionnaire that also questioned for family history. Venous blood samples were obtained from the subjects and genomic DNA was extracted and studied for the presence of Ala53Thr mutation in exon 4 and Ala30Pro mutation in exon 3 of the alpha-synuclein gene using a polymerase chain reaction restriction fragment length polymorphism method. RESULTS: None of the Chinese PD patients or controls had either the Ala53Thr (exon 4) or Ala30Pro (exon 3) mutation of the alpha-synuclein gene. CONCLUSION: We failed to discover Ala53Thr or Ala30Pro mutations in a large number of Chinese patients with PD and control subjects, adding to the emerging consensus that variations in the alpha-synuclein gene are associated with PD in few families worldwide.

Clinical characteristics of adult epilepsy patients in the 1997 Hong Kong epilepsy registry.

OBJECTIVE: To study the clinical characteristics of 2952 patients with epilepsy who had received drug treatment from the neurology outpatient clinics of eight major hospitals in Hong Kong. METHODS: Retrospective review of outpatient records. RESULTS: 1601 (54.3%) males and 1351 (45.7%) females with a median age of 35.8 years (range, 10-94.8) were studied. Seizure types included generalized tonic-clonic in 80.7% of patients, complex partial in 28.3%, simple partial in 14.4%, atypical absence in 2.6% and myoclonic in 1.4%, and 30.4% of patients had more than one seizure type. EEG, CT brain, MRI brain and neuropsychological evaluation were obtained in 81.2%, 61.7%, 17.0% and 2.2% of patients, respectively. The etiology of epilepsy was cryptogenic in 59.9%, symptomatic in 35.1% and idiopathic in 3.9%; the commonest were intracranial infection, cerebral vascular disease, cranial trauma and perinatal insult. Phenytoin, carbamazepine and valproate were the most frequently used drugs and 25.9% of patients were taking more than two drugs. 48.3% of patients had active seizures in the past six months and 26.4% were considered to have unsatisfactory control of their epilepsy. Medical refractoriness of epilepsy was associated with a history of perinatal insult, intracranial infection, congenital brain malformation, intracranial neoplasm, cerebral vascular disease, hippocampal sclerosis, mental retardation and a history of status epilepticus (P < 0.05). CONCLUSION: In this local cohort of adult patients with epilepsy under specialist care, there were a considerable number of patients falling into the category of cryptogenic epilepsy. Risk factors associated with medical refractoriness are similar to previous studies.

Consensus statement on ischaemic stroke care in Hong Kong.

OBJECTIVE: To issue guidelines for the care of acute stroke in Hong Kong, with the target audience of all health care professionals who are involved in acute stroke care. PARTICIPANTS: The Hong Kong Neurological Society and the Hong Kong Stroke Society. EVIDENCE: The panel applied the 'rule of evidence' used by the United States Agency for Health Care Policy and Research. When there is insufficient evidence, the recommendation was based on customary practice and was circulated among the members and fellows of the two societies before coming to a consensus. CONSENSUS PROCESS: Group meetings were held in 2002 to review the literature about acute care for patients with ischaemic stroke and to issue a consensus statement with reference to the local health care system. Participants of the meetings were appointed by the councils of The Hong Kong Neurological Society and the Hong Kong Stroke Society. The draft statement was circulated among the members and fellows of the two societies for comments before it was finalized. CONCLUSIONS: Ischaemic stroke is a heavy health care burden to Hong Kong. The current consensus statement provides a framework to establish a multidisciplinary approach towards its acute management.

Efficient and rapid affinity purification of proteins using recombinant fusion proteases.

In the affinity purification of recombinant fusion proteins, the rate-limiting step is usually the efficient proteolytic cleavage and removal of the affinity tail and the protease from the purified recombinant protein. We have developed a rapid, convenient and efficient method of affinity purification which can overcome this limitation. In one example of the method, the protease 3C from a picornavirus (3Cpro), which cleaves specific sequences containing a minimum of 6-7 amino acids, has been expressed as a fusion with glutathione S-transferase. The resultant recombinant 'fusion protease' cleaves fusion proteins bearing (from the amino-terminus) the same affinity tail as the fusion protease, a 3Cpro cleavage recognition site, and the recombinant protein of interest. The recombinant protein is purified in a single chromatographic step which removes both the affinity tail and the fusion protease. The advantages over existing methods include much improved specificity of proteolytic cleavage, complete removal of the protease and the affinity tail in one step, and the option of adding any desired amount of fusion protease to ensure efficient cleavage. The potential flexibility of the method is shown by the use of various affinity tails and alternative fusion proteases.

Presenile dementia: a case of Hashimoto's encephalopathy.

Hashimoto's encephalopathy may present with a variety of neurological symptoms and signs, including myoclonus, epileptic seizures, disturbance of consciousness, psychosis, ataxia, and presenile dementia. This report is of a 57-year-old woman with a history of thyroid disease who was investigated for generalised seizures, rapid decline in cognitive function, increasing dependency, and gradual change in personality. High thyroid autoantibody titres confirmed the diagnosis of Hashimoto's encephalopathy and her symptoms improved with treatment with prednisolone. The differential diagnosis of presenile dementia, aetiology and pathogenesis of Hashimoto's encephalomyelitis, and treatment options are discussed. Hashimoto's encephalomyelitis should be considered in the differential diagnosis of presenile dementia, particularly in patients with a history of thyroid disease.

Prevalence of asymptomatic intracranial atherosclerosis in high-risk patients.

We used transcranial Doppler to screen 3,057 patients who had at least one vascular risk factor of hypertension, diabetes, or hyperlipidemia and found 385 (12.6%) had middle cerebral artery stenosis. Elderly, hypertension, diabetes, and hyperlipidemia were associated factors. The prevalence escalated quadratically with increasing number of associated factors: from 7.2% for one, to 29.6% for four associated factors. Asymptomatic middle cerebral artery stenosis is common in patients with vascular risk factors.

Intermittent claudication: exercise-increased walking distance is not related to improved cardiopulmonary fitness.

OBJECTIVES: To assess if exercise training improves the symptoms of intermittent claudication by improvement in cardiopulmonary fitness. METHODS: Claudication distance (CD), maximum walking distance (MWD), calf endurance (repetitive heel raises), cardiovascular fitness (VO2 peak), and ankle-brachial pressure index (ABPI) were measured in 16 subjects with intermittent claudication before, and following an 8-week treadmill training programme. RESULTS: Training resulted in a median increase in CD of 65.5 m (p<0.01), MWD of 339.5 m (p<0.001) and HR of 19 (p<0.03). Notably, improvements in MWD correlated with those in HR (p=0.001; R=0.75). There was no training-associated change in VO2 peak (median increase of only 0.35 ml/kg/min; p=0.60) or ABPI (median increase of only 0.01; p=0.64). CONCLUSION: In this study, overall improvement in claudication was not related to an improvement in cardiopulmonary fitness.

Impaired transcriptional upregulation of Parkin promoter variant under oxidative stress and proteasomal inhibition: clinical association.

We provided data to show that the transcriptional activity of wildtype -258T in the parkin promoter region was significantly higher than the -258G variant in human cell lines. The transcriptional activity of wildtype -258T was significantly increased under oxidative stress by hydrogen peroxide, but this was not observed for the -258G variant. The transcriptional upregulation was significantly higher for wildtype -258T compared to -258G variant at 0.1, 0.2 and 0.4 mM of hydrogen peroxide. Similar results were obtained when the cells were treated with a proteasome inhibitor, MG132.Furthermore, in a case control study involving 753 subjects, we demonstrated that the parkin promoter -258G variant was associated with an increased risk of sporadic Parkinson's disease (PD) in the elderly ethnic Chinese population. Our clinical and laboratory data provide corroborative evidence that some older individuals who have the -258G variant may have a higher risk of developing PD.

Molecular cloning and characterization of two novel pro-apoptotic isoforms of caspase-10.

Caspase-10/a (Mch4) and caspase-10/b (FLICE2) are related death effector domain-containing cysteine aspartases presumed to be at or near the apex of apoptotic signaling pathways. We report the cloning and characterization of two novel proteins that are splice isoforms of the caspase-10 family. Caspase-10/c is a truncated protein that is essentially a prodomain-only form of the caspase that lacks proteolytic activity in vitro but efficiently induces the formation of perinuclear filamentous structures and cell death in vivo. Caspase-10/c mRNA is specifically up-regulated upon TNF stimulation, suggesting a potential role of this isoform in amplifying the apoptotic response to extracellular stimuli such as cytokines. Caspase-10/d is a hybrid of the known caspases Mch4 and FLICE2, as it is identical to FLICE2 except for the small (p12) catalytic subunit, which is identical to Mch4. Caspase-10/d is proteolytically active in vitro and also induces cell death in vivo, although it is less active than Mch4. The mRNAs for all known isoforms of caspase-10 are abundantly expressed in fetal lung, kidney, and skeletal muscle but are very poorly expressed or absent in these tissues in the adult, implying a possible role for the caspase-10 family in fetal development.

Mesenteric actinomycosis.

We report a case of abdominal actinomycosis demonstrated on computed tomography (CT) as an isolated mesenteric mass with radiating linear and nodular densities. The lesion mimicked a mesenteric tumor with desmoplastic reaction. The clinical and radiological features of this uncommon entity are reviewed.

Mutations which abolish phosphorylation of the TRAF-binding domain of TNF receptor 2 enhance receptor-mediated NF-kappa B activation.

We demonstrate that a 41 amino acid region (amino acids 379 to 419) in the cytoplasmic domain of tumor necrosis factor receptor 2 (TNFR2) is phosphorylated by unidentified kinase(s) both in vitro and in vivo. This domain (denoted x1c) corresponds almost exactly to the previously identified TRAF-binding domain and is by itself sufficient as a substrate for phosphorylation. In addition, the x1c domain is also crucial for TNFR2-mediated NF-kappa B activation. The cytoplasmic domain of TNFR2 lacks tyrosines, and conversion of all 12 potential serine and threonine phosphorylation targets in x1c to alanines either had no effect on NF-kappa B activation or resulted in enhanced NF-kappa B activity, depending on the structural context of x1c. The results show that while the TRAF-binding domain of TNFR2 is a major target of kinases, its phosphorylation is not required for NF-kappa B activation. Our data moreover suggest that phosphorylation of x1c negatively regulates the activation of NF-kappa B.