Surgical treatment for primary hyperparathyroidism in Hong Kong: changes in clinical pattern over 3 decades

HYPOTHESIS: With the introduction of the blood chemistry multichannel autoanalyzer, primary hyperparathyroidism (HPT) is increasingly diagnosed. The clinical pattern of primary HPT has undergone a significant evolution in Western countries. A similar change can be documented in a geographic region where this condition is considered to be relatively uncommon. DESIGN: Unselected case series. SETTING: A tertiary referral endocrine surgical unit. PATIENTS: All patients with primary HPT surgically treated over the past 30 years. MAIN OUTCOME MEASURES: The prevalence of patients per 100,000 hospital admissions, clinical presentation, biochemistry study results, pathologic status, and main outcome were compared over three 10-year spans according to the introduction of the multichannel autoanalyzer in 1982: 1973-1982 (n = 20), 1983-1992 (n = 31), and 1993-2002 (n = 190). RESULTS: A 7-fold increase in the prevalence of patients with primary HPT who were surgically treated per 100,000 hospital admissions was observed over the past 10 years. The clinical presentation of patients with primary HPT had evolved progressively with a higher proportion of older patients (P<.001) being asymptomatic. On presentation, the condition had decreased in severity with lower serum calcium (P =.04), parathyroid hormone (P<.001), and alkaline phosphatase levels (P<.001) as well as a smaller adenoma size (P<.001). There was no significant change in the underlying pathologic condition and surgical success. CONCLUSION: Similar to the West but in contrast to that observed in other Asian countries, an increase in the prevalence of patients surgically treated for primary HPT is documented and a change in disease presentation as well as its severity is observed in our population group.     

Indirect bronchial shunt flow measurements in AbioCor implantable replacement heart recipients

Bronchial shunt flows in the recipients of the electrohydraulic AbioCor implantable replacement heart have been measured indirectly. A built-in compliance chamber accommodates the differential flow output required of the two ventricles of the AbioCor. An occluder mechanism regulates the flow differential. For a thoracic unit, given a beat rate, an occluder setting, and the pressure differentials across the replacement heart ventricles, the atrial pressure difference depends only on the level of shunt flow present in the vasculature. For a replacement heart recipient, the bronchial shunt is the dominant shunt flow. For patients implanted with the AbioCor, the beat rates and the occluder settings are known and the pressure differentials across the ventricles are estimated. Atrial pressures were measured using catheters. The bronchial shunt flow was deduced from in vitro characterization data based on these parameters. Available data from five patients in the ongoing clinical trial of AbioCor showed 0-1.4 L/minute bronchial shunt flows. Maximum variation for any individual patient was 1.1 L/minute.     

Massive pulmonary embolism in a young patient on clozapine therapy

Clozapine-associated induction of venous thromboembolism has potentially catastrophic consequences. We report a case of sudden death caused by bilateral main pulmonary trunk thrombosis in a 31-year-old man receiving clozapine therapy. The patient presented with general weakness and exertional dyspnea. Bilateral main pulmonary trunk thrombosis was clearly demonstrated by helical chest computed tomography.     

2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine: an improved serotonin transporter imaging agent

Imaging serotonin transporters (SERT) is an emerging research tool potentially useful to cast light on the mechanisms of drug action as well as to monitor the treatment of depressed patients. We have prepared two new derivatives of 3, 2-(2-(dimethylaminomethyl)phenoxy)-5-iodophenylamine (4) and 2-(2-(dimethylaminomethyl)benzyl)-5-iodophenylamine (5) (K(i) for SERT = 0.37 and 48.6 nM, respectively). Both [(125)I]4 and [(125)I]5 displayed excellent brain uptakes in rats, and they showed a highest uptake in hypothalamus (between 60 and 240 min), a region populated with the highest density of SERT. The specific uptake of [(125)I]4 in the hypothalamus resulted in a target to nontarget ratio ([hypothalamus-cerebellum]/cerebellum) of 4.3 at 2 h. Autoradiography of rat brain sections (ex vivo at 2 h) of [(125)I]4 showed an excellent regional distribution pattern consistent with known SERT localization. These data suggest that [(123)I]4 may be useful for imaging SERT binding sites in the brain by single photon emission computed tomography (SPECT).     

Management of osteoporosis in Hong Kong

Osteoporosis is among the top 3 medical conditions that are associated with greatest morbidity and reduction of quality of life of Hong Kong elderly subjects. The genetic and environmental risk factors for osteoporosis in southern Chinese as well as the current approach towards managing this growing health problem in Hong Kong are presented.     

Development and evaluation of iodinated tracers targeting amyloid plaques for SPECT imaging

Successful development of iodinated ligands for various neurotransmitter receptors prompted us to explore the feasability of having iodinated ligands to target amyloid plaques of Alzheimer’s disease. Several potential iodinated tracers based on various chemical backbone structures have been successfully prepared and evaluated toward this purpose. High binding affinities for Aβ aggregates were consistently observed for those ligands. However, the desirable in vivo properties were generally missing in the majority of those iodinated ligands. Only ligands with the promising in vitro and in vivo characteristics such as IMPY will likely warrant their success to be potential imaging agents mapping amyloid plaques in living human brain.     

Binding of two potential imaging agents targeting amyloid plaques in postmortem brain tissues of patients with Alzheimer's disease

In vivo imaging of amyloid plaques may be useful for evaluation and diagnosis of Alzheimer's disease (AD) patients. Towards that end, we have developed 6-iodo-2-(4'-dimethylamino-)phenyl-imidazo[1,2]pyridine (IMPY), and 4-N-methylamino-4'-hydroxystilbene (SB-13) as ligands for specifically targeting amyloid plaques. These ligands can be readily radiolabeled with I-123 or C-11, for in vivo imaging using single photon emission computerized tomography (SPECT) or positron emission tomography (PET), respectively. However, in order to be useful in vivo, probes must show selective high affinity binding to a sufficiently abundant binding site on amyloid plaques. Therefore, as a prelude to in vivo imaging studies, we evaluated the binding properties of these two potential imaging agents to amyloid plaques present in human brain tissues. In vitro binding studies were carried out with [(125)I]IMPY and [(3)H]SB-13 in homogenates prepared from postmortem samples of affected cortex and cerebellum of pathologically confirmed AD patients and age-matched controls. Binding parameters such as K(d) and B(max) were estimated. Competition study was designed to evaluate the amyloid plaque binding specificity using human brain tissues. Plaque binding was confirmed by thioflavin-S staining. Specific [(125)I]IMPY or [(3)H]SB-13 binding can be clearly measured in the cortical gray matter, but not in the white matter of AD cases. There was a very low specific binding in cortical tissue homogenates of control brains. Cerebellar homogenates prepared from either AD or control brains did not show any specific [(125)I]IMPY or [(3)H]SB-13 binding. The K(d) values of AD cortical homogenates were 5.3+/-1.0 and 2.4+/-0.2 nM for [(125)I]IMPY and [(3)H]SB-13, respectively. High binding capacity and comparable values were observed for both ligands (14-45 pmol/mg protein). The location and density of specific signal detected by [(125)I]IMPY or [(3)H]SB-13 correlated with the distribution of amyloid plaques in these brain specimens, as confirmed by thioflavin-S staining. Competition profiles of known ligands suggest that the binding is highly selective and comparable to that reported by using preformed Abeta peptide aggregates. [(125)I]IMPY and [(3)H]SB-13 show an abundant binding capacity with high binding affinities for amyloid plaques in affected cortical regions of AD brains. These properties suggest that when labeled with I-123 or C-11, these two ligands may be useful to quantitate amyloid plaque burdens in the living AD patients.