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W H Hu

Publications and source records attributed to W H Hu.

At least 55 records · Page 3Linked to original sources
PubMed1998

Mechanism of the dynorphin-induced dualistic effect on free intracellular Ca2+ concentration in cultured rat spinal neurons.

In order to study the different mechanisms of dynorphin spinal analgesia and neurotoxicity at low and high doses, the effects of various concentrations of dynorphin A-(1-17) on the free intracellular Ca2+ concentration ([Ca2+]i) in the cultured rat spinal neurons were studied using single cell microspectrofluorimetry. While dynorphin A-(1-17) 0.1-100 microM had no significant effect on basal [Ca2+]i, dynorphin A-(1-17) 0.1 and 1 microM significantly decreased the high KCl-evoked peak [Ca2+]i by 94% and 83% respectively. Dynorphin A-(1-17) 10 and 100 microM did not affect the peak [Ca2+]i following K+ depolarization, but in all these neurons there was a sustained and irreversible rise in [Ca2+]i following high-K+ challenge. Pretreatment with the specific kappa-opioid receptor antagonist nor-binaltorphimine 10 microM, but not the competitive NMDA receptor antagonist, DL-2-amino-5-phosphonovalerate (APV) 10 microM, significantly blocked the inhibitory effect of dynorphin A-(1-17) 0.1 microM on peak [Ca2+]i. However, APV 10 microM and nor-binaltorphimine 10 microM significantly antagonized the sustained rise in [Ca2+]i induced by a high concentration of dynorphin A-(1-17) 10 microM. Furthermore, in the presence, and following the addition, of increasing concentrations of dynorphin A-(1-17) (0.1, 1, 10 and 100 microM), the high concentrations of dynorphin A-(1-17) failed to produce a sustained rise in peak [Ca2+]i. These results suggested that dynorphin exerted a dualistic modulatory effect on [Ca2+]i in cultured rat spinal neurons, inducing a sustained and irreversible intracellular Ca2+ overload via activation of both NMDA and kappa-opioid receptors at higher concentrations, but inhibiting depolarization-evoked Ca2+ influx via kappa-opioid but not NMDA receptors at lower concentrations. Serial addition of graded concentrations of dynorphin A-(1-17) prevented the effect of high concentrations of dynorphin A-(1-17) on [Ca2+]i.

Animals↗
PubMed1998

Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients.

1. To characterize the interconversion process between clozapine and its metabolite clozapine N-oxide (CNO), eight healthy male schizophrenics were administered a single dose of clozapine or CNO in a randomized crossover manner. 2. Using a general pharmacokinetic model for the interconversion process, the mean total clearances of clozapine and CNO were 28.45 L/hr and 45.30 L/hr, respectively. These values were similar to the values obtained by the usual model-independent method of pharmacokinetic analysis. 3. When administered clozapine, mean CNO plasma concentrations of 17.7 +/- 16.4 ng/ml were slightly lower than the other clozapine metabolite-desmethylclozapine (DCLOZ) plasma levels of 24.4 +/- 8.6 ng/ml at the 12 hour time point. When CNO was administered, plasma concentrations at the 12 hour time point of clozapine were twice the amount of CNO (28.1 +/- 8.9 ng/ml vs 14.4 +/- 8.8 ng/ml). 4. DCLOZ plasma concentrations were detected in all patients upon clozapine administration. Upon CNO administration, only one patient had detectable plasma DCLOZ levels. 5. The interconversion process of clozapine and CNO could partially account for the wide interpatient variability reported for clozapine plasma concentrations in schizophrenic patients.

Adult↗
PubMed1998

High seroprevalence of Helicobacter pylori in active bronchiectasis.

Helicobacter pylori causes chronic inflammation of the gastric mucosa and has been identified in tracheobronchial secretions. Serum IgG against H. pylori was therefore measured prospectively in consecutive subjects with bronchiectasis (n = 100; mean age +/- SD 55.1 +/- 16.7 yr), active pulmonary tuberculosis (n = 87; age, 57.3 +/- 19.1 yr), and healthy volunteers (n = 94; age, 54.6 +/- 7.6 yr). Seropositivity was found in 76.0% of bronchiectatic subjects, which was significantly higher than that of the control (54.3%, p = 0.001) and tuberculous (52.9%, p = 0.0001) groups. Multiple logistic regression, adjusted for age, sex, occupational social class, and number of persons living in the household, showed that H. pylori IgG levels of the bronchiectatic group were still significantly higher than that of the control (p = 0.0014) and tuberculous (p = 0.0154) groups. Multiple regression analysis revealed associations between H. pylori serology and sputum volume (p = 0.03) and age (p = 0.001) in the bronchiectatic patients, but not lung function indices or causes of bronchiectasis. The H. pylori seroprevalence in bronchiectasis was significantly (p = 0.0002) higher in patients who produced more (83.1%) than those who produced less than 5 ml sputum/24 h (58.6%). This is the first report of a high H. pylori seroprevalence in bronchiectasis which appears to be specific. Further studies are indicated to evaluate the possible pathogenic role of H. pylori in bronchiectasis.

Age Factors↗
PubMed1998

Prognostic implications of hyperkalemia in toad toxin intoxication.

The toad possesses several toxic substances. Toad toxin poisoning manifests itself primarily with digitalis-like, cardioactive effects which results in bradycardia, varying degrees of atrio-ventricular block, ventricular tachycardia, ventricular fibrillation and sudden death. We report a cluster poisoning in a family who became intoxicated after ingestion of cooked toad soup for a skin problem. The youngest one (15 months old) died of refractory bradydyarrhythmias soon after arriving at our hospital. A second child (20 months old), who survived, arrived in shock with hyperkalemia (potassium 7.3 mEq/ L) and varying degrees of atrio-ventricular block. She was successfully treated with atropine, lidocaine, and cardioversion, and had a transvenous temporary pacemaker implanted for 1 day. The third boy (16 years old) had hyperkalemia (potassium 6.3 mEq/L) and bradycardia. The remaining three adults had only mild symptoms of nausea, vomiting, watery diarrhea and a sensation of numbness over their oral mucosa. We found that the level of serum potassium had prognostic implications in toad intoxication. Determination of serum potassium level is readily available in almost every hospital and is therefore more convenient to measure than serum digoxin level. We conclude that if hyperkalemia develops, the treatment of toad intoxication must be more aggressive to prevent mortality.

Adolescent↗
PubMed1998

Unique cerebral dysfunction following triphenyltin acetate poisoning.

1. In animal studies, TPTA was found to be neurotoxic. In humans, variable CNS pictures have been described with or without significant EEG findings. Brain CT does not usually reveal any abnormalities. 2. Our patient presented with intermittent unique spontaneous involuntary movement of hands, facial twitching, silly smile and crying. Diplopia, drowsiness, giddiness, vertigo, bidirectional nystagmus, impairment of calculation ability, as well as disorientation to time, people and place also developed. EEG showed mild cortical dysfunction without seizures. MRI and Tc-99m HMPAO brain SPECT revealed no significant findings. TPTA may cause cellular dysfunction of brain without structural damage, which results in variable CNS clinical presentations. 3. Nadir of leucopenia was noted on the sixth day after consumption of TPTA. Liver impairment occurred on the ninth day. Borderline demyelinated neuropathy developed on the fifty-third day. CNS abnormalities, delayed peripheral neuropathy, hepatitis and leucopenia deserve monitoring for a prolonged period, even when the victim initially presents with GI upset only after consumption of TPTA.

Adult↗
PubMed1998

Calcium oxalate is the main toxic component in clinical presentations of alocasis macrorrhiza (L) Schott and Endl poisonings.

Alocasia macrorrhiza (L) Schott and Endl is called Hai Yu, Tien Ho, Shan Yu, Kuan Yin Lien, Tu Chiao lien, Lao Hu Yu and Lang Du in Chinese. Its common English name is Giant Elephant's Ear. The toxic effects of A macrorrhiza arise from sapotoxin and include gastroenteritis and paralysis of the nerve centers. From 1985 to 1993 all individuals who called the Poison Control Center asking for information regarding macrorrhiza were included in this retrospective study. A questionnaire filled out by the Poison Control Center staff collected the demographic data of the victim, the reason for consumption, the prescribed part, clinical symptoms and signs of the victim, and medical outcome of poisonings. Among 27 cases of A macrorrhiza poisoning, the age was 1.5 to 68 y with 12 females and 15 males. One had skin contact and 1 had eye contact. In the 25 cases that consumed the plant leaf or tuber either raw or cooked, the primary symptom was in injected sore throat and the secondary symptom was numbness of the oral cavity. Some patients had salivation, dysphonia, abdominal pain, ulcers of the oral cavity, difficulty in swallowing, thoracodynia, chest tightness and swollen lips. We believe the presence of sapotoxin alone is not sufficient to explain the injected swollen and ulcerative lesions. Calcium oxalate is reported distributed in the entire plant and results in inflammation of the oral cavity and mucous membranes just as our patients had.

Adolescent↗
PubMed1997

Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal.

Lofexidine is an analogue of clonidine, an agonist at the alpha 2 noradrenergic receptor. Reports from preliminary open studies have suggested that it may be at least as effective as clonidine in the management of opiate withdrawal, and without the same limitation of postural hypotension. We report on a randomised double-blind comparison of lofexidine versus clonidine in the treatment of heroin withdrawal. A total of 80 hospitalized heroin addicts were randomly assigned to treatment with lofexidine or clonidine during in-patient opiate withdrawal. Maximum daily doses were 1.6 mg for lofexidine and 0.6 mg for clonidine. There was marked diurnal variation of withdrawal symptoms with severity being greatest at the daytime reading at 16.00 h and being markedly less at the night-time reading (recorded at 08.00 h). Lofexidine and clonidine were equally effective in treating the withdrawal syndrome. However, significantly more problems relating to hypotension were encountered with subjects on clonidine, with twice as many instances of withholding medication due to hypotension in the clonidine group. Better treatment retention rates were seen in the lofexidine group, although no difference was found in the proportion who had reached minimal symptom severity by the time of their discharge. We conclude that lofexidine and clonidine are equally effective, but with significantly fewer hypotensive problems with lofexidine. Further benefit from lofexidine may be possible with revised dosing regimens. Outpatient studies of lofexidine are now indicated.

Adult↗
PubMed1997

Dose-dependent reduced haloperidol/haloperidol ratios: influence of patient-related variables.

Plasma reduced haloperidol (RH) concentrations or RH to haloperidol (HL) ratios have been suggested to be important in determining the clinical efficacy and extrapyramidal side effects of HL. In this study, we measured the steady-state plasma HL and RH levels by high performance liquid chromatography and analyzed the effects of various variables (dose, gender, age, and body weight) on RH/HL ratios in four dose groups of Chinese schizophrenic inpatients: 10 mg/day (n = 84), 20 (n = 111), 30 (n = 29), and 60 (n = 55). In addition, the polymorphic distribution of RH/HL ratios, suggested by previous investigators, was further tested in each dosage group (for controlling the potential dosage effect on RH/HL ratios). As a result, both age and body weight could influence RH/HL ratios. Each year increase in age (after adjusting the effects of gender, body weight, and dosage) would elevate the RH/HL ratio by 0.0067 (P < 0.0001). On the other hand, after adjusting gender, age, and dosage effects, each kg increment in body weight would decrease the RH/HL ratio by 0.0044 (P < 0.01). Gender did not influence the ratio. Furthermore, the high dosage groups had higher RH/HL ratios (even with other variables being controlled). In comparison with the 10 mg group, the 60 mg group exhibited a higher mean RH/HL ratio by 0.84 (P < 0.0001) and the 30 mg group did by 0.31 (P < 0.0001). The 20 mg group was almost equal to the 10 mg group in RH/HL ratios. Besides, at each dosage group, the frequency distribution of RH/HL ratios seemed to be predominantly unimodal with a small proportion of extreme outliers. The results of this study clearly indicate that aging or a high dose (> or = 30 mg/day) of HL could raise the plasma RH/HL ratio, while an increasing body weight would reduce that. In contrast, gender does not affect the ratios.

Adult↗
PubMed1997

[Effects of dynorphin A1-17 on the activities, immunoreactivities and mRNA expression of cNOS and iNOS in rat spinal cord and their mechanisms].

Intrathecal administration(i.t.) of Dynorphin A1-17(Dyn) 1.25-20 nmol produced dose-dependent paralysis of hindlimbs and tail as well as inhibition of tail flick and foot flinch reflexes. The Dyn spinal neurotoxicity and antinociception involve two differential mechanisms: Enhancement of NMDA-Ca(2+)-NOS/NO pathway and c-fos over-expression in the ventral spinal cord for neurotoxicity, and depression of NMDA receptor and NOS activities in the dorsal spinal cord for antinociception. Both brain-derived constitutive NOS (predominant at early stage) and inducible NOS (at later stage) are detrimental, but endothelial constitutive NOS might be beneficial to Dyn spinal neurotoxicity. Dyn exerts a dualistic modulatory effect on [Ca2+]i of the cultured rat single spinal neurons, inducing sustained overload of intracellular free calcium via both NMDA and kappa receptor activation at higher concentrations, and producing significant inhibition of the depolarization-evoked calcium influx only via kappa receptor activation at lower concentrations. Dyn exposure for 1 h produced direct neurotoxicity in the cultured spinal neurons within an optimal range of concentrations.

Analgesics↗
PubMed1997

Clozapine dosages and plasma drug concentrations.

Steady-state plasma concentrations of clozapine and its metabolites, desmethylclozapine and clozapine-N-oxide, were measured in 162 Taiwanese patients with refractory schizophrenia. The daily doses of clozapine ranged from 100 to 900 mg, with a mean value of 379.5 +/- 142.2 mg. A dosage of 400 mg/day or lower was used for most patients (n = 131, 81%). Plasma concentrations of clozapine and its two major metabolites were measured using high performance liquid chromatography with ultraviolet detection. The mean plasma clozapine concentration was 566.9 +/- 398.8 ng/mL. The plasma concentrations of desmethylclozapine and clozapine-N-oxide were 46% and 16% of the concentration of the parent drug, respectively. We used an approximate rule that each 100 mg/day dose results in about 150 ng/mL plasma clozapine. This value is about 30% to 50% higher than that reported in Caucasians. The suggested therapeutic plasma clozapine concentration range of 300 to 700 ng/mL can be achieved with a dose range of 200 to 500 mg/day in most Taiwanese patients. Dose-dependent plasma clozapine concentrations were found. The interpatient variation was up to 12-fold in patients receiving the same dose, eg, 400 mg/day (n = 62). In four of these patients, the plasma drug concentrations were very high (1,446 +/- 114 ng/mL). The application of therapeutic drug monitoring in clozapine-treated patients with refractory schizophrenia is important, not only in dose adjustment, prediction of severe side effects such as seizures, and exploration of drug interactions, but also in the effective use of this expensive drug.

Adult↗
PubMed1997

Histamine 2 receptor blocker-ranitidine and sinus node dysfunction.

BACKGROUND: Histamine 2 (H2) receptors were observed to be present in the sinus node. H2 receptor blockers could attenuate the histamine-induced increase in sinus rate and could thereby worsen sinus node dysfunction. However, the data pertaining to electrophysiological effects of H2 receptor blocker ranitidine on sinus node function are not available as yet, although bradycardia has been occasionally reported along with ranitidine. The present study evaluates the electrophysiological effects of ranitidine on sinus node function, and also determines the safety of administering ranitidine to patients suffering from sinus node dysfunction. METHODS: Thirty-nine patients with clinical diagnosis of sinus node dysfunction were selected for this study. Electrophysiological effects of intravenous injection of 150 mg ranitidine on sinus node function was evaluated. Tests were performed for 21 patients in the basal state (Group 1) and for 18 patients (Group 2) after autonomic blockade (propranolol 0.2 mg/kg, and atropine 0.04 mg/kg). The sinus cycle length (SCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), sinoatrial conduction time (SACT), atrio-His (AH) and His-ventricle (HV) intervals and blood pressure (BP) before and after ranitidine were analyzed. RESULTS: In Group 1, changes in SCL, SNRT, CSNRT, SACT, AH, HV and BP were not found to be significant. However, in Group 2, wherein the patients received ranitidine after autonomic blockade, it was observed that ranitidine significantly prolonged SCL (905.0 +/- 31.0 to 1000.0 +/- 40.0 msec, p = 0.001), decreased systolic BP (134.7 +/- 4.7 to 124.8 +/- 4.8 mmHg, p < 0.001), and diastolic BP (71.9 +/- 2.0 to 67.9 +/- 1.9 mmHg, p = 0.001), while the changes in SNRT, CSNRT, SACT, AH and HV were not significant. CONCLUSIONS: A clinical dose of 150 mg ranitidine must be administered by a slow intravenous infusion for at least 5 minutes in case of patients suffering from sinus node dysfunction. Continuous monitoring of BP and heart rate are necessary, especially in cases of autonomic denervation.

Adult↗
PubMed1996

Dynorphin neurotoxicity induced nitric oxide synthase expression in ventral horn cells of rat spinal cord.

Nitric oxide (NO) mediation in the spinal cord injury induced by intrathecal (i.t.) dynorphin (Dyn) administration was studied with NADPH-diaphorase (Nd) histochemistry. Normally, there was rarely NO synthase (NOS) activity in spinal cord motomeurons, and Dyn A(1-17) 10 nmol, which produced only transient paralysis, did not induce Nd/NOS expression in ventral horn cells. After a paralyzing dose of i.t. Dyn A(1-17) 20 nmol, which definitely produced permanent paraplegia and neuronal death, Nd/NOS began to express in motoneurons at 30 min, increased in numbers and intensities at 2-4 h and persisted up to 8 h. Most of Nd/NOS motoneurons disappeared at 24 h coincident with the neuronal death. Quite a few intensively-stained Nd-positive small cells and swollen varicosities became visible only in rats with permanent paraplegia and neuronal death, beginning at 2 h, maximizing at 3-4 h and remaining up to 24 h. These results suggest that NOS expression was induced in the ventral horn of spinal cord, including small cells and varicosities as well as motoneurons closely correlated in time and degree with pathological changes in motoneurons caused by spinal Dyn neurotoxicity.

Animals↗
PubMed1996

Abnormal gastro-oesophageal reflux in Chinese with atypical chest pain.

Although atypical chest pain has been well described in the Western population, its frequency in Chinese is unknown. Over a period of 42 months, we studied 521 Chinese patients with chest pain and identified 108 patients (20.7%) whose pain was not related to cardiac causes, as determined by exercise ECG or cardiac catheterization. Using 24 h ambulatory pH monitoring and baseline oesophageal manometry, 28.7, 19.4 and 5.6% of these patients were found to have abnormal reflux parameters, abnormal manometric findings or both, respectively. There were significantly more patients complaining of chest pain during the study in the gastro-oesophageal reflux disease (GERD) group than in the non-GERD group (16/31 vs 20/77; P < 0.001). The lower oesophageal sphincter pressure was lower in those with abnormal reflex parameters than in those with normal reflux parameters (12.7 +/- 5.4 vs 17.8 +/- 5.8 mmHg; P < 0.05). There was no significant difference in symptoms, such as heartburn (54.8 vs 42.9%), regurgitation (38.7 vs 35.1%) and dysphagia (19.4 vs 24.7%), among the two groups. Non-specific changes were the most frequent baseline motility pattern. In conclusion, atypical chest pain and gastro-oesophageal reflux disease are not uncommon in Chinese and this deserves special emphasis as the continuation of anti-anginal drugs may aggravate their condition.

Adolescent↗
PubMed1996

Plasma haloperidol and reduced haloperidol concentrations in a geriatric population.

Haloperidol (HL) and reduced haloperidol (RH) plasma concentrations were measured in geriatric patients (n = 45) and schizophrenic patients (n = 8). In the elderly patients, HL doses were 1-4 mg/day while only 2 mg/day was used in the schizophrenics. At HL 2 mg/day dose in both age groups, mean plasma HL levels were approximately twice as high in the elderly patients compared to the schizophrenics (1.39 +/- 0.82 vs. 0.56 +/- 0.23 ng/ml, p < 0.02). RH plasma concentrations were almost 5 times greater in the elderly patients (0.54 +/- 0.35 vs. 0.09 +/- 0.05 ng/ml, p < 0.0001). These results suggest that HL plasma concentrations in the elderly are greater than in adult schizophrenic patients treated with similar HL doses.

Adult↗
PubMed1996

Evidence of genetic heterogeneity of hypertrophic cardiomyopathy in eight Chinese patients.

BACKGROUND: The genetic basis causing hypertrophic cardiomyopathy (HCM) was found due to missense mutations in cardiac beta-myosin heavy chain (beta-MHC), cardiac troponin T and alpha-tropomyosin genes in certain affected families. However, most mutations and majority of the affected families were reported to be related to beta-MHC gene. Till now, 20 different missense mutations of beta-MHC gene identified in more than 40 independent families were distributed in exons 8, 9, 13, 14, 15, 16, 19, 20, 21 and 23. Therefore, we chose these 10 exons for screening. METHODS: Eight probands with HCM and 1 normal control were included for screening. 32P-labeled PCR products of these 10 exons of beta-MHC gene were amplified from genomic DNA obtained from peripheral lymphocytes. PCR-DNA single strand conformation polymorphism (PCR-SSCP) analysis was performed using electrophoresis with polyacrylamide gels with and without 10% glycerol. Large amount copies of these 10 exons were also made from genomic DNA with PCR. Detection of sequencing variation of these exons was determined by the direct sequencing method with dideoxy chain termination method and 35S. RESULTS: No abnormal extra bands were noted on PCR-SSCP analysis. Sequencing analysis showed no missense mutation in these probands. CONCLUSIONS: Genetic heterogeneity of HCM is evident in Chinese patients with HCM.

Aged↗