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Biomedical subjects

C Y Chan

Publications and source records attributed to C Y Chan.

At least 163 records · Page 9Linked to original sources

Modulation of neurotransmitter action: control of the gamma-aminobutyric acid response through the benzodiazepine receptor.

The ability of several homologous benzodiazepine and heterologous nonbenzodiazepine ligands to alter the conductance increase induced in spinal cord neurons by gamma-aminobutyric acid (GABA) was determined. Complete dose-response curves were carried out on individual neurons, reducing error introduced by cell-to-cell variability. The efficacies of modulation differ for "classical" benzodiazepines and novel nonbenzodiazepine drugs in a manner consistent with a model of control of GABA receptor action through a common receptor. There was no apparent correlation between efficacy and potency. CL 218,872, a triazolopyridazine, gave the lowest efficacy of the tranquilizers tested. Ro 15-1788 (an imidazobenzodiazepine) potentiated g GABA with high potency and low efficacy, consistent with an action as a partial agonist and an "antagonist" of classical benzodiazepine action. In order of increasing efficacy, Ro 15-1788, CL 218,872, and flurazepam are partial agonists, whereas clonazepam, chlordiazepoxide, diazepam, and flunitrazepam are full agonists. The beta-carboline drugs methyl-beta-carboline-3-carboxylate (beta-CCM) and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) are "anxiogenics" and convulsants that were found to exert through the benzodiazepine receptor-inhibitory and apparently insurmountable control of g GABA . beta-CCM and DMCM display large negative efficacies and act like effectors at a site distinct from the picrotoxin-sensitive chloride ionophore and coincident with the benzodiazepine site. The actions of these different benzodiazepine receptor ligands in vivo range from anxiolytic and anticonvulsant to anxiogenic and convulsant. Efficacy rather than potency almost certainly determines the qualitative nature of the pharmacological actions of these drugs.

Animals↗

Benzodiazepine receptor synthesis and degradation by neurons in culture.

The benzodiazepine-gamma-aminobutyric acid receptor complex was used to study functional receptor synthesis and degradation in primary cultures of neurons. Fifty percent of the receptors turned over with an unusually rapid half-life (4 hours); this was followed by a second, slower phase (32 hours). These results provide the basis for elucidating the mechanism by which neurons derived from the central nervous system control neurotransmitter receptor number, an important problem in cellular neurobiology. The findings may be of significance in the study of neurological and psychiatric disorders.

Animals↗

Multiple embryonic benzodiazepine binding sites: evidence for functionality.

We have found high-affinity binding (site-A) and low-affinity binding (site-B) of benzodiazepines to membrane homogenates of embryonic chick brain and spinal cord. A new technique was developed to permit the determination of complete electrophysiological dose-response curves on single neurons in cell culture, eliminating cell-to-cell variability as a problem that complicates the interpretation of pooled data. The electrophysiological potencies and binding affinities of a series of benzodiazepines correlate well for site-A but not for site-B or the micromolar site reported in adult rat brain. Site-A and the electrophysiological response are sensitive to photo-affinity blockade with flunitrazepam (FNZM) by about 75% while site-B is resistant to blockade. The FNZM-photolinked benzodiazepine receptor/GABA receptor complex is not chronically potentiated and thus exists in an 'unpotentiated' state. These experiments suggest that site-A in embryonic CNS membranes corresponds to a functional benzodiazepine receptor/GABA receptor complex in spinal cord cell cultures.

Animals↗

Cerebral motoneurons mediating tentacle retraction in the land slug, Ariolimax columbianus.

(1) Tentacle retraction in the land slug Ariolimax columbianus can be elicited by stimulation of all nerves and connectives of the ipsi-and contralateral cerebral ganglia. (2) Six neurons in the left cerebral ganglion were classified as tentacle retraction motoneurons because their action potentials are followed one-for-one with constant delay be action potentials in the left tentacle retractor nerve and their depolarization causes retraction of the ipsilateral tentacle. The motoneurons can be identified by size, pattern of pigmentation, position, and physiological characteristics. (3) Each retractor motoneuron discharges at a rather constant rate and had more than one source of excitatory input, but no IPSPs were observed. No synaptic connections between the six retractor motoneurons were found. The nerve action potentials that correspond to each motoneuron are distinguishable by waveform and size rank. (4) Each motoneuron elicits visible contractions in a particular region of the ipsilateral retractor muscle, but the motor fields of some motoneurons overlap. Some motoneurons mediate relatively rapid contractions while other cause slower responses. (5) There is one-for-one correspondence between action potentials of the largest unit recorded extracellularly in the retractor nerve and excitatory junction potentials recorded from the retractor muscle. No evidence of a peripheral neural plexus was found in serial sections of the retractor muscle.

Animals↗

Neurophysiological mechanisms underlying habituation of the tentacle retraction reflex in the land slug Ariolimax.

Habituation of the tentacle retraction reflex was studied at the following response levels: (1) Muscle tension elicited in the tentacle retractor muscle by repeated stimulation of a cerebral nerve (at 60-sec intervals) declined in parallel with evoked activity of the largest unit in the tentacle retractor nerve. (2) The largest unit in the tentacle retractor nerve (L4) showed spontaneous recovery and dishabituation. The rate of response decrement was inversely related to the strength of stimulus, and an optimal interstimulus interval ca. 60 s was found. Retention of habituation for 24 h was exhibited. (3) The major retractor motoneurons (L2, L3, L4) all showed habituation, dishabituation, and spontaneous recovery. The decline of L4 activity was parallelled by a decline in muscle response. (4) Compound EPSPs elicited in the retractor motoneurons by stimulation of sensory pathways showed habituation and dishabituation. (5) Unitary EPSPs elicited by stimulation of cerebral nerves and connectives with minimal stimulus strengths also showed habituation and were unaffected by spontaneously occurring EPSPs. Dishabituation by another pathway was also shown. (6) Depolarization of L4 by a constant current produced spike trains of constant firing rate and evoked a constant level of muscle tension in repeated trails, suggesting the absence of habituation in a peripheral nerve net or at the neuromuscular junction.

Action Potentials↗

Linitis plastica of the cecum.

Linitis plastica of the cecum is rare. The authors describe a case of this condition in a 16-year-old man. The commonest presenting symptom is a change in bowel habit. Histologically there are three recurring features--diffuse infiltration of the bowel wall by small darkly staining tumour cells, the presence of multiple "signet-ring" cells indicating mucin production and, third, an attempt at gland formation. The prognosis is poor; no patient has survived longer than 27 months.

Adenocarcinoma, Scirrhous↗

Compensating changes in fertility and mortality.

This paper illustrates a method of studying changes in vital rate schedules which have no effect on the intrinsic rate of population growth. These changes are described as compensating changes in fertility and mortality. The analysis proceeds from the discrete perspective of Leslie matrices, wherein the central idea is to establish the set of all compensating changes by identifying that class of Leslie matrices which possess the same positive eigenvalue, lambda1. A root-squaring technique is adapted for the purpose of estimating lambda1. Finally, a variety of compensating fertility and mortality changes is illustrated using data from Japan.

Adolescent↗

Long-term immunogenicity and efficacy of hepatitis B vaccine in infants born to HBeAg-positive HBsAg-carrier mothers.

In an attempt to evaluate the long-term immunogenicity and efficacy of plasma-derived hepatitis B vaccine in preventing hepatitis B virus infection, 199 infants born to hepatitis B e antigen-positive hepatitis B surface antigen-carrier mothers were found to be antibody to HBsAg-positive (greater than or equal to 10 mIU per ml) 2 months after the first booster of hepatitis B vaccination at age 1, and their serum HBsAg and anti-HBs were rechecked annually to ages 3 to 5. Of the nine infants whose initial anti-HBs were low (10 to 100 mIU per ml) in concentration, four (44%) were found to be anti-HBs seronegative at age 3, while none of the 127 vaccine responders with high anti-HBs levels (greater than 1,000 mIU per ml) lost their anti-HBs during the 4-year follow-up period. Also, in 63 infants whose initial anti-HBs titers were around 101 to 1,000 mIU per ml, only two lost their anti-HBs at age 4, and another two at age 5, respectively. Whether the vaccine responders lost their anti-HBs or not, no hepatitis B virus infection occurred in these vaccinees during the follow-up period. Thus, in the first 5 years of life, the protective efficacy in the high-risk infants who responded to plasma-derived hepatitis B vaccine was 100%. Because of the diversity of anti-HBs response in individuals, we suggest testing anti-HBs titer in all vaccinated infants after the first booster vaccination in order to calculate the time of next booster before the minimal protective level is reached.

Carrier State↗

Characterization of Mycobacterium fortuitum isolates from sternotomy wounds by antimicrobial susceptibilities, plasmid profiles, and ribosomal ribonucleic acid gene restriction patterns.

An outbreak of sternotomy infections due to Mycobacterium fortuitum in patients who had received cardiovascular surgery occurred in a cardiothoracic hospital in Hong Kong, and 21 such isolates from different patients had antimicrobial susceptibility studies against 14 drugs in vitro. These isolates were also studied for plasmid profiles and ribosomal ribonucleic acid gene restriction patterns. The latter method proved valuable in categorization of these isolates into two groups (comprising of nine and seven isolates, respectively) and five other sporadic strains. When the plasmid profiles and ribotyping are matched against the clinical and epidemiologic data, multisource contamination is suspected to be responsible for the outbreak. The organisms were probably derived from the environment rather than contaminated surgical equipments and materials.

Adult↗

Endoscopic injection for the arrest of peptic ulcer hemorrhage: final results of a prospective, randomized comparative trial.

A prospective, randomized comparative study was performed to compare the hemostatic effect of endoscopic injection with normal saline, 3% NaCl solution, 50% glucose/water solution, and pure alcohol during a period of 2 years. Only patients with peptic ulcers and active bleeding or nonbleeding visible vessels were considered. Each group comprised 50 patients. The four groups were matched at random for age, sex, location of bleeders, stigmata of recent hemorrhage, shock, hemoglobin, and concomitant illness. No statistically significant difference was observed among patients injected with normal saline, 3% NaCl solution, 50% glucose/water solution, or pure alcohol in achieving initial hemostasis (82%, 90%, 86%, and 92%, respectively); rebleeding rates (7.3%, 24.4%, 14%, and 10.9%, respectively); ultimate hemostasis (78%, 68%, 78%, and 84%, respectively); number of emergency operations (5, 7, 4, and 3, respectively); and average number of days in the hospital (6.7, 6.1, 6.1, and 5.8, respectively). A tendency toward a lower blood transfusion requirement was observed in the pure alcohol group, but this tendency failed to achieve statistical significance. One patient had a perforated ulcer develop 5 days after injection of 3 ml 50% glucose/water. Otherwise, no major complication was observed. We suggest that endoscopic injection with any of the above solutions can be used as the first-line modality for the arrest of peptic ulcer hemorrhage.

Adolescent↗

Primary biliary cirrhosis in Taiwan.

Among 30 consecutive patients diagnosed with primary biliary cirrhosis (PBC) in Taiwan, 27 were females and the median age of symptom onset was 54.5 years. Most had similar clinical manifestations to those reported in the Western countries, but ascites and oesophageal varices as commonly found at the late stages of cirrhosis of liver were noted in nine patients (30%) and 13 patients (43%) respectively. Only one patient was asymptomatic. Hyperbilirubinaemia was noted in 21 patients (70%) and hypoalbuminaemia in 8 patients (27%). All patients had elevated serum alkaline phosphatase and alanine aminotransferase and 28 (93%) had antimitochondrial antibodies. Ten out of 21 patients (48%) were positive in antinuclear antibodies, of which most were of speckled type. Sixteen out of 18 patients (89%) had elevated serum IgM levels. Interestingly, only one of 26 patients (3.8%) was positive for hepatitis B surface antigen, in contrast to its high prevalence (15%) in the Taiwan population. Special associated diseases, including systemic lupus erythematosus, scleroderma, malignant lymphoma and hepatocellular carcinoma, were each noted in one patient respectively. Eight patients had a history of gallstones before the diagnosis of PBC. The mean follow-up period was 23.6 +/- 19.8 months, and nine patients died during that period. In conclusion, the clinical manifestations of PBC in Taiwan are similar to those in Western countries, but most of our cases were at later stages.

Female↗

Prevalence of anti-HCV among Chinese patients with acute and chronic liver disease.

To assess whether the hepatitis C virus plays an important role in Chinese patients with acute and chronic liver disease, antibodies to HCV (anti-HCV) were measured by enzyme immunoassay in 67 patients with type A and B acute viral hepatitis, 165 patients with non-A, non-B (NANB) hepatitis, 438 patients with chronic hepatitis, 200 patients with postnecrotic liver cirrhosis, 72 patients with alcoholic liver disease, 55 patients with non-alcoholic fatty liver, 24 patients with toxic and drug-induced hepatitis, and 20 patients with other chronic liver diseases. Anti-HCV was not detected in sera from patients with type A and B acute viral hepatitis, toxic and drug-induced hepatitis, primary biliary cirrhosis, Wilson's disease, or lupoid hepatitis. The anti-HCV prevalence was found to be highest in patients with NANB hepatitis (59% in sporadic and 73.2% in transfusion-associated), 16.4% in non-alcoholic fatty liver, 5.6% in alcoholic liver disease, 6.8% in chronic hepatitis, and 16% in postnecrotic liver cirrhosis. In patients with chronic hepatitis, the anti-HCV prevalence was significantly higher in HBsAg-negative (15/34, 44.1%) than in HBsAg-positive cases (15/404, 3.7%; P less than 0.0001). The results indicate that HCV is a major agent of NANB hepatitis and plays an important role in HBsAg-negative chronic liver disease in Taiwan.

Acute Disease↗

Long-term follow-up of hepatitis B vaccination in susceptible hospital personnel.

Two hundred and sixty-seven susceptible hospital personnel who had been randomly divided into three groups to receive different doses (5 micrograms, 2 micrograms or 1 microgram) of a plasma-derived hepatitis B vaccine on a four-dose schedule were investigated annually for 4 years. Of them, 251 were vaccine responders. The percentages of persistence of antibody to hepatitis B surface antigen (anti-HBs) in these 3 groups were 95.5% (84/88), 92.3% (72/78) and 95.3% (81/85), respectively (P greater than 0.05). During the follow-up period, 12 of 21 (57.1%) responders with low anti-HBs titres (10-100 miu/mL) and 3 of 48 (6.3%) responders with medium anti-HBs titres (101-1000 miu/mL) were found to be anti-HBs seronegative, while none of the 182 candidates with high anti-HBs levels (greater than 1000 miu/mL) lost their anti-HBs. The 4 year cumulative rate of natural booster in the responders was 11.6% (29/251). None of the candidates became HBsAg positive during the follow-up period. This study revealed that low dose hepatitis B vaccine can provide satisfactory immunogenic response and long-term efficacy in Chinese adults and that the persistence of immunogenicity is not related to the vaccine dose but to the candidate's own initial anti-HBs response.

Female↗

Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a short-term, randomized, double-blind controlled, cross-over study with long-term follow up.

In order to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with primary biliary cirrhosis, a short-term, randomized, double-blind controlled, cross-over study was done with long-term follow up. In the first part of the study, 12 patients were randomly chosen to receive either UDCA 600 mg/day for 3 months followed by a placebo for 3 months or a placebo for 3 months followed by UDCA for 3 months. The clinical symptoms of pruritus improved when the patients were receiving UDCA but became worse when receiving a placebo. Mean serum levels of alkaline phosphatase (ALPase), gamma-glutamyl transferase (gamma-GT), total bilirubin, cholesterol, alanine aminotransferase (ALT) and aspartate aminotransferase all decreased below the baseline values when receiving UDCA treatment and all increased above the baseline values when receiving the placebo. The difference was statistically significant. In the second part of the study, 19 patients received long-term UDCA treatment (mean 20 months). The clinical symptoms of pruritus improved in 90% of the pruritic patients. Serum levels of ALPase, gamma-GT and ALT fell significantly from the pretreatment values, 6, 12 and from the mean 20 months after UDCA treatment. Serum levels of total bilirubin fell significantly 6 and 12 months after UDCA treatment but did not reach statistical significance at the last follow up. No patient lost antimitochondrial antibody and elevated immunoglobulin levels did not improve significantly, but the Mayo clinical risk score improved significantly after long-term UDCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

Hepatitis B vaccination alone is not adequate for the categorizing of adult subjects with isolated anti-HBc.

To evaluate the meaning of isolated antibody to hepatitis B core antigen (anti-HBc), 88 Chinese subjects with isolated anti-HBc received rescreening of hepatitis B virus (HBV) markers. Eighty (90.9%) of them were still positive for this antibody and 29 were also found to be positive for antibody to hepatitis B surface antigen (anti-HBs). The remaining 51 subjects (58.0%) were positive for anti-HBc alone; 50 of them received a four-dose schedule of hepatitis B (HB) vaccine. After the initial dose, only one vaccinee disclosed an amnestic anti-HBs response, that is, anti-HBs titre > 1000 miu/mL. Forty-five vaccinees completed the vaccination schedule and 44 (97.8%) had anti-HBs response. The anti-HBs responses in 25 of these vaccinees were compared with 25 age- and sex-matched normal susceptible vaccinees. The anti-HBs response rates in both groups were the same (96 vs 96%). However, the geometric mean titre was significantly lower in the vaccinees with isolated anti-HBc (512 mIU/mL vs 4688 mIU/mL, P < 0.001). Prevaccinated sera were available in 49 vaccinees with isolated anti-HBc for detection of antibody to hepatitis B e antigen (anti-HBe) and HBV DNA; 37 (75.5%) of them had one or two of these markers. As we regarded the rescreening of HBV markers, response to hepatitis B vaccination and presence or absence of anti-HBe and/or HBV DNA together for categorizing the 88 subjects with isolated anti-HBc, at least three-quarters of them had past infection of HBV. The subjects with false positive anti-HBc test were a minor group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Membranous obstruction of inferior vena cava in Taiwan.

Membranous obstruction of the inferior vena cava (MOVC) is a rare cause of Budd-Chiari syndrome. When compared to the West, the incidence of MOVC was reported to be higher in the Orient, India and South Africa. From 1979 to 1993, 16 consecutive Chinese patients (mean age 50 years) with MOVC were retrospectively evaluated. The diagnosis in these MOVC patients was usually delayed with a mean lag time of 111 months. Most of the cases were detected by a delicate ultrasonographic examination of the abdomen. Segmental narrowing of the inferior vena cava in 11 patients was the predominant type of MOVC, while five experienced a membranous obstructive type. Only one of five surgery-treated patients had a post-operation survival > 5 years, while five out of the nine patients who received conservative treatment still survived after a 6-15 year follow up. Two patients received percutaneous angioplasty (PTA). One survived 4 years and the other expired 5 years after the PTA. Two patients (12%) developed a hepatocellular carcinoma in their disease course, and the incidence was lower than in previous reports from Japan and South Africa. The incidence of hepatitis B surface antigen in MOVC did not increase in our patients compared with the general population. In conclusion, the inferior vena cava should be carefully evaluated in an ultrasonographic examination of the abdomen to increase the diagnosis rate of MOVC. Surgical intervention should be carefully justified according to the patient's symptoms and signs, the types of obstructive lesions and the expertise of the surgeons.

Adult↗

Efficacy of ursodeoxycholic acid in the treatment of patients with chronic hepatitis C.

A case-control study was conducted to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with chronic hepatitis C. Patients who failed to have sustained responses to interferon (IFN) therapy, refused to take IFN or were unsuitable for IFN treatment were enrolled into this study. The treatment group had 15 patients and they received UDCA 600 mg orally per day for 6 months. Another 15 patients with matched sex, age and initial serum alanine aminotransferase (ALT) levels were chosen as the control group. Three parameters (i.e. serum ALT levels, serum hepatitis C virus (HCV) RNA and serum cytokines) were measured before and after UDCA treatment. After the treatment period, the mean serum ALT levels in both groups were not significantly different (153.8 +/- 111.0 U/L vs 112.1 +/- 53.8 U/L, P > 0.05) and mean serum ALT level in the UDCA-treated group did not decrease after the treatment (pre-treatment vs post-treatment value: 139.1 +/- 73.1 U/L vs 153.8 +/- 111.0 U/L, P > 0.05). In addition, all of the patients with positive HCV RNA before treatment still had active HCV viraemia after the UDCA treatment. Also, the serum levels of interleukin-6 (IL-6) and the tumour necrosis factor-alpha (TNF-alpha) were not significantly different between the two groups before and after the treatment period. In conclusion, a regimen of UDCA as prescribed in the present study did not show obvious benefits in the treatment of Chinese patients with chronic hepatitis C.

Alanine Transaminase↗