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Biomedical subjects

K T Lin

Publications and source records attributed to K T Lin.

At least 19 recordsLinked to original sources

Monoclonal gammopathies and the related autoimmune manifestations in Taiwan.

A total of 50,000 patients were surveyed for the presence of monoclonal immunoglobulins during the past two decades. There were 411 cases of monoclonal gammopathies including 243 cases of plasma cell neoplasms and 168 cases of secondary plasma-cell dyscrasia. Among the 227 cases of multiple myeloma and Waldenström's macroglobulinemia, there were 49.3% IgG class, 22.9% IgA class, 9.7% IgM class and 13.2% light chain type. In addition, there were 1.3% of nonexcretory myeloma including an IgM type. A relatively high frequency (4.8%) of IgD M-proteins was detected but heavy chain disease was not encountered in the present series. Purified M-components from patients with possible autoimmune manifestations were subjected to immunofluorescence studies. Autoimmune activity of M-proteins was found in a patient of Waldenström's macroglobulinemia with peripheral neuropathy, and another patient of cryofibrinogenemia with recurrent purpura and gangrene. In conclusion, a high frequency of IgD myeloma is found in Chinese patients of this area. M-components may have autoimmune activity resulting in unusual clinical manifestations.

Adolescent

Immunochemical characterization and therapeutic effect of house dust extract in bronchial asthma.

The immunochemical characteristics of house dust extract used in hyposensitization were studied by SDS-polyacrylamide gel, isoelectrofocusing, counterimmunoelectrophoresis and Western blot. The gel electrophoregram and isoelectrofocusing plate demonstrated a complex mixture of acid proteins with molecular weights ranging from 56 to 12 KD and isoelectric point distributing from 4.6 to 5.6. The counterimmunoelectrophoresis revealed as many as five precipitating bands in sera from 60% asthmatic patients after hyposensitization. The Western blot showed heterogeneous IgE reaction bands varied from 45 to 22 KD, including a strong 27 KD reaction band found in 40% of the asthmatic patients not receiving hyposensitization. The efficacy of house dust extract hyposensitization was evaluated in 102 asthmatic patients, followed up at the Allergic Clinic since 1980. There were 42 malea and 60 females with a mean age of 30.8 (16 to 60), and the total follow-up patient-year was 512.6 with a mean of 5.0 year per patient (1 to 11). Complete remission of asthmatic symptoms and medication was found in 5% patients, and 12% patients had little or no improvement. The majority of patients (83%) had improvement in asthmatic symptoms and medication dosage. The average serum IgE levels and total eosinophil count dropped significantly after hyposensitization (p < 0.001). In conclusion, the immunochemical characteristics of house dust extract were analyzed and mite allergens, especially Group I antigens, may be the important constituents. Good therapeutic effect, both clinically and with laboratory evaluation, was obtained with more than 80% of the asthmatic patients achieving improvement under house dust hyposensitization.

Adolescent

Isolation of 6-mercaptopurine in human plasma by aluminum ion complexation for high-performance liquid chromatographic analysis.

A sample preparation technique and a high-performance liquid chromatographic method for 6-mercaptopurine (6-MP) that is simple, sensitive and without interference from its metabolites is described. 6-Thioguanine (6-TG) is added as an internal standard to the plasma sample, which is then treated with an aqueous solution of aluminum perchlorate to denature the plasma proteins and form complexes with 6-TG, 6-MP and its major metabolite, 6-thiouric acid (6-TUA). These complexes coprecipitate with proteins on centrifugation. 6-MP and its analogues are then extracted from the precipitate with perchloric acid containing sodium hydrosulfite and the extract is chromatographed on an Ultrasphere ODS column eluted with 0.1 M phosphoric acid and 0.001 M dithiothreitol in deionized water. The eluate is monitored at 340 nm. No interfering peak was encountered in over 300 clinical plasma samples. 6-TUA was separated from 6-MP and was found to be present in much higher concentration than 6-MP itself throughout the sampling time (6 h) following oral administration of the drug.

Aluminum

High-performance liquid chromatographic determination of mitoxantrone in plasma utilizing non-bonded silica gel for solid-phase isolation to reduce adsorptive losses on glass during sample preparation.

Mitoxantrone, a highly active antineoplastic agent, was found to bind strongly to non-bonded silica gel and glassware. When a Hamilton syringe was used to load and inject a mitoxantrone solution (0.4 microgram/ml in water) on to a high-performance liquid chromatographic (HPLC) system, about 95% of the loaded compound was found to bind to the glass surface of the syringe barrel and could not be removed by rinsing with water. It could, however, be removed slowly with an acidic solution and thus a small peak of mitoxantrone was present on the chromatogram whenever a blank acidic solution was injected with the syringe. The bound mitoxantrone could be removed effectively from the syringe surface with a solution of tetramethylammonium chloride, citric acid, methanol and water (elution solvent). This binding introduces a large error in assay results and might be one of the major factors responsible for contradictory pharmacokinetic data that have been reported. A new plasma preparation scheme and an HPLC method for mitoxantrone were developed to address this binding problem. Mitoxantrone was extracted directly from plasma samples with a plastic mini-column packed with non-bonded silica gel and eluted with the above elution solvent. The eluent was analysed by HPLC on an ODS column with an absorbance detector at 658 nm. The mobile phase was 0.1 M triethylamine phosphate (pH 3.0) in water-tetrahydrofuran-methanol (69:1:30) containing 0.02 M tetramethylammonium chloride. Methylene blue was added as an internal standard. Preliminary results showed that mitoxantrone levels in human plasma followed a triphasic decay curve after an intravenous bolus injection. The terminal elimination half-lives measured in three patients (mean t1/2 gamma = 25 min) were all shorter than the published values which ranged from 56 min to 9 days.

Chemical Phenomena

Endoscopic sphincterotomy in the treatment of biliary tract diseases.

Endoscopic sphincterotomy (EST) was performed in 53 patients with biliary disease. Indications for sphincterotomy were: 48 patients with choledocholithiasis, 3 patients with malignant biliary obstruction, and 2 patients with papillary stenosis. The procedure was successful in 52 patients (98.1%). In patients with choledocholithiasis, the stones were successfully removed or passed out spontaneously in 42 patients (87.5%). Endoscopic retrograde biliary drainage (ERBD) was successfully carried out in 2 cases of malignant biliary obstruction after EST. The clinical and biochemical evidence of cholestasis resolved in both patients with papillary stenosis. Complications consisted of hemorrhage (2 patients) and cholangitis (1 patient), resulting in one death. The overall complication and mortality rates were 5.7% and 1.9% respectively. Thirty-two patients received regular ultrasound examination follow-up with a mean of 13.4 months. Two patients had recurrent common bile duct stones and one had restenosis of papilla. The conditions were managed by endoscopic therapy. Endoscopic sphincterotomy is a relatively safe and effective means of relieving extrahepatic cholestasis; however, its comparison with surgical techniques needs long-term, randomized studies.

Adult

Milk could decrease the bioavailability of 6-mercaptopurine.

The bioavailability of 6-mercaptopurine (6-MP) administered orally for maintenance therapy of children with acute lymphoblastic leukemia is highly variable. Xanthine oxidase (XO) can transform 6-MP into 6-thioxanthine (6-TX) and 6-thiouric acid (6-TUA), which have no therapeutic value. XO is found in high concentration in cow's milk. Incubation at 37 degrees C for 30 min with commercial preparations of pasteurized cow's milk results in transformation of 30% of a clinically relevant concentration of 6-MP into 6-TUA. Milk boiled for 5 min has no effect on the 6-MP. Addition of gastric juice at ratios likely to be seen in children has negligible inhibitory effect on the 6-MP destroying activity of milk. Conversely, folic acid and allopurinol markedly inhibit this effect at clinically relevant concentrations. These observations may help to optimize modalities of administration of 6-MP.

Animals

An autopsy-proved case of AIDS in Taiwan.

The first case of AIDS positively identified in a non-foreigner in Taiwan was a 25-year-old unmarried male who had practiced homosexuality for ten years. The patient began to have abdominal pain accompanied with loose stools and weight loss in June 1985, followed by fever, cough, headache, dizziness, and loss of memory. Facial hyperpigmentation and extensive oroesophageal candidiasis were noted. Laboratory studies showed severe lymphopenia with a reversed T-helper to T-suppressor ratio, cutaneous anergy and polyclonal gammopathy. Human immunodeficiency virus (HIV) antibodies were positive by ELISA and Western blot, and the virus was isolated from the blood. At autopsy, disseminated cytomegalovirus infection, extensive CNS toxoplasmosis and early lesions of Kaposi's sarcoma were demonstrated. The detection of HIV in the adrenal medulla supports the consensus that the virus is neurotropic.

Acquired Immunodeficiency Syndrome

Diagnostic values of IgG-albumin index and agarose gel electrophoresis in neurologic diseases.

Sixty cerebrospinal fluids (CSFs) with paired serum samples from a variety of patients with neurologic diseases were studied using rate nephelometry to measure IgG-albumin index, and also agarose gel electrophoresis (EP) with protein blotting technique to characterize discrete IgG bands. The patients included: A) 16 cases of multiple sclerosis (MS); B) 23 cases of inflammatory diseases of the central nervous system (CNS); C) 21 cases of other non-inflammatory neurologic disorders. The average IgG-albumin index was 0.65 +/- 0.25 in Group A, 1.10 +/- 0.78 in B, and 0.50 +/- 0.12 in C. If 0.72 is taken as the upper normal limit, an increased index was found in 31%, 43% and 5% of Groups A, B and C, respectively. Discrete IgG bands were detected in 69%, 9% and 5% of Groups A, B and C, respectively. Gamma globulin bands were not always IgG, and true oligoclonal myeloma proteins were not encountered. It is concluded that both IgG-albumin index measurement and agarose gel EP are useful for diagnostic differentiation in neurologic diseases: the former, for inflammatory diseases of CNS; and the latter, for MS.

Brain Diseases

Detection of antibodies to HTLV-III by ELISA in AIDS risk groups in Taiwan: a preliminary report.

A total of 2321 serum samples were collected from a variety of AIDS risk groups. The samples were tested for anti-HTLV-III using ELISA. Low prevalences of seropositivity were detected in the high-risk groups. Among 120 homosexuals/bisexuals, one seropositive suffering from full-blown AIDS was an American traveler. Another native homosexual who yielded a high ELISA reading was a "possible" AIDS. Three hemophiliacs with strongly positive reactions received injections of a U.S.-produced factor VIII; all are asymptomatic currently. A patient with hairy cell leukemia had a markedly elevated ELISA reading. Another patient with syphilis also had a markedly high reading, despite having no other known risk factor. Among the low-risk groups a patient who had suffered from oral candidiasis for eight years had no risk factor, yet he yielded repeatedly high ELISA readings. Another patient with a weak positive reaction was a symptomless blood donor. This preliminary study concludes that Taiwan is several years behind the U.S. and is at present not an endemic area for AIDS. To achieve successful AIDS control in the future, however, the homosexuals in Taiwan should change their sexual behavior now. Since many initially weakly-reactive samples became negative on repeated testing it appears that non-specific or false positive ELISA reactions occur frequently. Accordingly when ELISA is used for diagnostic purposes, additional confirming tests are mandatory.

Acquired Immunodeficiency Syndrome