PubMed Health⌕ Search

Biomedical subjects

H C Hsu

Publications and source records attributed to H C Hsu.

At least 181 records · Page 10Linked to original sources

The significance of spontaneous hepatitis B e antigen seroconversion in childhood: with special emphasis on the clearance of hepatitis B e antigen before 3 years of age.

To investigate the significance of spontaneous hepatitis B e antigen (HBeAg) seroconversion during childhood, 415 hepatitis B surface antigen (HBsAg) carrier children (ages 0 to 15 years) were prospectively followed for 7.1 +/- 2.9 years. Hepatitis B virus (HBV) markers and liver function profiles of each child were tested at least once every 6 months. Among them, 50 were initially anti-HBe positive and 140 seroconverted from HBeAg to anti-HBe during follow-up. Before HBeAg seroconversion, jaundice occurred in 9 and alanine transaminase (ALT) activities elevated in 99 of the 140 seroconverters. Serum ALT returned to normal in all patients within 1 to 5 years of seroconversion. Six had reelevated ALT later after seroconversion. Only 7 (9.7%) of the 72 carrier infants seroconverted before 3 years of age. The peak ALT levels in five of them exceeded 100 IU/L, and two had jaundice before HBeAg seroconversion. One of the early seroconverters developed hepatocellular carcinoma (HCC) at 11 years of age, although his liver function profiles remained normal after HBeAg seroconversion. Liver biopsy specimens from 30 children during the anti-HBe-positive stag e showed inactive cirrhosis in 2 (including one with HCC), chronic hepatitis with marked fibrosis in 1, mild activity and moderate fibrosis in 2, mild activity and mild fibrosis in 9, and minimal histologic changes in the remaining 16. Although most will achieve a normalization of ALT and inactive liver histologic changes, the seroconversion of HBsAg carrier children from HBeAg to anti-HBe is not necessarily an indicator of favorable prognosis; a small proportion of children will develop cirrhosis or even HCC.

Adolescent↗

Clinicopathologic study of phyllodes tumor of the breast.

The clinical and pathologic features of 34 phyllodes tumors in 33 women were analyzed. These included 20 benign tumors, 7 borderline malignant tumors and 7 malignant tumors. The median age of the patients at the time of diagnosis was 38 years. Patients with malignant tumors were older and had larger tumors. The tumor size varied from 1.6 cm to 40 cm. Local recurrence was evident in 4 of 21 patients who were followed-up, irrespective of their tumor type (one benign, two borderline malignant and one malignant). The recurrence rate was higher in younger patients. No single pathologic feature was found to have prognostic significance. Distant or regional lymph node metastasis and mortality due to the disease were not identified. Based on these results, wide excision with an adequate margin continues to be the appropriate initial surgical treatment.

Adolescent↗

Morphology of the torn rotator cuff.

The morphological characteristics of shoulders with torn rotator cuffs were determined using 41 embalmed specimens. The following parameters were measured in the supraspinatus (SSP), infraspinatus (ISP) and subscapularis (SSC) muscles: the length, thickness and width of the extramuscular tendon; the length of the intramuscular tendon; the length and width of a tear, if present, muscle fibre length; and muscle volume. The cross-sectional area (CSA) of the tendon was measured on the photographic image of slices of the tendon using an image analysis system, and the CSA of the muscle was calculated by dividing the muscle volume by muscle fibre length. The rotator cuff was intact in 11 shoulders. A partial-thickness tear of the cuff was present in 12 shoulders, a full-thickness tear of the SSP in 11 shoulders, and a full-thickness tear of more than 2 tendons in 7. Overall incidence of full-thickness tears of the rotator cuff was 44%, and that of partial-thickness tears 29%. With increase of tear size, the functional tendon length (extramuscular tendon length plus tear length) increased by a statistically significant amount in the SSP, ISP and SSC, whereas muscle fibre length decreased in SSP and ISP. It is concluded that the increased functional tendon length and decreased muscle fibre length are the main morphological changes that make the rotator cuff a physiologically abnormal unit. Surgical repair of the torn cuff would be expected to improve these anatomical changes and restore the kinetics of the glenohumeral joint.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Fulminant amebiasis: a clinical evaluation.

Two patients with fulminant amebic colitis with colon perforation and concomitant liver abscess were collected over the last 5 years. One patient underwent emergency laparotomy to treat amebic cecal perforation. Diverted ileostomy saved his life. The ileostomy was successfully reversed 6 months later. The other patient underwent 4 laparotomies with more invasive procedures in less than 1 month due to sequential complications of amebiasis. Colon resection with enterostomy miraculously allowed him to survive. In comparison with the latter, who underwent more aggressive surgery and experienced more catastrophic complications, the former with conservative surgery had a smoother clinical result. Thus, conservative operation for colon perforation due to amebiasis is recommended. Besides, thanks to the alertness of doctors, the favorable age of the patients, the advent of new antiamebic and antimicrobial agents, excellent hyperalimentation, the great improvement in medical facilities and postoperative care, the two critical patients eventually survived after several operations, and had a better outcome as compared with the high mortality rate of 87.5% in our hospital 2 decades earlier.

Adult↗

Post-remission intensive consolidation with high-dose cytarabine-based chemotherapy and granulocyte colony-stimulatory factor in adults with acute myelogenous leukemia: a preliminary report.

BACKGROUND: Modern induction chemotherapy produce 60% to 80% complete remission in adults with newly diagnosed acute myelogenous leukemia (AML). A major challenge is to eradicate subclinical disease in remission and prevent leukemic relapse. Intensive post-remission chemotherapy was proved of comparable disease-free survival as BMT. METHODS: From February 1992 to to March 1995, twelve patients with AML, aged 15 to 57 y/o, received intensive consolidation chemotherapy immediately after the first complete remission. The chemotherapy included either 4 courses of high dose Arac (HiDAC), 3 gm/m2 q12h x3 days, or 2 courses of HiDAC (4 days) plus mitoxantrone for 3 days and etoposide for 7 days (HiDAC-3-7). Granulocyte colony-stimulating factor (G-CSF) used used 24 hours after chemotherapy until absolute neutrophile count greater than 500/mm3. RESULTS: Totally 24 courses of high dose chemotherapy were given. The median duration of severe neutropenia (absolute neutrophile count < or = 500/mm3) was 12 days, thrombocytopenia (< or = 50,000/mm3) 18 days, fever > or = 38 degrees C 6 days, and from severe neutropenia (absolute neutrophile count < or = 500/mm3) was 12 days, thrombocytopenia (< or = 50,000/mm3) 18 days, fever > or = 38 degrees C 6 days, and from severe neutropenia (< or = 500/mm3) to infection 4 days. Infection was the most frequent complication during HiDAC treatment. No toxic death was noted. After a median follow-up of 16 months, early relapse was noted in 3 patients (2, 4, and 5 months, respectively), and late relapse in two patients (11 and 20 months, respectively). Seven patients remained in complete remission status after a median follow-up of 14+ months (7+ to 37+ months). CONCLUSIONS: Intensive consolidation chemotherapy is well tolerable and may prolong remission duration when used in the early post-remission phase of AML.

Adolescent↗

[Distant metastasis after irradiation alone in carcinoma of the uterine cervix--the patterns and results].

From 1988 to May, 1992, there were 286 patients with pathology-proved carcinoma of the uterine cervix referred to Chang Gung Memorial Hospital, Kaohsiung to receive definite radiotherapy. Sixty-one (21%) patients were found to develop distant metastasis after radiotherapy for at least 2 years follow-up. By FIGO stage, the incidence of distant metastasis was as follows: I :2/39, II a:1/19, II b:20/118, III :34/101, IV a: 4/9. Eighty-five percent patients (52/61) began to develop distant metastasis within the first 2 years after radiotherapy. Twenty-three patients developed single organ metastasis, and 38 patients developed multiple organ metastasis. Lymph nodes (38 patients), lung (28 patients), bone (27 patients), and abdomen (20 patients) were the common sites of distant metastasis. Lymph nodes metastasis occurred most often at supraclavicular lymph nodes (15 patients), para-aortic lymph nodes (18 patients), and inguinal lymph nodes (5 patients). Spine (23 patients), especially the lumbar spine (20 patients) was the most common site of bony metastasis. Abdominal metastasis occurred in abdominal cavity (15 patients) or liver (5 patients). The incidence of metastasis within the first two years after radiotherapy was lung: 75% (21/28), bone: 62% (18/29), left supraclavicular lymph nodes: 60% (9/15), para-aortic lymph nodes: 72% (13/18), intra-abdominal cavity: 86% (13/15), liver: 66% (2/3), brain: 0% (0/4). The 2-year actuarial survival rate for the 61 patients after developing distant metastasis was 14%, with a median survival time of 6.4 months. There was no significant difference in survival when comparing patients with single organ metastasis and with multiple organ metastasis (p > 0.05), or patients with distant metastasis alone and with distant metastasis combined with local recurrence (p > 0.05). Otherwise, after distant metastasis twenty-three patients receiving chemotherapy or radiotherapy had a significantly higher 2-year survival rate than 38 patients receiving supportive care only after distant metastasis (34% vs. 2.4%, p < 0.05).

Female↗

Allelotype and loss of heterozygosity of p53 in primary and recurrent hepatocellular carcinomas. A study of 150 patients.

BACKGROUND: The allelotype and loss of heterozygosity (LOH) of the p53 gene in human hepatocellular carcinoma (HCC) were studied in 150 patients with resected primary HCC and 18 with recurrent HCC. METHODS: DNA samples of paired HCC and livers were cut with BanII enzyme for the study of p53 allelotype and allele loss. The medical records of the patients were carefully reviewed. RESULTS: Sixty-four (42.7%) patients were heterozygous for the p53 gene, 69 (46%) were homozygous for the 1.5/1.4 kb small (S) allele, and 17 (11.3%) were homozygous for the 2.9 kb large (L) allele. The frequencies of the minor L allele (0.323) and of the major S allele (0.677) in this population of Chinese patients differed from the frequencies previously reported for North American Caucasians (0.13 and 0.87, respectively). The heterozygous patients tended to have lower serum hepatitis B surface- and e antigens (HBsAg and HBeAg) and higher diabetes mellitus (DM) than did homozygous patients (SS and LL). Thirty-seven (57.8%) of the 64 heterozygous patients had a tumor-specific p53 allele LOH, being two times more common in HCC tumors larger than 8 cm than in HCC tumors 2 cm or smaller. The frequency of DM was four times higher in the heterozygous patients who had p53 LOH than in those who retained both alleles. LOH of p53 did not correlate with tumor invasiveness or differentiation, hepatitis B or C virus infection, or prognosis. CONCLUSION: The allelotype of p53 gene in HCC correlates with HBsAg and HBeAg seropositivities and DM. LOH of the p53 gene is a common event in HCC, correlates with DM, and occurs less often in familial HCC. LOH can identify the clonal origin of recurrent HCC but is not a critical prognostic factor.

Adult↗

Analysis of integrated hepatitis B virus DNA and flanking cellular sequences in a childhood hepatocellular carcinoma.

The DNA of tumor tissue K1 obtained at autopsy from a case of hepatocellular carcinoma (HCC) in a 9-year-old boy contained integrated hepatitis B virus (HBV) DNA at a single site in the chromosome (case 2, Chang et al.: Hepatology 13:316-320, 1991). To characterize further the integrated viral DNA sequences, a genomic library of the K1 DNA was constructed in the lambda L47.1 vector. One phage clone, designated KTM-1, containing integrated HBV DNA and cellular flanking sequences was obtained from this library. The restriction map and DNA sequence of this clone showed that the integrated HBV DNA was partially deleted and rearranged. The most conserved viral DNA sequences were surface and X genes and arranged in the opposite orientation. The viral core gene was not present. Using chloramphenicol acetyltransferase (CAT) assay, the C-terminal truncated X open reading frame was demonstrated to retain its trans-activating ability. The result suggested that the functional integrated X gene may play a role in hepatocarcinogenesis. The study also showed that the right cellular flanking sequences were human alphoid repetitive sequences.

Base Sequence↗

Homologous and heterologous neutralization antibody responses after immunization with Japanese encephalitis vaccine among Taiwan children.

Because 21 immunized children (13%) among the 162 confirmed Japanese encephalitis (JE) cases during 1986-1991 occurred in Taiwan, we collected 320 serum samples from Taiwan children aged 15-31 and 27-44 months immediately before the 1st dose (n = 41) and 1-3 months after the 2nd dose (n = 78, 27 pairs), and immediately before (n = 58) and 1-3 months after the 3rd dose (n = 143, 44 pairs) to determine neutralization antibody (Nt Ab) against the Nakayama (N) and Beijing-1 (B) strains and two Taiwan wild type JE viruses (JEV): CC-27 and CH-1392. Our Nt results showed that (1) B vaccine stimulated a better homologous Ab response than N vaccine for Nt Ab seropositivity rate (NASR), produced a higher level of Nt titer after the primary immunization [2 doses = 100% vs. 91%, geometric mean titer (GMT) = 115 vs. 22], had a greater booster effect (3 doses: 100% vs. 95%; GMT = 320 vs 33), and showed a better capability to neutralize two local Taiwan JEV strains, particularly only after 3 doses (ave. NASR for B vs. N = 90% vs. 10%; and GMT for B vs. N = 154 vs. 1); (2) the two wild type JEV strains had different plaque morphology and antigenic variation and the CC-27 strain was not neutralized as well as the CH-1392 strain after 3 doses of vaccine (BBB or NNN or NNB); and (3) 30% of the children had lost JEV Nt Ab one year after the 2nd dose of N vaccine and natural infection with JE virus did occur among those children after immunization. In conclusion, (1) three doses of mouse-brain vaccine are the minimum requirement to protect children against the local Taiwan JEV-, (2) the best strain for a JE vaccine depends on level of Nt Ab it induced, the molecular epidemiology and antigenic variation of the JEV in each local area; and (3) future vaccine must produce better B- and T-cell memory.

Antibodies, Viral↗

Management of avulsion injury of the PCL with reattachment.

Twenty-eight cases of avulsion injury of the posterior cruciate ligament (PCL) treated by reattachment were followed up to evaluate the results. Evaluation was based on appropriate functional and dynamic criteria: the results are classified as good, fair or poor. The interval between injury and repair ranged from 3 days to 2 months with a mean 4 weeks. The follow-up period ranged from 3 to 10 years with a mean of 5 years. The evaluation revealed 27 (96 per cent) good, one (4 per cent) fair and no poor results. It is apparent that operative reattachment is the treatment of choice for avulsion injury of the PCL, especially in early cases.

Adolescent↗

Effects of acute exercise on the changes of lipid profiles and peroxides, prostanoids, and platelet activation in hypercholesterolemic patients before and after treatment.

The effects of acute exercise on the changes of plasma lipid profiles and peroxides, prostanoids and platelet activation in hypercholesterolemic patients before and after pravastatin 5 mg twice daily treatment for 4 weeks was studied in 30 (M/F = 21/9, age = 52 +/- 7, Mean +/- SD) patients with plasma total cholesterol level > 240 mg/dl. Pravastatin significantly reduced plasma total and low density lipoprotein cholesterol levels as expected. All patients before and after treatment and 30 healthy controls performed a treadmill exercise test using the standard Bruce protocol. The cardiac performance was similar in all groups. Treadmill exercise did not influence lipid levels after plasma volume correction. Hypercholesterolemic patients had significantly higher pre-exercise levels of malondialdehyde, thromboxane beta 2 and beta-thromboglobulin than after treatment or than pre-exercise levels in the control group. Treatment with lipid lowering drug pravastatin lowered the levels of these three parameters. At peak exercise, superoxide dismutase activity and 6-keto-PGF1 alpha were elevated. At 10 min post exercise only malondialdehyde returned to pre-exercise levels. The superoxide dismutase, thromboxane B2 and beta-thromboglobulin remained significantly higher. In the control subjects plasma beta-thromboglobulin and thromboxane 2 returned to pre-exercise levels. These results suggest that hypercholesterolemia may induce lipid peroxidation and platelet activation in resting status. Lowering of plasma cholesterol of pravastatin causes a concomitant decrease in plasma malondialdehyde, thromboxane and beta-thromboglobulin suggesting a decrease in lipid peroxidation and platelet activation. These changes were more pronounced in the hypercholesterolemic patients. Pravastatin treatment attenuated the increase in both malondialdehyde, beta-thromboglobulin and the prostanoids, but not to the level of normal subjects.

Exercise↗

Fish oil supplementation attenuates free radical generation in short-term coronary occlusion-reperfusion in cholesterol-fed rabbits.

We studied the changes in lipid peroxidation and prostanoid metabolism in short-term coronary occlusion-reperfusion in controls and those rabbits (11 in each group) fed a 1% high cholesterol diet with or without 10% fish oil supplementation for one week. Acute coronary occlusion for 10 minutes was induced by ligating the marginal branch of the left circumflex coronary artery. The vessels were then reperfused for 1 hour. The cholesterol and fish oil treated rabbits had the lowest malondialdehyde levels both in the ischemic and non-ischemic (normal) areas, the least increase of malondialdehyde level in the ischemic area, and the highest 6-keto-PGF1 alpha/thromboxane B2 ratio in the non-ischemic area after reperfusion among the 3 groups. These rabbits had the highest myocardial superoxide dismutase levels both in the ischemic and normal areas, and the least decrease of superoxide dismutase level in the ischemic area. These data suggest that rabbits fed a high cholesterol diet with fish oil supplementation had an attenuated lipid peroxidation, which reflected a reduced free radical generation during a short-term coronary occlusion followed by reperfusion.

Animals↗

Effects of fish oil supplementation on the changes in myocardial cyclic adenosine monophosphate, inositol 1,4,5-triphosphate and mitochondrial calcium levels during acute coronary occlusion-reperfusion in cholesterol-fed rabbits.

We studied the changes in myocardial second messengers and mitochondrial calcium levels during acute coronary occlusion-reperfusion in New Zealand white male rabbits fed a high cholesterol diet with or without fish oil supplementation. Group I, control rabbits, were fed a standard laboratory rabbit chow. In addition to the standard chow, Group II rabbits received a 1% cholesterol-enriched diet for 2 weeks, while Group III rabbits were fed a 1% cholesterol and 10% fish oil supplemented diet for 2 weeks. Acute coronary occlusion for 10 min or 1 h was induced by ligating the marginal branch of the left circumflex coronary artery. The vessel was then reperfused for 1 or 4 h in short- and long-term ischemia studies respectively. In the short-term ischemia study, myocardial samples taken from the cholesterol-fed rabbits had the highest cyclic adenosine monophosphate, inositol 1,4,5-triphosphate and mitochondrial calcium levels among the normal (nonischemic) and the ischemic areas of the three groups. The cholesterol and fish oil treated rabbits significantly suppressed the elevation of cyclic adenosine monophosphate (P < 0.05 compared with the cholesterol-fed rabbits in normal and ischemic areas respectively), but did not significantly attenuate the elevation of inositol 1,4,5-triphosphate and calcium levels. In the long-term ischemia study, the cholesterol-fed rabbits had the highest levels of these three messengers among the normal areas. However, only inositol 1,4,5-triphosphate level reached statistical significance (P < 0.05 compared with control). This group of rabbits had the lowest level of cyclic adenosine monophosphate, but the highest inositol 1,4,5-triphosphate and calcium levels among the ischemic areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A clinicopathologic study of chronic non-A, non-B (type C) hepatitis in Taiwan: comparison between posttransfusion and sporadic patients.

To elucidate the clinicopathological course and the role of hepatitis C virus in posttransfusion and sporadic chronic non-A, non-B hepatitis in Taiwan, we retrospectively studied 85 histologically confirmed patients with long-term follow up. Antibodies against hepatitis C virus (anti-HCV) by a second-generation assay were positive in 81% of the patients: 88% in the posttransfusion group and 76% in the sporadic group. Clinical manifestations were generally mild, and were noted in only half of the patients. During follow up, 33% (28 of 85 patients) had episodes of acute exacerbation of chronic liver disease and 24% (20 of 85) had normalized liver tests. Patients with normalized liver tests were usually anti-HCV negative (55% vs. 8%, p < 0.001). In 34 patients who had had blood transfusions, initial liver biopsies revealed chronic active hepatitis in 41%, active cirrhosis in 6%, and inactive cirrhosis in 9%. Follow-up biopsies in eight patients in this group showed histological progression in three after an average of 40.6 months. In the 51 sporadically infected patients, initial work-up revealed chronic active hepatitis in 37%, active cirrhosis in 4%, and inactive cirrhosis in 14%. Among the nine who underwent repeated biopsies, only one (11%) had progression. Patients above age 40 displayed more severe histologic activity than those below 40 (p < 0.005). Three patients, all with cirrhosis, died of hepatocellular carcinoma 7 to 12 years after follow up. Further genotyping study of hepatitis C virus in 28 patients showed that type II virus was most predominant in Taiwan and histologic severity was similar among patients infected with different genotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Differential diagnosis of extrahepatic biliary atresia from neonatal hepatitis: a prospective study.

The clinical presentations of cholestasis in infancy caused by neonatal hepatitis and biliary atresia are very similar. Diagnosis may be difficult on many occasions, but the surgical treatment of biliary atresia should be performed as early as possible. We established a 3-day workup protocol for the differential diagnosis of biliary atresia and neonatal hepatitis and compared the diagnostic accuracy, sensitivity, specificity, and predictive values of various methods. One hundred and twenty-six infants, including 84 with neonatal hepatitis (age, 65.1 +/- 24.1 days) and 42 with biliary atresia (age, 60.3 +/- 31.1 days), were studied prospectively from July 1982 to December 1990. The diagnostic accuracy of various methods was as follows: liver histology, 96.8%; color of duodenal juice, 91.6%; peak radioisotope count in duodenal juice, 84.2%; ultrasonographic examination of the hepatobiliary system, 80.2%; and persistence of clay-colored stool, 80.2%. After stepwise logistic regression, the diagnostic methods of significance were liver biopsy, color of duodenal juice, abdominal ultrasonography, and stool color. However, stool color and the onset of jaundice could not differentiate severe neonatal hepatitis from biliary atresia. The diagnostic methods of significance then were liver biopsy and duodenal juice color. With this 3-day protocol, no biliary atresia was missed although four cases of neonatal hepatitis were misdiagnosed, resulting in unnecessary laparotomy; we found an overall diagnostic accuracy of 96.8%. We conclude that this 3-day diagnostic protocol is very helpful in the differential diagnosis of neonatal hepatitis and biliary atresia. Liver histologic examination is the most reliable single test for the differential diagnosis.

Biliary Atresia↗

Persistent gestational trophoblastic tumour with partial hydatidiform mole as the antecedent pregnancy.

OBJECTIVE: A 16 year review of persistent gestational trophoblastic tumour when the antecedent pregnancy was a partial hydatidiform mole. DESIGN: Cases of persistent gestational trophoblastic tumour with partial hydatidiform mole as the antecedent pregnancy were reviewed for the period 1976 to 1992. DNA ploidy was analysed by flow cytometry. SETTING: A University Hospital which is a reference centre for gestational trophoblastic tumour. SUBJECTS: The case notes of 207 women with persistent gestational trophoblastic tumour were reviewed. MAIN OUTCOME MEASURES: A rise (or failure to fall) of beta hCG titre, or sign of metastasis. RESULTS: Six (2.9%) women had partial hydatidiform mole as the antecedent pregnancy and all were initially judged to be low risk. However, two developed pulmonary metastasis; one woman developed persistent gestational trophoblastic tumour shortly after a hysterotomy, and none developed choriocarcinoma. The geometric mean of serum beta hCG concentrations at the initiation of chemotherapy was 868 mIU/ml (95% CI 114-1524). Of the six women, one achieved remission after total abdominal hysterectomy, and five after chemotherapy. The mean interval from starting treatment to remission was 68 days (95% CI 27.9-108.0). The initial beta hCG titre and interval were not statistically different from those found in cases of persistent gestational trophoblastic tumour when the antecedent pregnancy was not partial hydatidiform mole. Of the six, the DNA content was triploid in three and diploid in two. One of the two diploid cases required multiple courses of chemotherapy to achieve remission. CONCLUSION: Partial hydatidiform mole can have malignant sequelae and can develop very soon after treatment. Its DNA content can be either diploid or triploid, the lungs being the most common site of metastasis. After evacuation of partial hydatidiform mole, immediate chest X-ray and regular follow up of the serum beta hCG level is necessary.

Adult↗

Carcinoid tumours of the thymus.

BACKGROUND: Carcinoid tumours of the thymus are rare. The clinical manifestations, radiographic findings, and cytological features of eight histopathologically verified thymic carcinoid tumours have been assessed. METHODS: One hundred and sixty two patients of mean age 52 (range 31-68) years with malignant mediastinal tumours were reviewed retrospectively and eight cases of thymic carcinoid were identified. Four of the eight patients were diagnosed by percutaneous ultrasound guided fine needle aspiration biopsy via a parasternal approach. RESULTS: Two patients had Cushing's syndrome at presentation and four had symptoms and signs secondary to mediastinal compression. Two were asymptomatic. Local extension of the tumour to pleura, pericardium, great vessels, phrenic nerve or regional lymph nodes, or both, were found in seven patients. Only one had the tumour confined to the thymus at diagnosis. Distant metastases were found in two patients, one to both lungs and the other in the iliac bone. Local recurrence or distant metastases developed 15-60 months after surgery in four of the five patients who underwent radical resection of the thymic tumour. Three patients died at 17 months, 34 months, and 10 years after diagnosis. The other five patients are alive at 9-51 months. CONCLUSION: Thymic carcinoid is a slow growing tumour with a poor prognosis because of its tendency to local and distant spread. Cytological examination of samples obtained by ultrasound guided fine needle aspiration may provide a useful method for diagnosis in selected patients.

Adult↗

Regulation of ornithine decarboxylase in the kidney of autoimmune mice with the lpr gene.

The lymphoproliferative lpr gene confers a lupus-like disease with lymphadenopathy, antinuclear antibody production, and glomerulonephritis in MRL-lpr/lpr mice. Upregulation of ornithine decarboxylase (ODC) activity and polyamine levels have been observed in the kidney and lymphoid organs of this strain. Inhibition of ODC with 0.5-1.5% (w/v) difluoromethylornithine (DFMO) in drinking water prolonged life-span and ameliorated renal disease. Glomerulonephritis is a major cause of morbidity and mortality in human and murine lupus. In order to elucidate the mechanism(s) of ODC regulation in lupus nephritis, we characterized ODC at the protein and mRNA levels in 3 strains of autoimmune mice with the lpr genetic background (MRL-lpr/lpr, C3H-lpr/lpr and C57BL/6J-lpr/lpr) using Western blotting, enzyme kinetics, turnover rate measurements, Northern blot hybridization, and reverse transcription-polymerase chain reaction (RT-PCR). Normal BALB/c mice were used as a control. We found that ODC activity in the kidney of lpr strains was 4- to 6-fold higher than that of BALB/c mice. The intensity of the major ODC protein band at 54 kD in Western blot was 4-fold higher in MRL-lpr/lpr and C3H-lpr/lpr kidney compared to that of BALB/c kidney. Putrescine levels were 2- to 4-fold higher in kidney of lpr strains than that of BALB/c and DFMO-treated MRL-lpr/lpr mice. DFMO treatment significantly reduced ODC activity and polyamine levels. The half-life of ODC enzyme in MRL-lpr/lpr, C3H-lpr/lpr, B6-lpr/lpr and BALB/c mouse kidneys was 15, 5, 8 and 23 min, respectively. There was no significant difference in the Km values of different strains, whereas Vmax values differed significantly. There was no difference in the level of SAMDC, another enzyme involved in the polyamine biosynthetic pathway, in various strain. Steady-state levels of ODC mRNA were lower in lpr strains compared to that of BALB/c mouse. Our results suggest that the basis for up-regulation of ODC is not at the transcriptional level, but may involve post-transcriptional modification(s) in lpr strains. The link between aberrant regulation of ODC and the immunopathogenesis of murine lupus nephritis indicates novel targets for lupus therapy.

Adenosylmethionine Decarboxylase↗