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Biomedical subjects

C H Hsu

Publications and source records attributed to C H Hsu.

At least 217 records · Page 12Linked to original sources

Effects of ricin on the ability of rabbit arteries to contract and relax.

Ricin, a toxic lectin from castor beans, reduces blood pressure. The current studies determined the effect of ricin on contractions in response to norepinephrine (NE) of rabbit central ear artery, endothelium-dependent relaxations to methacholine and ATP of aorta rings and endothelium-independent relaxations to papaverine in central ear artery and aorta rings. Rabbits were given 0.11 or 0.22 micrograms kg-1 ricin i.v. and 18 h, 4 days, or 7 days later the arteries were removed and tested. Maximal contractions to NE were increased by 8-23% (P > 0.05) with ricin treatment. The EC50 was increased in five of six ricin-treated groups, although only significantly so at 18 h after a minimum lethal dose of ricin. Maximum relaxations to methacholine were increased by 20-57% (P > 0.05) at 18 h following both ricin doses but returned to control values at later time points. Relaxations in response to ATP were significantly enhanced in all ricin-treated groups (95-205%) except in the 18 h and 4-day 0.11 microgram kg-1 dose groups where the increase was 0-46%. Relaxations in response to papaverine were not altered in either artery. Thus, ricin decreases the sensitivity of the rabbit central ear artery to NE and increases endothelial-dependent relaxations of the rabbit aorta. Therefore, decreased blood pressure following ricin administration may be due to vasodilation caused by decreased vascular contractions and increased endothelial-dependent vascular relaxation.

Animals↗

Can cardiac catheterization accurately assess the severity of aortic stenosis? An in vitro pulsatile flow study.

An accurate hemodynamic assessment of aortic stenosis has important clinical implications. In clinical practice, cardiac catheterization is often used to assess the severity of aortic stenosis. However, in conducting catheterization, the precise position of the catheter tip is often not known or controlled. From the standpoint of hydrodynamics, the position of the catheter tip may affect pressure measurement due to the complicated flow fields distal to the valve. This fact is particularly true when the diagnosed valve is stenotic. The study was aimed to investigate how the position of the catheter tip in catheterizing aortic stenosis affects pressure measurement. The experiments were conducted in an in vitro pulse duplicator system. Laser flow visualization was used to examine the flow fields in the vicinity of varying degrees of aortic stenosis, and a pressure transducer with a side-hole catheter was used to measure pressures. Minimal variation in transvalvular pressure drop measured along the radial direction was observed for varying degrees of valvular aortic stenosis. This implies that, in catheterization, the placement of the catheter tip along the radial direction does not seem to affect pressure measurement. However, along the axial direction, pressure recovery was observed for all the cases studied. Therefore, within the region of pressure recovery, the position of the catheter tip may affect the pressure drop measurement. This may cause inaccuracy in assessing the severity of aortic stenosis. However, this concern may be overcome by pulling the catheter slightly further downstream, so that the position of the catheter tip is outside of the pressure recovery region.

Adult↗

Weekly 24-hour infusion of high-dose 5-fluorouracil and leucovorin in the treatment of advanced gastric cancers. An effective and low-toxic regimen for patients with poor general condition.

Systemic chemotherapy for advanced gastric cancer is frequently associated with significant treatment-related toxicity, which is particularly serve in patients presenting with a poor general condition. A search for effective and low-toxic regimens for this group of patients is mandatory. A weekly 24-hour infusion of high-dose 5-fluorouracil (5-FU) and leucovorin (HDFL) has previously been demonstrated to be an effective treatment for advanced colorectal cancer with minimal toxicity. In the past 3 years, this regimen has been tested at our institutes in patients with advanced gastric cancer, the general condition of whom had made the use of intensive combination chemotherapy impossible. The regimen consisted of a weekly 24-hour infusion of 2,600 mg/m2 of 5-FU and 300 mg/m2 of leucovorin. From August 1992 to December 1995, 34 patients had been treated with this regimen for a total of 488 courses (average: 14.4 per patient). Hematological toxicity of this regimen was minimal, with grade 3 or 4 leukopenia developing in only 1 (2.9%) patient. Other nonhematological toxicities were also negligible except a reversible neurotoxicity which developed in 2 patients. Twenty-five patients were eligible for response analysis. One complete response, 11 partial responses, 5 stable diseases, and 8 progressive diseases were observed. The response rate was 48% (32-72%, 95% CI). The median overall survival (OS) of the whole group was 7 months (range: 1-18+). The median OS and time to progression of the responders were 8.5 months (range: 2-18) and 5 months (range: 2-10+), respectively. The palliative effect was satisfactory with the Karnofsky performance status of the responders improving from a median of 50% (range: 20-90%) to 70% (range: 50-100%). Our retrospective data suggested that HDFL is an effective and low-toxic palliative treatment even in patients with a very poor general condition. We advocated that this regimen should be further tested in ordinary patients with advanced gastric cancer.

Adult↗

Role of renal papillae in the regulation of sodium excretion during acute elevation of renal perfusion pressure in the rat.

We studied the role of renal papillae in the mechanism of increased sodium excretion during acute increase in mean arterial pressure (MAP). Sodium excretion increased dramatically in normal rats after acute increase in MAP by epinephrine (E) infusion (0.4 micrograms/min/100g). Glomerular filtration rate (GFR), renal blood flow (RBF), and papillary plasma flow (PPF) remained unchanged after the E administration. To define the role of the medulla in the mechanism of pressure-induced natriuresis, experiments were performed in a group of rats 8 to 12 days after the development of papillary necrosis induced by bromoethylamine hydrobromide. Urinary sodium and fractional sodium excretions were 2.00 +/- 0.34 microEq/min and 2.37 +/- 0.53% (n = 7), respectively, in papillary necrosis rats infused with saline. Administration of E to papillary necrosis rats, however, failed to increase both urinary sodium (2.89 +/- 0.61 microEq/min) and fractional sodium (FENa, 2.82 +/- 0.63%, n = 6) excretions despite a marked increase in MAP (129 vs 150 mm Hg, p less than 0.01). The RBF increased slightly after E infusion (4.42 vs 3.24 ml/min/100 g, p less than 0.05), but the GFR was not different between the control (0.39 +/- 0.05 ml/min/100g, n = 7) and the E-treated rats (0.43 +/- 0.06, n = 6). Failure to increase sodium excretion during acute increase in MAP was not due to the decreased GFR, since control rats with bilateral partial nephrectomy were able to increase sodium excretion from 1.92 +/- 0.33 to 7.76 +/- 1.63 microEq/min (p less than 0.01) after E infusion. These findings, therefore, suggest that renal papillae play a major role in the mechanism of natriuresis during acute increase in MAP.

Acute Disease↗

Congenital rickets--a patient report.

We present a premature newborn with congenital rickets, born to a mother with untreated chronic renal insufficiency. X-ray films showed blurred metaphyseal ends and decreased bone density in the femurs and ribs. With treatment including calcium, phosphate, and vitamin D, her rickets healed and she grew normally.

Adult↗

Concurrent chemoradiotherapy for locally advanced esophageal cancer--a pilot study by using daily low-dose cisplatin and continuous infusion of 5-fluorouracil.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) has recently become a promising treatment for esophageal cancer. However, most investigators have adopted the conventional or modified Wayne-State PF (cisplatin plus 5-fluorouracil) regimen, which is inevitably associated with moderate to severe treatment-related toxicities. In this pilot study, we incorporated a daily low-dose regimen of cisplatin and 5-fluorouracil into CCRT in order to improve the compliance of the patients. PATIENTS AND METHODS: Between July 1993 and Dec. 1997, 25 patients with locally advanced esophageal cancer (T3, or N1 disease), received CCRT which consisted of daily low-dose cisplatin (6 mg/m2/day) and continuous infusion of 5-FU (225 mg/m2/day) with radiotherapy (fraction size = 200-250 cGy/day). Except for the initial 9 patients, for whom post-CCRT esophagectomy was compulsory, all subsequent patients underwent esophagectomy only when inadequate response to CCRT was noted. The scheduled radiation dose was 50 Gy for the first 9 patients, and 60 Gy for the rest of the patients. RESULTS: Eighteen patients (72%) completed the CCRT without interruption. Clinically, there were 8 CR and 9 PR, with a total response rate of 68% (47-87%, 95% C.I.). All patients were evaluable for toxicity. Grade 3/4 leukopenia and thrombo-cytopenia developed in 14 (56%) and 7 (28%) patients, respectively. Grade 3/4 non-hematologic toxicity was seen in 4 (16%) patients. The median survival of the whole group was 8 months (range: 2-59+). The projected 3-year overall survival was 24%. CONCLUSION: We suggest that for locally advanced esophageal cancer CCRT with the aforementioned daily low-dose regimen, is a treatment with good patient compliance.

Adult↗

Treatment of recurrent Kaposi's sarcoma of an AIDS patient with weekly paclitaxel.

Paclitaxel was recently recognized as an active chemotherapeutic agent for acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). However, the best way to administer paclitaxel in AIDS-KS patients remains unknown. Herein, we reported an AIDS-associated KS patient whose disease progressed on the first-line chemotherapy with doxorubicin and bleomycin, but later responded well to weekly 1-hour infusion of 70 mg/m2 paclitaxel. It is particular noteworthy that this weekly dosing schedule resulted in almost negligible toxicities. The authors suggested a prospective study of weekly paclitaxel for AIDS-KS should be started as soon as possible.

Acquired Immunodeficiency Syndrome↗

Factors affecting the mortality of sick newborns admitted to intensive care units.

In order to provide better understanding of the factors affecting the mortality of sick newborns in the Taipei metropolitan area, data of newborns admitted to the intensive care units (ICU) were analyzed retrospectively according to the hospital type of care. Fourteen of the 19 hospitals with an ICU admitting sick newborns joined the data collection: 3 were local hospitals, 7 were regional hospitals and 4 were medical centers. Perinatal and neonatal data of 1083 sick newborns were analyzed: 60% were premature newborns and 58% were male newborns. The maternal referral rate was 7.8% and the neonatal transport rate was 36.2%. Fifty-nine percent of very low birth-weight newborns and 66% of extremely low birth-weight (ELBW) newborns were admitted to the medical centers. The two most common illnesses were perinatal asphyxia and respiratory distress syndrome. About 40% needed assisted ventilation. There were higher incidence of maternal referral, fetal distress, resuscitation in the delivery room, perinatal asphyxia, and necrotizing enterocolitis; lower incidence of meconium aspiration syndrome, sepsis and pneumothorax in newborns admitted to the medical center than those newborns admitted to other hospitals. A total of 153 newborns (14%) died. The most common cause of death was sepsis (22.9%). Multivariate logistic regression analysis revealed that factors significantly related to the mortality were gestational age < 28 weeks, congenital anomaly, sepsis, resuscitation in the delivery room, neonatal transport, congenital heart disease, hospital type of care, ELBW, pneumothorax and high-risk pregnancy. The results of the study stress the importance of regionalization of perinatal and neonatal care, organization of neonatal transport system, newborn resuscitation training, infection control, and delicate ventilatory care in the further improvement of the outcome of sick newborns in the Taipei metropolitan area.

Cause of Death↗

Thyroid function in the sick very low-birth-weight infants.

This study was undertaken to determine postnatal changes in thyroid function in very low-birth-weight (VLBW) infants. A total of one-hundred VLBW infants participated. Serial examination of serum levels of thyroxine (T4), free T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) was performed in the neonatal period. A total of eighty-nine infants survived to discharge, while eleven died during hospitalization. Transient hypothyroxinemia was found in forty-one (46.1 percent) of the survivors. One of the surviving infants had primary hypothyroidism. His data was excluded from the analysis. In the other eighty-eight surviving infants, TSH levels were within normal limits throughout the six-week study period. T4 and free T4 values decreased after the first day of life, reaching a nadir at one week of age, followed by progressive increases. The mean cord blood T3 level was very low; the serum T3 value increased progressively in the postnatal period. We found a correlation between low T4 and free T4 values and mortality and neonatal illness. Hypothyroxinemia was associated with critical illness. In conclusion, the postnatal changes in thyroid function in VLBW infants were characteristic, with transient hypothyroxinemia being common in these infants. Further investigation of the relationship between thyroid function, death, neonatal illness, and developmental outcome is warranted.

Female↗

Cardiovascular function in young patients with type 1 diabetes mellitus.

Echocardiographic assessment of cardiovascular function was performed in 47 type 1 diabetic patients and 30 healthy control subjects of comparable age, height, weight, and heart rate. Indexed left ventricular mass, stroke volume, cardiac output, cardiac index, shortening fraction, indexed diastolic dimension, and indexed diastolic volume were calculated and compared between patient and control groups. Left ventricular mass and performance were slightly elevated in type 1 diabetic patients compared with 30 healthy control individuals. However, only cardiac output had borderline statistical significance (p = 0.06). The reason might be short duration (mean, 4.02 +/- 4.07 years) of diabetes in our patients group. In 18 of 47 patients the duration of type 1 diabetes was even less than two years. Relation of left ventricular mass to independent variables showed that, left ventricular mass was significantly correlated with stroke volume (p = 0.008), cardiac index (p = 0.0005), indexed systolic blood pressure (p = 0.0000199), indexed diastolic blood pressure (p = 0.0000172) and left ventricular contractility (p = 0.000273) in diabetic patients. Left ventricular contractility was also independently associated in diabetic patients with the indexed systolic and diastolic blood pressure (p = 0.0000755 and 0.000678 respectively). Albumin excretion, duration of diabetes, glycosylated hemoglobin (HbAlc), serum creatinine, and left ventricular preload did not have significant univariate correlation with left ventricular contractility.

Child↗

Final height of children with type 1 diabetes: the effects of age at diagnosis, metabolic control, and parental height.

Normal growth is one of the major goals in the treatment of children with type 1 diabetes. We prospectively monitored the linear growth and metabolic control of 44 children (13 boys) with type 1 diabetes from the time of diagnosis to the attainment of adult height and analyzed the relationship between the height and the age at diagnosis, metabolic control, and genetic target height. At diagnosis, girls at puberty were taller (height in standard deviation score: 0.60 +/- 0.94, p = 0.022), while boys (-0.03 +/- 0.67) and prepubertal girls (0.24 +/- 0.86) were similar to the age-controlled children. During the following years, they lost height compared to their height at diagnosis (p = 0.009), but they still attained an average final height (-0.13 +/- 0.66 in boys, -0.05 +/- 0.86 in girls) correlated with their height at diagnosis (r = 0.37, p = 0.014), as well as their genetic target height (r = 0.78, p < 0.005). The final height as well as the reduction in height was not linearly correlated with the age at diagnosis. The mean HbA1c level of the 44 children was 10.33 +/- 1.74%, boys had better control compared with girls (mean HbA1c 9.45 +/- 1.28 v.s. 10.71 +/- 1.78%, p = 0.013). The final height or the reduction in height was not linearly correlated with the mean HbA1c level.

Adolescent↗

Mutations of p53 gene in gastric carcinoma in Taiwan.

BACKGROUND: p53 gene mutation and p53 protein accumulation is the most common event in human cancers. The present study was conducted to investigate the occurrence of p53 mutations in patients with gastric carcinoma in Taiwan. MATERIALS AND METHODS: Tumor samples from 36 patients with primary gastric carcinoma undergoing radical gastrectomy were evaluated. The mutational status of the p53 (exons 5 to 8) was screened by polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. These results were compared with p53 protein expression as assessed by immunohistochemical staining. RESULTS: Of all 36 gastric carcinomas, mutations of the p53 gene were found in 7 cases (19.4%). These results from direct sequencing indicated that mutations consisted of five missence mutations, one silent mutation and one mutation within the splice donor site of intron 5. Mutations were found at codon 145 in exon 5 (1 case), intron 5 (1 case), codon 248 in exon 7 (1 case), codon 251 in exon 7 (2 cases), codon 285 in exon 8 (1 case) and codon 287 in exon 8 (1 case). The mutation hot spot at codon 251 in gastric cancer has not been observed previously. Over-expression of p53 oncoprotein was observed in 10 patients (27.8%) immunohistochemically. CONCLUSIONS: p53 gene mutation might contribute to the pathogenesis of human gastric carcinoma. However, the suggestion awaits further investigation for confirmation.

Adenocarcinoma↗

Combination chemotherapy of cisplatin, methotrexate, vinblastine, and high-dose tamoxifen for transitional cell carcinoma.

BACKGROUND: We have previously demonstrated that tamoxifen enhanced the chemosensitivity of bladder cancer cells in vitro. In this pilot study, we tested the modulating effect of high-dose tamoxifen to conventional cisplatin, methotrexate, and vinblastine combination chemotherapy (CMV-T) for transitional cell carcinoma (TCC). PATIENTS AND METHODS: Between Nov. 1994 and Mar. 1999, 30 TCC patients were enrolled. Nine patients had muscle-invasive bladder TCC; 21 patients had either unresectable locally advanced diseases or distant metastases. CMV-T consisted of cisplatin 50 mg/m2/day, day 1 & 2; methotrexate 30 mg/m2/day, day 1 & 8; vinblastine 3 mg/m2/day, day 1 & 8; and tamoxifen 200 mg/m2/day, days 1 through 4. RESULTS: A total of 98 courses had been given with an average of 3.27 courses per patient (range: 1-7). Grade III/IV leukopenia and thrombocytopenia occurred in 18% and 21% of total courses, respectively. There were 7 episodes of neutropenic fever, and 3 patients died of sepsis. Non-haematologic toxicities were generally mild. There was no venous thrombosis. Out of 26 patients eligible for evaluation of response, 1 complete and 14 partial responses with an overall response rate of 58% (95% confidence interval: 38-75%) were observed. The mean survival of all patients was 8 months. CONCLUSIONS: The toxicity of CMV-T chemotherapy is moderate, but generally manageable. The response rate of CMV-T for patients with advanced TCC seems to be only comparable to most conventional cisplatin-based combinations. The possible benefit of tamoxifen to enhance chemosensitivity of TCC needs further investigation.

Aged↗

A pilot study of AFL-T (doxorubicin, 5-fluorouracil, leucovorin, and tamoxifen) combination chemotherapy for hormone-refractory prostate cancer.

BACKGROUND: Tamoxifen had been used to treat advanced prostate cancer with limited success. In vitro data suggested that tamoxifen could enhance the cytotoxic effect of chemotherapeutic agents, including doxorubicin, on prostate cancer cell lines. We applied this observation into a phase II trial for patients with hormone refractory prostate cancer (HRPC). PATIENTS AND METHODS: The AFL-T regimen consisted of doxorubicin 30 mg/m2/day on day 1; 5-FU 2,000 mg/m2/day 24-hour infusion and leucovorin 200 mg/m2/day 24-hour infusion on days 15 and 29; tamoxifen 50 mg/m2 four times daily on days 1, 2, 16, 17, 30, and 31. The protocol was designed to be of low dose-intensity and tolerable to most HRPC patients who may have reduced bone marrow reserve and poor renal function. Between Feb. 1994 and April 1999, 17 patients (median age 67, range 60-81) with HRPC were enrolled. Extensive hormonal manipulations had been done prior to the chemotherapy. Three patients had measurable diseases, 14 had only bone metastases, and all had elevated PSA levels (median 498 ng/ml, range 7.4-3,970 ng/ml). RESULTS: All 17 patients were eligible for analysis of toxicity. ECOG Grade III/IV leukopenia and thrombocytopenia occurred in 1 and 3 patients, respectively. There was no febrile neutropenia; there was no treatment-related mortality. Grade III/IV nausea, vomiting, mucositis, and diarrhea were noted in 0, 0, 1 and 0 patient, respectively. There was no venous thrombosis. One partial response, 1 stable disease, and 1 progressive disease were found in the three patients with measurable lesions. Eleven of the 17 patients (64.7%, 95% confidence interval: 41-88%) who were eligible for the evaluation of PSA response (PSA decrease > 50% for at least 6 weeks) were responders. The median overall and progression-free survivals were 13 and 7 months, respectively. Seventy-six percent of patients showed decreased analgesic usage or enhanced performance status. CONCLUSION: AFL-T, that has a low toxicity profile, is comparable to most other active regimens in terms of the PSA response rate. Randomized trials are needed to determine if there exists a survival benefit for patients with HRPC.

Aged↗