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Biomedical subjects

B R Hsu

Publications and source records attributed to B R Hsu.

At least 19 recordsLinked to original sources

Reduction in primary nonfunction of syngeneic islet transplants with nordihydroguaiaretic acid, a lipoxygenase inhibitor.

To study the effectiveness of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), in the reduction of primary nonfunction, an insufficient number of syngeneic islets were transplanted underneath the renal capsule with NDGA administered daily for 4 weeks. After transplantation of the 150 islets, the decrement of blood glucose levels was significantly faster in the mice that had received NDGA than in the mice that had received no drug at all or dimethyl sulfoxide (DMSO) (p < 0.005, p < 0.05). The mean duration of temporary posttransplant hyperglycemia was 22.3 +/- 3.2 (n = 10), 35.9 +/- 2.3 (n = 14), and 33.7 +/- 4.1 (n = 6) days for the respective groups. The diabetic mice that received 300 islets had their blood glucose levels decrease faster than those that received 150 islets (19.7 +/- 1.6 vs. 35.9 +/- 2.3 days, n = 14. p < 0.0001). There was no significant difference in the blood glucose reducing effect between the mice that received 150 islets with NDGA and the mice that received 300 islets [22.3 +/- 3.2 (n = 10) vs. 19.7 +/- 1.6 (n = 14) days, p > 0.05]. The insulin content of the graft from the mice treated with 150 islets and NDGA (3.02 +/- 0.24 microg, n = 4) was higher than that from the mice that received 150 islets but no treatment (1.10 +/- 0.26 microg, n = 15, p < 0.005) or that had been treated with DMSO (1.21 +/- 0.30 microg, n = 4, p <0.05). The insulin content of the pancreas remnant had no significant differences among the three groups. The net glucose-stimulated insulin secretion was 0.82 +/- 0.14 vs. 0.20 +/- 0.10 microIU/islet x 60 min (n = 8, p < 0.005) and 0.59 +/- 0.08 vs. 0.04 +/- 0.02 microIU/islet x 60 min (n = 8, p < 0.0001) for islets cultured without NDGA vs. with NDGA at 1 and 2 weeks, respectively. However, the insulin content of the cultured islets was similar between the two groups for up to 2 weeks of incubation (at 1 week: 0.71 +/- 0.01 vs. 0.67 +/- 0.04 ng/islet, n = 8, p > 0.05; at 2 weeks: 0.71 +/- 0.02 vs. 0.80 +/- 0.07 ng/islet, n = 8, p > 0.05). Serum leukotriene B4 (LTB4) concentrations before and between the fifth and seventh days after transplantation were determined. For diabetic mice that received 150 islets, serum LTB4 levels were 25,835 +/- 3,335 and 27,631 +/- 3,136 pg/ml (n = 4, p > 0.05). For diabetic mice that received 150 islets and NDGA, the corresponding figures were 22,401 +/- 2,706 pg/ml and 27,530 +/- 2,190 pg/ml (n = 8, p > 0.05). The graft histology revealed viable islet cells and networks of close vascular structures around the islets and did not reveal microscopic differences among the samples of all four groups. In conclusion, our data revealed that daily administration of NDGA for 4 weeks enhanced isoislet engraftment and preserved three times more mass of the islet beta cells in the isografts. This result indicates that NDGA reduces primary nonfunction of islet syngeneic grafts in diabetic mice.

Animals↗

Influence of donor age on mouse islet characteristics and transplantation.

Old donor age has been considered as a risk factor and relative contraindication for transplantation. This study was designed to investigate the influence of donor age on islet characteristics and transplantation. Islets isolated from 8 (I-A)-, 32 (I-B)-, or 64 (I-C)-week-old C57BL16 mice were studied for number, size, insulin content, and secretion. After syngeneically transplanting 300 islets under the kidney capsule of streptozotocin-diabetic mice (R-A. R-B, and R-C, respectively), we measured recipients' metabolic parameters as well as the beta-cell mass and insulin content of the graft. Eight-week-old donors had better glucose tolerance than 32- and 64-week-old donors. However, 64-week-old donors had more pancreatic insulin content than 8- and 32-week-old donors. I-B and I-C were greater in number, larger in size, and higher in insulin content than I-A. But perifusion study showed I-C secreted less insulin, albeit with a similar stimulation index compared with that of I-A and I-B. After transplantation, the fall of blood glucose in R-C was faster than that in R-A and R-B. At 12 weeks, the recipients' blood glucose, body weight, HbA1c, and the beta-cell mass and insulin content of the graft were comparable in all groups. However, R-C had better glucose tolerance than R-A. During follow-up, R-A and R-B maintained lifelong normoglycemia and their glucose tolerance did not deteriorate. These data indicate that islets isolated from donors with different ages have different characteristics and effects on transplantation. The islets isolated from aged donors are functioning well and can be a potential source for transplantation; however, because we transplanted a large islet mass from the aged donors, the role of the islet dose needs to be further clarified.

Age Factors↗

Video-assisted endoscopic thyroidectomy.

BACKGROUND: Several experimental and clinical reports concerning endoscopic parathyroid surgery have appeared. However, reports concerning minimally invasive surgery for thyroid remains rare. Herein we present a new method, called video-assisted endoscopic thyroidectomy (VAET), for the management of various benign thyroid diseases. METHODS: In all, 16 consecutive patients who underwent VAET for benign thyroid diseases were retrospectively studied. The study group included nodular hyperplasia in 8 patients, follicular adenoma in 6, and Hurthle's tumor and simple cyst in 1 each. A 2 to 3 cm transverse incision was made on the suprasternal notch. The wound was deepened to expose the underlying trachea from which the plane of the thyroid fascia was accessed directly, and the working space was established with lifting method using conventional instrument. All surgical procedures could be manipulated and monitored under laparoscopy without gas insufflation. The ultrasonically activated scalpel was the principal instrument used for VAET. RESULTS: All 16 patients underwent VAET successfully without conversion to open thyroidectomy. The surgical procedures included lobectomy in 13 and extirpation in 3. The operation time ranged from 28 minutes to 5 hours (mean 1 hour, 42 minutes). For the 5 most recent cases, lobectomy took an average of 2 hours, whereas extirpation less than 40 minutes. The tumor size ranged from 3.5 cm to 8.0 cm (mean 5.8 cm). There were no surgical complications. All patients but 1 were discharged on postoperative day 2. During follow-up, all patients demonstrated euthyroid function and satisfactory cosmetic results. CONCLUSIONS: VAET emerges as a promising minimally invasive surgical technique replacing conventional thyroidectomy for benign thyroid diseases in selected cases, with the advantage of satisfactory cosmetic results.

Adenoma↗

Biodegradable alginate antibiotic beads.

The authors investigated the poly-L-lysine-coated alginate beads as an antibiotic delivery system for the treatment of various surgical infections. The sodium alginate was mixed with vancomycin, coated with poly-L-lysine, and lyophilized to form five types of the biodegradable antibiotic beads. Type I, 2.5% alginate, nonpoly-L-lysine coated and nonlyophilized; Type II, 2.5% alginate, poly-L-lysine coated but nonlyophilized; Type III, 2.5% alginate, poly-L-lysine coated and lyophilized; Type IV, 5% alginate, poly-L-lysine coated and lyophilized; and Type V, 7.5% alginate, poly-L-lysine coated and lyophilized. Cytotoxicity of the alginate beads to fibroblasts and HeLa cells was evaluated by the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] colorimetric assay. A study of in vitro elution of vancomycin of the alginate antibiotic beads was performed. The results suggested that the alginate antibiotic beads present no obvious toxic risk to their use as a drug delivery system. The concentration of vancomycin in these five types of beads was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for 9,11,12, 14, and 17 days respectively. The release was most marked during the first 3 days. The duration of antibiotic release was prolonged by using techniques of poly-L-lysine coating, lyophilization, and by increasing the content of alginate. This study offers a biodegradable delivery system of antibiotics to treat various surgical infections.

Alginates↗

Demonstration of reserved anterior pituitary function among patients with amenorrhea after postpartum hemorrhage.

To demonstrate the residual pituitary function of patients with Sheehan's syndrome years after the obstetric complication, 14 patients with postpartum hemorrhage followed by secondary amenorrhea and agalactia were included in this review. Due to their unfamiliarity with the clinical symptoms, these patients did not receive pretreatment hormonal therapy. The mean age at their last delivery was 29 years (range 21-38 years). The mean duration between postpartum hemorrhage and the subsequent clinical manifestations leading to the endocrine investigation was 18 years (range 1-33 years). Eight patients presented with symptoms of severe hyponatremia (serum sodium less than 125 mmol/l) more than 16 years (mean 23 +/- 10) after the occurrence of postpartum hemorrhage. The electrolyte abnormality was primarily due to adrenal dysfunction. Seven out of 14 patients had normal basal luteinizing hormone (LH) levels and adequate LH responses to gonadotropin releasing hormone stimulation. Administration of thyrotropin releasing hormone provoked thyrotropin release and/or prolactin secretion in four cases. The manifestation of clinical hypopituitarism and the degree of empty sella on computed tomography scanning did not accurately indicate the secreting ability of the pituitary in patients with Sheehan's syndrome. Although all the patients had amenorrhea, the gonadotropic functions of the pituitary still remain in some patients. Various degrees of other pituitary functions can also been demonstrated even several decades after the occurrence of obstetric complications. Our data suggest that the amenorrhea of Sheehan's patients is not simply due to a dysfunction of the pituitary gonadotrophs.

Adult↗

Recurrent fetal thyrotoxicosis in a woman with Graves' disease: case report.

The thyroid stimulating immunoglobulins are generally believed to be the cause of hyperthyroidism in Graves' disease. Placental transfer of these antibodies from a mother with autoimmune thyroid disease can result in fetal thyroid disorders. We report the case of a 31-year-old woman who had a history of Graves' disease. She received thyroxine therapy for post thyroidectomy hypothyroidism. Two years after the thyroidectomy, she became pregnant. Unfortunately, intrauterine fetal death occurred in midgestation. One year later, she became pregnant again. In the 26th week of gestation, fetal thyrotoxicosis was diagnosed using clinical pictures, including fetal tachycardia and cardiomegaly, and a hormonal evaluation of a periumbilical blood sampling (T4: 18 micrograms/dl, T3: 65.3 ng/dl, TSH: < 0.03 microU/ml) was performed. Antimicrosomal antibodies were not detectable in either the maternal or fetal blood. In this case, high levels of TBII were detected during pregnancy and crossed the placenta to result in a thyrotoxic fetus in the second pregnancy. We recommend that both the regular monitoring of the thyrotropin receptor antibodies of pregnant women with a history of autoimmune thyroid disease, and routine measurements of the fetal heart rate and intrauterine growth during gestation be mandatory for the early detection of fetal thyroid disorders. Cordocentesis for measuring fetal thyroid function is helpful in reaching a definite diagnosis and for guiding therapy.

Adult↗

Effect of cisapride, a serotonin-4 receptor agonist, on aldosterone secretion: absence of age-related change.

Twenty healthy volunteers (age ranging from 19 to 72) were studied for their aldosterone response to oral administration of 10 mg cisapride, a serotonin-4 receptor agonist. The participants were studied after minimum of 4-hour ambulation (high basal renin) and a repeated test after overnight bed rest (low basal renin). Oral administration of cisapride caused a two-fold increase in the plasma aldosterone levels (182.6 +/- 28.0% in high renin state and 203.4 +/- 38.6% in low renin state; P = 0.659 between the means of two states) without affecting the plasma renin levels, Scatterplot of percentile aldosterone increment against age distribution demonstrated that the R-square were very low (0.039 for high renin and 0.009 for low renin state). Our data suggest that the age does not alter the serotonergic mediated effect on aldosterone secretion. The cisapride effect is also independent of the different basal renin states. Cisapride, as a single oral dose, could serve as a simple test to assess the functional capacity of aldosterone secretion.

Administration, Oral↗

Inhibition of corticosteroid-binding globulin caused by a severe stressor is apparently mediated by the adrenal but not by glucocorticoid receptors.

The effect of stress on serum corticosteroid-binding globulin (CBG) was studied in adult male Sprague-Dawley rats. CBG was measured either by a homologous radioimmunoassay (RIA) or by a binding assay (BA) using 3H-corticosterone. Exposure of adult male rats to a severe stressor such as immobilization (IMO) for 1 h did not alter serum CBG levels, but a significant decrease was found after 6 and especially 24 h IMO. This decrease was not observed after 24 h exposure to a milder treatment such as food and water deprivation. The effect of different periods of exposure to two stressors, IMO or restraint, was also studied. The following results were obtained:serum CBG levels were reduced by IMO, but only by restraint; IMO-induced reduction of CBG levels was always observed 24 h after starting exposure to IMO, independently of the actual period of exposure to the stressor; and IMO-induced inhibition of CBG was proportional to the hours of exposure to the stressor. Although IMO-induced inhibition of CBG was prevented by adrenalectomy, a role for glucocorticoid acting through their classical type II receptors is unclear as far as treatment of rats with the glucocorticoid receptor antagonist RU486 (100 mg/kg) did not prevent the inhibition caused by IMO. The present data clearly indicate that acute exposure to a stressor is able to decrease CBG levels provided that duration of exposure to the stressor and its intensity are high and that the effect is tested at least 6 h after the onset of stress. The effect appears to be mediated by some adrenal factor(s) other than glucocorticoids.

Adrenal Glands↗

Paralytic myopathy--a leading clinical presentation for primary aldosteronism in Taiwan.

Between 1982 and 1995, 43 cases of primary aldosteronism, 36 cases of adenoma, and 7 cases of hyperplasia were treated in Chang Gung Medical Center. Twenty-one of these (49%) presented with muscular paralysis as an initial symptom (categorized as the paralytic group). Seven patients in the paralytic group (33%) had extralimb muscle involvement. Six of them presented with bulbar palsy and one patient had a peripheral-type facial palsy. The serum potassium levels in the paralytic group were significantly lower than those of the nonparalytic group (1.8 +/- 0.3 vs. 2.3 +/- 0.4 mmol/L, P = 0.0001). There were no significant differences in blood pressure or the serum aldosterone level between the two groups. Provocative factors such as a high carbohydrate diet, vigorous exercise, or seasonal variation did not appear to play a significant role in inducing the symptoms. Paralytic myopathy appears to be more common in Oriental people. The symptom is rarely reported among western populations. Primary aldosteronism should be considered in patients presenting with neuromuscular weakness associated with hypokalemia, regardless of the degree of hypertension.

Adult↗