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Biomedical subjects

L T Nguyen

Publications and source records attributed to L T Nguyen.

107 records · Page 6Linked to original sources

Amplification of bleomycin-mediated degradation of DNA.

Three simple and independent tests have been introduced for studying the effect of DNA intercalating compounds on the bleomycin-mediated digestion of DNA in vitro. These methods are based on hyperchromic changes of DNA solution, changes in viscosity of DNA solution, and HPLC quantitative analysis of the four bases released from digested DNA. All three tests give comparable results. However, the viscometric method is technically the simplest and at the same time the most sensitive. The amplification of the bleomycin-mediated degradation of DNA by three unfused heteropolyaromatic intercalator molecules, namely N-[2''-(dimethylamino)ethyl]-4-thien-2'-ylpyrimidin-2-amine (1N), N,N-dimethyl-2-[(4'-thien-2''-ylpyrimidin-2'-yl)thio] ethylamine (1S), and newly synthesized 2,5-bis[2'-[[2''-(dimethylamino)ethyl]thio]pyrimidin-4'yl]thiophene (2) correlates well with the respective DNA binding constants for these compounds and is concentration dependent. The amplification activity of these compounds increases with increasing concentrations. The strongly binding compound 2 is the best amplifier of bleomycin in vitro found so far. Fused heteropolyaromatic systems, like ethidium bromide, are modest amplifiers of bleomycin at low concentrations but strongly inhibit the bleomycin chemistry at high concentrations.

Animals↗

Meconium ileus: is a stoma necessary?

During the 15 years from 1970 to 1984, 38 infants, all with cystic fibrosis, were treated for meconium ileus at The Montreal Children's Hospital and Ste-Justine Hospital for Children. Thirteen patients (34%) had complicated meconium ileus that included 7 perforations (2 colon, 5 ileum), 4 volvulus, and 2 atresia with meconium pseudocyst. In this group, various operations were done: resection with primary anastomosis for atresia, or resection with enterostomy for peritonitis or volvulus. One died shortly after surgery. Of 25 patients with uncomplicated meconium ileus (66%), one died shortly after arrival from respiratory distress, leaving 24 patients available for study. Gastrografin enema was attempted on 20 patients with eight successes (40%). Of the remaining 16 patients with unresolved meconium ileus, nine were treated with laparotomy and ileostomy, and one with laparotomy and T-tube irrigation. Six patients were treated by laparotomy and enterotomy for irrigation with N-acetylcysteine and evacuation by Fogarty catheter, a technique not widely used. No one succumbed in this group. This latter method of management is recommended for patients with simple uncomplicated meconium ileus.

Cystic Fibrosis↗

Spontaneous deep vein thrombosis in childhood and adolescence.

Deep vein thrombophlebitis (DVT), unrelated to intravenous catheters, is unusual in children. During the period between 1970 to 1984, 15 cases of spontaneous DVT were seen at The Montreal Children's Hospital. The female to male ratio was 2:1. Age ranged from 10 to 17 years. Venogram was positive in the 14 patients in whom it was done. Significant factors were related to the DVT in 12 patients: oral contraceptives, pelvic fracture, Ewing's sarcoma and chemotherapy, brain tumor, nephrotic syndrome, and ulcerative colitis (2, one of whom developed the DVT 3 months before the onset of gastrointestinal symptoms). The sites of thrombophlebitis encountered were left iliofemoral vein, right iliofemoral, right tibial, and left subclavian. Three patients developed pulmonary emboli, which were recurrent in two and required iliac vein ligation or inferior vena cava clipping. Treatment usually consisted of intravenous heparin followed by oral anticoagulants for 3 to 6 months. Two patients received streptokinase with good results. All the patients recovered. With a limited follow-up (6 months to 5 years), we have not seen any postphlebitic sequelae.

Adolescent↗

Content uniformity of microdose tablets (dosage 1 microgram--10 mg) produced by fluid bed granulation of interactive mixtures.

Tablets (100 mg), containing microdose quantities of micronized model drug (1 microgram--10 mg), were produced from interactive powder mixtures which had been fluid bed granulated. Granulation prevents adhesion unit and constituent segregation occurring during compression. Single tablet assays were performed on 100 tablets from each batch. The content of tablets fell within +/- 15% of the mean, and the coefficient of variation was less than 5% (99% confidence) for all batches. Skewness in the content distribution showed little evidence of superpotent tablets and indicated the absence of significant agglomerates of particles of the micronized component. However, there was some indication that the mixtures produced were not totally agglomerate free. These results demonstrate that the true potential of interactive mixing may be realized, provided segregation in the mixture can be eliminated. The distribution of micronized model drug, as a function of carrier particle size, was determined for the different concentration mixtures before and after granulation. When 0.1-2% interactive mixtures were sieved gently, the proportions of micronized material adhering to the different size fractions of carrier were similar. However, the very low concentration mixtures (0.001-0.03%) proved to be relatively unstable, a significant proportion of the micronized component being transferred from the mixtures to the metal surfaces of the sieves. Granulation of the mixtures in a fluidized bed produced a uniform distribution of micronized material throughout the different sized granules. These granules were stable during vibration on the sieves and when compressed. All samples of tablets met the United States Pharmacopeia XXI content uniformity requirements.

Drug Compounding↗

Fetal rat intestinal transplantation: cryopreservation and cyclosporin A.

Successful preservation of small bowel by cryobiologic techniques would increase the feasibility of intestinal transplants. Immunosuppression by Cyclosporin A (CyA) has also increased interest in intestinal transplantation. We have investigated the effect of cryopreservation and immunosuppression in fetal rat intestinal transplantation. Segments of fetal bowel implanted isogeneically into the paravertebral gutter of young rats were found to grow in a high percentage of animals (53% to 100%). Segments frozen to -20 degrees C or -40 degrees C at two rates of cooling, grew isogeneically (50% to 89%), demonstrating the feasibility of cryopreservation. Histologic examination of this bowel showed preservation of structure. When these segments were cooled and implanted allogeneically, no immunosuppressive effect was found. Segments protected by daily CyA administration grew. No synergistic effect was seen by associating CyA and cryopreservation. These experiments suggest the possibility of creating fetal small bowel long-term banking.

Animals↗

Fluidized bed film coating of an ordered powder mixture to produce microencapsulated order units.

Very finely divided particulate salicylic acid (2-5 micrometers) was microencapsulated using conventional fluidized bed coating techniques. The process involved spray coating a preformed ordered mixture, in which the micronized particles are adsorbed on the surface of a coarser carrier material. The mixtures contained 0.1, 1.0 and 5.0% weight of microfine model drug (salicylic acid). Between 75 and 95% of the micronized particles were retained on the carrier surface beneath the film. This process offers a novel method of microencapsulating very fine particulate materials, which may find an application in the production of enteric coated and sustained release microdose products. A recent publication on electrostatic charge interactions in ordered mixtures reported that the addition of a third component can affect the stability of a binary ordered mixture. Addition of 2% talc increased the stability of some mixtures during coating and resulted in the microencapsulation of a significantly greater amount of micronized model drug. A 0.1% salicylic acid binary ordered mixture retained 74% of model drug beneath the film, the 0.1% ternary mixture (2% talc) gave a mean retention of 99%.

Capsules↗

Fluidized bed granulation of an ordered powder mixture.

The phenomenon of ordered unit segregation is of paramount importance in determining the homogeneity of an ordered mixture. This problem can be avoided by using a monodisperse carrier, but it is uneconomic. The fluidized bed granulation of a 0.1% ordered mixture has been studied as a method of reducing the effects of segregation. The ordered units were stable when fluidized and no significant loss of the microfine adsorbed material occurred during processing. The distribution of the minor component in the granules was significantly more uniform than in the original ordered mixtures. The demixing potential (formula: see text) (where p = proportion of cohesive minor component and w is the weight % of carrier material in a particular size range) was used to quantify the distribution of the minor component as a function of particle size. DP is a coefficient of variation and can be directly compared with the specification standard deviation sigma A. Batches of granules were compressed into 100 or 350 mg tablets, containing approximately 100 and 350 micrograms of model drug substance. The weight and content coefficients of variation (c.v.) were determined for 20 tablets. All batches had a weight c.v. less than or equal to 1.5% and a content c.v. less than or equal to 4.6%. Granulation of an ordered mixture greatly reduces the potential for segregation to decrease the mixture homogeneity. It also provides a solution to the problems which may be encountered when the mixing of small quantities of cohesive materials during conventional fluidized bed granulation is attempted.

Drug Compounding↗

Association between HLA-DQB1 and cervical dysplasia in Vietnamese women.

Host genetic background seems to play a key role in cervical carcinogenesis as only a small subset of women infected with high-risk human papillomaviruses (HPVs) develop cervical cancer. The rate of cervical cancer in Vietnamese women is notably high. To explore the association of human leukocyte antigen (HLA)-DQB1 alleles, HPV infection, and cervical dysplasia in this population, cervical smears were obtained from 101 women attending the obstetrics and gynecology clinic of Da Nang General Hospital in Vietnam. Besides the Papanicolaou test, HPV and HLA-DQB1 genotyping were performed using cervical smear DNA. Additionally, a subset of 30 blood samples was used as the gold standard for HLA genotyping. HLA-DQB1 alleles showed no association with HPV infection status. However, a positive association with cervical dysplasia was found for HLA-DQB1*0302 (P= 0.0229, relative risk (RR) = 4.737) and HLA-DQB1*0601 (P= 0.0370, RR = 4.038), whereas HLA-DQB1*0301 (P= 0.0152, RR = 0.221) was found negatively associated. The low diversity of HLA-DQB1 alleles, wide spectrum of HPV genotypes, and high prevalence of HPV 16 and HPV 18 observed in the study population suggest a permissive/susceptible genetic background that deserves further research. Total concordance of HLA-DQB1 genotyping results between blood and cervical cells confirms the potential value of cervical smears as an effective tool for the development of cervical cancer biomarkers.

Adult↗

Characterization of protein-tyrosine kinase activity in the canine prostate.

Following the measurement of the phosphorylation of the substrate poly(Glu80Na,Tyr20) and the analysis of the alkali-resistant phosphorylation of endogenous proteins, the protein-tyrosine kinase of the canine prostate was partially characterized with regard to its subcellular localization, as well as certain kinetic and molecular properties. This kinase was mainly found in the cytosolic fraction (75%); however, its specific activity was similar to that of the residual enzyme present in the particulate fraction. Conditions for optimal activity of both fractions were determined. Under these conditions, several endogenous phosphoproteins (44-63 kilodaltons upon electrophoresis) were alkali resistant and phosphotyrosine was present in all of the major ones (pp63, pp57, pp52, and pp44). The particulate protein-tyrosine kinase activity was partially solubilized (58%) with 0.5% Triton X-100; this percentage was increased to 85% in the presence of 0.25 M KCl. Upon gel filtration, both cytosolic and particulate kinases showed an apparent molecular mass of 44 kilodaltons; these enzymes also phosphorylated similar major alkali-resistant phosphoproteins. The soluble protein-tyrosine kinase, with a sedimentation coefficient of 4.0S and an isoelectric point of 5.5, could be separated from arginine esterase and prostatic acid phosphatase.

Acid Phosphatase↗

Single donor transplantation of fresh and cryopreserved pancreatic fragments into the liver parenchyma in syngeneic rats.

In a series of experiments on syngeneic rat islet (pancreatic fragments) transplantation we demonstrate that direct hepatic transplantation is successful to alleviate streptozotocin induced diabetes with tissue from a single donor. The experimental groups were: recipients of fresh, and cryopreserved pancreatic fragments. The fresh graft was prepared by collagenase digestion. Cryopreserved fragments were further treated by a standard freeze-thaw protocol which consists of slow cooling at 0.3 degrees C/min to -75 degrees C followed by transfer to -196 degrees C, in the presence of 1.4 M Me2SO, and storage at this temperature for one day or 1 wk, and then warming them back to room temperature at a rate of 35 degrees C/min. Streptozotocin-induced diabetes in rats can be reversed by injection of isolated pancreatic fragments from a single donor directly into the liver. No significant difference was observed between the recipients receiving fresh or cryopreserved tissue for 1 day or 1 wk. It is possible that elaborate purification itself is not conducive to successful alleviation of diabetes. This would corroborate the hypothesis that trophic factors are present in impure fragments. The direct infusion of islet fragments into the liver could allow for percutaneous administration in human transplantation.

Animals↗

Complement abnormalities with lower extremities discomfort in Vietnamese immigrants.

The objective was to measure complement C'l esterase inhibitor (CIINH) in a group of Vietnamese outpatients with lower extremities discomfort of undetermined etiology. All 25 female patients were followed between 1992 and 1995. Their age ranged from 24 to 82 years old (mean age, 46.68 +/- 13.77). They presented with unexplained lower extremities discomfort. They were found to have low levels of CIINH (mean, 11.36 +/- 1.44 mg/dL versus control subjects, 15.64 +/- 2.22 mg/dL). Twenty-one patients were treated with oral Danazol 200 mg daily for 1-2 months. The improvement of the symptoms in our patients coincided with increased CIINH level in all of our patients (pretreatment, 11.33 +/- 1.46 mg/dL versus posttreatment, 16.82 +/- 2.98 mg/dL with p < 0.001) and the return to normal functional activity of CIINH associated with and without Danazol treatment. These patients may represent a form of androgen-responsive limited to the lower extremity's discomfort associated with low levels of CIINH, normal levels of Clq and normal ratio of C4d/C4 that differentiated them from angioedema (hereditary or acquired form), having no known precipitating factors or a family history of hereditary angioedema.

Adult↗

Headache and complement C'1-esterase inhibitor deficiency in Vietnamese immigrants living in southern California.

The objective was to measure complement C'1-esterase inhibitor (C1INH) in a group of Vietnamese outpatients with headache. All 51 patients (7 males and 44 females), with either migraine or chronic tension-type headache, were evaluated during 1994 and 1995. Their ages ranged from 15 to 69 years old (mean age, 37.5 years). They were found to have low levels of C1INH (mean, 11 +/- 2 mg/dL versus control subjects, 15 +/- 2 mg/dL with p < 0.0001). Twenty patients (5 males and 15 females) were treated with a low dose of danazol, 200 mg daily for 1-2 months. The improvement of the headache coincided with the return to normal levels of C1INH in all of our patients (pretreatment, 11 +/- 2 mg/dL versus post-treatment, 16 +/- 2 mg/dL with p < 0.001). The levels of C1q and C4d/C4 ratios did not change as a result of treatment with danazol. Our patients may represent a form of androgen-responsive headache, which is associated with low levels of C1INH, normal levels of C1q and normal C4d/C4. It differentiated them from angioedema (hereditary or acquired form); they had no known precipitating factors or a family history of angioedema.

Adolescent↗

Coexisting hyperthyroidism and primary hyperparathyroidism with vitamin D-deficient osteomalacia in a Vietnamese immigrant.

OBJECTIVE: To present the first report of concurrent hyperthyroidism, primary hyperparathyroidism (PHP), and vitamin D-deficient osteomalacia. METHODS: We describe the complicated clinical course in a 65-year-old Vietnamese immigrant, and underlying factors potentially contributing to her condition are discussed. RESULTS: Our patient, who had hyperthyroidism and hypercalcemia, was found to have an inappropriately high level of intact parathyroid hormone (PTH) because of a parathyroid adenoma, detected on a parathyroid scan. With propranolol treatment, however, improvement was noted in both laboratory data--intact PTH, ionized calcium, serum total calcium, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and urinary cyclic adenosine monophosphate--and findings on ultrasonography and nuclear parathyroid scanning. Later, the adenoma was removed surgically. The improvement of PHP after administration of a beta-adrenergic blocker suggested that the parathyroid adenoma in this patient was not completely autonomous. The patient also had vitamin D-deficient osteomalacia that was confirmed by a low serum level of 25-hydroxyvitamin D3 (25OHD3) and by bone histomorphometry. This coexisting condition was caused by the long-term increase in conversion of 25OHD3 to 1,25(OH)2D3 from hyperparathyroidism in a patient with low stores of vitamin D (which were ascribed to aging, liver dysfunction in hyperthyroidism, a vegetarian diet, deprivation of sunlight, and avoidance of dairy products). CONCLUSION: The complex concurrence of hyperthyroidism, PHP, and vitamin D-deficient osteomalacia is rare but possible.

Journal Article↗

Some characteristics of primary hyperparathyroidism in Vietnamese immigrants living in Southern California.

OBJECTIVE: To characterize primary hyperparathyroidism (PHP) in Vietnamese immigrants living in southern California and to summarize the results of treatment. METHODS: We describe 11 patients (8 women and 3 men) with a mean age of 57.91 years who underwent follow-up from 1991 to 1995 after PHP was diagnosed. The patients had no specific complaints. Four patients had a history of kidney stones, and five had chronic hypertension. Only five patients had high levels of total serum calcium; the other six patients had normal or fluctuating levels of total serum calcium. All patients, however, had high levels of intact parathyroid hormone (PTH) and ionized calcium. Preoperatively, parathyroid imaging with technetium-99m sestamibi demonstrated persistently increased parathyroid gland uptake. RESULTS: In all nine patients who underwent surgical treatment, an adenoma was found in the parathyroid glands; two patients refused operative intervention. The mean serum phosphate was in the low-normal range and increased postoperatively (2.70 versus 3.52 mg/dL; P<0.001). The mean serum chloride level also decreased postoperatively (104.62 versus 100.78 mEq/L; P<0.001). The ratio of chloride/phosphate decreased significantly after adenoma removal (39.44 versus 29.21; P<0.001). Six patients received calcium gluconate either alone or in combination with vitamin D supplements for hypocalcemia postoperatively. The other three patients, however--who did not receive calcium supplements postoperatively--had persistently high levels of intact PTH but normal serum Ca++ levels and subsequently were treated effectively with calcium gluconate and vitamin D. CONCLUSION: The presence of hypercalcemia, especially Ca++, and an increased level of intact PTH establishes the diagnosis of PHP. After parathyroidectomy, the persistence of high levels of intact PTH in association with normal serum Ca++ suggested the presence of secondary hyperparathyroidism, which was treated effectively with calcium gluconate and vitamin D. These patients had the same clinical picture as other ethnic groups with PHP, but they needed either calcium alone or calcium and vitamin D supplements after parathyroidectomy because of their bone loss from prolonged PHP.

Journal Article↗

An antineutrophil cytoplasmic autoantibody associated with a propylthiouracil-induced adult respiratory distress-like syndrome: report of a case and review of the literature.

OBJECTIVE: To report the first case of propylthiouracil-induced adult respiratory distress-like syndrome associated with the presence of an antineutrophil cytoplasmic autoantibody. METHODS: We describe the initial manifestations, laboratory findings, and clinical course in a patient and discuss underlying factors potentially contributing to her condition. RESULTS: A 57-year-old woman with hyperthyroidism had an influenza-like illness and vasculitis during propylthiouracil therapy. Three days after she was admitted to the hospital, an adult respiratory distress-like syndrome developed. Results of perinuclear antineutrophil cytoplasmic antibody (pANCA) and antimyeloperoxidase antibody studies were positive. Her condition improved after the introduction of glucocorticoid therapy and the withdrawal of propylthiouracil treatment. The pANCA level, however, remained unchanged 3 months after her dismissal from the hospital. CONCLUSION: The propylthiouracil-induced adult respiratory distress-like syndrome may be a hypersensitivity phenomenon, and the presence of the pANCA could be a marker of a common mechanism of injury that stimulates its production rather than a pathogenic factor responsible for vascular injury in our patient.

Journal Article↗

Pharmaceutical container/closure integrity. IV: Development of an indirect correlation between vacuum decay leak measurement and microbial ingress.

The rational development of a physical test method to evaluate the microbial barrier properties of sterile containers necessitates its correlation to microbiological exclusion. This can be accomplished by direct or indirect correlation. In the former, the proposed physical test is directly compared to microbial challenges using appropriate test units that stimulate container leaks at both high and low probabilities of microbial ingress. Previous work has demonstrated the development of a direct correlation using helium leak rate methods and microbial immersion challenges. An indirect correlation can be established by comparing the proposed physical method to well-defined leakage standards that represent various known levels of microbial ingress. Thus the quality assurance properties of a physical test method can be established by comparison to another physical test method that has been previously characterized. This approach has the distinct advantages of being faster, quantitatively rigorous, and less subject to the vicissitudes, of microbial testing. This approach was demonstrated by comparing the helium leak rate method to vacuum decay testing. Additionally it was demonstrated that vacuum decay testing was a fast and reproducible method for detecting leaks of about 1 to 2 mm. Leaks were simulated by affixing micropipettes into glass vials.

Bacteria↗