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Biomedical subjects

H Nguyen

Publications and source records attributed to H Nguyen.

At least 181 records · Page 10Linked to original sources
PubMed1994

The efficacy of diaspirin crosslinked hemoglobin solution resuscitation in a model of uncontrolled hemorrhage.

Controversy exists whether early aggressive fluid therapy in the setting of uncontrolled hemorrhage worsens outcome by increasing blood loss from injured vessels. Since diaspirin crosslinked hemoglobin (DCLHb) is a vasoactive, oxygen-carrying solution, we compared the effects of DCLHb with other resuscitative fluids on blood loss, hemodynamics, and tissue oxygen delivery in a model of uncontrolled hemorrhage. Anesthetized rats (250-350 g) were subjected to a 50% tail transection and resuscitated 15 minutes later with 1:1 DCLHb, 3:1 lactated Ringer's solution (LR), 1:1 hypertonic saline (7.5% HTS), or 1:1 human serum albumin (8.3% HSA) based on initial volume of blood loss (average 4.7 +/- 0.3 mL/kg). An unresuscitated group served as a control. Cumulative blood loss was measured at 5 hours postresuscitation. By 15 minutes after tail transection, mean arterial pressure (MAP) decreased 19.2 +/- 3.8 mm Hg from the baseline value (102 +/- 5 mm Hg). The DCLHb solution restored and maintained MAP and subcutaneous tissue oxygen tension at baseline values better than all other resuscitative fluids. Although blood loss in DCLHb-treated animals was greater than in unresuscitated animals, it was no different from other resuscitative fluids and less than with HSA. There was no difference in 24-hour survival between all treatment groups. In conclusion, DCLHb elevates MAP but does not exacerbate blood loss or compromise tissue oxygen delivery compared with other resuscitative fluids in this model of uncontrolled hemorrhage.

Animals↗
PubMed1994

Laparoscopic creation of pericardial window.

Malignant pericardial effusions are frequently symptomatic and usually recur after aspiration. Surgical options include pericardiectomy and transthoracic or subxiphoid pericardial window formation and, more recently, thoracoscopic pericardial window formation. The authors report their first four cases of laparoscopic creation of pericardial windows. The treatment has been effective and minimally traumatic.

Aged↗
PubMed1994

In vitro susceptibilities of rapidly growing mycobacteria to newer antimicrobial agents.

The in vitro antimicrobial susceptibilities of 42 isolates of rapidly growing mycobacteria (Mycobacterium fortuitum, M. chelonae, and Mycobacterium species [other than M. fortuitum and M. chelonae]) to nine quinolones, including newer agents, two new aminoglycosides, and an aminocyclitol (trospectomycin) were determined by a broth microdilution method. The new quinolones, PD 117596, PD 127391, and PD 117558, showed excellent in vitro activities against M. fortuitum (MICs for 90% of isolates [MIC90s], 0.06, 0.06, and 0.12 microgram/ml, respectively). The MIC90 of ciprofloxacin for M. fortuitum was 0.5 microgram/ml. Only 14 to 28% of isolates of M. chelonae were susceptible to various quinolones. Most isolates of all three species were susceptible to the new aminoglycosides SCH 21420 and SCH 22591. The MIC90s of trospectomycin were 8 micrograms/ml for M. chelonae, 32 micrograms/ml for Mycobacterium species, and > 64 micrograms/ml for M. fortuitum.

4-Quinolones↗
PubMed1994

Effects of wake and sleep stages on the 24-h autonomic control of blood pressure and heart rate in recumbent men.

Fifteen recumbent young health volunteers underwent 24-h beat-to-beat blood pressure (BP) and interbeat interval (IBI) recordings to explore the effects of wake and polygraphically recorded sleep on the nyctohemeral variations in the spectral frequency components of BP and IBI and in the arterial baroreflex sensitivity (BRS), independent of the confounding effects of changes in posture and physical activity. Spectral analysis of BP and IBI provided markers of sympathetic and vagal controls and of arterial BRS. When falling asleep, the low-frequency (LF) BP and IBI components showed a marked decrease while there was a clear-cut increase in the high-frequency (HF) IBI component. In contrast, only a slight nighttime rapid eye movement-related arterial BRS increase was observed. The final morning awakening induced a pronounced decrease in arterial BRS and the HF IBI component while there was a marked rise in the LF BP component. Hence, a clear 24-h variation in sympathetic and vagal tone but not in arterial BRS persists, independent of changes in activity and position.

Adolescent↗
PubMed1994

Does cardiac denervation affect the short-term blood pressure variability in humans?

OBJECTIVE: To explore the repercussion of cardiac denervation on the short-term blood pressure variability in humans, in order to assess the extent to which the variability of blood pressure is linked to the variability of heart rate. METHODS: Beat-to-beat blood pressure and RR interval time were recorded in 16 heart-transplanted patients and were compared with those of 10 healthy control subjects in the resting supine, sitting and standing positions. Blood pressure and RR interval variabilities were assessed by spectral analysis. RESULTS: The total blood pressure power and the sitting very low-frequency, low-frequency, low-frequency and high-frequency blood pressure variability were similar in the heart-transplanted patients and in the controls, despite a marked reduction in the RR interval variability in the heart-transplanted patients. However, the heart-transplanted patients had lower standing low-frequency blood pressure variability than the control subjects. Moreover, very low-frequency and low-frequency RR interval variabilities reappeared in the long-term heart-transplanted patients but not in the short-term heart-transplanted patients (range of time after transplantation 53-124 and 3-25 months, respectively). CONCLUSIONS: Short-term RR interval fluctuations are not mandatory for the maintenance of normal blood pressure variability in the supine and sitting positions, but may contribute to the increase in the low-frequency blood pressure variability which occurs normally in the standing position. Moreover, the long-term heart-transplanted patients had increased RR interval variability, which may have been caused by the reappearance of limited autonomic cardiac modulation. However, this increased RR interval variability did not affect the corresponding blood pressure variability.

Blood Pressure↗
PubMed1994

Chemical hypoxia increases junctional permeability and activates electrogenic ion transport in human intestinal epithelial monolayers.

BACKGROUND: The intestinal epithelial tight junction restricts the paracellular permeation of ions and nonelectrolytes. We hypothesized that this function could be altered or disrupted during cellular adenosine triphosphate (ATP) depletion (chemical hypoxia). METHODS: T84 monolayers grown on permeable supports were studied by electrophysiologic and flux techniques. Mitochondrial and glycolytic inhibitors were used to deplete cellular ATP. RESULTS: Transepithelial resistance to passive ion flow (R) rapidly decreased to 36% of control values with chemical hypoxia, an effect that was reversible if control conditions were restored within 1 hour. As ATP levels declined, a transient Cl- secretory current developed but disappeared as ATP levels reached 5% of control values. Both the secretory current and fall in R were abolished when ambient Cl- was replaced with gluconate but not with Br- or NO3-, or when N-methylglucamine replaced Na+. Transepithelial flux of mannitol but not inulin was increased during ATP depletion. Dual Na(+)-mannitol flux analysis confirmed that the decrease in R was due to an increase in paracellular, not transcellular, permeability. Dilution potentials indicated altered charge selectivity of the junctional pathway. CONCLUSIONS: Chemical hypoxia in intestinal epithelial monolayers alters but does not disrupt the permselectivity properties of the junctional complex.

Adenosine Triphosphate↗
PubMed1993

Intraoperative high-dose rate interstitial irradiation of hepatic metastases from colorectal carcinoma. Results of a phase I-II trial.

BACKGROUND: Resection of liver metastases from colorectal carcinoma can be curative. Unresectable but liver-confined metastases might be ablated by high-dose radiation with a similar curative result. METHODS: At Georgetown University Hospital, 22 patients with unresectable hepatic metastases from colorectal carcinoma underwent 24 interstitial irradiation procedures at laparotomy in a Phase I-II study. A single dose was administered with a high-dose rate iridium-192 afterloader. Dose to the tumor periphery was 20 Gy, 25 Gy, and 30 Gy in 13, 9, and 2 procedures, respectively. RESULTS: No acute or chronic radiation toxicity has occurred at a median follow-up of 11 months. Median actuarial local control at irradiated sites was 8 months, with 26% actuarial local control at 26 months by computed tomography (CT) or magnetic resonance imaging (MRI) scanning. In the two patients undergoing two procedures each, a second biopsy of previously irradiated areas demonstrated tumor eradication. CONCLUSIONS: This innovative, radical approach to unresectable colorectal hepatic metastases proved safe. Additional study is needed to determine whether interstitial irradiation is as effective as surgical resection, or whether it alters the natural history of the disease or longevity.

Adult↗
PubMed1993

Basic fibroblast growth factor expression in human bone marrow and peripheral blood cells.

We have shown previously that basic fibroblast growth factor (bFGF) is a mitogen for human bone marrow (BM) stromal cells and that bFGF stimulates myelopoiesis in primary BM cultures. In this article, we demonstrate the presence of bFGF in two cell lineages in human BM and peripheral blood as well as the deposition of bFGF into the extracellular matrix of BM stromal cell cultures. In immunofluorescence experiments on BM and peripheral blood smears, megakaryocytes and platelets stained strongly for bFGF, whereas weaker staining was observed in immature and mature cells of the granulocyte series. The presence of bFGF in platelets was confirmed by enzyme-linked immunosorbent assay as well as by immunoprecipitation followed by immunoblotting. bFGF was synthesized by BM stromal cell cultures and was found either cell associated or localized in the nucleus and the nucleoli, and its location was dependent on the fixation procedure used. Addition of exogenous bFGF to stromal cells showed the presence of extracellular binding molecules for this cytokine. bFGF could be released from these sites by soluble heparin or phosphatidylinositol-specific phospholipase C. This study supports the role of bFGF as a stromal cell mitogen and stimulator of myelopoiesis. The data indicate that the stromal cells produce bFGF and that their extracellular matrix can serve as a reservoir for this growth factor. In addition, the results suggest a possible involvement of bFGF in platelet function as well as in megakaryocytopoiesis.

Antibodies, Monoclonal↗
PubMed1993

Kinetic study of collagen fixation with polyepoxy fixatives.

A new biomaterial has been developed by fixing native collagen with a polyepoxy compound (PC) fixative. In this study, bovine internal thoracic arteries were fixed with PC under various conditions to help understand the kinetics of the collagen-PC reactions and optimize the fixation process. At predetermined time intervals, small samples were cut from the arteries to determine the quantities of the remaining unreacted amino acids in the collagen. Temperature, concentration, and solution pH were among the key parameters studied. The overall fixation rate was found to be reaction-rate controlled, as the rate of fixation was relatively slow compared with the rate of diffusion of PC. As might be expected, the reaction rate was favored by a higher temperature, concentration, and solution pH. A kinetic model, with a 2.5th reaction order with respect to the reactive functional groups of collagen and a first order with respect to PC, was developed that gave a good fit to the experimental data. Based on this model, the degree of fixation, X, as a function of time, t, is given by (1 - X)-1.5 = 1 + Kt, where K is a constant related to the initial concentrations and the reaction rate constant.

Amino Acids↗
PubMed1993

Taxol sensitizes human ovarian cancer cells to radiation.

Taxol is an exciting antineoplastic agent with a novel mechanism of action. This study was designed to explore the potential use of taxol as a radiation sensitizer. Three human ovarian cancer cell lines were used: BG-1, SKOV-3, and OVCAR-3. These cell lines were treated in the proliferative and confluent state with taxol doses of 0.0001X, 0.0005X, 0.001X, 0.005X, and 0.01X peak plasma concentration of taxol for 90 min and then irradiated either 24 or 48 hr later. Doses of cobalt60 were 0, 2, 5, 8, and 10 Gy. ATP bioluminescence assays were performed on Day 7 after irradiation. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with t test and analysis of variance was performed. Taxol was found to have a significant radiosensitizing effect on all cell lines. Proliferating cells were more sensitive to taxol, radiation, and the combination than confluent cells. Treatment of proliferating cells with taxol 48 hr prior to irradiation had a greater radiosensitizing effect than treatment 24 hr prior to irradiation. In summary, taxol is a potent radiosensitizer in ovarian cancer cell lines and should be considered for further study.

Adenosine Triphosphate↗
PubMed1993

Taxol as a radiation sensitizer: a flow cytometric study.

Taxol is an exciting antineoplastic agent with a novel mechanism of action. Taxol has been shown to prolong the G2/M phase of the cell cycle. This cell cycle perturbation has been the explanation given for the radiation-sensitizing effects seen with taxol in vitro. The aim of this study is to evaluate the cell kinetics of the BG-1 human ovarian cancer cell line after treatment with nontoxic doses of taxol and radiation (RT). This cell line was treated in the proliferative state for 90 min with 5 nM taxol and then irradiated 48 hr later with 2 Gy of Cobalt60. Flow cytometric evaluations of cell cycle perturbations were performed at 24-hr intervals from 0 through 216 hr. ATP cell viability assay was performed in parallel to obtain survival data. Survival data was fit to the linear-quadratic model and mean inactivation dose D was calculated. Data analysis with t test was performed. At this nontoxic dose of taxol no cell cycle perturbations as compared to control were seen. Radiation sensitization was still found. Sensitizer enhancement ratio was 2.3 at 10% survival. The RT-related G2/M block peaked at 24 h after RT and then resolved. The combination of taxol and radiation resulted in a large prolonged block in G2/M that did not resolve through the duration of the experiment. In summary, taxol sensitized cells to radiation at a dose that was not cytotoxic and that did not cause cell cycle perturbations.

Cell Survival↗
PubMed1993

Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. I. Development and initial characterisation of the model.

A simple and reliable animal model to quantify interleukin-1 (IL-1) production at a site of inflammation has been developed and characterised. This model involves the subcutaneous implantation of sterile Teflon chambers (30 mm x 10 mm diameter) into the backs of mice. After 14 days, a straw coloured transudate fluid was present in the lumen of the implanted chamber which was withdrawn for the determination of baseline measurements of various inflammatory parameters. A localised chronic inflammatory response was then induced in the chambers by injection of 1% zymosan or Bordetella pertussis vaccine (BPV) (in presensitised animals). The local inflammatory reaction in the chamber, over a 30 day time course, was characterised by leucocyte infiltration, and marked increases in protein, prostaglandin E2, IL-1 and IL-6 concentrations in the chamber fluid. A rapid increase in plasma concentrations of the acute-phase reactant serum amyloid P (SAP) also occurred. This model allows repeated samples to be obtained from the same animal for the assessment of inflammatory parameters and may be useful for investigating the mechanisms controlling the production of IL-1 during the inflammatory response in vivo.

Animals↗
PubMed1993

Interleukin-1 (IL-1) production in a mouse tissue chamber model of inflammation. II. Identification of (tissue) macrophages as the IL-1 producing cells and the effect of anti-inflammatory drugs.

We have used our newly described mouse tissue chamber model [1], to investigate the process of IL-1 production in more detail. The inflammatory reaction in the tissue surrounding the implanted chambers was investigated histologically and by using the polymerase chain reaction (PCR). The inflammatory response included influx of leucocytes into the granuloma surrounding the tissue chamber, expression of IL-1 beta on macrophages present in the inflamed tissue and an increase in the mRNA coding for IL-1 beta and IL-6 proteins in the granuloma. The effects of three anti-inflammatory or immunosuppressive drugs, prednisolone, indomethacin and cyclosporin A, on IL-1 beta and PGE2 production in zymosan and Bordetella-pertussis-vaccine (BPV)-challenged tissue chambers were also examined. Oral treatment with prednisolone and cyclosporin A of zymosan-challenged animals showed a dose-dependent reduction of IL-1 beta concentrations, but no effect of indomethacin. Both prednisolone and indomethacin dose-dependently reduced PGE2 concentrations to control levels, while cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). In drug-treated BPV-challenged animals, prednisolone and cyclosporin A also showed a dose-dependent reduction of IL-1 beta, while indomethacin was again ineffective. Prednisolone and indomethacin also dose-dependently reduced the PGE2 concentrations to control levels, whereas cyclosporin A was effective only at the highest dose tested (100 mg/kg/day p.o.). This model will be useful for investigating the mechanisms controlling the production of IL-1 beta from the mRNA level to the secretion of mature biologically active protein [1], and in the search for new drugs which could selectively interfere with this process.

Animals↗
PubMed1993

Sleep quality and continuous, non-invasive beat-to-beat blood pressure recording.

OBJECTIVE: To investigate the effects of continuous, non-invasive, beat-to-beat finger blood pressure monitoring on sleep in healthy men. DESIGN: After 1 night of habituation to the laboratory environment, which consisted of the placement of electroencephalographic equipment without recording, polygraphic sleep recordings were performed during two consecutive nights (nights 1 and 2) in 15 healthy men (mean +/- SD age 25 +/- 6 years). Blood pressure was recorded continuously for 24 h from the end of night 1 to the end of night 2. RESULTS: The blood pressure recording procedure caused a decrease in the amount of rapid eye movement (REM) sleep and increased the duration of nocturnal awakenings. Consequently, sleep efficiency was decreased by approximately 5%. The blood pressure measurements did not affect the duration of light and of deep sleep. Although the respective predominance of deep sleep and of REM sleep at the beginning and at the end of the sleep period were preserved during the night of blood pressure recording, the blood pressure recording procedure hampered the rise in REM sleep during the final two thirds of the sleep period. CONCLUSION: In healthy young men continuous, non-invasive, beat-to-beat finger blood pressure monitoring induced modest reductions in sleep efficiency of similar magnitude to those observed previously with non-invasive ambulatory blood pressure monitoring.

Adult↗
PubMed1993

Comparative efficacies of cilofungin (Ly121019) and amphotericin B against disseminated Candida albicans infection in normal and granulocytopenic mice.

The efficacies of cilofungin (Ly121019), a semisynthetic lipopeptide antifungal agent, and amphotericin B in the treatment of disseminated candidiasis in normal and neutropenic mice were compared. In mice infected with 2 x 10(6) CFU of Candida albicans, treatment with cilofungin in twice-daily doses of 25 or 35 mg/kg of body weight by intraperitoneal injection for 10 days gave survival rates of 83 and 90%. In contrast, there was 97% mortality in infected controls receiving 2 x 10(6) CFU intravenously and 93% survival in mice treated with 1 mg of amphotericin B per kg once a day. Mice rendered granulocytopenic by the administration of cyclophosphamide showed survival rates of 83 and 80% when treated with 25 or 35 mg of cilofungin per kg for 10 days compared with 43% survival rate in mice treated with 1 mg of amphotericin B per kg (P = 0.0030 and P = 0.0080, respectively). Similar results were obtained when the two antifungal agents were administered for a period of 30 days. Administration of 25 or 35 mg of cilofungin per kg twice a day to granulocytopenic mice receiving 10(6) CFU of C. albicans gave survival rates of 93% and 93% compared with 53% survival with amphotericin B. With 15 mg of cilofungin per kg twice a day for 10 days, a survival rate of 43 to 50% was observed in both normal and granulocytopenic mice compared with 56 and 60%, respectively, when this dosage was continued for 30 days. Cilofungin eradicated C. albicans from the kidneys, spleens, and livers of surviving animals. No toxic effects were observed with any of the dosage regimens used. The clearance of C. albicans from the kidneys, spleens, livers, and brains in normal mice was studied following infection with 5 x 10(5) and 1 x 10(5) intravenously. The mice in the treatment groups received 25 mg of cilofungin per kg twice a day for 10 days. In 8 to 12 days, this treatment was able to clear the organisms from the kidneys, spleens, and livers of mice infected with 5 x 10(5) C. albicans. Mice infected with 10(5) C. albicans and treated with cilofungin (25 mg/kg) twice a day for 10 days had no organisms in the kidney, spleen, and liver at days 8, 2, and 8, respectively. There was 1-log-unit reduction in C. albicans counts in brain tissue from mice of one of the treated groups between 2 h and 2 days postinfection, after which the numbers of organisms remained the same until day 12. These data demonstrate the efficacy of cilofungin in the treatment of disseminated C. albicans infections in normal and granulocytopenic mice. The treatment regimen used in this study was able to clear C. albicans from the kidneys, spleen, and liver but not from brain tissue.

Agranulocytosis↗
PubMed1993

Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop.

The -300 region of the interleukin 1 beta (IL-1 beta) promoter contains a functional NF-kappa B binding site composed of the decamer sequence 5'-GGGAAAATCC-3'. Probes representing the -300 region or the NF-kappa B site alone interacted with NF-kappa B proteins present in phorbol myristate acetate-, lipopolysaccharide-, or Sendai virus-induced myeloid cell extracts as well as recombinant NFKB1 (p50) and RelA (p65); furthermore, NF-kappa B protein-DNA complex formation was dissociated in vitro by the addition of recombinant I kappa B alpha. Mutation of the NF-kappa B site in the context of the IL-1 beta promoter reduced the responsiveness of the IL-1 beta promoter to various inducers, including phorbol ester, Sendai virus, poly(rI-rC), and IL-1 beta. A 4.4-kb IL-1 beta promoter fragment linked to a chloramphenicol acetyltransferase reporter gene was also preferentially inducible by coexpression of individual NF-kappa B subunits compared with a mutated IL-1 beta promoter fragment. When multiple copies of the IL-1 beta NF-kappa B site were linked to an enhancerless simian virus 40 promoter, this element was able to mediate phorbol ester- or lipopolysaccharide-inducible gene expression. In cotransfection experiments, RelA (p65) and c-Rel (p85) were identified as the main subunits responsible for the activation of the IL-1 beta NF-kappa B site; also, combinations of NFKB1 (p50) and RelA (p65) or c-Rel and RelA were strong transcriptional activators of reporter gene activity. The presence of a functional NF-kappa B binding site in the IL-1 beta promoter suggests that IL-1 positively autoregulates its own synthesis, since IL-1 is a strong inducer of NF-kappa B binding activity. Thus, the IL-1 beta gene may be considered as an important additional member of the family of cytokine genes regulated in part by the NF-kappa B/rel family of transcription factors.

Base Sequence↗
PubMed1993

In vitro evaluation of the novel chemotherapeutic agents U-73,975, U-77,779, and U-80,244 in gynecologic cancer cell lines.

U-73,975 (U-73), U-77,779 (U-77), and U-80,244 (U-80) are analogs of the potent antitumor compound CC-1065. This class of drugs act as alkylating agents binding to DNA preferentially. Using the ATP-chemosensitivity assay, this study was designed to compare the potencies of U-73, U-77, and U-80 with cisplatin (DDP) or adriamycin (DXR) in 10 gynecologic cancer cell lines. The mean IC50s were: U-73, 0.173 +/- 0.115 ng/ml; U-77, 0.650 +/- 0.209 ng/ml; U-80, 3.0 +/- 3.0 ng/ml; DDP, 4.40 +/- 2.83 micrograms/ml; and DXR, 0.286 +/- 0.040 micrograms/ml. U-73 appears the most potent analog, being 10(3) to 10(4) times more cytotoxic than DDP and DXR. U-77 and U-80 were somewhat comparable, demonstrating approximately 10(2) to 10(3) greater potency than DDP and DXR. All the cervical, endometrial, and ovarian cell lines were sensitive to U-73, with decreasing sensitivity to U-77, U-80, DXR, and DDP in that order. U-73 as well as the other analogs appear promising chemotherapeutic agents.

Adenosine Triphosphate↗