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Biomedical subjects

D M Nguyen

Publications and source records attributed to D M Nguyen.

35 records · Page 2Linked to original sources
PubMed1996

The role of physical medicine and rehabilitation in pain management.

Physical medicine and rehabilitation frequently use the interdisciplinary team approach to the management of pain in the elderly because this would also address the psychosocial and functional deficits resulting from the pain symptom. The team prescribes a combination of pharmacologic agents, cognitive-behavioral therapies, physical modalities, occupational therapy, and physical therapy in the treatment plan. Management of patients with pain resulting from compression fracture and spinal stenosis is discussed also.

Aged↗
PubMed1995

The management of chylothorax/chylopericardium following pediatric cardiac surgery: a 10-year experience.

We reviewed the management of 25 cases of chylothorax/chylopericardium (CT/CP) in 24 patients (9 females, 15 male; 3 days to 11-years-old) following 1605 cardiothoracic procedures (incidence of 1.5%) between January 1984 and December 1993 at our institution. The surgical procedures preceding the occurrence of lymph leak included ligation of patent ductus arteriosus (6 patients), coarctation/double aortic arch repairs (3), complex intracardiac repairs (11), and systemic to pulmonary shunts (5). There were 3 CPs and 22 CTs. All of the patients were initially treated nonsurgically with diet modification using either total parenteral nutrition (TPN) or enteral low fat solid food or enteral elemental diet supplemented with intravenous lipid emulsion. Twenty-one cases (84%) responded to conservative therapy. Of those, 15 had TPN as the initial treatment; the average duration of lymph leak was 13.7 (range 7 to 30) days and the average maximal lymph leak was 39.4 (range 15 to 130) mL/kg per day. The other six cases had low-fat enteral diet as the initial treatment, four resolved completely. Two with high-central venous pressure had to be switched to TPN prior to complete resolution. The average duration of lymph leak in this subgroup was 30 (range 12 to 56) days with the average maximal lymph leak was 30.1 (range 8.5 to 59) mL/kg per day. Excluding these two cases, the average lymph leak of the rest of the group was very compatible to the TPN group of 15 days. Lymphocytopenia and hyponatremia were frequently seen during CT/CP (47.6% and 43%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Surgical Procedures↗
PubMed1994

Quantitative sweat testing using acetylcholine for direct and axon reflex mediated stimulation with silicone mold recording; controls versus neuropathic diabetics.

Sweat glands were stimulated by iontophoresed acetylcholine (ACh). Using a two-chamber capsule, one group of sweat glands was stimulated directly by ACh, and another stimulated indirectly via axon reflexes. Sweat droplets were recorded with a silicone mold and counted by a dissecting microscope and a computerized scanner. Responses from 32 diabetics with generalized somatic peripheral neuropathy were compared with 32 controls. Counting sweat droplets by computerized scanning was more accurate than by microscope. The numbers of droplets, their total areas, and mean areas were all larger in the direct response. Counts of droplet numbers was more diagnostically useful than measuring the total area and the mean areas of the droplets. There was a high correlation between droplet numbers of the direct and the indirect sweat responses. Droplet number counts of the direct response had a slightly higher diagnostic yield than those of the technically more complicated indirect response: for a specificity of 95%, the direct response had a sensitivity of 55%, the indirect being 50%.

Acetylcholine↗
PubMed1993

Lectin-dependent cell-mediated cytotoxicity and natural killer function in rejecting and infected lung allografts.

Differentiation between rejection and infection of lung allografts remains difficult. The effects of these two pathologic entities on the cytolytic activity of bronchoalveolar lavage (BAL) and PBL were investigated. Left lung allotransplantation was performed on 16 mongrel dogs of which 12 were available for complete studies. All animals received CA, AZA, and PRED for 2 weeks. Four grafts developed left lower lobe Gram negative pneumonia. The eight remaining recipients progressed gradually to severe rejection after acute reduction of immunosuppression. Cytolytic activity of blood and left lung BAL lymphocytes was quantitated by the natural killer (NK) and lectin-dependent cell-mediated cytotoxicity (LDCMC) assays. Two additional groups serving as controls were either given a 10-day course of immunosuppressants or had right lower lobe pneumonia induced by transbronchial inoculation of gram negative bacteria. Immunosuppressed control animals showed significant depression of PBL and BAL lymphocyte LDCMC and NK activity. Similarly, BAL lymphocytes expressed very low LDCMC in normal allografts (2.8 +/- 0.8%). Once rejection developed and progressed, LDCMC became significantly higher (15.6 +/- 2.2 and 52.7 +/- 2.8% in mild and severe rejection, respectively). There was no detectable NK activity in rejecting lung allografts. BAL lymphocytes from infected allografts, on the other hand, showed an elevation of both NK and LDCMC activity (9.1 +/- 1.1 and 14.6 +/- 1.0%, respectively). Similarly, bacterial pneumonia in control animals manifested an increase in NK and LDCMC activity in lung and blood. PBL lymphocytes of lung allograft recipients, however, had increased NK and LDCMC activity in both rejection and infection. LDCMC/NK activity ratio (LM/NK index) of lung lymphocytes was significantly higher in rejecting allografts (11.2 +/- 1.0 and 12.4 +/- 1.6 for mild and severe rejection, respectively) than in infected ones (1.2 +/- 0.3, P < 0.0001). It appears, from this study, that rejection of the lung allograft results in alterations in BAL lymphocyte phenotypes and functions that differ from those associated with bacterial infection. Such differences may be useful in distinguishing episodes of acute allograft rejection from bacterial infection.

Animals↗
PubMed1992

Effect of cardiopulmonary bypass on circulating lymphocyte function.

Extracorporeal cardiopulmonary bypass (CPB) has been associated with a wide variety of immunological derangements, including a transient postoperative impairment of lymphocyte function. We examined changes in phenotypic and nonspecific cytotoxicity of peripheral blood mononuclear cells after extracorporeal CPB. The peripheral blood samples obtained from 10 patients were subjected to natural killer and cytotoxic T lymphocyte activity assay before and at intervals after CPB. Phenotypic analysis of peripheral blood lymphocytes was performed in 5 patients before and immediately after CPB. We observed a significant increase in peripheral blood CD8+ cells (cytotoxic/suppressor T lymphocytes) (16.1% +/- 2.5% versus 22.5% +/- 2.1%; p less than .005) and a decrease in CD4+ cells (helper/inducer T lymphocytes) (46.1% +/- 3.5% versus 36.1% +/- 3.5%; p less than 0.02) immediately after extracorporeal circulation. The CD8/CD4 ratio in peripheral blood was significantly increased immediately after bypass (0.53 versus 0.80; p less than 0.001). No significant changes in percentages of other leukocyte subsets in peripheral blood were noted. The activity of cytotoxic T lymphocytes and natural killer cells in peripheral blood was impaired on postoperative days 1 and 3 but was restored to preoperative values by removal of mononuclear phagocytes from these cells. The decrease in natural killer cell and cytotoxic T lymphocyte activity in peripheral blood may signify a temporary impairment of the effector arm of the cell-mediated immunity in the post-operative period. The observed changes in peripheral blood phenotype and function may be involved in early organ injury and infectious complications after CPB.

Adult↗
PubMed1991

Altered cellular immune function in the atelectatic lung.

Pulmonary atelectasis is common and may predispose the lung to infection. We have previously shown that atelectasis impairs alveolar macrophage antibacterial function. This study examines the effect of atelectasis on the cytotoxic function of lymphocytes harvested from the bronchoalveolar space of atelectatic lung segments by bronchoalveolar lavage. Specifically, we studied natural killer and lectin-dependent cell-mediated cytotoxicity in peripheral blood and bronchoalveolar lavage lymphocytes from the atelectatic lower lobes and contralateral normal lobes in a group of 8 dogs. We observed a decline of natural killer and lectin-dependent cell-mediated cytotoxicity to 62.7% and 61.5%, respectively, of preatelectasis control values in the affected lung lobes (p less than 0.01). Simultaneous measurements of cytotoxic activity of bronchoalveolar lavage lymphocytes harvested from the unaffected contralateral normal lungs were comparable with control values. On the other hand, natural killer and lectin-dependent cell-mediated cytotoxicity activities in peripheral blood lymphocytes were significantly increased in animals having right lower lobe atelectasis (166.7% and 154.7% of pretreated normal control, respectively, p less than 0.01). Atelectasis was also associated with an influx of polymorphonuclear leukocytes into the bronchoalveolar compartment. These findings confirm the presence of natural killer cells and cytotoxic lymphocytes in the bronchoalveolar compartment and demonstrate an atelectasis-induced impairment of local bronchoalveolar lymphocyte function. Such a dysfunction of local lung cellular host defenses may render the atelectatic lung susceptible to infection.

Animals↗
PubMed1991

The reversibility of impaired mucociliary function after lung transplantation.

Impairment of mucociliary function occurs after lung transplantation and may predispose patients to repeated pulmonary infections. The purpose of this study is to determine whether and how soon such mucociliary function may recover. Ten dogs underwent left lung autotransplantation. Within 3 weeks five of these dogs underwent study for proximal airway clearance by observation through a bronchoscope of the movement of carbon particles placed at different locations on the tracheobronchial mucosa. The mechanical properties of collected mucus from specific sites were determined by magnetic rheometry. The right lung, which was not operated on, served as a paired control. Similar studies were conducted in the remaining five dogs at 12 weeks after autotransplantation. Lung autotransplantation caused significant depression of proximal airway clearance and a 35% increase in mucous rigidity (p = 0.05) soon after operation. At 12 weeks after operation, there was a partial recovery of proximal airway clearance. Mucous changes were no longer consistent. Histologic and electron microscopic examinations initially revealed focal denudation of ciliated cells and loss of the bronchial glands. At 12 weeks there was a regeneration of cilia and a reappearance of the bronchial glands. We conclude that the mucociliary function, observed to be depressed early after lung autotransplantation, recovers partially during the late postoperative period. Thus the mucociliary functional recovery should be attributed to revascularization rather than to reinnervation, since the latter is unlikely to occur during this period.

Anastomosis, Surgical↗
PubMed1988

Inhibition of natural killer cell-mediated lysis of tumor cells by normal and regenerating bone marrow.

The natural killer (NK) cells which can lyse certain tumor cells during brief incubation in vitro have also been postulated to be the cells responsible for natural resistance to transplanted hemopoietic cells in vivo. To test this hypothesis, we have now measured: 1) the ability of bone marrow cells to compete with tumor cells as targets for spleen NK cells and 2) the effect of a brief incubation with spleen cells on the hemopoietic grafting potential of bone marrow cells. Firstly, when CBA/J mouse spleen cells were incubated with 51Cr-labelled YAC tumor cells together with DBA/2 mouse bone marrow cells, tumor cell lysis was reduced compared with incubation of spleen cells with tumor cells alone. Tumor cell lysis was even less when post-irradiation regenerating bone marrow was used. Secondly, C57B1/6 mouse bone marrow cells incubated with an excess of DBA/2 mouse spleen cells showed a reduced ability to produce hemopoietic spleen colonies in irradiated 129/J mice, whereas incubation with either thymus cells or fewer spleen cells produced no such effect. The results show that, when incubated with spleen cells under the conditions of a standard NK cell assay, regenerating bone marrow cells competitively inhibit the killing of YAC tumor cells and bone marrow progenitor cells are rendered ineffective in their hemopoietic colony-forming potential (CFU-s). These findings suggest that certain hemopoietic progenitor cells and YAC tumor cells can both serve as targets for NK cells, consistent with the view that the spontaneous cytolysis of tumor cells in vitro and natural resistance to bone marrow transplantation in vivo are mediated by cells of a common lineage.

Animals↗
PubMed1988

Genetic mapping and physiological consequences of metE mutations of Bacillus subtilis.

Three metE mutations of Bacillus subtilis, which cause cells to have a 25- to 200-fold decrease in L-methionine S-adenosyltransferase (EC 2.5.1.6) activity, were mapped between bioB and thr. The corresponding three metE mutants contained three- to fourfold less intracellular S-adenosylmethionine (SAM) but at least sevenfold more methionine than the metE+ strain when grown in synthetic medium. This indicates a strong feedback control of SAM on its synthesis. However, only the metE2 strain, with the lowest SAM concentration, grew at a slightly lower rate than the parent, which showed that an intracellular concentration of about 25 microM SAM was critical for growth at the normal rate. Neither DNA methylation (measured by bacteriophage luminal diameter 105 restriction) nor sporulation was affected at this low SAM concentration. Addition of methionine to the growth medium caused an increase in the pool of SAM in some but not all metE mutants. Coaddition of adenine did not change this result. However, the extent of sporulation (induced by mycophenolic acid) was decreased 50-fold in all mutants by the addition of methionine and adenine. Therefore, the combination of methionine and adenine suppresses sporulation regardless of whether it causes an increase in the level of SAM.

Adenine↗
PubMed1986

Simultaneous external subretinal fluid drainage and intravitreal gas injection in nonvitrectomized eyes with a special 27-gauge needle.

In 12 patients with retinal detachment requiring a scleral buckle, simultaneous external subretinal fluid drainage, and intravitreal gas injection were performed to prevent "fishmouthed" retinal breaks in six patients and to achieve more complete drainage of subretinal fluid in six others with chronic inferior detachments. To simplify this technique in all of these nonvitrectomized eyes, we used a special 27-gauge needle sutured to the sclera.

Drainage↗
PubMedDate not supplied

Sequential 5-Aza-2 deoxycytidine-depsipeptide FR901228 treatment induces apoptosis preferentially in cancer cells and facilitates their recognition by cytolytic T lymphocytes specific for NY-ESO-1.

Global alterations in chromatin structure profoundly influence gene expression in thoracic neoplasms, silencing tumor suppressors while facilitating the expression of various cancer testis antigens such as NY-ESO-1. Although recent studies have shown that histone deacetylase inhibitors can potentiate tumor suppressor gene induction mediated by demethylating agents in cancer cells, the ability of these agents to augment cancer testis antigen expression have not been fully defined. The authors designed the current study to determine whether the histone deacetylase inhibitor, depsipeptide FR901228 (DP), could enhance NY-ESO-1 induction mediated by the DNA demethylating agent 5-Aza-2'-deoxycytidine (DAC) in cell lines established primarily from thoracic cancers. Quantitative reverse-transcriptase polymerase chain reaction analysis revealed that, under exposure conditions potentially achievable in clinical settings, DAC dramatically induced NY-ESO-1 expression in cultured cancer lines. DP alone mediated negligible target gene induction but significantly augmented DAC-mediated induction of NY-ESO-1. After DAC or sequential DAC-DP treatment, HLA-A*0201 cancer cells were recognized by an HLA-A*0201 CTL specific for NY-ESO-1. Although sequential DAC/DP exposure did not uniformly enhance immune recognition of target cells compared with DAC alone, this treatment mediated profound induction of apoptosis in cancer cells but not normal human bronchial epithelia. The apoptotic effects of DAC, DP, or sequential DAC-DP did not correlate in an obvious manner with histology, or the magnitude of NY-ESO-1 induction in cancer cells. Although the mechanisms have not been fully defined, sequential DAC-DP treatment may be a novel strategy to augment antitumor immunity in cancer patients.

Anti-Bacterial Agents↗
PubMedDate not supplied

Successful repair of recurrent coarctation after neonatal heart transplantation.

Neonatal orthotopic heart transplantation is an attractive primary surgical therapy for severe uncorrectable congenital heart defects such as variants of the hypoplastic left heart syndrome. Aortic arch reconstruction is frequently required to repair the hypoplastic aortic arch and the coarctation at the time of graft implantation. Residual coarctation of the aorta after neonatal heart transplantation for such a condition has satisfactorily been treated with percutaneous balloon dilatation. We describe the successful surgical repair of a recurrent coarctation of the aorta via a sternotomy in a 2-year-old patient who had previously undergone neonatal orthotopic heart transplantation. Postoperative periodic investigations have not shown any evidence of obstruction across the site of the primary end-to-end anastomosis.

Anastomosis, Surgical↗
PubMedDate not supplied

Gene delivery into malignant cells in vivo by a conjugated adenovirus/DNA complex.

Current viral delivery systems suffer from disadvantages that may limit the rate at which therapeutic gene expressing constructs can be tested both in vitro and in vivo. In this study, our focus was to develop a simple gene delivery system for the rapid and reproducible testing of therapeutic genes in cancer cells both in vitro and in vivo. We report here that a delivery system based on using a conjugated adenovirus in complex from with a DNA plasmid can be used for not only delivering genes in vitro but also for efficient and reproducible delivery in vivo. Replication defective adenoviral particles were chemically modified by covalent attachment of poly-L-lysine (PLL) to the viral capsid, allowing for direct interaction with DNA. The adenovirus/PLL conjugate (Adv/PLL) was used to deliver the plasmid pCMV/beta-gal to several different cancer cell lines (i.e., lung, cervical) in vitro and resulted in transduction efficiencies as high as 52% as determined by histochemical staining. On direct intralesional injection of the Adv/PLL/DNA complex into subcutaneous tumors, transduction efficiencies greater than 35% could also be achieved. As a result, this system provides a simple method for delivering and testing therapeutic genes in cells both in vitro and in vivo, prior to the further development of gene therapy vectors for both malignant and benign disease.

Adenoviridae↗
PubMedDate not supplied

Delivery of the p53 tumor suppressor gene into lung cancer cells by an adenovirus/DNA complex.

An adenovirus/DNA complex was constructed by chemically linking poly-L-lysine to the capsid of the replication-defective adenovirus dl312, allowing for coupling with plasmid DNA by an ionic interaction. We have previously demonstrated that this adenovirus/DNA complex can efficiently transduce malignant cells with a plasmid expressing the beta-galactosidase gene both in vitro and in vivo. In this report, we show that this system can deliver a therapeutic gene that encodes for the tumor suppressor protein p53 to lung cancer cells, both in vitro and in vivo, leading to significant biological effects. Transfection of the p53-negative human lung cancer cell line H1299 with the adenovirus/DNA complex carrying a plasmid expressing the p53 gene resulted in high levels of p53 protein and induction of apoptosis. Injection of the complex carrying the p53 gene to subcutaneous tumor sites 5 days after tumor cell implantation resulted in a significant inhibition of tumorigenicity as measured by the number and size of tumors that developed 21 days after treatment. Three and six injections of the complex carrying the p53 gene into H1299 subcutaneous tumor nodules led to significant dose-related tumor growth suppression 18 days after the first injection compared with control-treated tumors. This adenovirus/DNA complex, therefore, is capable of efficiently delivering the p53 gene into malignant cells in vitro and in vivo and now provides a general gene delivery vector that is simple to construct and capable of testing therapeutic genes in malignant cells.

Adenoviridae↗