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Biomedical subjects

P Nguyen

Publications and source records attributed to P Nguyen.

At least 127 records · Page 7Linked to original sources

Lengthening of the mesentery using the marginal vascular arcade of the right colon as the blood supply to the ileal pouch.

PURPOSE: Creation of a safe ileal pouch requires a tension-free anastomosis. The aim of this study was to evaluate a technical procedure that increases the length of the mesentery while preserving the blood supply to the ileal pouch. HYPOTHESIS: Preservation of the marginal vascular arcade (MVA) of the right colon will allow ligation of more mesenteric vessels and increase the mesenteric length. METHODS: Six fresh cadavers were dissected. Measurement of the apex of the terminal ileum was done in relation to the pubic symphysis. Measurements were taken after 1) complete mobilization of the terminal ileum, right colon, and hepatic flexure; 2) vascular ligation between colon wall and the MVA, preserving the latter from the right branch of the middle colic artery to the ileal branch of the ileocolic artery (ICA); 3) ligation of the distal third of the superior mesenteric artery; 4) ligation of the ICA at its origin; 5) ligation of the right colon artery; and 6) division of the terminal ileal mesentery. RESULTS: This technique enabled complete division of the terminal ileal mesentery, adding a mean additional 3.6 (range, 2.5 - 5.0) cm (36.5 +/- 16.5 percent) in length to the mesentery, compared with superior mesenteric artery, ICA, and right colic artery ligation. CONCLUSION: Patients who have a shorter mesentery and concern of excessive mesenteric tension should have colectomy performed, preserving the MVA from the middle colic artery to the ileal branch of the ICA. The preserved MVA can be a reliable alternative blood supply to the pouch if more mesenteric vessel ligations are necessary.

Anastomosis, Surgical↗

Binding of a new multidrug resistance modulator, S9788, to human plasma proteins and erythrocytes.

The interactions of S9788 with human plasma proteins have been investigated in vitro by an erythrocyte partitioning technique that allows an estimation of the plasma proteins and erythrocytes binding parameters. S9788 was 98% bound to plasma and blood. Lipoproteins bound S9788 with high affinities (binding constants of 0.645, 12.8 and 87.0 x 10(6) M-1 for HDL, LDL and VLDL, respectively) and accounted for more than 55% of the total circulating S9788. Albumin and alpha 1-acid glycoprotein also bound S9788 with lower binding constants of 0.022 and 0.245 x 10(6) M-1. S9788 was mainly distributed in the plasma blood compartment (75-80%) with blood-to-plasma concentrations ratio of 0.6 to 0.7. These results indicate that, in vivo, the fraction of blood S9788 available for tissue diffusion, i.e., the free drug fraction in blood, should depend on lipoprotein concentration in plasma.

Antineoplastic Agents↗

Immunodominance of major histocompatibility complex class I-restricted influenza virus epitopes can be influenced by the T-cell receptor repertoire.

We have used T-cell receptor beta-chain transgenic mice to determine the effects of a limited T-cell receptor repertoire on major histocompatibility complex class I-restricted epitope selection during the course of an influenza virus infection. Analysis of T-cell hybridomas generated from wild-type and transgenic mice demonstrated that the viral epitope recognized depended on the available T-cell receptor repertoire. Wild-type T-cell hybridomas recognized epitopes derived from the nucleoprotein and basic polymerase molecules, whereas hybridomas generated from transgenic mice recognized epitopes derived from the nonstructural protein and the matrix protein. There was no overlap in specificity between the two panels of hybridomas. This reciprocal pattern of specificity was also apparent in cytoxicity assays with brochoalveolar lavage cells isolated from the lungs of influenza virus-infected mice. T-cell receptor usage in the transgenic hybridomas was very restricted, with only one V alpha element used for ech of the two viral epitopes recognized. In the case of the hybridomas reactive to the nonstructural protein, sequence analysis showed that they all expressed V alpha 4J alpha 32 chains associated with the same junctional amino acids (Leu-Leu) that were encoded by five different nucleotide sequences, indicating a strong selection for T-cell receptor usage. Taken together, these data demonstrate that the available T-cell receptor repertoire can have a profound effect on the immunodominance of class I-restricted epitopes during a viral infection.

Amino Acid Sequence↗

EEG delta, positron emission tomography, and memory deficit in Alzheimer's disease.

Quantitative scalp EEG from 32 channels and the cerebral glucose metabolic rate from the 32 underlying cortical positions as assessed by positron emission tomography (PET) with 18F-2-deoxyglucose (FDG) were obtained on 36 patients with mild to moderate senile dementia of the Alzheimer type and 17 age- and sex-matched normal control subjects. Subjects performed a verbal memory task during uptake of FDG. There were significant correlations between both delta amplitude and metabolic rate and memory performance during FDG uptake. Patients with Alzheimer's disease had significantly greater left temporal delta amplitude and lower glucose metabolic rates. Both EEG delta in microvolts and metabolic rate had similar diagnostic sensitivity, but PET had fewer false positives among normals. The left amygdala had the highest sensitivity and percent correct diagnosis of any brain area. Temporal lobe EEG delta activity showed higher correlations with hippocampal metabolic rate than metabolic rate directly under the electrode.

Aged↗

[Respiratory burst of neutrophils and cytokine profile in the non-insulin-dependent diabetic].

Many clinical and experimental data are in favour of a participation of leukocytes in vascular disease. Diabetes, a risk factor, is associated with a dysfunction of neutrophils. If chemotaxis and phagocytosis are deficient, it is not clearly established whether superoxide generation is conserved in these patients. We have measured this function in 35 noninsulin dependent diabetic patients, compared with a control population. We have assessed, in parallel, a profile of the cytokines involved in vascular phenomenons including TNF alpha, IL-1 beta et IL-6. Our results indicate that the generation of free radicals is normal in diabetics, with a significant elevation of TNF alpha. These results suggest a possible participation of this cytokine in the modulation of granulocyte reactivity.

Adult↗

Evidence of gender differences in esophageal pain threshold.

OBJECTIVE: To compare esophageal sensation thresholds between healthy males and females. METHODS: We used esophageal balloon distention to compare sensory thresholds between nine male and 10 female volunteers with a latex balloon (length 3 cm) positioned 5 cm proximal to the lower esophageal sphincter. Subjects indicated feeling: 0 (no sensation), 1 (aware of balloon but no discomfort), 2 (pain or discomfort) during rapid (170 cc/s) or slow (0.7 cc/s) balloon inflation rates as the balloon was inflated with increasing volumes of 2 cc. Females were studied on two separate occasions, days 5-7 and days 20-22 of their menstrual cycles, with day 1 being the first day of menses. RESULTS: Females had a significantly lower pain threshold and a trend toward lower awareness level. No significant differences in sensory perception were found between the two phases of the female cycle. Poor correlation (r = 0.35 in rapid, r = 0.4 in slow inflation) was found between subject height and balloon volume at perception of pain. CONCLUSION: Healthy females demonstrate a lower threshold to esophageal pain induced by balloon distention than healthy males. This difference is not explained by hormonal changes during normal menstrual cycle or by body size. This observation may explain in part the observed preponderance of females with unexplained chest pain of possible esophageal origin.

Adult↗

Endoscopic ultrasound-guided fine needle aspiration of pleural and ascitic fluid.

Endoscopic ultrasound (EUS) has been established as an important modality for staging gastrointestinal malignancies. We have previously described the new technique of EUS-guided fine needle aspiration (FNA) in diagnosing submucosal and extraluminal tumors and lymph nodes. We now report the novel application of EUS and EUS-guided FNA in diagnosing malignant ascites and malignant pleural effusion in two patients with gastric carcinoma. In the first patient, CT did not detect any effusion or ascites. EUS-guided FNA diagnosed cytologically that both fluids were malignant, thereby precluding surgery. The second patient had a small pleural effusion on CT that was not detected on the chest x-ray. EUS-guided FNA made the cytological diagnosis of recurrent adenocarcinoma in the pleural fluid. These two cases demonstrate for the first time that EUS combined with EUS-guided FNA can be used for the diagnosis of malignant pleural or ascitic fluid in patients with gastrointestinal malignancies and might further extend the staging capabilities of EUS.

Adenocarcinoma↗

[Outpatient treatment of deep venous thromboses].

Deep vein thromboses (DVT), which are serious because of their associated risk of pulmonary embolism and troublesome due to the possible development of a post-phlebitic syndrome, require rigorous management. However, the diagnosis is facilitated by Doppler ultrasound and treatment by low molecular weight heparins (LMWH) is simple to administer and follow. It is therefore logical to propose out patient treatment, provided certain rigorous rules are respected: establishment of an objective diagnosis of DVT, as the clinical signs are relatively nonspecific, admission to hospital of patients with a haemorrhagic risk or presenting a contraindication to anticoagulants, extensive DVT (extending beyond the mid-femoral zone), floating thrombus, patients with moderate signs may suggest pulmonary embolism. The recommended dosage for LMWH is 100 IU/kg twice a day (s.c.) (or 175 IU/kg once a day for the LMWH most recently available in France) which must be followed by oral anticoagulants for 5 months (aspirin is not sufficiently effective). Contention and rigorous clinical follow-up are obviously essential. The management of DVT is fascinating and requires coordination of several competent specialists.

Ambulatory Care↗

Imputability of heparin in heparin induced thrombocytopenia: a 10 year experience of the Centre Regional de Pharmacovigilance of Reims-Champagne Ardenne.

The imputability of heparin in heparin induced thrombocytopenia (HIT) was analysed retrospectively in the chart records of 86 cases documented by the Centre Regional de Pharmacovigilance (CRPV) of Reims-Champagne Ardenne over a period of 10 years. Considerable difficulties are encountered in evaluating the degree of imputability. Chronological criteria seem to be determinant in the final imputability score, whereas semiological criteria are particularly difficult to interpret, especially as it is not yet clearly established whether biological tests should be taken into account. The method of assessment requires more precise adaptation to the specific case of HIT and could be improved by redefinition of the criteria in collaboration between pharmacologists and haematologists.

Adult↗

Epidermal growth factor receptor and transforming growth factor alpha expression in papillary and nonpapillary renal cell carcinoma: correlation with metastatic behavior and prognosis.

Papillary renal carcinomas are a cytogenetically unique subset of renal carcinomas that have been reported to be clinically less aggressive. We have examined 19 papillary tumors for immunohistochemical expression of the epidermal growth factor receptor (EGF-R) and its ligand, transforming growth factor alpha (TGF-alpha). EGF-R and TGF-alpha expression was also studied in 149 nonpapillary tumors and 7 mixed papillary/solid tumors. EGF-R and TGF-alpha expression were compared to histology, stage, metastatic behavior, and survival. Formalin-fixed, paraffin-embedded nephrectomy specimens collected between 1977 and 1986 were stained with antibodies to EGF-R and TGF-alpha. Patients with papillary tumors were found to present with earlier stage disease and had significantly longer survival. Papillary tumors had a significantly lower rate of EGF-R positivity than solid pattern tumors (21% versus 73%, P < 0.001). Intermediate or strong cell membrane immunoreactivity for EGF-R was associated with high tumor grade and poor disease-specific survival. EGF-R positivity in the primary tumor was associated with the presence of metastatic disease and with metastatic spread to lung versus bone. Tumor parenchymal TGF-alpha staining was present in 50% of the cases and was not associated with stage or grade. Unrelated to tumor parenchymal TGF staining, tumor vessels stained for TGF-alpha in 56% of the cases. Vessel TGF-alpha staining was absent in papillary tumors (P < 0.001). The improved clinical behavior of papillary tumors as compared to nonpapillary renal tumors may be related, in part, to their relatively lower levels of EGF-R expression.

Adult↗

Characterization of discrete classes of binding sites of human serum albumin by application of thermodynamic principles.

The binding interactions of four ligands differing in acid-base properties with human serum albumin (HSA) were examined as a function of temperature. Binding to HSA decreased with increasing temperature for all four ligands. The bound and free ligand concentrations obtained at different temperatures were satisfactorily fitted to a model that incorporates the effect of temperature as an independent covariable and that directly allows the estimation of the enthalpic and entropic components of the ligand-albumin interaction, along with the precision of this estimation. Using this analysis, the binding of acidic ligands could be resolved into two classes of saturable sites, with the determination of the corresponding number of sites, whereas interpretation of binding data at each isolated temperature allowed only the determination of one saturable plus one non-saturable class of site. The thermodynamic constants indicate that binding of ionizable ligands to HSA involves electrostatic plus hydrophobic interactions, whereas only hydrophobic interactions are involved in binding to a second low-affinity class of site when present. Binding of non-ionizable ligands resembles that of the second class of low-affinity sites of ionizable ligands.

Benzothiazoles↗

Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP.

Recent clinicopathologic studies have shown that many prostatic adenocarcinomas express focal neuroendocrine differentiation and that neuroendocrine differentiation is most apparent in advanced anaplastic tumors. While studying growth-regulatory signal transduction events in human prostate carcinoma cell lines, we found that in two of four cell lines, the androgen-sensitive line LNCaP and the highly metastatic androgen-independent line PC-3-M, elevation of cAMP through addition of cAMP analogues or phosphodiesterase inhibitors induced a markedly neuronal morphology. Also in LNCaP cells ultrastructural analysis showed that cAMP induced the appearance of neurosecretory cell-like dense-core granules. Phenotypic analysis of untreated LNCaP and PC-3-M cells showed that both cell lines express markers of the neural crest including S-100, chromogranin A, pp60c-src, and neuron-specific enolase as well as the epithelial marker KS1/4 and stage-specific embryonic antigen 4. In PC-3-M cells, cAMP markedly elevated neuron-specific enolase protein and caused an increase in the specific activity of the neuroendocrine marker pp60c-src, and in both cell lines expression of KS1/4 and stage-specific embryonic antigen 4 was down-regulated. In addition to effects on lineage markers, cAMP treatment induced G1 synchronization, growth arrest, and loss of clonogenicity, indicating terminal differentiation. Our data provide direct evidence of plasticity in the lineage commitment of adenocarcinoma of the prostate. We have shown that cell-permeant cAMP analogues can induce terminal differentiation, suggesting that hydrolysis-resistant cyclic nucleotides may present an additional approach to the treatment of advanced prostate cancer.

Adenocarcinoma↗

Composition of meal influences changes in postprandial incremental glucose and insulin in healthy dogs.

Postprandial hyperglycemia and insulin secretion depend on many factors, such as food composition, carbohydrate type and processing. The purpose of this study was to evaluate the effects of foods differing in composition in nonobese clinically normal dogs. These dogs were offered in a single meal one of the four foods. Blood samples were collected before feeding and during the 180 min after the meal. Plasma glucose and insulin concentrations were determined. The integrated areas under the postprandial glucose and insulin response curves were calculated. Times to response peaks, maximum plasma insulin elevation, area under the insulin response curve and the insulinemic index differed between dog foods. Crude fiber content had no significant effect. The time to glucose peak was higher and the time to insulin peak lower with the food highest in protein and ether extract content. The time to glucose peak was correlated to protein, fat and nitrogen-free extract content of foods, whereas the time to insulin peak and the area under the insulin curve were correlated to protein and nitrogen-free extract.

Animal Feed↗

Stimulation of esophageal mechanoreceptors is dependent on rate and duration of distension.

We randomly compared rapid (170 ml/s) and slow (0.7 ml/s) rates of balloon distension in 19 volunteers (9 male, 10 female) using a latex balloon (length 3 cm) positioned 5 cm proximal to the lower esophageal sphincter. The balloon was inflated/deflated (1-s dwell; 5- to 10-s interval) with increasing 2-ml volumes during rapid inflation studies and progressively distended during slow inflation studies while subjects blindly indicated feeling, rated as follows: 0 (no sensation); 1 (aware of balloon, but no discomfort); 2 (pain or discomfort). In a second set of studies, the balloon was left inflated for 60 s at a volume 2 ml below that producing sensation 1, and time until a change in sensation was recorded. This was repeated at a volume 2 ml below that producing sensation 2. Mean volume to sensation 1 with slow inflation was 14.6 +/- 1.2 ml (SE) and with rapid inflation was 8.5 +/- 0.8 ml (P < 0.001). Mean volume to sensation 2 with slow inflation was 23.7 +/- 1.0 ml and with rapid inflation was 17.4 +/- 1.0 ml (P < 0.001). With sustained (60 s) inflation, most subjects noted increasing sensation, independent of initial inflation rate. We conclude that distal esophageal sensory perception (both awareness and discomfort) is dependent on rate of stimulation of mechanoreceptors. A sustained distension stimulus appears to recruit additional receptors and increase the level of sensory awareness.

Adult↗

Improvement in Obesity-associated Medical Conditions following Vertical Banded Gastroplasty and Gastrointestinal Bypass.

Thirty-nine patients undergoing either Silastictrade mark ring vertical banded gastroplasty (SRVG, n = 23) or Roux-en-Y gastrointestinal bypass (RGB, n = 16) over a 1-year period were analyzed retrospectively. Weight loss averaged 40 kg (89 lb). Clinical diabetes mellitus was markedly improved in seven out of nine patients (p = 0.023). Shortness of breath resolved in all 26 patients who had this condition preoperatively (p < 0.001). Orthopedic problems, high blood pressure, and self-assessment of general health and quality of life were also dramatically improved. We conclude that bariatric surgery serves as an effective method to alleviate a multitude of conditions associated with morbid obesity.

Journal Article↗

Identification, localization and functional analysis of imidazoline and alpha adrenergic receptors in canine prostate.

In nonsurgical management of benign prostatic hyperplasia, drugs which interfere with prostate contraction mediated through the alpha-1 adrenergic receptor are used. Clonidine acts at alpha adrenergic and I1-imidazoline receptors. In the present study, we found the Kd for [3H]clonidine binding to I1 sites in canine prostate to be 4 +/- 1 nM; the Bmax was 18 +/- 2 fmol/mg of protein. Inhibition of binding by imidazolines and by brain extracts containing putative endogenous ligand confirmed the identity of these sites as I1-imidazoline. Autoradiographic studies showed localization of both I1 and alpha-2 sites to the glandular epithelium. We sought to determine whether in vivo activation of the I1-imidazoline sites by clonidine mediates its contractile action in canine prostate. Dose-response curves were generated for para-aminoclonidine in the presence of vehicle alone, yohimbine (alpha-2 antagonist), idazoxan (alpha-2/I1/I2 antagonist) and prazosin (alpha-1 antagonist). Prazosin was the most effective antagonist. Yohimbine was less effective and did not effectively discriminate between para-aminoclonidine and phenylephrine, an alpha-1-selective agonist. Idazoxan antagonized para-aminoclonidine, but by not more than 50% at any dose. These results suggest that clonidine is active primarily at alpha-1 receptors on prostate smooth muscle in vivo. Thus the function of the I1 and alpha-2 receptors in the prostate remains to be determined; however, they may be involved in epithelial cell function.

Animals↗