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Biomedical subjects

D Quan

Publications and source records attributed to D Quan.

36 records · Page 2Linked to original sources

The safety of continuous hepatic inflow occlusion during major liver resection.

To evaluate the safety of temporary hepatic inflow occlusion during major liver resection, we reviewed 71 consecutive noncirrhotic patients who underwent elective liver resection using this technique. There were 27 males and 44 females (mean age, 54.4 years), the majority of whom had hepatic malignancies. There were 31 right hepatectomies, 21 left hepatectomies, and 19 extended right hepatectomies. Ischemic injury of the liver was assessed using changes in postoperative liver function tests and patient outcome was assessed using morbidity and mortality rates. After preliminary ligation of the blood supply to the lobe to be removed, global hepatic ischemia was produced by temporary occlusion of the main portal vein and hepatic artery proper while the liver parenchyma was divided. The average duration of inflow occlusion was 59 minutes (range, 25 to 90 minutes). There was no operative mortality, and no patient developed liver failure. The liver enzymes reached their peak on the first postoperative day (mean aspartate aminotransferase [AST] level, 283 +/- 227 IU/L; mean alanine aminotransferase [ALT] level, 269 +/- 238 IU/L) and they returned to normal by 7 days. The most common postoperative complications were related to the chest, wound, and urinary tract. The mean intraoperative transfusion was 3.4 +/- 2.6 U of packed red blood cells, and 0.94 +/- 2.13 U of fresh frozen plasma. We conclude that continuous hepatic inflow occlusion for periods of 1 hour during major liver resection is safe and well-tolerated when there is no underlying parenchymal liver disease.

Adult↗

In vitro percutaneous absorption of model compounds glyphosate and malathion from cotton fabric into and through human skin.

Chemicals are introduced to fabric at many steps during manufacture and use. Fabrics containing chemicals can cause medical problems such as dermatitis and death. Insecticides impregnated into uniforms worn by "Desert Storm" personnel are implicated in "Gulf War Syndrome'. These chemicals must get from fabric into and through skin to cause toxic effects. The objective of the present study was to determine in vitro percutaneous absorption of model chemicals glyphosate (water soluble) and malathion (relative water insoluble) from cotton fabric into and through human skin. The percutaneous absorption of glyphosate from water solution was 1.42 +/- 0.25% dose. This decreased to 0.74 +/- 0.26% for glyphosate added to cotton sheets and immediately put onto skin. If the cotton sheets were dried for 1 or 2 days, then applied to skin, absorption was 0.08 +/- 0.02% and 0.08 +/- 0.01% respectively. However, wetting the 2-day dried cotton sheet with water to simulate sweating or wet conditions increased absorption to 0.36 +/- 0.07%. Similar results were found for malathion. Absorption of malathion from aqueous ethanol solution was 8.77 +/- 1.43%. This decreased to 3.92 +/- 0.49%, 0.62 +/- 0.11% and 0.60 +/- 0.14% for 0, 1- and 2-day-treated cotton sheets. However, malathion absorption from 2-day treated/dried cotton sheets increased to 7.34 +/- 0.61% when wetted with aqueous ethanol. These results show that chemicals in fabric (clothing, rug, upholstery, etc.) can transfer from fabric into and through human skin to cause toxic effects.

Dose-Response Relationship, Drug↗

Altered gene expression of cytokine, ICAM-1, and class II molecules precedes mouse intestinal allograft rejection.

Rapid and severe rejection remains a major obstacle to successful clinical intestinal transplantation (IT). The aggressive nature of rejection in IT has been attributed to the increased massive immune stimulus provided by large numbers of resident lymphocytes, antigen presentation capacity of enterocytes, and graft damage mediated by luminal microflora. Early small bowel expression of proinflammatory cytokines, MHC class II, and adhesion molecules may also promote IT rejection, but the lack of a mouse model has hampered extensive studies of gene expression in IT. Using a recently developed surgical model, we examined the temporal pattern of gene expression in CB6F1 (H-2b/d) vascularized, heterotopic intestinal allografts transplanted into BALB/c (H-2d) mice. Although histological evidence of rejection was not present until day 7 in allografts, Northern blot analysis demonstrated increases in TNF alpha gene transcripts as early as day 3, followed by the expression of IL-1 beta, intercellular adhesion molecule-1, and MHC class II by day 5. Using reverse-transcriptase polymerase chain reaction, IFN-gamma was detected in allografts by day 3 and persisted to day 10. In contrast, IL-2, IL-4, IL-5, and IL-6 mRNA transcripts peaked by day 5 and then decreased, suggesting that both Th1 and Th2 subsets are involved in the rejection of unmodified small bowel allografts. The early and progressive expression of TNF alpha and IL-1 beta as well as IFN-gamma, intercellular adhesion molecule-1, and MHC class II in IT rejection may contribute to the difficulty in controlling IT rejection with present immunosuppression.

Animals↗

Endotoxin in the peripheral blood during acute intestinal allograft rejection.

Intestinal rejection is associated with increased gut permeability and bacterial translocation. The present study examined endotoxin and proinflammatory cytokines in the peripheral circulation during acute intestinal rejection. Heterotopic intestinal transplants were performed using Lewis rats (RT1(1)) as donors and DA rats (RT1a) as recipients. DA rats with intestinal isografts were used as controls. Serum samples were obtained at sacrifice on postoperative days (POD) 7 and 14. Lipopolysaccharide (LPS) was measured using the limulus amoebocyte lysate assay. Interleukin-1 (IL-1) and 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured using bioassays. Large amounts of LPS were detected in the serum of intestinal allograft recipients concurrent with the development of graft rejection. Serum IL-6 and TNF-alpha levels were significantly elevated in the allograft recipients on both POD 7 and 14 when compared to DA isografts (P < 0.05). Serum IL-1 activity was not detected in the allograft or isograft recipients at either of the two time points. Further studies are warranted to determine the role of intraluminal bacteria and their products in the pathophysiology of intestinal allograft rejection.

Acute Disease↗

Development of a mouse intestinal transplantation model.

We have recently developed a mouse intestinal transplantation model. The proximal segment of donor jejunum is transplanted into the recipient in a heterotopic position. End-to-side anastomoses are performed between donor aorta and recipient aorta and between donor portal vein and recipient inferior vena cava. Mortality rates were initially high due to shock, arterial thrombosis, and postoperative sepsis. Refinements in surgical techniques reduced these complications, resulting in a high rate of success. Important technical factors included (1) minimizing ischemic injuries to the graft in both the donor and the recipient, (2) using an aortic patch and elliptical aortotomy for anastomosis, (3) administering large volumes of crystalloid to maintain normal blood pressure during the donor and recipient surgeries, and (4) using broad-spectrum antibiotics as postoperative prophylaxis. The mice with isografts had normal intestinal function and histology when they were sacrificed 1 month after surgery. This new model of small bowel transplantation will be a useful tool to study the immunology of intestinal grafting at the molecular level.

Anastomosis, Surgical↗

Promoting effect of 2-n-alkylcyclohexanones on the percutaneous absorption of indomethacin.

We previously evaluated the promoting effects of 2-tert-butylcyclohexanone and its analogues on the percutaneous absorption of indomethacin (IMC), and showed that the 2-position of the cyclohexanone ring plays an important role in drug permeability through the skin. The present study investigates the in vitro penetration enhancement of IMC by five 2-n-alkylcyclohexanone derivatives. 2-n-Octylcyclohexanone was the most effective enhancer, but the other four enhancers also had significant promoting actions on skin permeability of IMC. Maximum absorption enhancement was associated with a defined range of enhancer lipophilicity. We propose that the enhancer penetrates into the stratum corneum and improves skin permeability of a drug by dissolving some of the hard lipid components or modifying the dense lipid stratum corneum.

Animals↗

Prevalence of human T-cell leukemia/lymphoma virus (HTLV) type II infection among high-risk individuals: type-specific identification of HTLVs by polymerase chain reaction.

The extent of human T-cell leukemia/lymphoma virus type II (HTLV-II) infection and its rate of spread have been difficult to determine owing to the serological cross-reactivity between HTLV-I and HTLV-II. The present study overcame this problem by directly detecting type-specific proviral sequences by means of the polymerase chain reaction (PCR) and liquid hybridization. Screening was performed on a cohort of primarily white intravenous drug abusers (IVDAs), and individuals of other behaviorally defined risk groups from the New York City area. Eleven percent (19 of 169) of the individuals in these high-risk groups were determined by PCR to have HTLV-II proviral infections. One of these patients displayed an exfoliative erythrodermatitis. Thirteen of the 19 subjects were positive in an HTLV-II enzyme-linked immunosorbent assay (ELISA). The remaining six individuals, although negative in the HTLV-II ELISA, were confirmed as HTLV-II positive by analyzing their DNA with a second HTLV-II-specific primer detector system. Four additional individuals were reactive in the HTLV-II ELISA but were PCR-negative for HTLV-II. PCR analysis for HTLV-I revealed that all four were positive for that virus. Thirty-seven percent (seven of 19) of the HTLV-II PCR-positive subjects were also PCR-positive for HTLV-I, and 84% (16 of 19) of the HTLV-II positive individuals were infected with human immunodeficiency virus (HIV-1). Six individuals were triply infected with HTLV-I, HTLV-II, and HIV-1.

Enzyme-Linked Immunosorbent Assay↗