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Biomedical subjects

D M Young

Publications and source records attributed to D M Young.

At least 19 recordsLinked to original sources
PubMed1999

Diet-induced protection against lipopolysaccharide includes increased hepatic NO production.

The host response to Gram-negative infection includes the elaboration of numerous proinflammatory agents, including tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO). A component of the hepatic response to infection is an elevation in serum lipids, the so-called "lipemia of sepsis," which results from the increased production of triglyceride (TG)-rich lipoproteins by the liver. We have postulated that these lipoproteins are components of a nonadaptive, innate immune response to endotoxin [lipopolysaccharide (LPS)] and have previously demonstrated the capacity of TG-rich lipoproteins to protect against endotoxicity in rodent models of sepsis. Herein we report the capacity of a high-fructose diet to protect against LPS, most likely by inducing high circulating levels of endogenous TG-rich lipoproteins. The protective phenotype included the increased production of NO by hepatic endothelial cells. Rats, made hypertriglyceridemic by fructose feeding, experienced decreased LPS-induced mortality (P < 0.03) and systemic TNFalpha levels (P < 0.05) as compared with normolipidemic (chow-fed) controls. The increased survival was associated with elevated levels of inducible NO synthase (NOS2) mRNA levels and NO production (82 +/- 26 vs 3 +/- 3 nmol nitrite/10(6) cells, P < 0.001) by hepatic endothelial cells. Nonselective NOS inhibitors reversed the protective phenotype in vivo and readily decreased NO production by cultured endothelial cells from hypertriglyceridemic rats in vitro. This study suggests that a high-fructose diet can protect against endotoxicity in part through induction of endogenous TG-rich lipoproteins and hepatic endothelial cell NO production. This is the first report of diet-induced hyperlipoproteinemia and subsequent protection against endotoxemia.

Animals↗
PubMed1999

Phenotypic expression of PCR-generated random mutations in a Pseudomonas putida gene after its introduction into an Acinetobacter chromosome by natural transformation.

Localized sets of random point mutations generated by PCR amplification can be transferred efficiently to the chromosome of Acinetobacter ADP1 (also known as strain BD413) by natural transformation. The technique does not require cloning of PCR fragments in plasmids: PCR-amplified DNA fragments are internalized by cells and directly incorporated into their genomes by homologous recombination. Previously such procedures for random mutagenesis could be applied only to Acinetobacter genes affording the selection of mutant phenotypes. Here we describe the construction of a vector and recipient that allow for mutagenesis, recovery, and expression of heterologous genes that may lack a positive selection. The plasmid carries an Acinetobacter chromosomal segment interrupted by a multiple cloning site next to a kanamycin resistance marker. The insertion of heterologous DNA into the multiple cloning site prepares the insert as a target for PCR mutagenesis. PCR amplifies the kanamycin resistance marker and a flanking region of Acinetobacter DNA along with the insert of heterologous DNA. Nucleotide sequence identity between the flanking regions and corresponding chromosomal segments in an engineered Acinetobacter recipient allows homologous recombination of the PCR-amplified DNA fragments into a specific chromosomal docking site from which they can be expressed. The recipient strain contains only a portion of the kanamycin resistance gene, so donor DNA containing both this gene and the mutagenized insert can be selected by demanding growth of recombinants in the presence of kanamycin. The effectiveness of the technique was demonstrated with the relatively GC-rich Pseudomonas putida xylE gene. After only one round of PCR amplification (35 cycles), donor DNA produced transformants of which up to 30% carried a defective xylE gene after growth at 37 degrees C. Of recombinant clones that failed to express xylE at 37 degrees C, about 10% expressed the gene when grown at 22 degrees C. The techniques described here could be adapted to prepare colonies with an altered function in any gene for which either a selection or a suitable phenotypic screen exists.

Acinetobacter↗
PubMed1998

Staging of colorectal cancer: biology vs. morphology.

PURPOSE: An accurate determination of the extent or staging of a disease is critical, because it provides the basis for making therapeutic decisions. Staging is a collaborative effort by the surgeon and the pathologist. Radioimmunoguided surgery has been evaluated for its ability to help surgeons determine the extent of disease during surgery, when management decisions have the most impact on patient care. This study was done to compare radioimmunoguided surgery "biostaging" with traditional pathologic staging (TNM) as predictors of survival in patients undergoing curative resections for colorectal cancer. METHODS: Ninety-seven patients with colorectal cancer were prospectively enrolled in radioimmunoguided surgery protocols. Evaluation of follow-up survival data was performed. All patients underwent exploratory laparotomy and radioimmunoguided surgery with resection of their primary colorectal tumor. Survival data were analyzed with the Kaplan-Meier method with log-rank comparisons. RESULTS: Of 97 patients enrolled in the study, 59 were evaluable and completely resectable by radioimmunoguided surgery. Mean follow-up was 62 months, with a range of 34 to 89 months. By traditional staging 13 patients were pStage I, 18 patients were pStage II, and 28 patients were pStage III. By radioimmunoguided surgery biostaging, 24 patients were radioimmunoguided surgery-negative whereas 35 patients were radioimmunoguided surgery-positive. Survival rates by pathologic stage approached a significant difference, but did not, as of the conclusion of the study period, reach it (P = 0.12). Survival rates based on radioimmunoguided surgery status demonstrated a highly significant difference (P = 0.0002). CONCLUSIONS: Radioimmunoguided surgery biostaging provides new information intraoperatively on cancer staging that has not been available before. This may lead to new strategies for therapy that can be individualized and optimized for each patient with cancer.

Adult↗
PubMed1998

Intraorbital squamous epithelial cyst: an unusual complication of Silastic implantation.

Thin Silastic sheet alloplasts (Dow Corning, Midland, MI, U.S.A) are commonly used to reconstruct posttraumatic orbital floor defects. Complications associated with orbital Silastic implantation include infection, migration, and extrusion. The authors report an unusual case of an intraorbital, squamous, epithelial-lined cyst appearing as progressive vertical globe dystopia and proptosis occurring after Silastic reconstruction of a traumatic orbital floor defect.

Bone Cysts↗
PubMed1997

Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid.

Vascular endothelial growth factor (VEGF) is an angiogenic factor, and its expression has been rarely demonstrated in thyroid tumors. We, therefore, investigated the expression of VEGF messenger RNA (mRNA) and production of VEGF protein in cell lines from human primary and metastatic follicular (FTC-133, FTC-236, and FTC-238), papillary (TPC-1), Hürthle cell (XTC-1), and medullary thyroid cancers (MTC-1.1 and MTC-2.2), and in human thyroid tissues (papillary, follicular, medullary, and Hürthle cell cancers, follicular adenomas, and Graves' thyroid tissue) by Northern blot, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) studies. All thyroid cell lines expressed a 4.2-kilobase VEGF mRNA. The VEGF mRNA levels were higher in the thyroid cancer cell lines than in primary cultures of normal thyroid cells, and higher in thyroid cancers of follicular than those of parafollicular cell origin. The VEGF mRNA levels were similar in primary and metastatic thyroid tumors. Immunohistochemical staining and Northern blot analysis of the cell lines correlated positively, thus thyroid cancer cell lines stained more intensely than normal thyroid cells and follicular tumor cells more intensely than parafollicular tumor cells. Again, no difference was noted in VEGF staining between primary and metastatic thyroid tumors. Deparafinized sections of papillary, follicular, and Hürthle cell cancers also stained much stronger than those of medullary thyroid cancers, benign, or hyperplastic (Graves' disease) thyroid tissue. Thyroid cancer cell lines (XTC-1 > TPC-1 > FTC-133 > MTC-1.1) also secreted more VEGF protein as measured by ELISA than did normal thyroid cells. VEGF secretion of cell lines derived from primary and metastatic thyroid tumors were similar. VEGF mRNA is therefore expressed, and VEGF protein is secreted by normal, hyperplastic, and neoplastic thyroid tissues. The higher levels of VEGF expression in differentiated thyroid cancers of follicular cell origin suggests a role in oncogenesis.

Adenocarcinoma↗
PubMed1997

Human acellular dermal matrix as a novel model of malignant epithelial cell invasion.

Cancer invasion and metastasis are associated with matrix degradation. We describe a novel in vivo model of invasion by squamous epithelial neoplastic cells derived from transgenic mice grown on acellular human dermis. Human dermis was subjected to multiple freeze-thaw cycles to render it acellular, maintaining the basement membrane of the former dermal-epidermal junction. Cells representing discrete stages of a multistep transgenic mouse model of epidermal carcinogenesis (neonatal transgenic keratinocytes, moderately/poorly differentiated squamous cell carcinoma, and lymph node metastasis) were seeded onto the basement membrane surface, grown in culture for 4 days, grafted in a subpannicular pocket of athymic mice, and harvested after 3 weeks. Histological analysis demonstrated that neonatal transgenic keratinocytes did not degrade the basement membrane or invade the underlying dermis. In contrast, malignant cells derived from both a moderately differentiated squamous carcinoma and a lymph node metastasis were highly invasive. Immunohistochemical analysis revealed collagenase only in nests of invading malignant cells in contact with the dermal matrix, but not in the tumor mass remaining above the basement membrane, suggesting that this proteinase may be required for stromal invasion. This novel model recapitulates the events seen in malignant invasion: transgenic keratinocytes are unable to penetrate the dermis while cells from a moderately differentiated carcinoma and from lymph node metastasis consistently invade.

Animals↗
PubMed1996

Acellular human dermal matrix as a small vessel substitute.

In both vascular and microvascular surgery, there is a need for a non-thrombogenic, small-caliber, arterial substitute. Clinically, most vessel substitutes with diameters under 4 mm have low patency rates. An arterial conduit made from a biocompatible human acellular dermis may be useful as a small vessel conduit. The purpose of this study was to evaluate and compare the patency rates of a vascular conduit made from rolled human acellular dermal (ACD) matrix and a similar-sized polytetrafluoroethylene (PTFE) tube, using the rat femoral artery interposition model. Twenty-eight days after implantation, 9 or 10 (90 percent) ACD grafts and 5 of 8 (62.5 percent) PTFE grafts were patent. False aneurysms formed in 6 ACD conduits along the longitudinal suture line. The three patent non-aneurysmal ACD conduits developed an endothelial luminal lining. While further studies are needed, acellular dermis appears to be a promising material for use as a vessel substitute.

Aneurysm, False↗
PubMed1996

Modular group therapy in a community mental health center.

To use staff resources more efficiently, a community mental health center in South Carolina initiated an eight-session modular psychoeducational and group therapy program with a classroom format. Groups were composed of three to 12 patients with the same or similar diagnoses. Each session in the series constituted a complete module and included didactic presentations and group discussion about the material. At follow-up two years after the program started, the program was well accepted by staff and patients. The proportion of patient contacts for group therapy and revenue generated by group contacts had increased. Although an aim of the program was to reduce the frequency of contacts for individual therapy, these contacts did not decline over the follow-up period.

Case Management↗
PubMed1996

Risk factors for hypothermia in psychiatric patients.

Hypothermia occurs when the core body temperature falls below 95 degrees F (35 degrees C). Several conditions which can occur in the psychiatric population increase the risk of hypothermia: nocturnal enuresis, seizure disorder, debilitating physical illness, and mental retardation. The risk of hypothermia is further increased by the use of several classes of medications used to treat psychiatric disorders: antipsychotics, beta-adrenergic antagonists, benzodiazepines, and other sedatives. Air-conditioning is also identified as a risk factor for hypothermia. Hypothermia is posited as a possible link between antipsychotic medication and sudden unexplained death. Suggestions for further investigation are made, and clinical recommendations are offered to reduce the risk of hypothermia in the psychiatric patient population.

Air Conditioning↗
PubMed1996

Shrinking the western Pacific: psychiatric training for medical students from Micronesia.

In 1989 the Hawaii State Hospital became the primary site for clinical teaching of psychiatry to students of the Pacific Basin Medical Officer Training Program, a program designed to train clinicians for the western Pacific. The psychiatry clerkship was developed to provide practical training in psychiatry to clinicians who will practice in Micronesia. Challenges encountered by the educators, including transcultural issues, are discussed. Interventions found to be effective in resolving these challenges are described.

Clinical Clerkship↗
PubMed1995

Duplex diagnosis of venous insufficiency in a free flap.

Venous monitoring and evaluation present a dilemma in free flap care. Duplex ultrasonography provides information on vessel flow and anatomy. This case demonstrates the use of duplex technology in identifying problems following vascular microsurgery, and it raises discussion of possible future roles for the application of duplex ultrasonography in the management of free flaps.

Aged↗
PubMed1995

Evaluation of a rapid specific ward based assay for creatinine in blood.

We have evaluated a dry reagent stick test for the quantitation of creatinine in plasma employing a whole blood sample. The assay was found to be specific for creatinine and correlated well (r = 0.993) with an established laboratory procedure. The precision found indicated that the method was suitable for use in the diagnosis and monitoring of renal disease.

Clinical Enzyme Tests↗
PubMed1994

The need for preoperative leg angiography in fibula free flaps.

Among arterial anatomic conditions which will adversely affect the harvest of the fibula are 1) significant arteriosclerotic disease within the tibial-peroneal vessels; 2) peroneal arteria magna (PAM), a condition in which only the peroneal artery supplies the foot; and 3) absence of the peroneal artery, either congenitally or as an acquired defect. In each of these anatomic conditions, removal of the peroneal vessels and the fibula free flap will jeopardize either the donor leg, the fibula flap, or both. All patients considered for fibula flaps were evaluated with preoperative leg angiograms. In 28 consecutive patients evaluated with angiography for planned free-fibula flap reconstructions, 23 actually underwent free-fibula harvest. Angiographic abnormalities that altered the operative plan were found in seven (25 percent) patients. Four of the seven patients had vascular examinations prior to surgery with abnormal findings. Three of the seven (11 percent) patients with abnormal arterial anatomy had normal vascular examinations prior to surgery. Thus, if a preoperative angiogram had not routinely been done, the abnormal anatomy would not have been discovered until surgery. This could have resulted in an unusable flap in one patient, and an ischemic or gangrenous foot in two other patients. With this angiographic guidance, there were no vascular complications from harvest of the fibula. The routine use of preoperative bilateral leg angiography is recommended, or an alternative method of vessel imaging, in all patients evaluated for microvascular free-tissue transfer of the fibula.

Angiography↗
PubMed1993

Enhancing fibula free flap skin island reliability and versatility for mandibular reconstruction.

Although the fibula osteocutaneous free flap has many advantages when used in mandibular reconstruction, many investigators have found the skin island is not always reliable. We present a technique that enhances skin island reliability by including a maximal number of skin perforators. This method has been used in 10 consecutive osteocutaneous free flaps without any skin loss. This technique also expands the usefulness of the fibula free flap, allowing it to be used for shorter bone defects or in cases when skin coverage is needed at a distance from the bone. In addition, this method provides additional vascularized soft tissue for neck contour restoration and coverage of fixation plates.

Bone Plates↗
PubMed1993

Chemiluminescent restriction fragment length polymorphism analysis (DNA fingerprinting) to identify keratinocytes from two donors in co-culture.

The transplantation of allogeneic cells such as pancreatic islet cells, bone marrow, and keratinocytes for skin replacement is in growing use clinically. Present techniques which are used to distinguish transplanted allogeneic cells from phenotypically identical host cells in chimeric tissue have serious limitations. This study assesses the feasibility of using chemiluminescent restriction fragment length polymorphism (RFLP) analysis to distinguish between keratinocyte cell lines from 2 different donors grown in co-culture. We evaluated the sensitivity of this technique in tissue cultured cells in order to define its usefulness in clinical situations. RFLP analysis readily detects heterologous DNA comprising only 10% of a 5 micrograms sample. This was a detection threshold of 500 ng of high molecular weight DNA. With standard extraction methods, this represents the DNA obtained from 4000 cells. This new chemiluminescent technique is as sensitive as older techniques which employ radioactive probes, but avoids the hazards of handling radioactive material. Using this RFLP analysis, the presence of transplanted allogeneic cells can be readily detected in small biopsy specimens. This technique has wide potential application in allogeneic cellular transplantation investigations.

Cell Line↗
PubMed1990

Nurses' knowledge and attitudes and AIDS patients' perception of confirmation: a pilot study.

The purpose of this pilot study was to describe registered nurses' knowledge of and attitudes toward the acquired immunodeficiency syndrome (AIDS) and people with AIDS and the AIDS patients' perceptions of confirmation in interpersonal relationships with nurses. Convenience sampling was used to obtain 11 patient and registered nurse subject pairs in a large midwestern university hospital. Nurse subjects completed the AIDS Questionnaire: Beliefs and Information, and patient subjects completed the Perceived Confirmation Scale. It was found that patients perceived a high level of confirmation in relationships with nurses and that the nurses had an average knowledge of AIDS and fairly tolerant attitudes toward people with AIDS. No significant correlations were found among nurses' knowledge, nurses' attitudes, and patients' perception of confirmation in relationships with nurses.

Acquired Immunodeficiency Syndrome↗