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Biomedical subjects

D H Adams

Publications and source records attributed to D H Adams.

At least 91 records · Page 5Linked to original sources

Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis.

Alcoholic liver disease is associated with three histologically distinct processes: steatosis (parenchymal fat accumulation), alcoholic hepatitis (characterized by parenchymal infiltration by neutrophil polymorphs), and alcoholic cirrhosis (in which chronic inflammation and fibrosis dominate). Chemokines are cytokines that promote subset-specific leukoycte recruitment to tissues and could therefore play a crucial role in determining which leukocyte subsets are recruited to the liver in alcoholic liver disease. This paper reports that chemokine expression is increased in the liver of patients with alcoholic liver disease and, moreover, that distinct patterns of chemokine expression are associated with the different inflammatory responses to alcohol. Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were all detected in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflammatory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoidal cells, leukocytes, and fibroblasts in areas of parenchymal inflammation, but hepatocytes, despite staining strongly for chemokine protein, were negative. In alcoholic cirrhosis, chemokine mRNA was detected in portal tract endothelium, leukocytes, and fibroblasts. Thus, alcoholic hepatitis and alcoholic cirrhosis are associated with distinct patterns of chemokine expression that are likely to be important factors in determining whether a patient develops acute parenchymal inflammation and alcoholic hepatitis, or chronic septal inflammation and alcoholic cirrhosis.

Chemokine CCL2↗

Twenty-year follow-up of the Hancock modified orifice porcine aortic valve.

BACKGROUND: The entire experience with the Hancock modified orifice porcine bioprosthetic aortic valve from 1976 to 1996 at the Brigham and Women's Hospital has been reviewed. Eight hundred forty-three patients received this valve with a total follow-up of 61,114 months, and a mean follow-up of approximately 72.5 months. There were 490 men and 353 women, and the predominate lesion was aortic stenosis (636 of 843); 365 (43%) patients required a concomitant coronary artery bypass graft operation. METHODS: Patients were followed prospectively in the Brigham Cardiac Valve Data Registry, and the data were analyzed by the SAS statistical package, using actuarial survival curves and incidence per patient-year of morbidity and mortality. RESULTS: The overall operative mortality was 45 of 843 (5.3%) with 23 of 478 (4.8%) for isolated aortic valve replacement and 22 of 365 (6.0%) for aortic valve plus coronary artery bypass graft operation. The major morbidity of this valve was structural valve dysfunction, which was significantly related to the age of the patient in whom the valve was placed. Actuarial probability of freedom from structural valve degeneration at 5, 10, and 15 years overall was 99%+/-1%, 79%+/-3% and 57%+/-4%, at 15 years, respectively. In patients younger than 50 years, freedom from structural valve dysfunction was 16%+/-8%, whereas in the age group older than 70 years it was 87%+/-5% (p = 0.0005). Thromboembolism at 10 and 15 years was 81%+/-3% overall, 84%+/-2% in patients in normal sinus rhythm, and 57%+/-13% in patients with chronic atrial fibrillation. CONCLUSIONS: The Hancock modified orifice aortic valve, despite its more complicated fabrication, has been a reliable porcine bioprosthetic valve and can be used reliably in patients older than 70 years because of its low structural valve degeneration rate, and protection from stroke and anticoagulant hemorrhage in those patients in sinus rhythm.

Actuarial Analysis↗

Techniques and results of direct-access minimally invasive mitral valve surgery: a paradigm for the future.

OBJECTIVES: Our objective was to determine whether direct-access minimally invasive mitral valve surgery can improve recovery and cost while maintaining the efficacy of conventional surgery. METHODS: Minimally invasive mitral valve operations were performed on 106 patients, 58% male, average age 58.1 years, with good ventricular function. Ninety underwent repair of a regurgitant, myxomatous valve, and 16 underwent mitral valvuloplasty for prematurely calcified mitral stenosis. The valve was approached with standard instruments through a 5- to 8-cm right parasternal incision. Eighty-five had open femoral artery-femoral vein cannulation, but this technique has recently been replaced by direct cannulation of the aorta and percutaneous cannulation of the femoral vein for most patients. RESULTS: There were no operative deaths. The mean mitral regurgitation score (0-4) decreased from 3.7 to 0.7 after the operation. Although ischemic and bypass times were increased, postoperative recovery was accelerated. Ventilatory support time, intensive care unit stay, hospital stay, need for rehabilitation, and return to "normal activities" all improved. Hospital charges, pain medications, and blood transfusions were also reduced. New atrial fibrillation contributed significantly to increased length of stay and charges. There were no deep wound infections. Other complications included re-exploration for bleeding (n = 1), transient ischemic attacks (n = 2), stroke (n = 1), femoral artery injury (n = 5), pseudoaneurysm (n = 2), and antegrade dissection of the ascending aorta (n = 1). Two patients died and 1 required reoperation during a mean follow-up of 8.8 months. CONCLUSIONS: Direct-access minimally invasive mitral valve surgery can accelerate recovery, decrease charges, and decrease pain, while maintaining overall surgical efficacy. It has become our standard approach for isolated primary mitral valve operations.

Adult↗

A dual pathway for the transmission of spongiform encephalopathy disease.

The nature of the infective process in the transmissible spongiform encephalopathy (SE) diseases has been a longstanding problem--in particular, whether the causative agents are (unusual) nucleic-acid-mediated viruses, or replicating non-nucleic acid molecules such as protein. Although there is much (conflicting) evidence supporting both views, it does not seem to have been considered that many of the outstanding problems could be resolved if both mechanisms are operating--either separately or together--i.e. that there is a dual, but interconnected, pathway leading to disease development. It is suggested that this is in fact the case, and the implications are discussed.

Animals↗

Interleukin 2 restores CD3-zeta chain expression but fails to generate tumour-specific lytic activity in tumour-infiltrating lymphocytes derived from human colorectal hepatic metastases.

Metastatic colorectal cancer is usually progressive despite infiltration of the tumours by T lymphocytes, suggesting that these tumour-infiltrating lymphocytes (TILs) are functionally deficient. Recently, TILs from other tumours have been shown to express reduced levels of the T-cell receptor signal-transducing CD3-zeta chain. We were interested to determine whether a similar abnormality existed in TILs from human colorectal hepatic metastasis (CHM) and, if so, whether correcting the abnormality in vitro would restore anti-tumour activity and provide support for the development of immunotherapy for colorectal hepatic metastases. Twelve of 19 TILs from colorectal hepatic metastases were successfully expanded in vitro in high-dose recombinant interleukin 2 (rlL-2) and their specific anti-tumour cytolytic activity was determined. CD3-positive (CD3+) TILs were HLA-Drhigh and CD69high, suggesting that they had been activated by exposure to antigen but expressed low levels of CD25, CD71 and the nuclear proliferation antigen Ki-67. Furthermore, they showed reduced expression of CD3-zeta compared with autologous peripheral blood T cells (PBTs) and failed to proliferate in the absence of high-dose rIL-2. Expansion of TILs in rIL-2 resulted in restoration of CD3-zeta expression and the ability to lyse K562 and Daudi cells but not autologous tumour cells. The absence of autologous tumour-specific cytolytic T-cell (CTL) activity may be due to the poor immunogenicity of colorectal tumour cells, which we found expressed only low levels of MHC I antigens and CD54 and failed to express MHC II antigens or the co-stimulatory molecules CD80, CD86 or CD106. The inability of rIL-2 to generate tumour-specific CTLs despite restoration of CD3-zeta expression and the presence of an intact lytic mechanism suggests that successful immunotherapy may require the development of strategies to increase the immunogenicity of this tumour.

Adult↗

Chemokines: leucocyte recruitment and activation cytokines.

Chemokines are a family of structurally related proteins that share the ability to induce migration of specific subsets of leucocytes. These specialised cytokines play a critical part in the generation of cellular inflammation, both in the protective responses to invading pathogens and in the pathological processes associated with infection and immune-mediated diseases. Chemokines are more than simple chemotactic factors, since they are also implicated in leucocyte activation, angiogenesis, and antimicrobial functions, including a protective role in HIV infection. These molecules provide potentially valuable targets for therapeutic intervention in a wide range of diseases.

Chemokines↗

Holmium:YAG laser and pulsed dye laser: a cost comparison.

BACKGROUND AND OBJECTIVE: This study was designed to evaluate the relative cost effectiveness of the Holmium:YAG laser and the pulsed dye laser for the treatment of ureteral calculi. Cost containment is a priority for every health care facility. As a result, the staff of the Lutheran Medical Center (Wheat Ridge, CO) looked at alternative ways to provide quality laser treatment of ureteral stones. As part of our study, the laser committee offered the Holmium:YAG laser to urologists for ureteral lithotripsy. Previously, the pulsed dye laser was rented for ureteral calculi on a per case basis at $1,500. A hospital processing fee was added to this cost, resulting in a total charge of $1,638 to the patient. Our organization owns a Holmium:YAG laser and uses it primarily in orthopedics. STUDY DESIGN/MATERIALS AND METHODS: Two ureteral lithotripsy cases were performed and compared. One case used the Holmium:YAG for ureteral lithotripsy; the other procedure used the pulsed dye laser. A cost analysis was performed after the procedures. RESULTS: The data indicated a significant difference in cost between the two lasers. Approximately $1,000 was eliminated when using the Holmium:YAG laser. CONCLUSION: A cost savings of $15,000 per year would be realized if 15 cases were performed. The Holmium:YAG laser also can be used on cystine calculi, a procedure for which the pulsed dye laser is ineffective. The potential for ureteral injury exists. When using the Holmium:YAG laser, appropriate training is required. Due to this risk, not all urologists will use the Holmium:YAG laser. We also found a positive correlation between the proficiency of the urologists' laser skills and overall cost effectiveness.

Cost Savings↗

In vitro stimulation by tumour cell media of [3H]-thymidine incorporation by mouse spleen lymphocytes.

Mouse spleen lymphocyte (SL) cells show a three to four-fold increase in [3H]-thymidine incorporation when incubated in tumour cell media, or in media containing tumour cell cytosol. Agarose gel chromatography of both [3H]-thymidine-labelled tumour cell media and cytosol shows a sharp peak of DNA-associated material eluting at about 60 kDa. This DNA-associated material is imported rapidly and efficiently by SL cells and is recoverable from their cytosol. The stimulating effect on SL cell thymidine incorporation resides primarily, if not exclusively, in this extruded/cytosolic 60 kDa DNA material. Tumour cells incubated in media containing normal or liver, but not tumour, cytosol show a reduced rate of [3H]-thymidine incorporation, indicating competition between normal and tumour associated DNA complexes. The results indicate that such cell-extruded DNA complexes may transmit 'genetic messages' to other cells, and are discussed in terms of interactions in the tumour-bearing host.

Animals↗

Axilloaxillary cardiopulmonary bypass: a practical alternative to femorofemoral bypass.

BACKGROUND: Peripheral arterial and venous cannulation for cardiopulmonary bypass is used increasingly for patients undergoing minimally invasive cardiac operations, complex reoperations, or repair of aortic dissection or aneurysm, and for patients with extensive arteriosclerotic aortic disease in whom aortic cannulation is a prohibitive embolic risk. The common femoral artery and vein are most commonly used for peripheral cannulation, but these sites may be predisposed to complications, primarily because the femoral vessels are commonly involved with arteriosclerotic disease. We have recently begun to use the axillary artery and axillary vein as alternative cannulation sites, achieving full cardiopulmonary bypass, providing antegrade aortic flow, and avoiding many of the complications associated with other sites. METHODS: Seven patients with peripheral vascular or aortic disease, or both, prohibiting safe aortic or femoral cannulation underwent cardiopulmonary bypass through axillary artery and axillary vein cannulation, approached through a small single subclavicular incision. RESULTS: All patients were successfully cannulated and axilloaxillary cardiopulmonary bypass was possible without the need for additional cannulas. All axillary vessels were closed primarily without complication. CONCLUSION: For an expanding population of patients with peripheral vascular and aortic disease, axilloaxillary bypass is a safe and practical alternative to aortic or femoral cannulation.

Aged↗

Microbial colonization of closed-system suction catheters used in liver transplant patients.

The microbial colonization and the associated risk of respiratory infection during the application of a multiple-use closed-system suction catheter (CSSC) and a single-use open-system suction catheter (OSSC) on liver transplant patients was evaluated in this preliminary study. The cost differential for the two systems was also compared. Twenty post-orthotopic liver transplant (OLTx) patients who were mechanically ventilated via an endotracheal (ET) tube were studied. Ten subjects were randomly allocated ET suction by the CSSC and 10 with OSSC. Both groups were similar according to age, sex, clinical severity, presence of a naso-gastric tube, use of H2 antagonists and antibiotics used. Standard protocols were followed to intubate and suction the patients and to change ventilatory equipment. Suctioning performed with the CSSC did not significantly increase the risk of microbial colonization of the respiratory tract. Similarly there was no apparent difference in the incidence of nosocomial pneumonia between the two suction systems, based on the microbiological and clinical data. The mean daily cost of using the CSSC compared to the OSSC was 11.6 times higher. This may be balanced by a reduction in nursing time and reduced risk of spread of infection associated with the CSSC.

Adult↗

Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and functional analysis.

Efficacy of cancer immunotherapy with cultured tumour-infiltrating lymphocytes (TILs) depends upon infused TILs migrating into tumour-bearing tissue, in which they mediate an anti-tumour response. For TILs to enter a tumour, they must first bind to tumour endothelium, and this process depends on TILs expressing and regulating the function of relevant cell-surface receptors. We analysed the cell-surface phenotype and endothelial binding of TILs cultured from human melanoma and compared them with peripheral blood T cells and with allostimulated T cells cultured under similar conditions. Compared with peripheral blood T cells, TILs expressed high levels of five integrins, two other adhesion molecules, including the skin homing molecule CLA, and several activation markers and showed markedly enhanced integrin-mediated adhesion to a dermal microvascular endothelial cell line in vitro. Compared with the allostimulated T cells, TILs expressed higher levels of the cutaneous lymphocyte antigen (CLA), the adhesion molecule CD31 and the activation markers CD30 and CD69, but lower levels of several other adhesion and activation molecules. These phenotypic and functional properties of TILs should have complex effects on their migration in vivo. Expression of CLA, the skin homing receptor, may increase migration to melanoma (a skin cancer), whereas integrin activation may cause non-specific binding of TILs to other endothelium. Manipulation of the culture conditions in which TILs are expanded might result in a phenotype that is more conducive to selective tumour homing in vivo.

Cell Adhesion↗