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Biomedical subjects

David H Adams

Publications and source records attributed to David H Adams.

80 records · Page 5Linked to original sources
PubMed2002

New approaches to immunosuppression in liver transplantation.

With the continued improvements in outcome following liver transplantation, the drawbacks associated with conventional immunosuppression regimens become increasingly apparent. Although up to 70% of patients develop a histological infiltrate of the graft (acute rejection), many of these will resolve spontaneously, and chronic rejection is rare. If a robust form of allograft acceptance or tolerance can be established, then immunosuppression can be withdrawn along with all the accompanying risks. The liver is already known to be associated with downregulated immune responses; the mechanism for this is unclear, but may be related to a number of mechanisms known to be involved in peripheral tolerance. There are many strategies being studied for achieving allograft tolerance, including the use of modern immunosuppressants, antibodies that target key molecules in the immune response, and recruitment of leukocytes to allografts. In the interim, it is necessary to look for safe protocols that allow trials of tolerance strategies without putting patients at increased risk.

Animals↗
PubMed2002

The role of hemochromatosis susceptibility gene mutations in protecting against iron deficiency in celiac disease.

BACKGROUND & AIMS: Celiac disease and hereditary hemochromatosis are common HLA-defined conditions in northwestern Europe. We sought to determine whether there is a genetic relationship between the 2 diseases and if hemochromatosis susceptibility gene (HFE) mutations are protective against iron deficiency in celiac disease. METHODS: Polymerase chain reaction amplification using sequence-specific primers capable of identifying the 2 HFE gene mutations (H63D and C282Y) and the HLA class I and II alleles was used to type 145 white patients with celiac disease and 187 matched controls. Hemoglobin and fasting serum iron levels in celiac patients were measured at diagnosis. RESULTS: HFE gene mutations, H63D or C282Y, were identified in 70 celiac patients (48.3%) and 61 controls (32.6%) (P = 0.004). The C282Y mutation was associated with HLA-A*03 and B*07 alleles in controls and with A*01, A*03, B*08, and DRB1*0301 alleles in celiac patients; the H63D mutation was associated with HLA-A*25 and DRB1*03 alleles in controls and A*29 and DRB1*03 alleles in celiac patients. At diagnosis, celiac patients with the C282Y mutation had higher mean hemoglobin and fasting serum iron levels compared with the HFE wild type (P = 0.0002 and 0.006, respectively). This was not observed with the H63D mutation. CONCLUSIONS: In celiac disease, HFE gene mutations are common and are in linkage disequilibrium with different HLA alleles compared with controls. A disease-specific haplotype that carries C282Y and DQB1*02 is suggested. We propose that HFE gene mutations provide a survival advantage by ameliorating the iron deficiency seen in celiac patients.

Adult↗
PubMed2002

Surgical treatment of the ischemic mitral valve.

The best management for moderate mitral regurgitation (MR) at the time of coronary revascularization remains controversial. During the era preceding standardization of mitral annuloplasty, coronary artery bypass grafting (CABG) alone was the most common strategy for ischemic MR. This approach avoided mitral valve replacement, and there was an expectation that myocardial revascularization would improve papillary muscle function and valve performance. Long-term follow up revealed, however, a relationship between residual MR and mortality. Recent studies have further refined management of ischemic MR. It is now understood that Carpentier type IIIb dysfunction is the basis for ischemic MR, and that a reduction remodeling annuloplasty can improve leaflet coaptation in this setting. Mortality after combined CABG and mitral annuloplasty has decreased in our institution from 14% to 4% over the past decade. Furthermore, a strategy of CABG alone will leave a significant number of patients (approximately 40%) with moderate to severe MR. Our current approach is to explore all valves at the time of CABG with documented grade 3+ MR on preoperative transthoracic echocardiography. Intraoperative transesophageal echocardiography (TEE) underestimates moderate MR. In patients with a lesser degree of MR, intraoperative provocative testing guides our valve strategy. Severe left ventricular dysfunction and a history of congestive heart failure will also influence the decision regarding valve exploration at the time of CABG. A prospective randomized trial between CABG and CABG + mitral annuloplasty is necessary to further define the best management strategy for patients with moderate ischemic MR.

Humans↗
PubMed2002

Management of mild to moderate aortic stenosis at the time of coronary artery bypass grafting.

An increasing number of patients are referred for coronary artery bypass surgery (CABG) with the presence of mild to moderate aortic stenosis (AS). It is well accepted that patients with severe AS and coronary artery disease (CAD) should undergo combined aortic valve replacement (AVR) and CABG, which carries an operative mortality of approximately 5-7%. For patients with CAD and mild AS, controversy persists regarding concomitant AVR during CABG. It has been shown that AS progresses at a rate of 5-10 mmHg per year, and the valve area decreases by about 0.1 cm2 per year. The progression of AS is more rapid in elderly patients, in the presence of CAD, and in patients with a calcific degenerative etiology. In contrast, patients with congenital bicuspid valves or rheumatic pathology demonstrate slower progression of disease. Despite these observations, it is difficult to predict reliably the progression of disease for an individual. Thus, an attempt should be made to identify patients who are likely to progress rapidly from mild to severe AS and who would therefore benefit from AVR/CABG. Our approach regarding the decision to perform an AVR/CABG is based on aortic valve gradient and area. If the gradient is >25 mmHg, AVR should be considered. If the gradient is <10 mmHg, then only CABG is performed. Severities of leaflet calcification and leaflet mobility are factors that should be taken into account when deciding to perform concomitant AVR/CABG for intermediate gradient (10-25 mmHg). Additional important variables include the etiology of aortic valve disease, the rate of progression of AS, the patient's life expectancy, and general condition. For patients with mild AS who are undergoing CABG, a tailored approach involving intraoperative transesophageal echocardiography and valve inspection is the most appropriate surgical option.

Aortic Valve Stenosis↗
PubMedDate not supplied

Lymphocyte homing in the pathogenesis of extra-intestinal manifestations of inflammatory bowel disease.

Inflammatory bowel disease is associated with extra-intestinal manifestations which occur either at the same time as flares of bowel inflammation (skin and eye disease) or run a course that is independent to inflammation in the bowel (liver and some joint syndromes). It has been suggested that the skin and eye complications occur as a consequence of the recruitment of activated effector cells released from the gut into the circulation to extra-intestinal site where they cause acute damage. However, this does not explain how patients can develop primary sclerosing cholangitis many years after having their colon removed for colitis. We propose that long-lived populations of memory lymphocytes arise as a consequence of bowel inflammation and that these cells express homing receptors that direct their subsequent migration not only to the gut but also to the liver. These long-lived cells may recirculate to the liver for many years and, in the absence of a local activating stimulus, will not cause damage. However, if they are subsequently activated in the liver this will lead to the development of inflammation and tissue damage which promotes the recruitment of more mucosal lymphocytes resulting in persistent inflammation and disease. The recent findings that MAdCAM-1 and CCL25, previously thought to be restricted to the gut, are up-regulated in the liver during inflammatory liver diseases that complicate IBD support the concept that common mechanisms control lymphocyte recruitment to the inflamed liver and gut.

Cell Movement↗