A Targeted Genetic Association Study of the Rare Type of Osteomyelitis.

Chronic nonbacterial osteomyelitis is a rare bone disorder that can be found in the jaw. It is often associated with systemic conditions, including autoimmune deficiencies. However, little is known about how the genetic and immunologic background of patients influences the disease. Here, we focus on human leukocyte antigen (HLA), killer cell immunoglobulin-like receptors (KIRs), and their specific combinations that have been difficult to analyze owing to their high diversity. We employed a recently developed technology of simultaneous typing of HLA alleles and KIR haplotype and investigated alleles of the 35 HLA loci and KIR haplotypes composed of centromeric and telomeric motifs in 18 cases and 18 controls for discovery and 472 independent controls for validation. We identified an amino acid substitution of threonine at position 94 of HLA-C in combination with the telomeric KIR genotype of haplotype tA01/tB01 that had significantly higher frequency (>20%) in the case population than in both control populations. Multiple logistic regression analysis based on a dominant model with adjustments for age and sex revealed and validated its statistical significance and high predictive accuracy (C-statistic ≥0.85). Structure-based analysis revealed that the combination of the amino acid change in HLA-C and the telomeric genotype tA01/tB01 could be associated with lower stability of HLA-C. This is the first case-control study of a rare disease that employed the latest sequencing technology enabling simultaneous typing and investigated amino acid polymorphisms at HLA loci in combination with KIR haplotype.

Coronary artery bypass surgery in patients with angina pectoris and hypothyroidism.

The treatment of hypothyroidism in patients undergoing coronary artery bypass surgery is a difficult clinical problem. To determine perioperative thyroid replacement therapy in patients with hypothyroidism, plasma total thyroxine (T4), total triiodothyroxine (T3), free T4, free T3 and thyroid-stimulating hormone levels were measured preoperatively and at 1, 2, 3, 7, and 14 days after operation in 9 patients with hypothyroidism and were compared with levels in 14 patients with normal thyroid function who underwent coronary bypass surgery. In the normal control group, total T4 decreased to its lowest level on the 1st postoperative day and then increased gradually to the preoperative level at 7 days. Total T4 remained within the normal range throughout the entire postoperative course. In 6 patients with hypothyroidism who were treated with thyroid hormone before surgery, total T4 decreased immediately after operation and only increased after starting thyroid replacement therapy. In 3 hypothyroid patients without prior thyroid replacement, total T4 showed a change similar to patients in the control group but remained below the normal range until starting thyroid replacement therapy. Coronary bypass surgery was performed safely in patients with hypothyroidism. Preoperative thyroid replacement with suboptimal doses was safe in patients with severe hypothyroidism. Adequate postoperative thyroid replacement was achieved in all patients without complications.

[Surgical treatment of ischemic heart disease combined with hypothyroidism].

Treatment for patients with ischemic heart disease and hypothyroidism contains many difficulties, such as a dilemma that thyroid hormone to hypothyroid patients may worsen angina. The purpose of this study is to propose an appropriate control of thyroid function in these patients before coronary artery bypass grafting (CABG), and to clarify the change of thyroid function during postoperative period. Because of progressive angina pectoris, five hypothyroidism patients underwent CABG. Preoperatively, minimal dose of L-Thyroxine (0-75 micrograms, daily) was administered orally to keep thyroid function at slightly low level before CABG. Ten consecutive CABG patients with normal thyroid function were selected as control group. Between both groups, there was no significant difference in age, coronary artery disease, and the number of bypass grafts. Serum T4, free-T4, T3, free-T3, and TSH were measured at 1st, 2nd, 3rd, and 7th P.O.D. In control group, pituitary-thyroid function was suppressed transiently. In hypothyroid group, T4 revealed no change and was kept at slightly low level during observed period. There was no significant difference in postoperative hemodynamics between both groups. Postoperatively all of hypothyroid patients got free from angina and received an adequate thyroid hormone replacement therapy without complications. It is concluded that CABG for patients with angina and hypothyroidism can be performed safely by keeping preoperative thyroid function at slightly low level.

Evaluation of postoperative flow capacity of internal mammary artery.

The internal mammary artery has been advocated for use in coronary artery bypass grafting because of its excellent long-term patency. We compared the flow capacities of internal mammary artery and saphenous vein grafts under exercise conditions by means of radionuclide angiocardiography. Fifty-two patients were divided according to the type of bypass graft done to the left anterior descending artery: group 1 comprised 27 patients with the internal mammary artery graft, and group 2 included 25 patients with the saphenous vein graft. Saphenous vein grafts were placed into the right and circumflex systems. Before the operation, global and regional ejection fractions decreased similarly in both groups with exercise. After the operation, the global ejection fraction measured in groups 1 and 2 increased significantly from 54% +/- 2% to 57% +/- 2% and from 54% +/- 1% to 60% +/- 2%, respectively, the anteroseptal ejection fraction from 29% +/- 1% to 32% +/- 2% and from 29% +/- 1% to 35% +/- 1%, respectively, and the apical ejection fraction from 75% +/- 3% to 82% +/- 2% and from 77% +/- 2% to 86% +/- 2%, respectively. There were no differences in exercise-induced increases in the global and regional ejection fractions between groups 1 and 2. Six patients in group 1 had exercise-induced wall motion abnormalities at the anteroseptal and/or apical segments. In contrast, patients in group 2 had no exercise-induced wall motion abnormalities at these segments (p less than 0.05, group 1 versus group 2). Results of this study show that internal mammary artery grafts respond to the increased blood flow demand of exercise in essentially the same way as saphenous vein grafts. However, there seems to be a slightly greater potential for inadequate flow in patients with the internal mammary artery graft, as evidenced by the small group of patients with exercise-induced wall motion abnormalities.

[Evaluation of internal mammary artery graft patency by intraarterial digital subtraction angiography].

Intraarterial digital subtraction angiography (DSA) was performed to evaluate graft patency in 45 patients undergoing coronary artery bypass grafting with the use of internal mammary artery (IMA). Fourty-five IMA grafts and 59 saphenous vein grafts were evaluated using a DSA equipment with a pulse mode of 2 frames per second. A 4F catheter was introduced percutaneously into the left brachial artery. Nonionic contrast medium was nonselectively injected into the left subclavian artery for visualization of IMA grafts and also into the aortic root for visualization of vein grafts. No serious complications occurred. Forty-four IMA grafts and 53 vein grafts were patent. The patency rate was 97.8% for IMA grafts, 89.8% for vein grafts, and 93.3% for all grafts. In 11 patients (24%), intercostal or pericardial branches were visualized. Two patients showed a string sign of the IMA. Intraarterial DSA with nonselective injection of contrast medium into the subclavian artery is a new method for evaluation of IMA graft patency with a low risk.

Intraarterial digital subtraction angiography for evaluation of internal mammary artery graft in coronary bypass surgery.

Digital subtraction angiography (DSA) was performed to evaluate graft patency in 60 patients who had undergone coronary artery bypass grafting with the internal mammary artery (IMA). Sixty IMA grafts with 62 distal anastomoses, and 84 saphenous vein grafts with 85 distal anastomoses were evaluated by intraarterial DSA with an image frequency of 4 frames/sec. A No. 4 Fr. angiography catheter was introduced percutaneously into the left brachial artery and contrast medium was injected both into the subclavian artery for opacification of the IMA grafts and into the ascending aorta for opacification of aortocoronary saphenous vein grafts. Bypass grafts were defined as patent when grafts were opacified through their entire course, including anastomotic sites. Fifty-nine IMA grafts with 61 distal anastomoses (98%) and 76 saphenous vein grafts with 77 distal anastomoses (91%) were patent. The overall patency rate for total grafts was 94%. In 4 patients, DSA showed a "string sign" in the IMA graft which was patent but narrowed at its distal segment. In 5 patients, large first intercostal branches were opacified. Intraarterial DSA with the retrograde brachial approach is not difficult, and is an excellent low risk method of evaluating the patency of IMA and saphenous vein grafts. DSA provided information about functional patency as well as anatomical patency of the IMA graft.

[Application of a lung stapler to reduce tension on the internal mammary artery].

In-situ internal mammary artery (IMA) grafts have a better patency rate than free IMA grafts. Every effort is made to leave the IMA as an in-situ graft attached to the subclavian artery. A 56-year-old patient underwent reoperation because of occlusion of the vein graft to the left anterior descending coronary artery (LAD). At the second operation, the left IMA was anastomosed to the segment of the LAD distal to the first anastomotic site. The hyperinflated lung crossed the midline and stretched the IMA graft. The herniated portion of the left lung which stretched the IMA graft was resected with a 9-cm long linear stapler along the course of the IMA graft. No harmful effects were observed. This is a simple and safe method to reduce the tension on the IMA graft due to the hyperinflated lung.