A cemented mobile-bearing total knee replacement prevents periprosthetic loss of bone mineral density around the femoral component: a matched cohort study.

Bone mineral density (BMD) around the femoral component has been reported to decrease after total knee replacement (TKR) because of stress shielding. Our aim was to determine whether a cemented mobile-bearing component reduced the post-operative loss of BMD. In our study 28 knees receiving a cemented fixed-bearing TKR were matched with 28 receiving a cemented mobile-bearing TKR. They underwent dual-energy x-ray absorptiometry, pre-operatively and at three weeks and at three, six, 12, 18 and 24 months post-operatively. The patients were not taking medication to improve the BMD. The pre-operative differences in the BMD of the femoral neck, wrist, lumbar spine and knee in the two groups were not significant. The BMD of the femur decreased postoperatively in the fixed-bearing group, but not the mobile-bearing group. The difference in the post-operative change in the BMD in the two groups was statistically significant (p < 0.05) at 18 and 24 months. Our findings show that a cemented mobile-bearing TKR has a favourable effect on the BMD of the distal femur after TKR in the short term. Further study is required to determine the long-term effects.

Relationships between matrix metalloproteinases and tissue inhibitor of metalloproteinases in the wall of abdominal aortic aneurysms.

AIM: The pathologic feature of aortic aneurysm is considered to be the remodeling of the aortic wall, involving fragmentation and decrease of elastic fibers in the tunica media. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated in collagen and elastin degeneration within the aortic wall. The precise relationship among MMPs and tissue inhibitor of metalloproteinases (TIMPs) is still unclear. We have studied the expression of MMP-2, MMP-9 tissue inhibitor of metalloprotein-1 (TIMP-1), TIMP-2 and membrane type 1-MMP (MT-1-MMP) in the wall of small AAAs (30-45 mm), large AAAs (>45 mm) and controls (<25 mm). We investigated the relationship among expressions of MMP-2, TIMP-2 and MT1-MMP in the walls. METHODS: The aortic walls in the patients with AAA were harvested from the maximum diameter, while the aortic walls in autopsy cases were harvested as controls. We analyzed tissue distribution of cell types by immunochemistry, protein expression by Western blotting and mRNA expression by competitive polymerase chain reaction. RESULTS: They consisted of 11 in controls, 8 in small AAAs and 26 in large AAAs. Among the MMPs-positive-cells, mainly macrophage, MMP-2-positive cells were in the intima, but MMP-9-positive cells in the intima and adventitia. In the small size, MMP-2 and MMP-9 mRNA were higher than those of control. In the large size, MT1-MMP and MMP-9 mRNA were higher than those of the controls. In the mRNA level of the whole AAA, significant correlations were present between MMP-2 and MMP-9, between MMP-2 and TIMP-1, and between MMP-9 and TIMP-1. These expressions were confirmed by Western blotting. CONCLUSION: We concluded as follows: 1) MMP-2 and MMP-9 may play an important role in the developmental process of AAA. 2) TIMP-1 plays an important role of interacting MMP-2 and/or MMP-9. 3) MMP-2 and MT1-MMP may play an important role in the early stages of AAAs.

Left-side dominance for song discrimination in Bengalese finches (Lonchura striata var. domestica).

Male Bengalese finches are left-side dominant for the motor control of song in the sensorimotor nucleus (the high vocal center, or HVc) of the telencephalon. We examined whether perceptual discrimination of songs might also be lateralized in this species. Twelve male Bengalese finches were trained by operant conditioning to discriminate between a Bengalese finch song and a zebra finch song. Before training, the left HVc was lesioned in four birds and the right HVc was lesioned in four other birds. The remaining four birds were used as controls without surgery. Birds with a left HVc lesion required significantly more time to learn to discriminate between the two songs than did birds with a right HVc lesion or intact control birds. These results suggest that the left HVc is not only dominant for the motor control of song, but also for the perceptual discrimination of song.

Limited auditory memory for conspecific songs in a non-territorial songbird.

Males of territorial songbird species have to remember a large number of conspecific songs to defend their territories, while non-territorial songbirds do not need to. A study of a territorial species suggested seemingly unlimited auditory memory size. We measured auditory memory in Bengalese finches, a non-territorial songbird species, to examine whether the auditory memory size for conspecific songs depends on the ecological requirements for song use. Five birds were trained by operant techniques to classify song stimuli into two arbitrary categories. The learning curve reached an asymptote within approximately 100 sessions in all five birds and only eight songs were concurrently remembered on average. Results suggest that ecological requirements for song use are correlated with the auditory song memory capacity.

Percutaneous balloon fenestration in a case of traumatic abdominal aortic dissection with lower extremity ischemia.

A 38-year-old man was involved in a traffic accident and experienced a heavy blow to the abdomen. He had traumatic abdominal aortic dissection with right lower extremity ischemia. He underwent percutaneous balloon fenestration, which is safe and minimally invasive, for relief of right lower extremity ischemia. He has been working for 2 years without any signs of vascular compromise. Percutaneous balloon fenestration is one of the few treatments for traumatic abdominal aortic dissection.

[Coronary artery bypass grafting for a patient with bronchial asthma seceeded from cardiopulmonary bypass by additional bypass for spasm of radial artery graft: a case report].

A 78-year-old male who had a bronchial asthma underwent coronary artery bypass grafting (CABG) using the left internal thoracic artery and the radial artery. The patient could not be weaned from the cardiopulmonary bypass because the radial artery which anastomosed to the obtuse marginal artery (OM) had a spasm after CABG. An additional bypass using a long saphenous vein to OM was carried out immediately. It brought a weaning from cardiopulmonary bypass. If the cardiac function after CABG is insufficient in patients with bronchial asthma, CABG must be re-done immediately, considering that they cause the arterial spasm more than patients without bronchial asthma.

Effect of bezafibrate treatment on the altered lipoprotein profiles in hypertriglyceridemic subjects.

The effects of bezafibrate treatment on lipoprotein metabolism were investigated in hypertriglyceridemic subjects. Bezafibrate, a fibric acid derivative, was administered at 200-400 mg/day to 8 patients with hyperlipoproteinemia (type IIb and IV) for 3-6 months. We evaluated the effects of bezafibrate on the plasma levels of total cholesterol(chol), triglyceride(TG), and apoB. In addition, the lipid and apoB contents were also analyzed in VLDL, IDL, LDL and HDL fractions before and after the treatment. It was revealed that plasma levels of chol, TG and apoB significantly decreased after the treatment, 236.3 vs 210.9,192.4 vs 90.2 (p< 0.01) and 129.8 vs 116.2 (p<0.05) mg/dl respectively. VLDL-chol, VLDL-TG and VLDL-apoB dropped from 26.5,127.6 and 11.1 mg/dl to 9.1, 49.5 and 6.7 mg/dl respectively after the treatment. Regarding qualitative alterations of VLDL, TG/apoB, chol/apoB and TG + chol/apoB ratios in VLDL were significantly reduced, indicating that the size of VLDL was diminished by the treatment. In addition, HDL-chol increased from 40.4 to 60.8 mg/dl after the treatment. Consequently LDL-chol/HDL-chol significantly decreased. In conclusion, bezafibrate administration decreased the TG, chol and apoB content in VLDL, suggesting a reduced number of VLDL. Significant rise of HDL-chol and decrease of LDL-chol/HDL-chol are additional beneficial effects following bezafibrate treatment.

Pulmonary embolism in patients with isolated soleal vein thrombosis.

This study investigated the features of calf deep vein thrombosis (DVT) as a pulmonary embolic source. Fifty-eight lower limbs in 29 patients who were suspected of having DVT distal to the popliteal vein were screened by ultrasonography. Then, ascending venography was performed to confirm the diagnosis. Pulmonary embolism (PE) was diagnosed in suspected patients by use of pulmonary perfusion scanning or pulmonary angiography. Venography revealed calf DVT in 33 limbs in 28 patients. Of 28 patients, six had symptomatic PE. Thrombosis was found in the muscle veins in 18 limbs, the trunk veins in 11, and both veins in four. Isolated single vein thrombosis was found in the soleal vein in 14 limbs (42%), the posterior tibial vein in eight, the peroneal vein in two, and the gastrocnemius vein in two. The overall percentage of soleal vein thrombi was 61%. All six patients with symptomatic PE had isolated soleal vein thromboses. Calf DVT was a pulmonary embolic source when isolated thrombosis of the large soleal vein was more than 7 mm in diameter. Soleal veins were the most frequent and important location of calf DVT, suggesting that these were an occasional embolic source of critical PE.

Pioglitazone enhances splanchnic glucose uptake as well as peripheral glucose uptake in non-insulin-dependent diabetes mellitus. AD-4833 Clamp-OGL Study Group.

To evaluate the effect of pioglitazone on insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) patients, a double-blind placebo-controlled trial was carried out with 30 NIDDM patients. Twenty-one subjects, three on diet alone and 18 on sulfonylurea (SU), orally received 30 mg pioglitazone once daily for 12 weeks. Nine subjects, one on diet alone and eight on SU, received a matching placebo once daily for 12 weeks. Euglycemic (5.2 mmol/l) hyperinsulinemic (1200 pmol/l) clamp combined with an oral glucose load (OGL) was performed before and after 3-month treatment with pioglitazone or placebo to determine insulin-stimulated glucose disposal and splanchnic glucose uptake (SGU). No significant differences existed in the patients' characteristics, including age and body mass index, between the two study groups. The pioglitazone treatment increased the mean glucose infusion rate (GIR) prior to OGL from 8.2 +/- 2.2 to 9.2 +/- 2.0 mg/kg.min (mean +/- SD, P = 0.003) and increased the SGU rate from 28.5 +/- 19.4 to 59.4 +/- 27.1% (P = 0.010). The placebo treatment produced no significant changes in either GIR or SGU after treatment. A significant difference (P = 0.042) was observed in change of SGU between the pioglitazone and placebo treatment groups. In conclusion, the results indicate that pioglitazone is effective for ameliorating insulin resistance in NIDDM by enhancing SGU as well as peripheral glucose uptake.

Recovery from sublethal damage is reversibly inhibited by hypertonic saline: the effects of 0.23 M sodium chloride.

We previously showed that 0.23 M NaCl was able to fix slowly repairing potentially lethal damage (PLD), and that this slowly repairing PLD is distinct from rapidly repairing PLD that is sensitive to 0.5 M NaCl (Ikebuchi et al., Radiat. Res. 141, 19-27, 1995). In the present study, the effect of 0.23 M NaCl on repair of sublethal damage (SLD) was examined in cells of three rodent cell lines with normal radiosensitivity (Chinese hamster V79, BALB/c 3T3, RD13B2) and two radiosensitive lines derived from severe combined immunodeficient (scid) mice. Repair of SLD was detected as an increase in survival when the radiation dose was fractionated with an interval of incubation between the two doses. Repair of SLD occurred in V79 and BALB/c 3T3 cells but did not occur in the two scid cell lines which were defective in repair of double-strand breaks (DSBs), demonstrating that repair of DSBs is involved in repair of SLD. This was confirmed by the observation that repair of SLD occurred in RD13B2 cells, the scid line which had regained the ability to repair DSBs. When the V79 and BALB/c 3T3 cells were treated with 0.23 M NaCl during the interval between the split doses, repair of SLD was completely inhibited. On the other hand, repair of SLD occurred when the cells were incubated in culture medium between the treatment with 0.23 M NaCl and the second dose. From these observations, it is concluded that the inhibition of repair of SLD by 0.23 M NaCl is reversible, which is in contrast to the irreversible inhibition of repair of PLD by 0.23 M NaCl found previously. In addition, the fact that scid cells that were shown to have the ability to repair PLD that is sensitive to 0.23 M NaCl had little capacity to repair SLD suggests that there may be different processes involved in the two types of cellular repair.

Development of approximate formula for LDL-chol, LDL-apo B and LDL-chol/LDL-apo B as indices of hyperapobetalipoproteinemia and small dense LDL.

Estimation of LDL-chol and LDL-apo B is useful for the diagnosis of hyperapobetalipoproteinemia (normal LDL-chol with increased LDL-apo B), which is one of the most commonly occurring lipoprotein disorders associated with atherosclerotic cardiovascular diseases. The LDL-chol/LDL-apo B ratio reflects the level of small dense LDL, which is an important risk factor for IHD, CVD and ASO. In order to estimate LDL-apo B and LDL-chol/LDL-apo B ratio from blood chol, TG, HDL-chol and apo B values, we developed a formula for LDL-chol ¿0.94Chol- 0.94HDL-chol - 0.19TG¿, LDL-apo B ¿apo B - 0.09Chol + 0.09HDL-chol-0.08TG¿, and LDL-chol/LDL-apo B [¿0.94Chol-0.94HDL-chol - 0.19TG¿/¿apo B - 0.09Chol + 0.09HDL-chol-0.08TG¿] using ultracentrifugal data from 2179 subjects. These were calculated by the least squares method on the assumption that a certain compositional relationship exists between Chol, TG and apo B in VLDL, IDL and LDL. Friedewald's formula for LDL-chol (Chol - HDL-chol - 0.2TG) includes IDL-chol, but the present new formula theoretically excludes IDL-chol. It suggests a better estimation for the correct LDL-chol. Estimated LDL-apo B is useful for the diagnosis of hyperapobetalipoproteinemia and detection of small dense LDL. Without performing ultracentrifuge, additional information is obtained for the quantitative and qualitative alteration of LDL, such as small dense LDL. The above formulae and a new classification of lipoproteinemia including apo B were applied to the analyses of lipoprotein profiles of subjects with cardiovascular diseases, which were compared with those in the general population. Hyperapobetalipoproteinemia with high TG was observed 2-3 times more frequently in subjects with CAD, MI and ASO than in the Suita population. Lower ratios of LDL-chol/LDL-apo B, reflecting preponderance of small dense LDL, were observed in the above three groups. Type IIb and combined low HDL-chol were also frequent phenotypes in CAD, A-Th and ASO. The present formulae are useful for the detailed analyses of lipoprotein disorders in both qualitative as well as quantitative aspects.

Pyruvate improves deleterious effects of high glucose on activation of pentose phosphate pathway and glutathione redox cycle in endothelial cells.

In our previous study (Diabetes 44:520-526, 1995), endothelial cells cultured in high glucose condition showed impairment of an oxidant-induced activation of the pentose phosphate pathway (PPP) and a reduced supply of NADPH to the glutathione redox cycle. To gain insight into the mechanisms of this impairment, the protective effect of pyruvate was studied in human umbilical vein endothelial cells cultured in either 5.5 mmol/l glucose (normal glucose [NG] condition) or 33 mmol/l glucose (high glucose [HG] condition). Through pretreatment of cells with 0.2 mmol/l pyruvate for 5-7 days in the HG condition, glucose oxidation through the PPP and total cellular NADPH content in the presence of 0.2 mmol/l H2O2 were increased by 54 (P < 0.05) and 34%, respectively, and glutathione-dependent degradation of H2O2 in HG cells was enhanced by 41% (P < 0.01), when compared with those cells to which pyruvate was not added. The addition of pyruvate significantly reduced the fructose 1,6-bisphosphate (FDP) content and free cytoplasmic NADH/NAD ratio, estimated by increased pyruvate/lactate ratio in NG and HG cells exposed to H2O2. Furthermore, the addition of pyruvate also showed a 46% reduction (P < 0.01) of endothelial cell damage induced by H2O2 in HG cells. These results indicate that abnormalities in PPP activation and glutathione redox cycle activity induced by H2O2 in HG cells are compensated, and that the accentuated reductive stress is improved by an addition of pyruvate. These pyruvate effects are associated with protection against an oxidant-induced endothelial cell injury in the high glucose condition.

The scid mutation does not affect slowly repairing potentially lethal damage that is sensitive to 0.23 M NaCl.

The repair of slowly repairing potentially lethal damage (PLD) in radiosensitive cells from the severe combined immunodeficient (scid) mouse was compared with that in Balb/c 3T3 cells with "wild-type" radiosensitivity and that in RD13B2 cells derived from scid cells whose sensitivity is normal because of the presence of fragments of human chromosome 8. Treatment with 0.23 M NaCl was used for fixation of slowly repairing PLD. The scid cells repaired PLD sensitive to 0.23 M NaCl to a great extent whin 3-4 h, similarly to Balb/c 3T3 and RD13B2 cells. This indicates that the scid mutation hardly affects the repair of PLD sensitive to 0.23 M NaCl. On the other hand, as reported previously, the rapidly repairing PLD that is sensitive to 0.5 M NaCl was repaired only slowly (3-4 h) in scid cells, in contrast to the rapid repair (within 1 h) seen with Balb/c 3T3 and RD13B2. This suggests that scid mutation is responsible for this repair at reduced rate. To confirm the independence of repair of 0.23 M NaCl-sensitive PLD from that of 0.5 M NaCl-sensitive PLD, both treatments with 0.23 M NaCl and 0.5 M NaCl were combined in each line. It is found that the repair of either PLD was not affected by the other treatment. The scid mutation impaired only the repair of 0.5 M NaCl-sensitive PLD.

Lipoprotein analyses in patients with stable angina and acute coronary syndrome.

We have performed lipid analyses by using a table-top ultracentrifuge based on the Hatch and Lees' method in 77 subjects (60 men, 17 women: mean age, 63 years) to clarify lipoprotein disorders in coronary artery disease. Sixty-four subjects had coronary artery disease and 13 normal subjects were controls. They were divided into the groups with stable angina pectoris and with unstable angina pectoris or acute myocardial infarction (acute coronary syndromes). In patients with coronary artery disease, there were no significant differences from control in age, body mass index, total cholesterol, however, HDL cholesterol was significantly lower than those in the controls. LDL cholesterol:LDL apoB ratio, which is thought to reflect the size of LDL in coronary artery disease, was significantly smaller than that in the controls; mean values were 1.2 in coronary artery disease and 1.4 in controls. There were no significant differences in those lipoprotein disorders between the patients with stable angina and those with acute coronary syndromes. Though these lipoprotein abnormalities would not play a trigger role in acute coronary syndrome, they are characteristic of the lipid profile of patients with coronary artery disease.

Quantitative and qualitative derangement of apolipoprotein B-containing lipoproteins as a risk factor for diabetic macroangiopathy in nonobese NIDDM subjects.

Cholesterol, triglyceride (TG), and apolipoprotein (apo) B were determined in plasma and in lipoprotein subfractions (VLDL, intermediate-density lipoproteins [IDL], LDL, and HDL) in nonobese NIDDM subjects, who were classified into well-controlled, fairly controlled, or poorly controlled states with or without macrovascular complications (macroangiopathy [MA]). The same analyses were also performed on subjects who had coronary artery disease (CAD) with stable angina pectoris (SA) or unstable angina pectoris (UA) and acute myocardial infarction, cerebrovascular disease (CVD) with atherothrombotic or lacunar infarction, and arteriosclerosis obliterans (ASO). In nonobese NIDDM subjects, the number of apoB-containing lipoproteins (VLDL, IDL, and LDL) increased. This alteration was more prominent in subjects with poorly or fairly controlled disease as well as in subjects with MA, but not in those with well-controlled NIDDM. Cholesterol/apoB in LDL decreased in subjects with poorly or fairly controlled diabetes or with MA and was correlated with low HDL cholesterol. The disorder is characterized by hyperbetalipoproteinemia with elevated LDL cholesterol and small dense LDL. In obese NIDDM subjects, the similar disorder was more pronounced. Glycemic control had less effect and hyperinsulinemia, if present, aggravated the lipid disorder. In those with CAD, the number of IDLs increased and the LDL fraction had the properties of small dense LDL. HDL cholesterol decreased. In those with UA, the LDL number increased without elevation of LDL cholesterol, indicating typical hyperbetalipoproteinemia. The subjects with atherothrombotic brain infarction, an increased number of small-sized LDLs was noted. In those with ASO, the number of VLDL and IDL increased with small LDL. HDL cholesterol decreased in those with CAD, cerebrovascular disease, and ASO. Since similar quantitative and qualitative alterations of apoB-containing lipoprotein have been observed in NIDDM patients as well as in those with macrovascular diseases, diabetic patients are thought to be more susceptible to the initiation and progression of atheromatous lesions in coronary, brain, and peripheral arteries.

Mechanism and clinical implication of insulin resistance syndrome.

The insulin resistance syndrome has been noted as an interesting and important new risk factor for coronary artery disease. The syndrome consists of hypertension, glucose intolerance, and dyslipidemia, all of which are likely to be derived from insulin insensitivity. In subjects with nonobese and nondiabetic essential hypertension, steady-state plasma glucose (SSPG) was higher than in normotensive subjects during an insulin sensitivity test, indicating reduced insulin sensitivity to glucose metabolism in the hypertensive group. SSPG correlated with the percentage decrease of branched chain amino acids, free fatty acids, and serum potassium during the insulin sensitivity test. With a 2-h insulin infusion, serum norepinephrine, epinephrine, plasminogen activator inhibitor 1, and intraplatelet Ca2+ decreased significantly, but 6-keto-prostaglandin (PG) F1 alpha and PGE2 did not change. Insulin resistance decreased by using antihypertensive treatments with bunazosin, cilazapril, amlodipine, and benidipine in hypertensive subjects. Diagnostic criteria for the insulin resistance syndrome, including clinical values for each risk factor, were developed. Lowered insulin sensitivity and hyperinsulinemia were demonstrated in subjects with both vasospastic and coronary artery stenotic angina. The insulin resistance syndrome together with hyperinsulinemia is likely to induce atherosclerotic changes, possibly through reduced rather than excessive action of insulin.

Glycation, oxidative stress, and scavenger activity: glucose metabolism and radical scavenger dysfunction in endothelial cells.

It has been reported that oxidative stress is increased in vivo in the diabetic state. Increased oxidative stress is caused not only by accelerated production of oxygen-free radicals but also by decreased scavenging of those molecules. Endothelial cells are extremely sensitive to oxidative stress, resulting in impairments of various endothelial cell function. In this report, we studied the association of intracellular glucose metabolism and oxygen radical scavenging function via the glutathione redox (GR) cycle in cells exposed to high-glucose conditions using cultured human umbilical vein endothelial cells. Glutathione-dependent H2O2 degradation in cells exposed to 33 mmol/l glucose (HG) for 5-7 days was reduced by 48% vs. 5.5 mmol/l glucose (NG). This impairment under the oxidative stress was D-glucose-specific and concentration-dependent and was also associated with a 42% decrease in intracellular NADPH content. Exposure of cells to 200 micromol/l H2O2 stimulated the GR cycle and the pentose phosphate pathway (PPP) at the same time. In the HG condition, activation of PPP was reduced by 50%, which was consistent with a decrease in NADPH content. Inhibition of glycolysis by H2O2 was less marked in HG cells versus NG cells. Activation of polyol pathway in HG cells is not responsible for the decrease in intracellular NADPH content. These results indicate that activation of the PPP and NADPH supply to the GR cycle is impaired in HG cells exposed to H2O2, which may result in increased oxidative stress to endothelial cells.

Improvement of insulin sensitivity and dyslipidemia with a new alpha-glucosidase inhibitor, voglibose, in nondiabetic hyperinsulinemic subjects.

This study was undertaken to investigate the effect of voglibose, a new alpha-glucosidase inhibitor, on glucose and lipid metabolism in nondiabetic hyperinsulinemic subjects. Sixteen nondiabetic subjects with hyperinsulinemia participated in the study. They were divided into two groups of eight subjects with normal (NGT) and impaired (IGT) glucose tolerance. A meal tolerance test and a 75-g oral glucose tolerance test (OGTT) were performed at the beginning (baseline phase) and end (treatment phase) of the 12-week treatment. Serum lipid levels were measured every 4 weeks throughout the treatment phase and follow-up phase (8 weeks). All patients received 1 0.2-mg tablet of voglibose before each test meal (3 tablets per day). We also measured insulin sensitivity using a steady-state plasma glucose (SSPG) method in eight normotensive hyperinsulinemic subjects and in eight age- and body mass index (BMI)-matched control subjects before and after the drug treatment. Voglibose significantly decreased the responses of plasma glucose and insulin on the meal tolerance test. The area under the curve for 2-hour insulin during the 75-g OGTT decreased after treatment, whereas that for 2-hour glucose did not change before and after treatment. SSPG was reduced after treatment, indicating improvement of insulin sensitivity. Moreover, treatment with voglibose resulted in a significant decline of triglyceride level and an elevation of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1. These values returned to near-baseline levels after the drug was discontinued. Consequently, we conclude that this agent not only has a direct hypoglycemic effect through decreased absorption of carbohydrate, but also a hypoinsulinemic and hypolipidemic effect via improved insulin sensitivity.