Monocyte chemoattractant protein-1 is associated with silent cerebral infarction in patients on haemodialysis.

BACKGROUND: In patients with chronic renal failure undergoing haemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of monocyte chemoattractant protein-1 (MCP-1) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased MCP-1 concentration correlate with the occurrence of SCI in HD patients. METHODS: Using cranial magnetic resonance imaging (MRI) findings, 52 Japanese patients undergoing HD were divided into two groups: with SCI (61 ± 7 years, mean ± SD, n= 28) and without SCI (60 ± 6 years, n= 24). The gender, metabolic profiles and MCP-1 concentration were compared between the two groups. RESULTS: The level of MCP-1 was higher in the with-SCI group than in the without-SCI group (P < 0.0001). The proportion of smokers was higher in the with-SCI group (P < 0.05) than in the without-SCI group. Plasma level of high-density lipoprotein cholesterol was lower, while uric acid level was higher, in the with-SCI group (P < 0.05 and P < 0.05 respectively) compared to the without-SCI group. Multiple logistic regression analysis identified MCP-1 level as being significantly associated with the presence of SCI (odds ratio 1.48, 95% confidence interval = 1.10-5.75, P < 0.0001). CONCLUSIONS: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI, and that MCP-1 is significantly associated with the presence of SCI in HD patients.

Interleukin-6 and silent cerebral infarction in hemodialysis patients: a cross-sectional study.

BACKGROUND: In patients with chronic renal failure undergoing hemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of interleukin-6 (IL-6) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased IL-6 levels correlate with the occurrence of SCI in HD patients. METHODS: Using cranial magnetic resonance imaging findings, we divided 50 Japanese patients undergoing HD into two groups: with SCI (60 ± 7 years, mean ± SD, n = 27) and without SCI (60 ± 6 years, n = 23). We compared the gender, body mass index, metabolic profiles, IL-6 levels, and smoking habits between the two groups. RESULTS: We made the following observations: (i) The prevalence of diabetes or hypertension did not differ between the two groups, (ii) the level of IL-6 was higher in the with-SCI group than in the without-SCI group (P < 0.0001), (iii) the proportion of smokers was higher in the with-SCI group (P < 0.05), (iv) plasma level of high-density lipoprotein cholesterol was lower, whilst uric acid level was higher, in the with-SCI group (P < 0.05 and P < 0.05, respectively), and (v) multiple logistic regression analysis identified IL-6 levels as being significantly associated with the presence of SCI (odds ratio 3.13, 95% CI = 1.42-7.89, P < 0.0001). CONCLUSIONS: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI and that IL-6 is significantly associated with the presence of SCI in HD patients.

Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and renders protection against ischemia/reperfusion injury in rat heart.

BACKGROUND: Induction of heat-shock proteins (HSPs) results in cardioprotection against ischemic insult. Geranylgeranylacetone (GGA), known as an antiulcer agent, reportedly induces HSP72 in the gastric mucosa and small intestine of rats. The present study tested the hypothesis that oral GGA would induce HSP72 in the heart and thus render cardioprotection against ischemia/reperfusion injury in rats. METHODS AND RESULTS: Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. Ten minutes of whole-body hyperthermia induced HSP72 expression in the rat hearts. A single oral dose of GGA (200 mg/kg) also induced expression of HSP72, which peaked at 24 hours after administration. Therefore, isolated perfused heart experiments using a Langendorff apparatus were performed 24 hours after administration of 200 mg/kg GGA (GGA group) or vehicle (control group). After a 5-minute stabilization period, no-flow global ischemia was given for 20, 40, or 60 minutes, followed by 30 minutes of reperfusion. During reperfusion, the functional recovery was greater and the released creatine kinase was less in the GGA group than in the control group. Electron microscopy findings revealed that the ischemia/reperfusion-induced damage of myocardial cells was prevented in GGA-treated myocytes. CONCLUSIONS: The results suggest that oral GGA is cardioprotective against ischemic insult through its induction of HSP72.

Fluorescence changes of a label attached near the myosin active site on nucleotide binding in rat skeletal muscle fibres.

1. Trinitrophenyl AMP (TNP-AMP) in the concentration range 10-300 microM induced an increase in fluorescence intensity at around 530 nm in skinned skeletal muscle fibres freshly obtained from rat psoas muscle. 2. The fluorescence intensity of the fibres depended on TNP-AMP concentration up to approximately 200 microM. The Kd of TNP-AMP binding to the muscle fibres was 38.0 +/- 8.4 microM (mean +/- s.d., n = 4 measurements) in three fibres. TNP-AMP fluorescence was readily washed out. 3. Various nucleotides affected the fluorescence of the fibres incubated in 20 microM TNP-AMP. MgATP (1 mM) and caged ATP (5 mM) reduced the fluorescence in 20 microM TNP-AMP by more than 40 % of the value measured in the absence of nucleotide. 4. When the fibres were stretched to almost no filament overlap, the extent of the quenching of the TNP-AMP (20 microM) fluorescence due to ATP binding was reduced by 14 %. This might be explained by assuming that the association of the thin filament affected the TNP-AMP fluorescence in muscle fibres. 5. The distance between the active site and the specific site for TNP was measured by the fluorescence resonance energy transfer between N-methylanthraniloyl-ATP (Mant-ATP) bound to the active site and the TNP-AMP bound to the TNP-specific site in muscle fibres. The results showed that the distance between the two may be less than 2 nm. 6. It may be concluded that the fluorescence intensity at 530 nm in skinned muscle fibres in low concentrations of TNP-AMP changes directly reflecting the conformational state of the nucleotide-binding region that is determined by the binding of nucleotides.

Rapid coronary vasodilation by nitroglycerin tapes.

We analyzed the acute, direct effects of nitroglycerin (NTG) tape on the coronary arteries and hemodynamics in 38 patients who underwent coronary angiography. The diameters of the 3 main coronary arteries were compared among the angiograms obtained at baseline, 15 minutes following transdermal administration of 10 mg (8 patients) or 25 mg (30 patients) of NTG (Millisrol tape), and after intracoronary injection of 2.5 mg isosorbide dinitrate (ISDN). Only the left main trunk and proximal portion of the left anterior descending artery dilated after 10 mg of transdermal NTG administration (p < 0.05). However, every measured coronary segment (segments 1-8, 11, and 13) dilated (p < 0.05) after 25 mg of NTG. Systemic blood pressure decreased slightly but significantly from 150 +/- 22 to 147 +/- 21 mmHg during the study, with no change in heart rate. Left ventricular end-diastolic pressure decreased significantly from 16 +/- 7 to 14 +/- 5 mmHg. We conclude that 25 mg of transdermal NTG tape dilates coronary arteries and is applicable for acute coronary syndrome, with few complications.

Plasma plasminogen activator inhibitor-1, tissue plasminogen activator and serum lipoprotein(a) after reperfusion therapy in acute myocardial infarction: comparison between sequential and direct percutaneous transluminal coronary angioplasty.

To determine which reperfusion therapy for acute myocardial infarction (AMI) is advantageous to avoid subsequent thrombotic coronary occlusion, 8 patients with AMI were studied. Four of them (group S) underwent sequential PTCA following unsuccessful intracoronary thrombolysis and the others (group D) direct PTCA. Serial changes in plasma plasminogen activator inhibitor-1 (PAI-1), plasma tissue plasminogen activator (t-PA) antigen and serum lipoprotein(a) levels were compared between the two groups. In group S, plasma PAI-1 levels showed no significant serial change after PTCA. However, in group D, plasma PAI-1 levels increased significantly 4-24 h after PTCA. We suggest that more attention should be focused on the prevention of thrombotic coronary closure as well as mechanical abrupt occlusion after direct PTCA.

Gas gangrene following sacral pressure sores.

We report two cases of gas gangrene developed from sacral pressure sores. The first case was clostridial and the second, non-clostridial gas gangrene. Both patients died within two months. The first patient, a 56-year-old woman suffering from palsy of the lower half of the body for 3 weeks, developed a sacral pressure sore. One month later, crepitus by palpation and gas formation in the X-ray film were detected in the hip and right thigh. A culture of odoriferous pus yielded Clostridium limosum in addition to Staphylococcus intermedius, Enterococcus faecalis, Pseudomonas aeruginosa, and Bacteroides fragilis. Blood culture yielded Bacteroides fragilis. The patient died 50 days after admission in spite of surgical debridement and aggressive therapy with high doses of antibiotics and hyperbaric oxygen. The second patient, a 70-year-old man suffering from diabetic nephropathy, arteriosclerosis obliterans of the lower limbs, and cerebral infarction, developed a large decubitus ulcer covering the whole sacral area. Crepitus and gas were detected in the soft tissue of the left gluteal region. Almost the entire gluteus maximus muscle was necrotic. Bacteroides fragilis, methicillin-resistant or -sensitive Staphylococcus aureus and Escherichia coli were isolated from the muscle. Bacteroides fragilis was also obtained by blood culture. The patient died on the 72nd day after admission.

Silent cerebral infarction associated with coronary artery disease.

To investigate the relationship of coronary artery disease and silent cerebral infarction, 50 patients who underwent coronary arteriography and cranial magnetic resonance imaging were studied. The patients were divided into three groups. The incidence of silent cerebral infarction (chiefly lacunar infarction) was significantly higher in patients with old myocardial infarction and in those with angina pectoris than in the control group (80, 78 and 29%, respectively, p < 0.05). Silent cerebral infarction is considered to be a risk factor for symptomatic cerebrovascular disease, so more attention should be focussed on the prevention of stroke in patients with coronary artery disease.

Atrial filling fraction obtained by aortic root echocardiogram in man.

Atrial filling fraction obtained by left ventricular echocardiogram (AFF by LV echo) is considered to be a reliable measure of AFF of LV. However, in patients with LV asynergy, AFF by LV echo cannot be evaluated correctly by this method. To obtain AFF, we devised a new echocardiographic index of AFF, obtained from the aortic-left atrial echogram (AFF by Ao echo), and examined the significance of this index in 9 normal subjects (Normals) and 49 patients with various heart diseases. The correlation between AFF by Ao echo and left ventricular end-diastolic pressure (LVEDP) also was examined. In an additional 20 patients with acute myocardial infarction (acute MI), the relationship between AFF by Ao echo and pulmonary arterial end-diastolic pressure (PAEDP) was studied for several days following the onset of MI. Results were as follows: In Normal patients and patients without asynergy, a significant correlation was seen between AFF by LV echo and AFF by Ao echo (r = 0.710, p less than 0.001). The value of AFF by Ao echo was always greater than that by LV echo. AFF by Ao echo in patients with hypertensive heart disease (HHD), angina pectoris (AP) and old myocardial infarction (old MI) was significantly higher than that in Normal patients. A significant curvilinear correlation was seen between AFF by Ao echo and LVEDP (r = 0.673, p less than 0.005). In patients with acute MI, AFF by Ao echo correlated well with PAEDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of atrial contraction in sick sinus syndrome using conventional and esophageal echocardiography.

To evaluate the active systolic function of both atria in sick sinus syndrome (SSS), conventional and esophageal echocardiograms were recorded in 22 normal subjects (Normal), 5 patients (pts) with sinus bradycardia (Group I), 9 with sinoatrial block or sinus arrest (Group II), 10 with bradycardia-tachycardia syndrome (BTS, Group III) and 6 with transient atrial fibrillation (Group IV). Two pts in Group II and 8 in Group III had a history of syncope. Atrial filling fraction obtained by the left ventricular echogram (AFF by LV echo) and posterior wall excursion of the aorta during atrial contraction (Ea) were determined by the conventional echocardiogram. The excursion of the interatrial septum during atrial contraction (Eb) and the dimensional shortening of the right atrium during atrial contraction (Ec) were determined by the esophageal echocardiogram. Results were as follows: AFF was almost the same in Normal, and Group I, II and IV, but it was significantly lower in Group III. AFF was also decreased in 2 pts in Group II who had a history of syncope. Both Ea and Eb in Group III were significantly lower than those in the other groups. Ec was not significantly different among all groups, although one patient in Group III had markedly decreased Ec. There was a significant correlation between Ea and AFF (r = 0.638, p less than 0.001). We conclude that in a number of cases with SSS, especially BTS, left atrial active contraction is significantly impaired in addition to the electrophysiological abnormality.

An experimental study on the enhancing effects of phenylalanine on acupuncture analgesia.

In this preliminary study we examined the enhancing effect of D-phenylalanine on acupuncture anesthesia. We made 4 different kinds of experiments with 3 volunteers. The results show that D-phenylalanine extends the analgesic effect of acupuncture analgesia remarkably, with no exception in 3 cases. According to these facts, we believe that these findings have an important meaning for those who are engaged in acupuncture treatment or research.