Sympathovagal effects of spinal anaesthesia with intrathecal or intravenous fentanyl assessed by heart rate variability.

BACKGROUND: Although many investigators previously reported the sympathovagal effect of spinal anaesthesia, there is no information about the sympathovagal effects of supplementation with fentanyl. The aim of this study was to evaluate the sympathovagal effects of intrathecal or intravenous fentanyl added to spinal anaesthesia. METHODS: One hundred and twenty patients undergoing elective transurethral surgery under spinal anaesthesia were randomly allocated to receive intrathecally either isobaric bupivacaine alone (Group B), bupivacaine supplemented with intrathecal (Group Ft) or with intravenous fentanyl (Group Fv). Heart rate variability was estimated using the MemCalc method (Tarawa, Suwa Trust, Japan) before and after spinal anaesthesia. RESULTS: In all groups, spinal anaesthesia significantly decreased low frequency/high frequency (LF/HF) as a marker of sympathovagal balance. However, patients in Group B with a low block height developed a marked increase in LF/HF after spinal anaesthesia, which was attenuated in Group Ft. Meanwhile, intravenous fentanyl did not attenuate this response. CONCLUSION: We conclude that sympathetic activation observed in patients with a low block height was attenuated by intrathecal fentanyl but not by intravenous fentanyl.

Preinfarction angina as a major predictor of left ventricular function and long-term prognosis after a first Q wave myocardial infarction.

OBJECTIVES: The purpose of this study was to assess the prognostic significance of preinfarction angina after a first Q wave myocardial infarction. Patients with anterior or inferior myocardial infarction were compared. BACKGROUND: The effect of preinfarction angina on prognosis after anterior and inferior myocardial infarction remains unclear. METHODS: A total of 291 patients with a first Q wave anterior (n = 171) or inferior (n = 120) myocardial infarction were examined to assess the effect of preinfarction angina on short- and long-term prognosis. The relation between predischarge left ventriculographic findings and preinfarction angina was also examined. RESULTS: The presence of preinfarction angina was associated with lower peak creatine kinase activity, a lower in-hospital incidence of sustained ventricular tachycardia and fibrillation and a lower incidence of pump failure and cardiac mortality in patients with either anterior or inferior infarction. Among patients with anterior infarction, preinfarction angina was associated with a lower incidence of cardiac rupture and less need for readmission for heart failure within 1 year after the onset of infarction. In this subgroup it was also associated with a higher ejection fraction, a smaller end-diastolic volume and a lower incidence of aneurysm formation noted on ventriculography during convalescence. In patients with inferior infarction, these variables did not differ significantly in the presence or absence of preinfarction angina. Multivariate analysis confirmed that the presence of preinfarction angina was an independent predictor of development of ventricular aneurysm, late phase heart failure and 1-year cardiac mortality. CONCLUSIONS: The presence of preinfarction angina has a favorable effect on infarct expansion and late phase left ventricular function, especially in patients with anterior myocardial infarction. The mechanisms responsible for this phenomenon are not known but may be secondary to limitations of infarct size through unidentified mechanisms other than collateralization (e.g., ischemic preconditioning).

A clinical study of Japanese patients with ulcer induced by low-dose aspirin and other non-steroidal anti-inflammatory drugs.

BACKGROUND: The incidence and severity of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastro-duodenal ulcer have not been extensively studied in Japan. AIM: We performed a prospective study to clarify NSAIDs-induced gastro-duodenal injury, focusing especially on low-dose aspirin (L-A). METHODS: Two hundred and thirty-eight patients with bleeding peptic ulcers admitted to our hospital. History of taking NSAIDs and anti-ulcer drugs was obtained from all patients who underwent endoscopic examinations. The lesion scores of patients taking L-A were classified numerically from zero (no lesion) to five (ulcer). RESULTS: The NSAIDs were associated with 28.2% of hemorrhagic ulcers. The rates of patients using L-A, loxoprofen, diclofenac, and combination of two of these drugs were 27, 16, 10 and 9%, respectively. Co-administered anti-ulcer drugs were cytoprotective anti-ulcer drugs (27%), H2 receptor antagonists (16%), PPI (4%), and none (53%). In patients taking L-A, H2 receptor antagonists were used most frequently. The HP was positive in 63% of L-A-induced ulcer cases and in 69% of NSAIDs other than low-dose aspirin-induced ulcer cases. The lesion scores of patients taking L-A with H2 receptor antagonists or PPI were significantly lower than those of patients who were taking only L-A (P < 0.05). CONCLUSIONS: Approximately one-third of hospitalized patients with NSAIDs-induced hemorrhagic ulcer showed an association with L-A. Prospective randomized controlled trials including H2 receptor antagonists are required to establish preventive efforts aimed at L-A-induced gastro-duodenal injury.

Inhibition of glycolysis or increased perfusate H+ buffering capacity, but not their combination, attenuates myocardial stunning.

OBJECTIVE: Both inhibition of glycolysis and enhancement of the H+ buffering capacity of the perfusate during ischaemia reduce myocardial reperfusion injury. The aim of the study was to investigate whether these manoeuvres, performed separately or together, could reduce myocardial stunning after brief global ischaemia. METHODS: The hearts of male Sprague-Dawley rats were preperfused for 10 min with oxygenated or hypoxic buffer (pH 7.4) containing 100 mM sucrose, 100 mM HEPES, or 5 mM 2-deoxyglucose plus 100 mM sucrose, followed by 15 min of total ischaemia and 30 min of reperfusion. In some hearts, 5 mM 2-deoxyglucose was combined with 100 mM HEPES during the 10 min preperfusion period. RESULTS: Brief hypoxic preperfusion, 2-deoxyglucose, or HEPES reduced myocardial stunning as well as improving the metabolic recovery and reducing Ca2+ overload after reperfusion. These changes were associated with a smaller increase in intracellular Na+ and a smaller decrease of coronary effluent pH at the end of ischaemia. In contrast, the combination of HEPES with hypoxic preperfusion or 2-deoxyglucose depressed functional recovery and increased the intracellular Na+ level at the end of ischaemia as well as increasing Ca2+ overload after reperfusion. This happened even though the decrease in coronary effluent pH was attenuated to the same extent as before. CONCLUSIONS: Both inhibition of glycolysis and enhancement of the perfusate H+ buffering capacity before ischaemia attenuated myocardial stunning, but the protective effect of each manoeuvre was lost when they were combined.

Effect of brief hypoxia on reperfusion arrhythmias and release of Ca2+ by rat heart homogenate blocked by ryanodine.

OBJECTIVES: We previously reported that a brief period of hypoxic perfusion (BHP) prior to ischemia in rat hearts improved functional recovery upon reperfusion with reduced Ca2+ overload. The present study was designed to determine whether the effect of BHP would be associated with a reduction in reperfusion arrhythmias and a preservation of function of the sarcoplasmic reticulum (SR). METHODS: Hearts were subjected to 40 min of global ischemia and 30 min of reperfusion after a 20 min period of oxygenated perfusion (oxygenated group: OG), or a 10 min period of oxygenation and 10 min of hypoxic perfusion (hypoxic group: HG). We evaluated the release of Ca2+ by SR blocked by ryanodine, the recovery of left ventricular function, and the reperfusion induced ventricular tachycardia/fibrillation (VT/VF). RESULTS: Functional recovery improved and the incidence and duration of reperfusion VT/VF were reduced in HG. In HG the uptake of Ca2+ in SR decreased during ischemia, but this decrease was less than that in OG. However, recovery of Ca2+ uptake after reperfusion did not differ between groups. The release of Ca2+ by SR blocked by ryanodine was inhibited in HG throughout the ischemia-reperfusion sequence. CONCLUSIONS: Observations suggest that the benefits of BHP on recovery of function and reperfusion arrhythmias were associated with a decrease in release of Ca2+ by SR blocked by ryanodine.

Compound heterozygous mutations in the gamma subunit gene of ENaC (1627delG and 1570-1G-->A) in one sporadic Japanese patient with a systemic form of pseudohypoaldosteronism type 1.

The systemic form of pseudohypoaldosteronism type 1 (PHA1) is a rare autosomal recessive disorder with salt-wasting, hyperkalemia, metabolic acidosis, and multiorgan aldosterone unresponsiveness. Recently, this form of PHA1 was found to be caused by the loss-of-function mutations in the gene of each subunit (alpha, beta, and gamma) of the epithelial sodium channel (ENaC). To investigate the molecular basis of one sporadic Japanese patient with a systemic form of PHA1, we determined the nucleotide sequence of the genes of every subunit of ENaC of this patient. The patient was found to be a compound heterozygote for one base deletion in exon 12 (1627delG) in combination with 1570-1-->GA substitution at the 5' splice acceptor site of intron 11 in the gamma subunit gene of ENaC. The 1627delG mutation altered a reading frame, resulting in a premature stop codon in exon 12. Messenger RNA from the allele harboring the splice site mutation was not identified by RT-PCR. In conclusion, two novel mutations in the gamma subunit gene of ENaC caused systemic PHA1 in the sporadic Japanese patient. Identification of the molecular basis of PHA1 is helpful for early diagnosis and understanding the pathophysiology of the disease.

Influence of cellular incorporation of n-3 eicosapentaenoic acid on intracellular Ca2+ concentration and membrane potential in vascular smooth muscle cells.

Long-term treatment with n-3 eicosapentaenoic acid (EPA) has been shown to exert hypotensive effects and have beneficial effects on atherosclerosis. To elucidate one of the underlying mechanisms of these effects, intracellular calcium concentration [Ca2+]i, and resting membrane potential were measured in rat vascular smooth muscle cells (A7r5 cell) treated with EPA, using Ca2+-sensitive dye fura-2 AM and the patch clamp technique. The alterations in fatty acid compositions of phospholipids and cell migration after treatment with EPA (30 microM) for 6 h-7 days were also examined. After treating cells with EPA, the EPA and DPA (docosapentaenoic acid) content of the phospholipid fraction (mol.%) increased in a time-dependent manner. Alternatively, arachidonic acid (AA) decreased, and then the ratio of EPA and AA (EPA/AA) increased significantly. The resting [Ca2+]i decreased from 170 +/- 46 nM (n = 16) in control cells to 123 +/- 29 nM (n = 16) in cells treated with EPA (30 microM) for 7 days. Vasopressin (100 nM), endothelin-1 (100 nM) and platelet-derived growth factor (PDGF 5 ng/ml) evoked an initial peak of [Ca2+]i, followed by a smaller sustained rise of [Ca2+]i in the presence of extracellular Ca2+. In EPA-treated cells, both the peak and the sustained rise of [Ca2+]i induced by these agonists decreased in comparison to the control cells. EPA treatment also decreased the transient [Ca2+]i rise evoked by these agonists in the absence of extracellular Ca2+. Under the current clamp condition, resting membrane potential was significantly higher in EPA-treated cells (-49.8 +/- 10.4 mV, n = 41) than in control cells (-44.6 +/- 7.4 mV, n = 41, P < 0.05), and the input resistance of the cell was lower in EPA-treated cells, while cell size and capacitance were not statistically different. In addition, long-term treatment with EPA for 7 days significantly inhibited PDGF-induced cell migration. These results suggest that cellular incorporation of n-3 eicosapentaenoic acid attenuates intracellular mechanisms related to changes of [Ca2+]i and affects membrane potential, thereby inhibiting migration of vascular smooth muscle cells. These actions of EPA may contribute to its vasorelaxant and antiatherosclerotic effects.

Evaluation of scaffolding effects of five different types of stents by intravascular ultrasound analysis.

The acute elastic recoil of 5 types of stents immediately after deployment by intravascular ultrasound and quantitative coronary angiography measurements was analyzed. Successfully implanted stents were: Palmaz-Schatz in 104 lesions, Gianturco-Roubin in 65, Wiktor in 45, gfx in 22, and Multi-Link stents in 22. Before and after stenting, the cross section of the smallest luminal area and vessel area was measured with intravascular ultrasound. The postdilatation balloon area was calculated by quantitative coronary angiography. Percent recoil was calculated as: [1-(preluminal area)/balloon area)] x 100. The ratio of balloon area-to-vessel area was also compared. Although preluminal areas in Gianturco-Roubin and Palmaz-Schatz stents were similar (2.4 +/- 0.1 vs 2.5 +/- 0.1 mm2, p = NS), postluminal area in the Gianturco-Roubin was significantly smaller than the area in the Palmaz-Schatz (6.3 +/- 0.2 vs 8.3 +/- 0.3 mm2, p <0.05). Although both the balloon area/vessel area (0.68 +/- 0.05, 0.80 +/- 0.08 vs 0.83 +/- 0.02, p <0.05) and the preluminal area (2.1 +/- 0.4, 1.6 +/- 0.2 vs 2.5 +/- 0.1 mm2, p <0.05) were smaller in gfx and Multi-Link than in the Palmaz-Schatz, postluminal area was comparable to the area in the Palmaz-Schatz (7.8 +/- 0.4, 7.4 +/- 0.4 vs 8.3 +/- 0.3 mm2, p = NS). Percent recoil in the Gianturco-Roubin was poorest among these 5 groups. More favorable initial gain can be obtained with Palmaz-Schatz, Wiktor, gfx, and Multi-Link stents than with the Gianturco-Roubin stent.

Effect on short-term prognosis and left ventricular function of angina pectoris prior to first Q-wave anterior wall acute myocardial infarction.

The prognostic significance of angina pectoris before the development of first Q-wave anterior wall acute myocardial infarction (AMI) was assessed in 153 patients. A total of 100 patients in this study had angina before Q-wave AMI, whereas 53 patients had no antecedent symptoms of angina. The presence of angina before AMI was associated with a lower incidence of complications including sustained ventricular tachycardia or fibrillation (7% vs 25%, p = 0.0022), pump failure (24% vs 47%, p = 0.0035), cardiac rupture (1% vs 17%, p = 0.0001), and a lower in-hospital mortality rate (11% vs 28%, p = 0.0067). The peak creatine phosphokinase activity was lower in patients with than without antecedent angina (1,727 +/- 1,238 vs 2,675 +/- 2,569 IU/liter, respectively, p = 0.023). There was no difference in the prevalence of multivessel coronary artery disease or the presence of collateral circulation between the 2 groups. Left ventriculography revealed a higher left ventricular ejection fraction (54 +/- 13% vs 46 +/- 11%, p = 0.034) and smaller left ventricular end-diastolic volumes (75 +/- 15 vs 86 +/- 18 ml/m2, p = 0.017) in patients with than without antecedent angina. These findings suggest that the presence of angina before AMI may be associated with a protective effect on left ventricular function during anterior wall AMI. Although the precise mechanisms underlying the beneficial effects are unknown, they may be related to the development of collateral channels or ischemic preconditioning.

Insulin insensitivity in nonobese, nondiabetic essential hypertension and its improvement by an alpha 1-blocker (bunazosin).

To investigate insulin insensitivity and its reversibility, we performed an insulin sensitivity test using the steady state plasma glucose (SSPG) method in 10 lean hypertensive subjects with normal glucose tolerance before and after treatment with alpha 1-blocker bunazosin, and 14 age body mass index-adjusted healthy control subjects. Steady state plasma glucose was significantly higher in the hypertensive subjects compared with the control group (182 +/- 10 mg/dL v 104 +/- 7, P < .01, mean +/- standard error of the mean (SEM). Steady state plasma glucose significantly decreased to 136 +/- 12 mg/dL (P < .01) after the treatment with alpha 1-blocker bunazosin, with a decrease of blood pressure. Hypertensive subjects had shown an increased area under the curve of glucose and insulin during the oral glucose tolerance test compared with normal controls. The glucose area decreased significantly, but the insulin area did not change after the treatment. There was no difference in plasma epinephrine, norepinephrine, and fractional excretion of Na between normal and hypertensive subjects both before and after treatment with bunazosin at basal and during insulin sensitivity tests (2 h). Serum total cholesterol level decreased and HDL cholesterol increased significantly after treatment with bunazosin. A significant correlation was observed between SSPG and blood pressure, but not between insulin level and blood pressure. The results indicate that insulin sensitivity is better related than hyperinsulinemia to hypertension and that this insensitivity is partially reversible by alpha 1-blocker, bunazosin.

A cruciform in the direct repeats of the yeast 2 micron DNA: Selective S1 nuclease cleavage at one of the three homologous palindromes.

An S1-hypersensitive site was found at the 60 bp direct repeats of the cis-acting, stability and/or copy number control region of the yeast 2 micron DNA in the supercoiled hybrid plasmid pDB248'. It was retained in a different plasmid, pYK2121, consisting of pBR322 and the 300 bp long repeated DNA. Analyses of 5'-end-labeled fragments and nucleotide sequence determination showed that the S1-cleavage site was at the central part of an AT-rich 19 bp palindrome present in the repeats. Two other homologous palindromes (21 and 15 bp) containing the 12 bp consensus sequences were not cleaved. The nucleotide sequences at the base of the stem and/or loop may determine the efficiency of the cruciform extrusion.

Improvement of insulin sensitivity for glucose metabolism with the long-acting Ca-channel blocker amlodipine in essential hypertensive subjects.

To clarify whether the long-acting calcium-channel blocker amlodipine restores insulin insensitivity in essential hypertension, insulin sensitivity tests were performed at the physiological steady-state insulin level (45 to 55 microU/mL) before and after amlodipine (2.5 to 7.5 mg/d) administration for 2 to 4 months in borderline and mild essential hypertensive subjects. Instead of somatostatin, Sandostatin (Sandoz, Basel, Switzerland) was used for the determination of steady-state plasma glucose (SSPG) in the same way as previously described. SSPG, which was initially high (212.9 +/- 18.0 mg/dL, mean +/- SE), was significantly reduced to 169.8 +/- 14.7 after amlodipine treatment. Responses of ketone bodies during the test at 30 minutes, which reflect the insulin effect on lipolysis in adipose tissue and hepatic fatty acid oxidation, also improved after amlodipine treatment. Norepinephrine, noted to be mildly elevated after amlodipine treatment, decreased during the sensitivity test at 2 hours probably due to the sedative effect, without any change in the fractional extraction of Na. This indicates that the physiological level of insulin does not activate sympathetic nerve activity or stimulate Na reabsorption. The long-acting calcium-channel blocker amlodipine has significantly improved the initially decreased insulin sensitivity for glucose metabolism at least partially in borderline or mild essential hypertension.

Synthetic peptide from the V3 loop consensus motif with a potent anti-HIV activity inhibits ristocetin-mediated vWF-GPIb interaction.

The V3 loop consensus motif. Arg-Gly-Pro-Gly-Arg-Ala-Phe-Val-Thr-Ile (HIV-1 IIIB), inhibits an interaction of HIV with CD4-positive lymphocytes. Recently, both proline-rich peptides and peptides containing proline-glycine loops (beta-turns) form a complex with ristocetin dimers. These peptides interact with ristocetin-loaded platelet membrane glycoprotein (GP) Ib and act as inhibitors of von Willebrand factor (vWF)-GPIb interaction by preventing the subsequent formation of ristocetin dimer bridges. The Pro-Gly sequence is also present in the V3 loop consensus motif, Arg-Gly-Pro-Gly-Arg-Ala-Phe-Val-Thr-Ile (HIV-1 IIIB). In this report, we have evaluated the effect of the HIV-1 IIIB peptide on vWF binding to GPIb. This peptide only inhibited vWF binding to GPIb as well as platelet aggregation in the presence of ristocetin while it had no effect on botrocetin-mediated vWF interaction with platelets. The peptide inhibited a binding of anti-vWF monoclonal antibody (RG-46) to immobilized vWF. Furthermore, ristocetin inhibited the binding of HIV-1 IIIB peptide to immobilized CXC-chemokine receptor-4 (CXCR-4) peptide. These results indicate that ristocetin may prevent HIV infection and would be useful a tool to understand the mechanism of HIV tissue tropism and infection.

Eicosapentaenoic acid inhibits vasopressin-activated Ca2+ influx and cell proliferation in rat aortic smooth muscle cell lines.

The purpose of this study was to clarify how eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, modulates the vascular action of vasopressin in rat aortic smooth muscle cell lines. The effects of EPA on Ca2+ mobilization and DNA synthesis elicited by vasopressin were investigated and compared to those of Ca2+ channel blocking agents, by means of Ca2+ measurements and the incorporation of [3H]thymidine. Patch-clamp techniques were also employed. Vasopressin (100 nM) elicited an initial peak of intracellular Ca2+ ([Ca2+]i), followed by a sustained phase due to Ca2+ entry. Nifedipine or nicardipine (1 microM), a potent L-type Ca2+ channel blocker, partly inhibited the sustained phase, but La3+ completely abolished it. EPA (10 microM) also inhibited it even in the presence of nicardipine. Under voltage-clamp conditions with CsCl-internal solution, depolarizing pulses positive to -30 mV from a holding potential of -40 mV elicited a slow inward current. The inward current was blocked by La3+, nicardipine, and nifedipine (1 microM), suggesting that the inward current mainly consisted of the voltage-dependent L-type Ca2+ channel (ICa.L). EPA (1-30 microM) also inhibited ICa.L in a concentration-dependent manner. The inhibitory effect of EPA was observed at concentrations higher than 1 microM, and its half-maximal inhibitory concentration (IC50) was 7.6 microM. Vasopressin induced a long-lasting inward current at a holding potential of -40 mV. The vasopressin-induced current was considered as a non-selective cation current (Icat) with a reversal potential of approximately +0 mV. Both nifedipine and nicardipine (10 microM) failed to inhibit it significantly, but La3+ completely abolished Icat. EPA also inhibited vasopressin-induced Icat in a concentration-dependent manner; its IC50 value was 5.9 microM. Vasopressin (100 nM) stimulated [3H]thymidine incorporation. Exclusion of extracellular Ca2+ with EGTA or La3+ markedly inhibited it. EPA (3-30 microM) also inhibited the incorporation induced by vasopressin, while nifedipine and nicardipine (1 microM) only partly inhibited it. These results suggested that EPA, unlike nifedipine and nicardipine, inhibited vasopressin-induced Ca2+-entry and proliferation in rat vascular smooth muscle cells, where the inhibitory effects of EPA on Icat as well as ICa.L might be involved. Thus, EPA would exert hypotensive and antiatherosclerotic effects.

Restoration of nitric oxide production by aldose reductase inhibitor in human endothelial cells cultured in high-glucose medium.

The effects of elevated glucose and aldose reductase inhibitor (ARI:ONO-2235) on nitric oxide (NO) production in cultured human umbilical endothelial cells (HUVEC) were evaluated. Aldose reductase and nitric oxide synthase(NOS) share NADPH as an obligate cofactor, therefore it is suggested that the enhanced of glucose flux (27.5 mM) by aldose reductase inhibited NO production by blunting NOS activity. However, the addition of ONO-2235 (100 microM) prevented the inhibition of [NO2-] production. Since ARI decreases glucose-mediated inhibition of NO production in HUVEC. this agent might ameliorate endothelial function associated with diabetes.

The search for a potent DNA vaccine against AIDS: the enhancement of immunogenicity by chemical and genetic adjuvants.

DNA vaccination is a new way to generate antigen specific immune responses by inoculating plasmid DNA encoding microbial genes. We believe that the use of immunologic adjuvants together with DNA vaccines is a promising way to enhance and optimize DNA-derived immunity. Various chemical and genetic adjuvants have been explored in our recent study. Data from these studies suggests that adjuvants exert their immunomodulatory properties through several mechanisms such as lymphoid cells recruitment, cytokine induction, and the facilitation of DNA entry into cells. Furthermore, each adjuvant has unique immunomodulatory effects on cell-mediated and humoral immune responses induced by DNA vaccination to human immunodeficiency virus type 1. To optimize the desirable immune response, the choice of adjuvant and decision of immunization route are important considerations. A similar approach may be useful potentiating anticancer immunotherapy as well.

Long-term effects of eicosapentaenoic acid on diabetic peripheral neuropathy and serum lipids in patients with type II diabetes mellitus.

The present study was undertaken to investigate the efficacy of a new, highly purified (purity greater than 91%), ethyl esterification product from natural eicosapentaenoic acid (EPA-E, C20:5 omega 3) in patients with type II diabetes mellitus (NIDDM). Hemodynamic changes were assessed at the level of the dorsalis pedis artery using an ultrasonic color Doppler duplex system before and after oral administration of EPA-E at a dose of 1800 mg/day for 48 weeks. The cross-sectional area of the dorsalis pedis artery increased significantly from 2.5 +/- 0.2 to 3.9 +/- 0.4 mm2 (48 weeks, mean +/- SE, p < 0.05). Moreover, EPA-E improved the clinical symptom (coldness, numbness) as well as the vibration perception threshold sense of the lower extremities [from 32.1 +/- 8.5 to 16.1 +/- 4.8 (48 weeks) microns]. A significant decrease of serum triglycerides was also noted by EPA-E administration. Furthermore, significant decrease of the excretion of albumin in urine [from 24.4 +/- 3.3 to 13.9 +/- 1.8 (48 weeks) mg/g.Cr, p < 0.05]. The results of this study suggest that EPA-E has significant beneficial effects on diabetic neuropathy and serum lipids as well as other diabetic complications such as nephropathy and macroangiopathy.

Repeat intervention for in-stent restenosis: re-expansion of the initial stent is a predictor of recurrence of restenosis.

BACKGROUND: In-stent restenosis has become a significant clinical problem as use of stents has increased. The optimal strategy for dealing with in-stent restenosis needs to be evaluated. OBJECTIVE: To compare the acute and late results of interventions for in-stent restenosis according to the device used, and to analyze the clinical and procedural variables of the lesions treated and identify the determinants of recurrence of restenosis and target lesion revascularization (TLR). METHODS: Procedural and late outcomes for 58 lesions in 50 patients who underwent repeat intervention for in-stent restenosis were analyzed. The results of interventions according to the device employed were compared. The predictors of recurrence of restenosis and TLR within 6 months were analyzed. The ratio of balloon diameter in repeat intervention to minimal lumen diameter after initial stenting (MLD0) was used as an index of re-expansion of stents. Serial intravascular ultrasound imaging was performed before and after repeat intervention for 33 lesions, and re-expansion of the initial stent was evaluated. RESULTS: Repeat intervention was successful in treating all lesions. Angiographic follow-up was possible for 49 lesions (84%). The overall incidences of recurrence of restenosis and TLR were 40.1 and 27.6%, respectively. Despite the immediate results having been good, the late results of stenting for in-stent restenosis were not favorable. Diffuse-type in-stent restenosis, early in-stent restenosis, and balloon diameter:MLD0 ratio > 1.25 are independent predictors of poor late results. Intravascular ultrasound findings have shown that expansion of the initial stent leads to recurrence of restenosis and TLR. CONCLUSIONS: Re-expansion of the initial stent can cause further vascular injury and there is a risk of recurrence of restenosis. Alternative therapeutic strategies that work without dilating the initial stent may be necessary for treating lesions with high risk of recurrence of restenosis.

Absence of preinfarction angina is associated with a risk of no-reflow phenomenon after primary coronary angioplasty for a first anterior wall acute myocardial infarction.

BACKGROUND: No-reflow phenomenon after primary coronary angioplasty is associated with poorer left ventricular (LV) function and prognosis after acute myocardial infarction (AMI). The purpose of this study was to determine the clinical significance of preinfarction angina in the no-reflow phenomenon. METHODS AND RESULTS: A total of 40 patients with first anterior AMI were examined. All patients underwent primary balloon angioplasty or stenting within 12 h of the onset of AMI. No-reflow, defined as TIMI grade 2 flow or less without residual stenosis after angioplasty, was observed in 15 patients. Patients with no-reflow were older (67+/-9 vs. 58+/-10 years, P=0.006) and had a lower incidence of preinfarction angina (7% vs. 48%, P=0.01) than those without no-reflow. Patients with no-reflow had poorer LV function at predischarge and a higher incidence of pump failure, LV aneurysm, malignant ventricular arrhythmias or cardiac death during the hospital course in association with higher peak serum C-reactive protein levels (12.7+/-8.0 vs. 7.1+/-5.5 mg/dl, P=0.02). Multivariate analysis showed that the absence of preinfarction angina was a major independent determinant of no-reflow (RR=17.1, P=0.02). CONCLUSIONS: The absence of preinfarction angina is more frequently observed in patients with no-reflow. The beneficial effect of preinfarction angina on LV function may be explained, at least in part, by prevention of no-reflow after reperfusion.

Case report: inhalation therapy of paromomycin is effective for respiratory infection and hypoxia by cryptosporidium with AIDS.

A 24-year-old man with AIDS and hemophilia A had intractable diarrhea and fever. Upon examination of stool and of a sigmoidal biopsy specimen, cryptosporidium was revealed. Approximately 2 months after admission, respiratory infection with hypoxia due to cryptosporidium developed. Paromomycin inhalation was effective therapy. To the authors' knowledge, this is the first case of respiratory cryptosporidiosis treated successfully by paromomycin inhalation.