Additional value of adenosine-stress dynamic CT myocardial perfusion imaging in the reclassification of severity of coronary artery stenosis at coronary CT angiography.

AIM: To assess the additional value of adenosine-stress dynamic computed tomography (CT) perfusion (ASDCTP) imaging compared with coronary CT angiography (CCTA) alone to detect significant coronary artery stenosis for each threshold of 50% and 70% diameter stenosis. MATERIALS AND METHODS: The study included 34 patients (65 ± 11 years, 79% men) with suspected coronary artery diseases who underwent ASDCTP imaging using a 128-section dual-source CT (DSCT) and invasive coronary angiography (ICA). Two investigators classified coronary artery stenosis on CCTA as severe or not. If appropriate image quality could not be acquired due to artefacts, the segment was classified as a lesion with significant stenosis. After the interpretation of ASDCTP imaging, the degree of stenosis was reclassified. All parameters of diagnostic accuracy were calculated before and after ASDCTP analysis for detection of significant coronary artery stenosis with ICA as the reference standard. RESULTS: The diagnostic accuracy parameters per vessel for the detection of ≥50% stenosis before and after ASDCTP analysis changed as follows: sensitivity, from 80% to 83%; specificity, from 83% to 98%; positive predictive value (PPV), from 87% to 98%; and negative predictive value (NPV), from 75% to 80%. The addition of ASDCTP resulted in reclassification from one class of stenosis severity to another in a significant number of vessels with threshold of 50% stenosis [net reclassification improvement (NRI), 0.176; p < 0.01]. Conversely, the addition of ASDCTP did not result in significant reclassification of stenosis severity in vessels with threshold of 70% stenosis (NRI, 0.034; p = 0.51). CONCLUSIONS: ASDCTP imaging provides incremental value in the detection of significant coronary artery stenosis using a threshold of 50%.

Valsartan increases circulating adiponectin levels without changing HOMA-IR in patients with type 2 diabetes mellitus and hypertension.

Evaluating increasing circulating adiponectin levels is becoming an important strategy in the prevention of diabetes mellitus and cardiovascular events. This study was designed to investigate the effect of the angiotensin II receptor blocker valsartan on blood adiponectin levels and insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension. A total of 91 Korean patients were treated with 80 mg/day valsartan for 4 weeks followed by 160 mg/day for a further 8 weeks. Blood pressure, adiponectin levels and metabolic parameters were measured before and after treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated as an insulin sensitivity index. Valsartan significantly decreased mean blood pressure and increased circulating adiponectin levels. There were no differences in metabolic parameters, including HOMA-IR, glycosylated haemoglobin and lipid levels before and after treatment. These results indicated that valsartan increases circulating adiponectin levels, but does not change insulin sensitivity in patients with type 2 diabetes and mild-to-moderate hypertension.

The relationship between adipokines, metabolic parameters and insulin resistance in patients with metabolic syndrome and type 2 diabetes.

This study was designed to investigate the relationship between adipokines in metabolic syndrome and insulin resistance. Sixty male and female subjects with or without metabolic syndrome and type 2 diabetes were included. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Compared with lean control subjects, patients with metabolic syndrome and type 2 diabetes had lower circulating levels of total adiponectin and high molecular weight (HMW) adiponectin, and higher levels of leptin and interleukin-6 (IL-6). Total and HMW adiponectin and the adiponectin/leptin (A/L) ratio were negatively correlated with HOMA-IR. After adjusting for age and sex, leptin, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were positively correlated with HOMA-IR. After also adjusting for body mass index, HOMA-IR was found to be independently associated with leptin, A/L ratio and TNF-alpha levels. In conclusion, decreased total adiponectin and HMW adiponectin and increased leptin and IL-6 levels are characteristic of patients with metabolic syndrome and type 2 diabetes.

Binding and transport of melanoma-specific antigenic peptides by the transporter associated with antigen processing.

To gain insight into how tumor antigens are generated and presented, a panel of peptides corresponding to melanoma-specific T cell epitopes were tested for their transport capacity by the transporter associated with antigen processing (TAP). The melanoma epitopes exhibited differential capacities to be transported by TAP in streptolysin O-permeabilized cells, as well as differential competition for peptide binding to TAP. The data indicate that some melanoma-specific epitopes are good substrates for TAP, while others are poor substrates for TAP. One of the epitopes, derived from tyrosinase, was transported into the endoplasmic reticulum (ER), in spite of being a poor competitor for reporter peptide transport and for peptide binding. These results suggest that the melanoma antigens follow distinct pathways for presentation, along the MHC class I pathway.

Crustacean hyperglycemic hormone in the lobster nervous system: localization and release from cells in the subesophageal ganglion and thoracic second roots.

Crustacean hyperglycemic hormones (CHHs) are neuropeptides involved in the regulation of hemolymph glucose. The primary source of CHHs has been identified as the neurosecretory neurons of the eyestalk X-organ and its associated neurohemal organ, the sinus gland. We have identified another source of CHH-like peptides in the nervous system. With the use of immunocytochemistry, cells in the second roots of the thoracic ganglia have been observed to stain positively for CHH-reactive material. We also identified a pair of cells in the subesophageal ganglion that contain large amounts of CHH-reactive material. Depolarization of these cells with elevated potassium mediates a calcium-dependent release of CHH-like material from the ganglion as quantified with an enzyme-linked immunosorbent assay (ELISA).

Detection of ischaemic myocardial lesions with coronary CT angiography and adenosine-stress dynamic perfusion imaging using a 128-slice dual-source CT: diagnostic performance in comparison with cardiac MRI.

OBJECTIVE: We assessed the diagnostic performance of adenosine-stress dynamic CT perfusion (ASDCTP) imaging and coronary CT angiography (CCTA) for the detection of ischaemic myocardial lesions using 128-slice dual-source CT compared with that of 1.5 T cardiac MRI. METHODS: This prospective study included 33 patients (61±8 years, 82% male) with suspected coronary artery diseases who underwent ASDCTP imaging and adenosine-stress cardiac MRI. Two investigators independently evaluated ASDCTP images in correlation with significant coronary stenosis on CCTA using two different thresholds of 50% and 70% diameter stenosis. Hypoattenuated myocardial lesions on ASDCTP associated with significant coronary stenoses on CCTA were regarded as true perfusion defects. All estimates of diagnostic performance were calculated and compared with those of cardiac MRI. RESULTS: With use of a threshold of 50% diameter stenosis on CCTA, the diagnostic estimates per-myocardial segment were as follows: sensitivity, 81% [95% confidence interval (CI): 70-92%]; specificity, 94% (95% CI: 92-96%); and accuracy 93% (95% CI: 91-95%). With use of a threshold of 70%, the diagnostic estimates were as follows: sensitivity, 48% (95% CI: 34-62%); specificity, 99% (95% CI: 98-100%); and accuracy, 94% (95% CI: 92-96%). CONCLUSION: Dynamic CTP using 128-slice dual-source CT enables the assessment of the physiological significance of coronary artery lesions with high diagnostic accuracy in patients with clinically suspected coronary artery disease. ADVANCES IN KNOWLEDGE: Combined CCTA and ASDCTP yielded high accuracy in the detection of perfusion defects regardless of the threshold of significant coronary stenosis.

Left atrial remodelling in patients with successful percutaneous mitral valvuloplasty: determinants and impact on long-term clinical outcome.

BACKGROUND: Left atrial (LA) volume is an independent prognosticator in various cardiac diseases. The authors assessed the changes of LA volume after successful percutaneous mitral valvuloplasty (PMV) and the impact of LA enlargement on long-term clinical outcome after PMV. METHODS AND RESULTS: From a prospective PMV registry started in 1988, 303 patients (242 women, age: 39.3+/-10.8 years) who had undergone successful PMV were followed for 4-20 years (median 11 years). Echocardiographic examination including LA volume measurement was performed before PMV and repeated after PMV. LA volume decreased from 92+/-50 to 69+/-42 ml (p < 0.001) immediately after PMV and remained stationary until 1 year after PMV. Since then, LA volume subsequently increased exceeding the pre-PMV level by 8 years after PMV. Multivariate analysis showed that LA volume increase at 10 years after PMV was independently related to the post-PMV mitral valve area, the echo score, the presence of atrial fibrillation and post-PMV LA volume. On multiple regression analysis, pre-PMV LA volume and percentage change of LA volume immediately after PMV emerged as independent predictors of event-free survival along with age, pre-PMV tricuspid regurgitation and post-PMV mitral valve area. Ten-year survival rate was 93% in patients with smaller LA before PMV (< or =72 ml/m(2)), whereas it was only 60% in those with larger LA (>72 ml/m(2)). CONCLUSIONS: Progressive increase of LA volume was observed even after successful PMV. Larger pre-PMV LA volume was associated with poor prognosis.

Left ventricular twist mechanics in patients with apical hypertrophic cardiomyopathy: assessment with 2D speckle tracking echocardiography.

OBJECTIVE: Left ventricular (LV) apical rotation significantly contributes to LV twist, which has been reported to have a vital role in maintaining LV systolic and diastolic function. Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathological LV hypertrophy at the apex. We aimed (1) to evaluate LV twist mechanics in ApHCM and (2) to demonstrate the influence of predominantly local, pathological involvement of the apical myocardium on LV twist mechanics. METHODS: 21 patients diagnosed with ApHCM were consecutively enrolled and compared with normal controls. After a standard echocardiographic examination, we scanned parasternal basal and apical short-axis planes to quantify LV rotations and LV twist using the speckle tracking technique. For better understanding of LV twist mechanics in ApHCM, LV radial and biplanar strains and LV twist-volume curve were also evaluated. RESULTS: Compared with the normal controls, apical rotation was markedly decreased in ApHCM patients (p<0.001), but the decreases in basal rotation were not significant. As a consequence, LV twist was significantly lower in ApHCM patients (p = 0.007). Apical radial (p = 0.01) and biplanar (p<0.001) strains in ApHCM were also significantly decreased. Compared to normal controls, LV twist-volume and twist-radial displacement curves clearly showed a decrement in the slope of the linear systolic phase and a loss of an inflection point separating the early from late untwisting phase in ApHCM patients. CONCLUSION: LV twist in ApHCM was significantly decreased due to a reduction in apical rotation, suggesting that regional myocardial changes in ApHCM can modify the global LV twist mechanics. Given the close interconnection between LV systolic and diastolic function, impairment of LV twist may lead to the loss of early diastolic suction and finally generate diastolic dysfunction in ApHCM.

Peripheral blood stem cell mobilisation by granulocyte-colony stimulating factor in patients with acute and old myocardial infarction for intracoronary cell infusion.

BACKGROUND/AIMS: Peripheral blood stem cells (PBSC) are one of the most promising stem cell sources for treatment of ischaemic heart disease. However, the experience of mobilisation and collection of PBSC using granulocyte-colony stimulating factor (G-CSF) in patients with myocardial infarction (MI) is still limited. We report our experiences with the feasibility and safety of collection of mobilised PBSC with G-CSF in MI patients, and the influence of acute ischaemia on efficacy of PBSC collection. METHODS: 74 patients with acute or old myocardial infarction (AMI vs OMI, n = 46 and n = 28) underwent PBSC collection after administration of G-CSF twice a day at a dose of 5 microg/kg for 3 days. Flow cytometric analysis of cell surface markers was performed. RESULTS: No evidence of inflammation or ischaemia was observed during G-CSF mobilisation and PBSC collection. The yield of CD34(+) cells was 12.9 (SD 15.92) x10(9)/l (5.04% (5.30%) of total cells) with a product volume of 37.9 (8.4) ml after 5650 (987) ml of blood were processed during PBSC collection. Stem cell mobilisation and collection by G-CSF is more efficient in AMI than in OMI, and proportions of cells positive for VE-cadherin or KDR/CD34 are significantly greater in AMI than in OMI (p<0.01). CONCLUSION: We could obtain sufficient numbers of PBSC for intracoronary infusion with the G-CSF-based mobilisation strategy without complications even in patients with MI. PBSC collection after mobilisation with G-CSF is a safe and feasible method of stem cell collection for therapeutic purpose in patients with MI.

Restoration of left ventricular synchronous contraction after acute myocardial infarction by stem cell therapy: new insights into the therapeutic implication of stem cell therapy for acute myocardial infarction.

OBJECTIVE: To evaluate the effects of stem cell therapy on restoration of the left ventricular (LV) synchronous contraction in patients with acute myocardial infarction (AMI). METHODS: 40 patients with AMI who underwent successful coronary revascularisation were randomly allocated to the cell infusion or the control group. Evaluations were performed with echocardiographic tissue synchronisation imaging to determine LV dyssynchrony and with cardiac magnetic resonance imaging to estimate LV ejection fraction (LVEF) at baseline and at 6 months. To quantify the severity of systolic LV dyssynchrony, the standard deviations of time to peak systolic velocity of the 12 LV segments (Ts-SD) were calculated. RESULTS: At 6 months, greater improvements of Ts-SD (DeltaTs-SD: -45.0 (40.2) vs 5.0 (39.9) ms, p<0.001) and LVEF (DeltaLVEF: 6.8% (9.1%) vs -0.2% (6.9%), p = 0.015) relative to the corresponding baseline values were observed in the cell infusion group than in the control group. By multivariate analysis, DeltaTs-SD and baseline LVEF emerged as the independent determinants of LVEF improvement and cell infusion, and baseline Ts-SD as the determinant of DeltaTs-SD improvement. Maximal exercise capacity measured by symptom-limited treadmill testing correlated well with Ts-SD but not with LVEF at 6 months of follow-up. CONCLUSION: Stem cell therapy had a favourable effect on the restoration of LV synchronous contraction in patients with AMI.

Quantification of crustacean hyperglycemic hormone by ELISA in hemolymph of the lobster, Homarus americanus, following various stresses.

An ELISA was developed for the crustacean hyperglycemic hormone (CHH) from the lobster, Homarus americanus. It is sensitive to as little as 0.2 fmol of peptide. The assay was used to measure CHH in the hemolymph of intact lobsters after various environmental stresses. Increases in CHH were observed following emersion, exposure to high temperatures (23 degrees and 28 degreesC), and salinity stress (50 and 150% seawater). During emersion, concentrations of hemolymph glucose increased concomitantly with increases in CHH. Significant levels of hemolymph CHH were also measured in lobsters that had been eyestalk-ablated. These latter observations indicate that there may be a source of CHH other than the X-organ/sinus gland in the lobster.

Carbohydrate dynamics and the crustacean hyperglycemic hormone (CHH): effects of parasitic infection in Norway lobsters (Nephrops norvegicus).

The effects of a dinoflagellate parasite (Hematodinium sp.) on carbohydrate metabolism were examined in the Norway lobster, Nephrops norvegicus. Five stages of infection were observed. These included uninfected (Stage 0), subpatently infected (SP), and patently infected (Stage 1-4) lobsters. During patent infection, the concentration of glucose in the hemolymph was reduced significantly from its value of 180 microg ml(-1) in uninfected (Stage 0) lobsters to 25.3 microg ml(-1) in Stage 3-4. These changes were accompanied by significantly lower levels of hepatopancreatic glycogen in lobsters at Stage 2 (2.01 mg g(-1)) and Stage 3-4 (0.84 mg g(-1)) of infection than in those at Stage 0 (16.19 mg g(-1)) and Stage 1 (14.71 mg g(-1)). Due to disruption of the normal feedback loops which control the release of crustacean hyperglycemic hormone (CHH), plasma concentrations increased with the severity of infection from 32.2 fmol ml(-1) in Stage 0 to 106.6 fmol ml(-1) in Stage 3-4. The increased CHH concentrations occurred concomitantly with reduced concentrations of plasma glucose and tissue glycogen. A significantly increased hemolymph CHH titer (107.7 fmol ml(-1)) was also observed during SP infection. It is concluded that the parasite places a heavy metabolic load on the host lobster.

Enzyme immunoassay for detection of Neisseria gonorrhoeae antigens.

An enzyme immunoassay (EIA; Gonozyme, Abbott Laboratories) for the detection of Neisseria gonorrhoeae antigens was assessed. Clinical isolates of N. gonorrhoeae or specimens obtained from male urethra or female cervix were tested by EIA. EIA results were compared with results of conventional culture identification for N. gonorrhoeae. Fifty clinical isolates of gonococci reacted positively with Gonozyme. Five strains of E. coli showed negative reaction to Gonozyme. Five strains of nonpathogenic Neisseria reacted differently with Gonozyme depending upon the viable number of the test organisms. The sensitivity and specificity of EIA for specimens form both sex were 72.4% and 93.8%, respectively. The corresponding figures for the male specimens were 84.6% and 71.4%, and for the female specimens 62.5% and 95%, respectively.

Surgical treatment for pathological long bone fracture in patients with multiple myeloma: a retrospective analysis of 22 cases.

BACKGROUND: The purpose of this study was to retrospectively review the cases of pathologic long bone fractures caused by multiple myeloma treated in our hospital, to analyze the surgical method, complications, radiation therapy, survival time, and influence on quality of life. METHODS: In a retrospective study, 22 patients with the pathological long bone fractures due to multiple myeloma who were surgically treated between 1987 and 1997 were analyzed. All patients received open reduction and internal fixation either with plates or intra-medullary nailing. Cement augmentations were performed in the majority of cases (91%). A detailed retrospective analysis was done to correlate the surgical methods, radiation therapy, functional results, and complications post-surgically. RESULTS: The most common site of fracture was the femur. The mean postoperative survival time was around 19 months. Post-operative pain relief was satisfactory, and only two patients required narcotics. No major complications were observed. However the union rate was only 30%, which might have been due to the inhibitory effect of radiation therapy on bone healing, or insufficient osteogentic ability of the myeloma-involved bone. CONCLUSION: Satisfactory pain relief and low implant failure rate was achieved and no definite evidence of tumor dissemination was found in this study. The authors suggest that open reduction and internal fixation with cement augmentation is a favorable treatment option for those patients suitable for surgery. However, postoperative radiation therapy may be associated with a low rate of union.

Detection of antibodies to HTLV-III by ELISA in AIDS risk groups in Taiwan: a preliminary report.

A total of 2321 serum samples were collected from a variety of AIDS risk groups. The samples were tested for anti-HTLV-III using ELISA. Low prevalences of seropositivity were detected in the high-risk groups. Among 120 homosexuals/bisexuals, one seropositive suffering from full-blown AIDS was an American traveler. Another native homosexual who yielded a high ELISA reading was a "possible" AIDS. Three hemophiliacs with strongly positive reactions received injections of a U.S.-produced factor VIII; all are asymptomatic currently. A patient with hairy cell leukemia had a markedly elevated ELISA reading. Another patient with syphilis also had a markedly high reading, despite having no other known risk factor. Among the low-risk groups a patient who had suffered from oral candidiasis for eight years had no risk factor, yet he yielded repeatedly high ELISA readings. Another patient with a weak positive reaction was a symptomless blood donor. This preliminary study concludes that Taiwan is several years behind the U.S. and is at present not an endemic area for AIDS. To achieve successful AIDS control in the future, however, the homosexuals in Taiwan should change their sexual behavior now. Since many initially weakly-reactive samples became negative on repeated testing it appears that non-specific or false positive ELISA reactions occur frequently. Accordingly when ELISA is used for diagnostic purposes, additional confirming tests are mandatory.

Juxtaglomerular cell tumor of the kidney: a case report.

We report a case of renin-secreting juxtaglomerular cell tumor which developed in a hypertensive 47-yr-old Korean man. Presumptive clinical diagnosis was made before surgery based on the high level of plasma renin and the radiologic evidence of renal mass. Grossly, a round, bulging, well-encapsulated mass of 3 x 3 cm was located in the mid-portion of the right kidney. On microscopic examination, the tumor was composed of ovoid to polyhedral cells with bland nuclei, indistinct nucleoli and light eosinophilic cytoplasm. The immunostaining for renin showed strong positivity in the cytoplasm of tumor cells. The characteristic rhomboid shaped renin protogranules were observed in ultrastructural analysis.

Hypodipsic hypernatremia with intact AVP response to non-osmotic stimuli induced by hypothalamic tumor: a case report.

Anatomical lesions of hypothalamic area associated with hypodipsic hypernatremia have been reported only rarely. We report here a case of hypodipsic hypernatremia induced by a hypothalamic lesion. A 25-yr-old man, who had been treated with radiation for hypothalamic tumor 5-yr before, was admitted for evaluation of hypernatremia and hypokalemia. He never felt thirst despite the elevated plasma osmolality and usually refused to drink intentionally. Plasma arginine vasopressin (AVP) level was normal despite the severe hypernatremic hyperosmolar state and urine was not properly concentrated, while AVP secretion was rapidly induced by water deprivation and urine osmolality also progressively increased to the near maximum concentration range. All of these findings were consistent with an isolated defect in osmoregulation of thirst, which was considered as the cause of chronic hypernatremia in the patient without an absolute deficiency in AVP secretion. Hypokalemia could be induced by activation of the renin-angiotensin-aldosterone system as a result of volume depletion. However, inappropriately low values of plasma aldosterone levels despite high plasma renin activity could not induce symptomatic hypokalemia and metabolic alkalosis. The relatively low serum aldosterone levels compared with high plasma renin activity might result from hypernatremia. Hypernatremia and hypokalemia were gradually corrected by intentional water intake only.

The effect of cilostazol on glucose tolerance and insulin resistance in a rat model of non-insulin dependent diabetes mellitus.

BACKGROUND: It has been reported that many peripheral vasodilating drugs might improve insulin resistance. Cilostazol, a antithrombotic agent, increases peripheral blood flow in non-insulin dependent diabetic patients. The effect of cilostazol treatment on insulin resistance in streptozotocin (STZ)-induced non-insulin dependent diabetic Wistar rats was examined. METHODS: About a half of two-day old neonate siblings were injected intraperitoneally with STZ and maintained for six months, at which time they were compared with age-matched control rats for intraperitoneal glucose tolerance test (IPGTT) and for glucose infusion rate (GINF) in a euglycemic hyperinsulinemic glucose-clamp study. After that, these studies were also performed after feeding rat chow containing cilostazol (100 mg/kg/day) to rats with STZ-induced non-insulin dependent diabetes mellitus for four-weeks and compared with those of age-matched control rats. RESULTS: In the intraperitoneal glucose tolerance test studies, plasma glucose levels of STZ-induced non-insulin dependent diabetic rats were significantly higher and plasma insulin levels significantly lower than those of age-matched control rats in the age of six months. Glucose infusion rate was lower in STZ-induced non-insulin dependent diabetic rats than those of age-matched control rats. However, after a four-week cilostazol treatment, glucose infusion rate of STZ-induced non-insulin dependent diabetic rats was not significantly different from that of control rats. CONCLUSION: These findings suggested that cilostazol may improve insulin resistance in STZ-induced non-insulin dependent diabetic rats.