Comparison of the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by tissue characterization using serial virtual histology intravascular ultrasound

Thin-cap fibroatheroma (TCFA) is the most common type of vulnerable plaque and is the precursor of plaque rupture. However, rupture of a TCFA is not the only mechanism underlying thrombus formation or acute coronary syndrome. Although statin therapy changes the composition of coronary artery plaques, the effects of statins, particularly different types of statins, on plaque phenotype have not been fully examined. This study compared the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by virtual histology (VH) intravascular ultrasound (IVUS) in patients with angina pectoris (AP). Coronary atherosclerosis in nonculprit lesions was evaluated using VH-IVUS at baseline and 8 months after statin therapy; analyzable IVUS data were obtained from 83 patients with stable AP (39 patients treated with pitavastatin and 44 with pravastatin) and 36 patients with unstable AP (19 patients treated with pitavastatin and 17 with pravastatin). Pitavastatin had a strong effect on reducing pathologic intimal thickening (PIT), especially in patients with unstable AP, but had no impact on VH-TCFA or fibroatheroma (FA). By contrast, pravastatin had weak effects on reducing PIT, VH-TCFA, or FA. Increases in the number of calcified plaques were observed for both statins. In conclusion, pitavastatin and pravastatin changed coronary artery plaque phenotype as assessed by VH-IVUS in patients with AP. However, the effects of these statins on coronary artery plaque phenotype were different.     

Effects of heart rate on coronary circulation and external mechanical efficiency in elderly hypertensive patients with left ventricular hypertrophy

Background and hypothesis: Mechanisms of heart failure in elderly hypertensive patients with hypertrophy have not been studied sufficiently. We hypothesized that impaired increment of coronary blood flow in response to increases in heart rate could be responsible for the occurrence or aggravation of heart failure. Methods: To test this hypothesis, we measured coronary hemodynamics and lactate balance during basal conditions and atrial pacing in 21 elderly patients aged ≥ 65 years (mean 74 ± 6 years) without coronary arterial disease: 7 normoten-sive control patients (Group 1), 7 hypertensive hypertrophic patients without a history of congestive heart failure (Group 2), and 7 patients with such history (Group 3). Coronary sinus blood flow (CSBF) was measured in coronary sinus using a thermodilution catheter. Results: During basal conditions, heart rate did not differ among the three groups (67 ± 3 in Group 1,65 ±11 in Group 2, and 63 ± 6 beats/min in Group 3). CSBF was significantly higher in the two hypertrophic groups than in the control group, but CSBF normalized by left ventricular mass was significantly lower in both hypertrophic groups. External mechanical efficiency (EME) obtained as left ventricular work divided by myocardial oxygen consumption did not differ among groups during basal conditions (36 ± 9% in Group 1, 35 ± 8% in Group 2, and 29 ± 9% in Group 3, NS). During atrial pacing to increase heart rate by 25 ± 5% (lower) and 54 ± 6% (higher), the increases in CSBF were markedly limited in both hypertrophic groups, and the response in Group 3 was more depressed than that in Group 2. EME did not change in the control group or in Group 2, but did decrease to 21 ± 5% in Group 3 during the higher pacing rate (p <0.01 vs. basal conditions). in this group, the relationship between EME and heart rate showed a significant negative correlation (r = —0.56, p = 0.02). Lactate balance in coronary sinus blood showed a tendency to production in Group 3 during the higher pacing rate, suggesting myocardial ischemia. Conclusion: These findings suggest that in hypertensive hypertrophic patients with a history of heart failure, the coronary circulation system is vulnerable to increasing heart rate. in medical treatment of elderly hypertensive patients, control of heart rate in addition to blood pressure control should be considered to minimize the occurrence or aggravation of heart failure.     

Relationship between exercise performance and water distribution measured by new bioelectrical impedance analysis in patients with chronic obstructive pulmonary disease

Body composition analysis is useful for objective evaluation of malnutrition in patients with chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate the influence of body composition on exercise performance by patients with COPD using a new method of bioelectrical impedance analysis. Twenty patients with COPD performed incremental exercise ramp tests to the symptom-limited maximum and constant work rate tests for 10 min. Their body compositions were measured by bioelectrical impedance analysis with eight electrodes and four frequencies, which could estimate the amount of intra- and extracellular water (ICW, ECW) and water distribution of the extremities separately. Some pulmonary function parameters of airflow limitation or hyperinflation and body composition parameters were significantly correlated with peakVO2. Stepwise multiple regression analysis revealed that independent predictors of peakVO2 included ECW/ICW ratio, lower extremity water and FEV1.0 (P<0.0001, R = 0.892), which explained 27, 31 and 21% of peakVO2, respectively. Furthermore, there was a significant correlation between ECW/ICW ratio and time constant of oxygen consumption in constant work rate tests. These findings indicate that increased ECW/ICW ratio and lower extremity water correlated with exercise intolerance independent of pulmonary function, and that changes in cellular hydration state might affect oxygen utilization of skeletal muscle in patients with COPD. In conclusion, the BIA used in our study, which can easily and simultaneously evaluate the water distribution of the extremities and cellular hydration state, is useful for the evaluation of exercise performance in COPD patients.     

Pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis

We report a 58-year-old woman with pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis. She was receiving treatment for liver cirrhosis and hepatic failure when sudden severe right upper abdominal pain and fever developed. Abdominal radiograph disclosed pneumatosis intestinalis, involving the ascending colon, and small collections of free air along the right hemidiaphragm. The pneumatosis intestinalis appeared in both cystic and linear form. Autopsy revealed necrosis and multiple gas-filled mural cysts in the ascending colon. To our knowledge, this is the first case to be reported of pneumatosis intestinalis and necrotizing enterocolitis associated with liver cirrhosis.     

Recurrence pattern after conservative surgery for papillary thyroid carcinoma

Objective

Risk-based treatment represents the optimal management strategy for papillary thyroid carcinoma; however, the optimal extent of thyroidectomy and neck dissection remains controversial. This study aims to clarify the pattern of recurrence after conservative surgery in patients with papillary thyroid carcinoma.

Methods

We retrospectively reviewed 93 patients with papillary thyroid carcinoma treated with conservative surgery. We analyzed recurrence rate, recurrence pattern, risk factors for recurrence, salvage treatment, and disease-free survival (DFS) in patients stratified according to risk.

Results

The recurrence rate was significantly lower in the low-risk group compared with the high-risk group (14% vs 34%; p < 0.01). The recurrence pattern also differed between the two groups, with ipsilateral lateral neck recurrence being more common in the low-risk group (9%), while contralateral lateral neck recurrence was more common in the high-risk group (18%). Patients with contralateral thyroid lobe metastasis and/or direct contralateral thyroid lobe invasion showed a significantly higher rate of contralateral lateral neck metastasis than patients negative for both these features. The overall 5-year DFS was 81% in all patients. Advanced T and N classification, large primary tumor (≥4 cm), extrathyroidal invasion, and high-risk group were significantly associated with poorer 5-year DFS in univariate analysis.

Conclusion

Conservative surgery may represent a good treatment option for patients with low-risk papillary thyroid carcinoma. Tumor recurrence patterns differ between risk groups, with contralateral thyroid lobe lesions and direct contralateral lobe invasion being risk factors for contralateral lateral neck recurrence.     

Effect of preanesthetic intramuscular ranitidine on gastric acidity and volume in children

Study Objective: To evaluate the effects of preanesthetic administration of intramuscular (IM) ranitidine on pH and volume of gastric contents in children.

Design: Three randomized treatment groups.

Setting: Central operating rooms at a university hospital.

Patients: Forty children age 1 to 10 years undergoing a variety of elective surgical procedures requiring general anesthesia with endotracheal intubation.

Interventions: IM ranitidine 1 mg/kg (n = 15) or 2 mglkg (n = 15) was administered 2 hours prior to induction of anesthesia. Ten patients without ranitidine served as the control group. An orogastric tube was inserted into each patient.

Measurements and Main Results: Gastric fluid pH and volume were measured every hour in the three groups. Plasma ranitidine concentrations were measured in ten patients of the ranitidine-treated groups. The mean volume of gastric fluid at induction of anesthesia was significantly lower in the ranitidine-treated patients (2.4 ml for ranitidine 1 mg/kg, 3.2 ml for ranitidine 2 mglkg) than in the controls (8.6 ml, p < 0.05). The mean pH values at induction of anesthesia were significantly higher in the ranitidine-treated patients (4.6 for 1 mg/kg, 6.7 for 2 mg/kg) than in the controls (2.1; p < 0.05). Dose-dependent plasma ranitidine concentrations were obtained.

Conclusions: Preanesthetic IM ranitidine 1 to 2 mglkg resulted in a higher pH and lower volume of gastric fluid at the time of induction and in a higher pH during 3 hours of anesthesia. This therapy may be a useful adjunct to premeditation for children who have a greater than normal risk of pulmonary aspiration during anesthesia.     

Immunohistochemical differentiation of extra-ocular sebaceous carcinoma from other skin cancers

We performed an immunohistochemical study using routinely processed formalin-fixed and paraffin-embedded tissue specimens from 26 cases of extra-ocular sebaceous carcinoma (EOSC) and eight easily available antibodies. They were polyclonal anti-carcinoembryonic antigen (CEA) antibody, monoclonal anti-CEA antibody, anti-breast carcinoma associated antigen-225 antibody (CU18), anti-CA15.3 antibody (CA15.3), anti-CD15 antibody (CD15), anti-breast carcinoma associated antigen antibody (B6.2), anti-gross cystic disease fluid antigen-15 antibody (GCDFP15) and anti-Thomsen-Friedenreich antigen antibody (TFA). Squamous cell carcinoma, porocarcinoma, syringomatous carcinoma, malignant clear cell hidradenoma, apocrine adenocarcinoma, and extramammary Paget's disease with underlying adenocarcinoma were used as controls. EOSC was positive for CU18 and CA15.3 in most cases, and for CD15 in a few cases. Squamous cell carcinoma of the skin was positive for CA15.3 in only one case. Porocarcinoma, syringomatous carcinoma and malignant clear cell hidradenoma were positive for CEA, CU18, CA15.3, and B6.2 in most cases. Apocrine adenocarcinoma and extramammary Paget's disease with underlying adenocarcinoma were positive for CEA, CU18, CD15, GCDFP15, CA15.3, and B6.2 in most cases. TFA was positive not only in EOSC but also in other skin cancers. Immunohistochemical examinations using these seven of eight antibodies except for TFA and routinely processed formalin-fixed and paraffin-embedded tissue specimens are beneficial in differentiating EOSC from other skin cancers.     

Novel Complications with HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis: Interstitial Cystitis and Persistent Prostatitis

Lower urinary symptoms associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSF) are common, but have been regarded as 'neurogenic' due to spinal involvements. However, in some cases, these symptoms are persistent, progressive, and not directly correlated with the severity of other neurologic symptoms of the lower spinal cord. These findings prompted us to locate organic lesions in the lower urinary tract and to correlate them with HTLV-1 infection. Among 35 HAM patients with lower urinary symptoms, we found 4 cases with the symptoms persistent and progressive: 3 with contracted bladder and another with persistent prostatitis. Histological or cytological examinations indicated local lymphocytic infiltrations in the lower urinary tract in all cases: 3 by the infiltration in the bladder and the other by a high concentration of lymphocytes in expressed prostatic secretions. Of 3 cases whose urinary samples were available, 2 showed significant increase in the concentration of urinary anti-HTLV-1 antibody of IgA class. The urinary IgA antibody of the third case was not elevated, but the sample had been obtained after resection of the affected bladder. None of the control cases showed significant anti-HTLV-1 IgA antibody in urine except for a case of gross hematuria due to chemotherapy directed against adult T-cell leukemia. We suggest inclusion of these processes into the spectrum of complications for HAM/TSP. The elevated excretion of anti-HTLV-1 of IgA class in urine may be an indicator of these complications.     

Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12

Fusions of cancer cells and dendritic cells (DCs) are effective in the treatment of animal tumor models and patients with metastatic renal carcinoma. In this study, we have fused DCs with mouse 4TOO plasmacytoma cells. The results demonstrate that vaccination of mice with the fusion cells (FC/4TOO) is associated with induction of antitumor humoral and cytotoxic T lymphocyte (CTL) responses. Immunization with FC/4TOO cells protected mice against tumor challenge. In addition, treatment of established multiple myeloma with FC/4TOO cells was associated with prolongation of survival but not with eradication of disease. As interleukin (IL)-12 potentiates the induction of immune responses, recombinant mouse IL-12 was administered with the FC/4TOO vaccine. Treatment of mice with FC/4TOO and IL-12 was associated with increased CTL activity and T-cell proliferation responses. Treatment with FC/4TOO and IL-12 also resulted in eradication of established disease. These findings demonstrate that immunization with FC/4TOO fusion cells and IL-12 potentiates antitumor immunity and the treatment of murine multiple myeloma.     

Portal venous blood flow while breath-holding after inspiration or expiration and during normal respiration in controls and cirrhotics

In this study, we used magnetic resonance (MR) imaging to measure portal blood flow in 12 healthy controls and 17 cirrhotics while they were breath-holding after inspiration and after expiration. We then compared the results with measurements made during normal respiration in the healthy controls and cirrhotics. Blood flow in the main portal vein under basal fasting conditions was quantitated using the cine phase-contrast MR velocity mapping method. Three measurements were made on one occasion, as follows: (1) throughout the cardiac cycle during normal respiration, (2) with the subject breath-holding after maximal inspiration, and (3) with the subject breath-holding after maximal expiration. During normal respiration, portal blood flow was 1.3 ± 0.2 l/min in controls vs 1.0 ± 0.1 l/min in cirrhotics (P < 0.0001); while subjects were breath-holding after inspiration, portal blood flow was 1.0 ± 0.2 l/min in controls vs 0.9 ± 0.1 l/min in cirrhotics; and while subjects were breath-holding after expiration, portal blood flow was 1.5 ± 0.2 l/min in controls vs 1.1 ± 0.2 l/min in cirrhotics (P < 0.0001). The differences were primarily due to changes in flow velocity. When the magnitude of these hemodynamic changes in the three respiratory conditions was compared in controls and cirrhotics, analysis of variance (ANOVA) showed a significant difference (P < 0.0001). In controls, portal blood flow decreased during maximal inspiration relative to flow during normal respiration (−24.6 ± 8.3%). Changes in portal blood flow in controls were greater than in cirrhotics (−13.5 ± 4.5%) (P < 0.0001); however, the difference in blood flow increase associated with maximal expiration between the two groups (+11.8 ± 9.4% vs +5.9 ± 11.5%) was not significant. We found that the respiration-induced hemodynamic variation in portal blood flow was less in cirrhotics than in the healthy controls. Portal blood flow measurements made during normal respiration using MR imaging closely reflect nearly physiologic conditions. Received: November 19, 1998 / Accepted: March 26, 1999