Prognostic relevance of elevated plasma osmolality on admission in acute decompensated heart failure with preserved ejection fraction: insights from PURSUIT-HFpEF registry.

BACKGROUND: Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. METHODS: We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan-Meier curve analysis and Cox proportional hazard testing. RESULTS: 216 (22.5%) patients reached the primary endpoint. Kaplan-Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25-23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46-21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e', and N-terminal pro-B-type natriuretic peptide elevation. CONCLUSIONS: Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

Impact of the number of removed lymph nodes on recurrence-free survival in stage I ovarian clear cell carcinoma.

BACKGROUND: Although there have been several reports regarding the significance of staging lymphadenectomy for early stage ovarian clear cell carcinoma (CCC) patients, there have been few reports focusing on the number of removed lymph nodes. The aim of this study was to evaluate the impact of the number of removed lymph nodes on recurrence-free survival (RFS) in stage I ovarian CCC. METHODS: The subjects were patients with ovarian CCC who underwent surgery between January 1988 and December 2013. Clinicopathological variables were obtained from the medical records retrospectively. Statistical analysis using Kaplan-Meier method, log-rank test, and Cox proportional hazards model was performed. RESULTS: A total of 68 patients were entered into this study. The median number of removed lymph nodes was 56.5 (21-135). We calculated that the cutoff value of the number of removed lymph nodes for predicting recurrence was 35. RFS of the group with ≥ 35 removed lymph nodes was significantly better than that of the group with < 35 removed lymph nodes (p = 0.001). Similarly, RFS of stage IA and PS 0 or 1 was significantly better than that of stage IC (p = 0.029) and PS 2 or 3 (p = 0.001), respectively. Multivariate analysis revealed that the number of removed lymph nodes, stage, and PS was independent predictors for RFS. CONCLUSIONS: This study showed that the number of removed lymph nodes ≥ 35 was an independent predictor for improved RFS for stage I ovarian CCC. Sufficient lymphadenectomy may improve prognosis for stage I ovarian CCC.

Short communication: Temporal changes in the skin morphology of dairy cows during the periparturient period.

Management of dairy cow productivity requires monitoring of their nutritional status by visual observation. It has been suggested that changes in hair coat appearance are among the indicators of nutritional state in dairy cows. Temporal changes in the skin morphology in cows, however, have not been reported. In this study, we examined the changes in the skin of dairy cows that occur during the peripartum period. Seven pluriparous cows were used. Skin samples were collected at 28 d before the due date and 28 d and 56 d after calving for morphological examination. Hair follicle width was 108.8 ± 5.9 µm (±SD) in the dry period, 95.5 ± 5.5 µm at 28 d after calving, and 104.2 ± 5.3 µm at 56 d postpartum. The percentages of anagen hair follicles during these 3 periods were 41.4 ± 3.4, 18.5 ± 3.4, and 32.3 ± 3.3%, respectively. The corresponding sebaceous gland sizes were 8,362.0 ± 707.6, 7,800.0 ± 831.4, and 9,186.8 ± 962.6 µm2, respectively. Hair follicle width was positively correlated with percentage of anagen hair follicles. The thickness of epidermal and proliferation rate of epidermal cell were also correlated. However, the hair follicle width, sebaceous gland size and cell proliferation rate, and thickness and proliferation rate of epidermal cells did not show any marked changes.

Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure.

While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = -0.33, p < 0.05; r = -0.28, p < 0.05, respectively), and HR (r = -0.31, p < 0.05; r = -0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction.

Radiation therapy for chemotherapy-resistant recurrent epithelial ovarian cancer.

OBJECTIVES: While radiation therapy is administered as a palliative treatment for recurrent ovarian cancer, it remains unclear whether it improves the prognosis. METHODS: The effects and adverse events of radiation therapy for patients with recurrent epithelial ovarian cancer were investigated using medical records. RESULTS: Herein, 46 subjects comprising 33 patients whose recurrent lesions were contained within the irradiation field (therapeutic radiation group; TRG) and 13 patients with some recurrent lesions outside the irradiation field (palliative radiation group; PRG) were included. The TRG achieved a response rate (RR) of 66%, a disease control rate (DCR) of 100%, a progression-free survival (PFS) of 10 months, and an overall survival (OS) of 20 months. The PFS after radiation therapy was significantly longer than that following chemotherapy received just before radiation therapy. The PFS of patients with recurrent intrapelvic lesions was longer than that of patients with some extrapelvic recurrence. There was no significant association between PFS after radiation therapy and the duration from the previous chemotherapy or histological type. The RR, DCR, PFS, and OS of the PRG were 30 and 90% and 2 and 6 months, respectively. Serious adverse events were rare. CONCLUSIONS: Radiation therapy is a potential option for chemotherapy-resistant, localized recurrent ovarian cancer. © 2014 S. Karger AG, Basel.

The impairment of the parasympathetic modulation is involved in the age-related change in mitral E/A ratio.

The mitral early to late diastolic flow velocity ratio (E/A ratio) is age-dependent. It has been considered that its age dependency reflects the age-related lengthening of left ventricular (LV) relaxation; however, the change in E/A ratio is far larger than that expected from those in LV relaxation. We hypothesized that an age-related reduction of the parasympathetic activity increases left atrial (LA) contractility, and that this accounts for the age-related change in E/A ratio. (1) Exercise stress test was performed in 61 normal subjects (age range, 8-80 years, mean, 40 years) to assess heart rate (HR) recovery because slowed HR recovery indicates lowered parasympathetic activity. There were good interrelations among age, E/A ratio, and HR recovery. Among those aged ≤30 years, the age no longer correlated with E/A ratio or HR recovery, but there was a significant correlation between HR recovery and E/A ratio (r = 0.44, p < 0.05). (2) Pulsed Doppler and two-dimensional speckle tracking echocardiography (2DSTE) were performed before and after administration of parasympathetic blockade (atropine) in ten young healthy subjects. LA booster pump function was assessed with LA emptying index calculated by 2DSTE. LA emptying index was calculated from ([LA volume before the atrial contraction - minimal LA volume]/LA volume before the atrial contraction) × 100. Atropine increased mitral A velocity (p < 0.001) and LA emptying index (p < 0.05) along with a decrease in E/A ratio (p < 0.001). Parasympathetic withdrawal enhances LA contraction and increases mitral A velocity, which likely cause a reciprocal decrease in mitral E velocity and E/A ratio. Thus, parasympathetic deactivation with aging should be closely involved in the age-related change in mitral E/A ratio.

Predictors and Outcomes of Heart Failure With Preserved Ejection Fraction in Patients With a Left Ventricular Ejection Fraction Above or Below 60.

Background Although potential therapeutic candidates for heart failure with preserved ejection fraction (HFpEF) are emerging, it is still unclear whether they will be effective in patients with left ventricular ejection fraction (LVEF) of 60% or higher. Our aim was to identify the clinical characteristics of these patients with HFpEF by comparing them to patients with LVEF below 60%. Methods and Results From a multicenter, prospective, observational cohort (PURSUIT-HFpEF [Prospective Multicenter Obsevational Study of Patients with Heart Failure with Preserved Ejection Fraction]), we investigated 812 consecutive patients (median age, 83 years; 57% women), including 316 with 50% ≤ LVEF <60% and 496 with 60% ≤ LVEF, and compared the clinical backgrounds of the 2 groups and their prognoses for cardiac mortality or HF readmission. Two hundred four adverse outcomes occurred at a median of 366 days. Multivariable Cox regression tests adjusted for age, sex, heart rate, atrial fibrillation, estimated glomerular filtration rate, N-terminal pro-B-type natriuretic peptide, and prior heart failure hospitalization revealed that systolic blood pressure (hazard ratio [HR], 0.925 [95% CI, 0.862-0.992]; P=0.028), high-density lipoprotein to C-reactive protein ratio (HR, 0.975 [95% CI, 0.944-0.995]; P=0.007), and left ventricular end-diastolic volume index (HR, 0.870 [95% CI, 0.759-0.997]; P=0.037) were uniquely associated with outcomes among patients with 50% ≤ LVEF <60%, whereas only the ratio of peak early mitral inflow velocity to velocity of mitral annulus early diastolic motion e'(HR, 1.034 [95% CI, 1.003-1.062]; P=0.034) was associated with outcomes among patients with 60% ≤ LVEF. Conclusions Prognostic factors show distinct differences between patients with HFpEF with 50% ≤ LVEF <60% and with 60% ≤ LVEF. These findings suggest that the 2 groups have different inherent pathophysiology. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414; Unique identifier: UMIN000021831 PURSUIT-HFpEF.

Right Ventricular Dimension for Heart Failure With Preserved Ejection Fraction Involving Right Ventricular-Vascular Uncoupling.

Background: Right ventricular (RV) to pulmonary artery (PA) uncoupling is known to be important for the prognosis of not only heart failure (HF) with reduced ejection fraction but also HF with preserved ejection fraction (HFpEF). We further investigated key factors in the poor prognosis for HFpEF patients with RV-PA uncoupling. Methods: We studied 817 patients with HFpEF who were discharged alive in a multicentred cohort using post hoc analyses, with a primary endpoint of cardiac mortality or HF readmission. A total of 288 RV-PA uncoupled patients were observed, namely those with a tricuspid annular plane systolic excursion (TAPSE)/PA systolic pressure (PASP) ratio < 0.46 mm/mm Hg. Results: Among the RV-PA uncoupled patients, 101 adverse outcomes occurred over a median of 340 days. Echocardiographic RV dimension (RVD) was significantly important for prognosis in both univariable and multivariable Cox regression testing (hazard ratio 1.044, 95% confidence interval 1.014-1.074, P = 0.0042, and hazard ratio 1.036, 95% confidence interval 1.001-1.072, P = 0.0438, respectively) considered with the covariates of age, atrial fibrillation, renal function, N-terminal pro-brain natriuretic peptide, and other echocardiographic parameters. We further divided the patients into 4 groups, first into 2 groups with a TAPSE/PASP either ≥ or < 0.46 mm/mm Hg, and then into 4 groups by RVD medians of 31.9 mm and 33.3 mm, respectively. Kaplan-Meier curve analysis showed that outcomes were worst in patients with a low TAPSE/PASP ratio and larger RVD (log-rank P < 0.0001). Conclusions: This multicentre observational study highlighted the further prognostic importance of larger RVD among HFpEF patients with RV-PA uncoupling.

Contexte: On sait que le découplage entre le ventricule droit (VD) et l'artère pulmonaire (AP) est important pour établir le pronostic de l'insuffisance cardiaque à fraction d'éjection réduite, mais également celui de l'insuffisance cardiaque à fraction d'éjection préservée (ICFEP). Nous avons étudié en détail les facteurs clés liés au pronostic défavorable de l'ICFEP chez les patients présentant un découplage VD-AP. Méthodologie: À partir des données d'une cohorte multicentrique, nous avons réalisé des analyses a posteriori sur 817 patients présentant une ICFEP qui sont sortis de l'hôpital en vie, avec comme critère d'évaluation principal la mortalité d'origine cardiaque ou la réadmission en raison de l'insuffisance cardiaque. Au total, 288 patients affichant un découplage VD-AP ont été observés, principalement ceux dont le rapport excursion systolique dans le plan annulaire tricuspide (TAPSE; tricuspid annular plane systolic excursion)-pression artérielle pulmonaire systolique (PAPs) était < 0,46 mm/mm Hg. Résultats: Au total, 101 événements indésirables ont été recensés sur une période médiane de 340 jours chez les patients qui présentaient un découplage VD-AP. La dimension ventriculaire droite mesurée par échocardiographie était un facteur pronostique significativement important dans les analyses de régression de Cox à une et à plusieurs variables (rapport des risques instantanés [RRI] : 1,044; intervalle de confiance à 95 % : 1,014 à 1,074; p : 0,0042; et RRI : 1,036; intervalle de confiance à 95 % : 1,001 à 1,072; p : 0,0438; respectivement) avec prise en compte des covariables de l'âge, de la fibrillation auriculaire, de la fonction rénale, du fragment N-terminal du propeptide natriurétique de type B, et d'autres paramètres échocardiographiques. Nous avons ensuite réparti les patients en quatre groupes, d'abord en deux groupes, selon que leur rapport TAPSE-PAPs était ≥ ou < 0,46 mm/mm Hg, puis en quatre groupes selon des dimensions ventriculaires droites médianes de 31,9 et de 33,3 mm, respectivement. L'analyse de la courbe de Kaplan-Meier a révélé des résultats moins favorables chez les patients qui présentaient un faible rapport TAPSE-PAPs et une grande dimension ventriculaire droite (valeur de p < 0,0001 selon le test du log-rank). Conclusions: Cette étude observationnelle multicentrique a mis en évidence l'importance d'une grande dimension ventriculaire droite dans l'établissement du pronostic chez les patients atteints d'ICFEP qui présentent un découplage VD-AP.

Days in milk at first AI in dairy cows; its effect on subsequent reproductive performance and some factors influencing it.

The aim of the present study was to show the distribution of cows by days in milk (DIM) at first AI, effect of DIM at first AI on reproductive performance and some factors influencing DIM at first AI. A total of 767 Holstein Frisian cows that calved from January 2004 to December 2007 in 14 dairy herds were used. The first AI conception rate (FAICR) was 34.0%. Seventy-five percent of the cows were first inseminated within 100 days after calving. FAICR increased linearly up to 100 DIM. A one unit (20 days) longer DIM at first AI within the first 100 days postpartum increased the likelihood of a 2.4% FAICR. However, cows first inseminated at an earlier stage of lactation showed better reproductive performance in terms of pregnancy rate and calving to conception interval than cows first inseminated at a later stage. A one day increase in the interval from calving to first AI reduced the likelihood of 0.85 days to become pregnant. Herd or region located in southwestern Japan, tie-stall herd, first AI in spring, higher parity, uterine infection, metabolic diseases and/or mastitis and abnormal resumption of postpartum ovarian cycles contributed to delaying first AI.

Prognostic Importance of Pulmonary Arterial Capacitance in Acute Decompensated Heart Failure With Preserved Ejection Fraction.

Background Although the prognostic importance of pulmonary arterial capacitance (PAC; stroke volume/pulmonary arterial pulse pressure) has been elucidated in heart failure with reduced ejection fraction, whether its significance in patients suffering from heart failure with preserved ejection fraction is not known. We aimed to examine the association of PAC with outcomes in inpatients with heart failure with preserved ejection fraction. Methods and Results We prospectively studied 705 patients (median age, 83 years; 55% women) registered in PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction). We investigated the association of echocardiographic PAC at discharge with the primary end point of all-cause death or heart failure rehospitalization with a mean follow-up of 384 days. We further tested the acceptability of the prognostic significance of PAC in a subgroup of patients (167/705 patients; median age, 81 years; 53% women) in whom PAC was assessed by right heart catheterization. The median echocardiographic PAC was 2.52 mL/mm Hg, with a quartile range of 1.78 to 3.32 mL/mm Hg. Univariable and multivariable Cox regression testing revealed that echocardiographic PAC was associated with the primary end point (unadjusted hazard ratio, 0.82; 95% CI, 0.72-0.92; P=0.001; adjusted hazard ratio, 0.86; 95% CI, 0.74-0.99; P=0.035, respectively). Univariable Cox regression testing revealed that PAC assessed by right heart catheterization (median calculated PAC, 2.82 mL/mm Hg) was also associated with the primary end point (unadjusted HR, 0.70; 95% CI, 0.52-0.91; P=0.005). Conclusions A prospective cohort study revealed that impaired PAC diagnosed with both echocardiography and right heart catheterization was associated with adverse outcomes in inpatients with heart failure with preserved ejection fraction. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.

Distinctive prognostic factor of heart failure with preserved ejection fraction stratified with admission blood pressure.

AIMS: The prognostic importance of admission systolic blood pressure (SBP) in heart failure with preserved ejection fraction (HFpEF) is elusive. We aimed to clarify the pathophysiological differences between patients categorized with admission SBP among HFpEF patients. METHODS AND RESULTS: We studied 1008 inpatients from PURSUIT-HFpEF, a multicentre prospective observational registry. We classified patients as having elevated (>140 mmHg), preserved (90-140 mmHg), or low (<90 mmHg) admission SBP. Most cases had elevated (n = 584) or preserved (n = 420) SBP; the four cases with low SBP were excluded. Univariable Cox regression testing revealed that preserved SBP patients had a higher risk of a composite of cardiac death and heart failure re-hospitalization [hazard ratio (HR) 1.48, 95% confidence interval (CI) 1.14-1.92, P = 0.0035] than elevated SBP patients. In multivariable Cox regression models, while prior heart failure hospitalization (HR 1.36, 95% CI 1.01-2.84, P = 0.0453), atrial fibrillation (HR 1.82, 95% CI 1.10-2.99, P = 0.0209), and N-terminal pro-B-type natriuretic peptide (HR 1.94, 95% CI 1.10-3.43, P = 0.0229) at discharge were significantly associated with adverse outcomes in elevated SBP patients, N-terminal pro-B-type natriuretic peptide (HR 2.06, 95% CI 1.04-4.07, P = 0.0373) and right ventricular-pulmonary artery uncoupling reflected by the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (HR 0.19, 95% CI 0.05-0.65, P = 0.0075) at discharge were significant prognostic factors in preserved SBP patients. CONCLUSIONS: Patients with preserved admission SBP had significant higher risks for adverse outcomes than those with elevated SBP in HFpEF. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure was the distinctive prognostic factor between the two groups.

Effects of Casein Hydrolysate Ingestion on Thermoregulatory Responses in Healthy Adults during Exercise in Heated Conditions: A Randomized Crossover Trial.

Food ingestion has been shown to affect thermoregulation during exercise, while the impact of protein degradant consumption remains unclear. We investigated the effects of casein hydrolysate ingestion on thermoregulatory responses during exercise in the heat. In a randomized, placebo-controlled, double-blind, crossover trial, five men and five women consumed either 5 g of casein hydrolysate or placebo. Thirty minutes after ingestion, participants cycled at 60% VO2max until voluntary exhaustion wearing a hot-water (43 °C) circulation suit. Exercise time to exhaustion, body core temperature, forearm sweat rate, and forearm cutaneous vascular conductance did not differ different between the conditions. However, chest sweat rate and mean skin temperature increased upon casein hydrolysate ingestion compared with placebo during exercise. Increased chest sweat rate upon casein hydrolysate ingestion was associated with elevated sudomotor sensitivity to increasing body core temperature, but not the temperature threshold for initiating sweating. A positive correlation was found between chest sweat rate and plasma total amino acid concentration during exercise. These results suggest that casein hydrolysate ingestion enhances sweating heterogeneously by increasing peripheral sensitivity of the chest's sweating mechanism and elevating skin temperature during exercise in the heat. However, the physiological link between plasma amino acid concentration and sweat rate remains unclear.

Prognostic Importance of Right Ventricular-Vascular Uncoupling in Acute Decompensated Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Recent accumulating evidence reveals that the right ventricular (RV)-pulmonary artery (PA) uncoupling is associated with poor outcome in patients with heart failure (HF), RV dysfunction, and pulmonary hypertension. However, the prognostic utility of RV-PA uncoupling in HF with preserved ejection fraction (HFpEF) remains elusive. In this study, we aim to investigate the associations of RV-PA uncoupling with outcomes of HFpEF inpatients. METHODS: We prospectively studied 655 patients, registered in PURSUIT-HFpEF (The Prospective Multicenter Obervational Study of Patients with Heart Failure with Preserved Ejection Fraction), a multicenter observational study of Japanese HFpEF inpatients. We assigned registered patients based on the determined value of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio that can predict primary outcome as an indicator of RV-PA uncoupling. RESULTS: Univariable Cox regression testing revealed that RV-PA uncoupling was associated with the primary endpoint of all-cause death, HF rehospitalization, and cerebrovascular events (hazard ratio [HR] 1.77 [95% CI, 1.34-2.32], P<0.0001) and the secondary endpoints of all-cause death and HF rehospitalization (HR 2.75 [95% CI, 1.77-4.33], P<0.0001, HR 1.63 [95% CI, 1.18-2.26], P=0.0036, respectively). Multivariable analysis also showed that RV-PA uncoupling was significantly associated with primary endpoint and all-cause death independent of age, sex, atrial fibrillation, renal dysfunction, elevated E/e', and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) (HR 1.38 [95% CI, 1.01-1.88], P=0.0413, HR 1.85 [95% CI, 1.14-3.01], P=0.0129, respectively). CONCLUSIONS: Prospective study of a hospitalized cohort revealed that RV-PA uncoupling was independently associated with adverse outcomes in acute decompensated patients with HFpEF. Registration: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.

Trifluoromethoxy-benzylated ligands improve amyloid detection in the brain using (19)F magnetic resonance imaging.

The chemical properties of probes that improve amyloid detection by non-invasive (19)F magnetic resonance imaging (MRI) are of interest. We synthesized benzoxazole compounds with trifluoromethoxy groups, and found that these compounds displayed sharp (19)F nuclear magnetic resonance (NMR) signals in an assay buffer. However, the intensities of the (19)F NMR signals were dramatically reduced in mouse brain lysates. Our results indicate that the inhibitory effect of brain tissue on the (19)F NMR signals from these probes can be attributed to the hydrophobicity of the tissue. These results highlight the importance of using hydrophilic (19)F-MRI agents to avoid the inhibitory effects of brain tissues on (19)F NMR signals.

Value of assessment of left atrial volume and diameter in patients with heart failure but with normal left ventricular ejection fraction and mitral flow velocity pattern.

AIMS: We assessed the comparative value of measurements of tissue Doppler early diastolic mitral annular velocity (E'), left atrial diameter (LAD), and left atrial volume (LAV) in patients with possible heart failure (HF) but with normal left ventricular (LV) ejection fraction (EF) and mitral flow velocity pattern. METHODS AND RESULTS: We determined LAV and LAD indexes in addition to the ratio of peak early diastolic mitral flow velocity (E) to E' (E/E' ratio) in 91 patients with all three of the followings: HF, LVEF of greater than 55%, and normal mitral E/A ratio between 0.8 and 1.5. Twenty healthy subjects were used as controls. E/E' ratio was abnormal (>1.5) in 38 of the 91 patients (sensitivity=44%). LAV index was 32 mL/m(2) or greater in 71 of the 91 patients (sensitivity=78%), while LAD index was 27 mm/m(2) or greater in 81 of 91 patients (sensitivity=89%). The area under the curve by receiver-operator curve analyses was 0.995 for LA volume index, 0.998 for LAD index, and 0.885 for E/E' ratio. CONCLUSION: LAV and LAD indexes are more useful in detecting with HF and normal EF patients than E' related parameters.

A case of freemartin with atresia recti and ani in Japanese Black calf.

A female Japanese Black calf was born on 25 March 2003 at Hiroshima University Farm as a co-twin to a male Japanese Black calf. The male calf showed no external urogenital abnormalities. The absence of anal opening and external features of freemartinism were observed in the female. A small opening to the vulva (about 1.5 cm in length) with fused lips and a prominent clitoris were seen. The hair around the vulva was 3.5 cm in length and was heavy and dense. The distance from the vulva to the atretic anus was 9.0 cm. There were no other detectable abnormalities on physical examination. The PCR-based DNA test showed male-specific sequences confirming the calf to be freemartin. At autopsy 1 day after the calf birth, the gonads were found to be small and hard and the left uterine horn showed segmental aplasia near its proximal end. Two seminal glands (remnants of mesonephric duct) were located on both sides of the uterine body. A cervix was absent. The vagina was underdeveloped and looked like a tubual structure. The rectal end was closed, while the distance from the end of the atretic rectum to the absent anal opening was about 4.0 cm. On histological examination, the gonads exhibited extensive morphologic alteration; there was no cortex with the absence of ovarian structures. The seminal glands consisted of hypoplastic glandular tissue surrounded by extensive fibrous connective tissue. In conclusion, this is a case report of a freemartin with atresia recti and ani.

Atresia ani with diphallus and separate scrota in a calf: a case report.

Atresia ani, a common genetic defect in animals, is often accompanied by urogenital defects in calves. This paper reports a case of atresia ani with diphallus and separate scrota in a calf. The calf was born with atresia ani; surgery (to open the anus) was performed 3 days after birth. No urogenital abnormalities were noticed until 4 months after birth. At that time, two separate scrota (each containing a testis) and a sac-like structure in the middle of two scrota, were visible. The gait was abnormal, with abduction of the hind limbs while walking. Additionally, the hind legs appeared wider than usual at the hip joints. Two weeks later, two peni (diphallia) was observed, each in a separate preputial sheath. The calf had a normal karyotype on cytogenetic examination. Plasma concentrations of testosterone at 5.5, 6, and 7 months of age were 3.5, 1.9, and 1.7 ng/ml, respectively. At necropsy (7 months of age), the prepuce was thick and the glans of the right penis was adhered to the prepuce. The left penis did not have a urethra or retractor penis muscles. The sac-like structure in the middle of the two scrota contained the urinary bladder and a loop of small intestine. The pubic bone had failed to fuse at the pelvic symphysis. In conclusion, this is the first reported case of atresia ani with diphallus, separate scrota, and pubic bone separation in a calf.

Intraleaflet haemorrhage as a mechanism of rapid progression of stenosis in bicuspid aortic valve.

BACKGROUND: The mechanisms are unknown why aortic stenosis (AS) progresses faster in patients with bicuspid aortic valve (BAV) than those with tricuspid aortic valve (TAV). The objective of this study is to examine whether neoangiogenesis, haemorrhage in the aortic valve leaflet (intraleaflet haemorrhage) and macrophage infiltration are involved in the mechanisms of rapid progression of AS with BAV. METHODS: We retrospectively examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve replacement for AS (AS with BAV: n=22, AS with TAV: n=86). The stenotic valve leaflets were examined by immunohistochemistry to detect vascular endothelial cells, red blood cell remnant and macrophage. We assessed the progression of AS by annualized changes in the aortic valve area (ΔAVA: cm(2)/year) which was evaluated by serial echocardiography with the continuity equation. RESULTS: Neoangiogenesis, intraleaflet haemorrhage and macrophage infiltration were frequently observed in leaflets obtained from AS patients with BAV (neoangiogenesis: 82%, intraleaflet haemorrhage: 91%, macrophage infiltration 91%). These pathological changes were more severe in AS with BAV than TAV, and they were positively correlated with progression of AS in patients with BAV. Multivariated analysis revealed that bicuspid anatomy was the only factor that predicted neoangiogenesis, intraleaflet haemorrhage and macrophage infiltration when patients with BAV and those with TAV were combined. CONCLUSIONS: Neoangiogenesis, intraleaflet haemorrhage and macrophage infiltration are more severe in leaflets from AS with BAV than TAV and associated with rapid progression of AS with BAV. This pathological process may account for rapid progression of AS with BAV.