Cardiac energetics analysis after aortic valve replacement with 16-mm ATS mechanical valve

The 16-mm ATS mechanical valve is one of the smallest prosthetic valves used for aortic valve replacement (AVR) in patients with a very small aortic annulus, and its clinical outcomes are reportedly satisfactory. Here, we analyzed the left ventricular (LV) performance after AVR with the 16-mm ATS mechanical valve, based on the concept of cardiac energetics analysis. Eleven patients who underwent AVR with the 16-mm ATS mechanical valve were enrolled in this study. All underwent echocardiographic examination at three time points: before AVR, approximately 1 month after AVR, and approximately 1 year after AVR. LV contractility (end-systolic elastance [Ees]), afterload (effective arterial elastance [Ea]), and efficiency (ventriculoarterial coupling [Ea/Ees] and the stroke work to pressure–volume area ratio [SW/PVA]) were noninvasively measured by echocardiographic data and blood pressure measurement. Ees transiently decreased after AVR and then recovered to the pre-AVR level at the one-year follow-up. Ea significantly decreased in a stepwise manner. Consequently, Ea/Ees and SW/PVA were also significantly improved at the one-year follow-up compared with those before AVR. The midterm LV performance after AVR with the 16-mm ATS mechanical valve was satisfactory. AVR with the 16-mm ATS mechanical valve is validated as an effective treatment for patients with a very small aortic annulus. The cardiac energetics variables, coupling with the conventional hemodynamic variables, can contribute to a better understanding of the patients’ clinical conditions, and those may serve as promising indices of the cardiac function.     

Infradiaphragmatic malperfusion of acute aortic dissection associated with previous abdominal aortic aneurysm repair

Purpose

To evaluate the association of previous abdominal aortic aneurysm (AAA) graft replacement with infradiaphragmatic malperfusion in patients with acute aortic dissection.

Methods

Between November 2006 and June 2011, 133 patients were referred to our hospital for management of acute aortic dissection. Eight (6.0 %) of these patients had undergone AAA graft replacement prior to the acute aortic dissection. We compared the computed tomography (CT) images of these 8 patients with those of the remaining 125 patients without previous AAA graft replacement, in terms of organ ischemia as a complication induced by acute aortic dissection.

Results

Infradiaphragmatic malperfusion from acute aortic dissection was confirmed in four of the eight patients who had undergone AAA graft replacement. Contrasted CT scan images indicated that the main cause of infradiaphragmatic malperfusion was collapse of the true lumen from compression by the false lumen into the suprarenal aorta. Although there was no significant difference between the groups in terms of cerebral ischemia and myocardial ischemia, bilateral leg ischemia and visceral ischemia occurred more frequently in the patients who had undergone AAA graft replacement.

Conclusion

Previous AAA graft replacement is a risk factor for infradiaphragmatic malperfusion in patients with acute aortic dissection.     

AN ELECTRON MICROSCOPIC EXAMINATION OF AGE-RELATED CHANGES IN THE RAT LIVER. The Influence of Diet

The influence of age and diet on the ultrastructure of hepatocytes is reported. The following dietary manipulations were investigated: Group 1, fed ad libitum a diet containing 21% protein; Group 2, fed a similar diet but restricted to 60% of the intake of Group 1 from 6 weeks of age onwards; Group 3, restricted from 6 weeks to 6 months of age and thereafter fed ad libitum; Group 4, restriction started at 6 months of age; Group 5, fed ad libitum a diet containing 12.6% protein. In all groups the size of hepatocytes was found not to increase during adult life. The size of hepatocytes in Groups 2 and 4 was the same as or larger than that of the other groups; thus food restriction resulted in a decreased number of hepatocytes. Changes in the structure of some organelles and the accumulation of lipofuscin granules occurred with advancing age and the extent of these age-related changes was less in Groups 2 and 4 than in the other groups. These morphologic findings in conjunction with our previously reported metabolic findings provide a new view of the action of food restriction on the aging process. ACTA PATHOL JPN 38: 1119∼1130, 1988.     

stx genotype and molecular epidemiological analyses of Shiga toxin-producing Escherichia coli O157:H7/H? in human and cattle isolates

The relationship between human diseases caused by infection with Shiga toxin (Stx)-producing Escherichia coli (STEC) O157 strains and O157 strains isolated from cattle was investigated in an area where stockbreeding is prolific. For this purpose, the stx genotypes, the molecular epidemiological characteristics of 268 STEC O157 strains including 211 human-origin strains and 57 cattle-origin strains, and clinical manifestations of 210 STEC-infected people were analyzed. Of 211 human-origin strains, 92 strains (44%) were of the stx1/stx2 genotype, and 74 strains (35%) were of the stx2c genotype. Most of the people infected with stx2c genotype strains presented no symptoms or mild symptoms such as slight diarrhea, except for 3 patients with bloody diarrhea. Of the 57 cattle-origin strains, 27 strains (47%) were of the stx2c genotype and 17 strains (30%) were of the stx1/stx2 genotype. Pulsed-field gel electrophoresis (PFGE) and insertion sequence (IS) analysis demonstrated that 11 isolates (41%) of the 27 cattle isolates of the stx2c genotype had high homology (>95% identity) with human isolates. These results suggest that some genetic patterns of the stx2c genotype strains might be preserved in cattle or their surrounding environment for several years, and during these periods, they might have opportunities to infect people through various routes. Because of the mild virulence of the stx2c genotype strains, they seemed to be transmitted asymptomatically from cattle to humans and then spread from person to person. It may be a public health concern. Further, they occasionally cause severe symptoms in humans; therefore, caution is warranted for infections by stx2c genotype O157 strains, in addition to stx2-possessing genotype O157 strains.     

Cellular and molecular mechanisms of TSLP function in human allergic disorders--TSLP programs the "Th2 code" in dendritic cells

Thymic stromal lymphopoietin (TSLP) has been recently implicated as a key molecule for initiating allergic inflammation at the epithelial cell-dendritic cell (DC) interface. In humans, aberrant TSLP expression is observed in allergic tissues, such as lesional skins of atopic dermatitis, lungs of asthmatics, nasal mucosa of atopic rhinitis and nasal polyps, and ocular surface of allergic keratoconjunctivitis. TSLP is produced predominantly by damaged epithelial cells and stimulates myeloid DCs (mDCs). TSLP-activated mDCs can promote the differentiation of naive CD4⁺ T cells into a Th2 phenotype and the expansion of CD4⁺ Th2 memory cells in a unique manner dependent on OX40L, one of the tumor necrosis factor superfamily members with Th2-promoting function, and lack of production of IL-12. From a genetic point of view, multiple genome-wide association studies have repeatedly identified the TSLP gene as one of the loci associated with susceptibility to allergic diseases. Thus, TSLP is a rational therapeutic target for the treatment of allergic disorders. Elucidating the mechanisms that regulate TSLP expression and the effects of TSLP on orchestrating the immune response toward a Th2 phenotype is essential for developing anti-TSLP therapy.     

Impact of Adjuvant Immunochemotherapy Using Protein-bound Polysaccharide-K on Overall Survival of Patients with Gastric Cancer

Protein-bound polysaccharide K (PSK) is an anticancer agent used for adjuvant therapy against gastric cancer. The aim of this study was to evaluate the effect of PSK on the overall survival of patients with gastric cancer. A total of 254 patients who underwent surgical curative resection were included in this retrospective study. We identified 138 patients who received antimetabolites alone (control group) and 115 patients who received antimetabolites plus PSK (PSK group). In patients with early tumor recurrence, overall survival was significantly better in the PSK group (p=0.023). In patients with pN3 lymph node metastasis, median overall survival was better in the PSK group compared with the control group (p=0.032). Our results suggest that adjuvant immunochemotherapy with PSK increased the overall survival for patients with pN3 and early tumor recurrence. Thus, the combination of PSK with oral chemotherapeutic agents might be suitable for postoperative adjuvant therapy against gastric cancer in patients with lymph node metastases.     

Membraneous glomerulonephritis and non-Hodgkin's lymphoma in a patient with primary Sjögren's syndrome

The most common renal manifestation of Sj?gren's syndrome is tubulointerstitial nephritis, and glomerular disease is rare (3). A 62-year-old woman with primary Sj?gren's syndrome developed nephrotic syndrome. Kidney biopsy was consistent with membraneous glomerulonephritis. Steroid pulse therapy was not effective. Three months later she was diagnosed with non-Hodgkin's lymphoma of the tongue, and she was given CHOP therapy and radiation. Both the lymphoma and membraneous glomerulonephritis were resolved.     

Different Critical Perinatal Periods and Hypothalamic Sites of Oestradiol Action in the Defeminisation of Luteinising Hormone Surge and Lordosis Capacity in the Rat

Female rats show a gonadotrophin‐releasing hormone (GnRH)/luteinising hormone (LH) surge in the presence of a preovulatory level of oestrogen, whereas males do not because of brain defeminisation during the developmental period by perinatal oestrogen converted from androgen. The present study aimed to identify the site(s) of oestrogen action and the critical period for defeminising the mechanism regulating the GnRH/LH surge. Animals given perinatal treatments, such as steroidal manipulations, brain local implantation of oestradiol (E₂) or administration of an NMDA antagonist, were examined for their ability to show an E₂‐induced LH surge at adulthood. Lordosis behaviour was examined to compare the mechanisms defeminising the GnRH/LH surge and sexual behaviour. A single s.c. oestradiol‐benzoate administration on either the day before birth (E21), the day of birth (D0) or day 5 (D5) postpartum completely abolished the E₂‐induced LH surge at adulthood in female rats, although the same treatment did not inhibit lordosis. Perinatal castration on E21 or D0 partially rescued the E2‐induced LH surge in genetically male rats, whereas castration from E21 to D5 totally rescued lordosis. Neonatal E₂ implantation in the anterior hypothalamus including the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) abolished the E₂‐induced LH surge in female rats, whereas E₂ implantation in the mid and posterior hypothalamic regions had no inhibitory effect on the LH surge. Lordosis was not affected by neonatal E₂ implantation in any hypothalamic regions. In male rats, neonatal NMDA antagonist treatment rescued lordosis but not the LH surge. Taken together, these results suggest that an anterior hypothalamic region such as the AVPV/POA region is a perinatal site of oestrogen action where the GnRH/LH regulating system is defeminised to abolish the oestrogen‐induced surge. The mechanism for defeminisation of the GnRH/LH surge system might be different from that of sexual behaviour, in terms of the site(s) of oestrogen action and critical period, as well as the neurotransmitter system involved.     

SLCO1B1 (OATP1B1, an uptake transporter) and ABCG2 (BCRP, an efflux transporter) variant alleles and pharmacokinetics of pitavastatin in healthy volunteers

To investigate the contribution of genetic polymorphisms of SLCO1B1 and ABCG2 to the pharmacokinetics of a dual substrate, pitavastatin, 2 mg of pitavastatin was administered to 38 healthy volunteers and pharmacokinetic parameters were compared among the following groups: 421C/C(*)1b/(*)1b (group 1), 421C/C(*)1b/(*)15 (group 2), 421C/C(*)15/(*)15 and 421C/A(*)15/(*)15 (group 3), 421C/A(*)1b/(*)1b (group 4), 421A/A(*)1b/(*)1b (group 5), and 421C/A(*)1b/(*)15 (group 6). In SLCO1B1, pitavastatin area under plasma concentration-time curve from 0 to 24 h (AUC(0-24)) for groups 1, 2, and 3 was 81.1+/-18.1, 144+/-32, and 250+/-57 ng h/ml, respectively, with significant differences among all three groups. In contrast to SLCO1B1, AUC(0-24) in groups 1, 4, and 5 was 81.1+/-18.1, 96.7+/-35.4, and 78.2+/-8.2 ng h/ml, respectively. Although the SLCO1B1 polymorphism was found to have a significant effect on the pharmacokinetics of pitavastatin, a nonsynonymous ABCG2 variant, 421C>A, did not appear to be associated with the altered pharmacokinetics of pitavastatin.