The changes of hepatic sinusoidal microcirculation and effects of nitric oxide synthase inhibitor during sepsis

BACKGROUND/AIMS: Sepsis may cause changes in liver blood flow, which may result in liver injury. Microcirculation in organ undergoes moderate alteration during sepsis or septic shock. The changes in hepatic microcirculation corresponding to liver functions and the effects of nitric oxide synthase inhibitor on the liver during sepsis were studied. METHODOLOGY: Sepsis was produced by CLP (cecal ligation and two-hole puncture). In part I, the leukocyte adherence, leukocyte rolling numbers, and velocity of sinusoidal microcirculation of liver were compared with in vivo microscopy among early septic, late septic and control rats. In part II, the rats were randomly divided into two groups after CLP procedure, group A was given L-NAME (NG-nitro-L-arginine-methylester hydrochloride), 10 mg/kg BW, and group B was given normal saline as a control. The hepatic microcirculation, measured with a Laser-Doppler Flowmeter, was performed at 0, 2, 4, 6, and 8 hours after the CLP procedure. Their liver functions were also examined and compared with the microcirculation. RESULTS: The results showed that the adherent and rolling numbers of leukocytes in the sinusoidal capillary significantly increased in early and late septic rats; and the centralized velocity of flow significantly decreased in late septic rats. For rats without L-NAME, their sinusoidal flux of the liver increased 2 and 4 hours after CLP, and then decreased gradually. Their GOT levels progressively increased after CLP, but the albumin levels decreased. For rats with L-NAME (group A), their sinusoidal flux levels at 2, 4 and 6 hours after CLP were significantly lower than those in rats without L-NAME (group B), but their GOT levels were higher since the 4th hour after CLP. CONCLUSIONS: Our conclusions are that hepatic microcirculation initially increased then decreased and the liver functions deteriorated gradually after sepsis was induced. These changes were aggravated when the nitric oxide synthesis was inhibited.     

Angiotensinogen gene haplotype and hypertension: interaction with ACE gene I allele

There are many reports demonstrating the association of renin-angiotensin system gene polymorphisms with hypertension in different populations. In the present study, we used haplotype analyses of the angiotensinogen gene with a new permutation-based hypothesis testing method to determine the association between multilocus angiotensinogen gene polymorphisms and hypertension in a relatively homogeneous Taiwanese population. We also genotyped angiotensin-converting enzyme gene insertion/deletion polymorphism and angiotensin II type 1-receptor gene A1166C polymorphism to detect epistatic gene-gene interactions. There were 408 patients with hypertension (hypertensives) and 286 controls. The angiotensinogen gene haplotype frequencies were significantly different between hypertensives and controls, and this finding was only present in subjects with angiotensin-converting enzyme gene II genotypes when the analysis was stratified by genotype of this polymorphism. In addition, the angiotensinogen gene haplotype structure of hypertensives was more heterogeneous than that of controls. Our results showed that angiotensinogen gene haplotypes were associated with hypertension and might act synergistically with I allele of the angiotensin-converting enzyme gene.     

Perceived enactment of autonomy and related factors among elders

This study aims to investigate the perceived enactment of autonomy (PEA) of Chinese elders as well as its relationship to other variables, such as morale, life satisfaction, need for assistance, subjective overall health status, etc. Selected demographic attributes (gender, age, living arrangements, etc.) were also examined for their relationship to PEA. A purposive sample of 324 subjects over 64 years old was recruited from homes and long-term care facilities in southern Taiwan. A Chinese version of the PEA scale (PEA-CV) and the Revised Philadelphia Geriatric Center Morale Scale (R-PGCMS) were used to measure PEA and morale. Data were analyzed using SPSS/PC software version 10.0. The results show that these elders had high perceived enactment of autonomy (mean = 2.99). Through multiple regression analysis, these results also revealed that need for daily living assistance, type of living arrangement, scores for morale and marital status significantly affected perceived enactment of autonomy among Chinese elders. The results suggest that we should help elders recognize possible choices, respect the choices they have made, advocate elders' autonomy while providing assistance, and design appropriate activities for them so that they gain a sense of freedom, individuality and independence. Directions for future studies are suggested.     

Clinical analysis of cervical radiculopathy causing deltoid paralysis

In general, deltoid paralysis develops in patients with cervical disc herniation (CDH) or cervical spondylotic radiculopathy (CSR) at the level of C4/5, resulting in compression of the C5 nerve root. Therefore, little attention has been paid to CDH or CSR at other levels as the possible cause of deltoid paralysis. In addition, the surgical outcomes for deltoid paralysis have not been fully described. Fourteen patients with single-level CDH or CSR, who had undergone anterior cervical decompression and fusion for deltoid paralysis, were included in this study. The severity of deltoid paralysis was classified into five grades according to manual motor power test, and the severity of radiculopathy was recorded on a visual analog scale (zero to ten points). The degree of improvement in both the severity of deltoid paralysis and radiculopathy following surgery was evaluated. Of 14 patients, one had C3/4 CDH, four had C4/5 CDH, three had C4/5 CSR, one had C5/6 CDH, and five had C5/6 CSR. Both deltoid paralysis and radiculopathy improved significantly with surgery (2.57+/-0.51 grades vs 4.14+/-0.66, P=0.001, and 7.64+/-1.65 points vs 3.21+/-0.58, P=0.001, respectively). In conclusion, the current study demonstrates that deltoid paralysis can develop due to CDH or CSR not only C4/5, but also at the levels of C3/4 and C5/6, and that surgical decompression significantly improves the degree of deltoid paralysis due to cervical radiculopathy.     

Gastrodin decreases immunoreactivities of gamma-aminobutyric acid shunt enzymes in the hippocampus of seizure-sensitive gerbils

Gastrodin is one of the natural compound isolated from Gastrodia elata and has known anticonvulsant effects, although the exact pharmacological principles of this natural compound and its effects on other aspects of gamma-aminobutyric acid (GABA) metabolism in vivo have not been explored. Therefore, in the present study, the effects of gastrodin on GABA metabolism in the gerbil hippocampus were examined, in an effort to identify the antiepileptic characteristics of this substance. Gastrodin reduced the seizure score in the treated group, although the immunoreactivities of GABA synthetic enzymes and GABA transporters were unaltered in gastrodin-treated animals. Interestingly, in the gastrodin-treated group, GABA transaminase (GABA-T) immunoreactivity in the hippocampus, particularly in neurons, was significantly decreased. In the gastrodin-treated group, both succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR) immunoreactivities in the hippocampus was also decreased significantly, which stood in contrast to the nontreated group, in which strong SSADH and SSAR immunoreactivities were detected. From the neuroanatomical viewpoint, these findings suggest that gastrodin may cause the elevation of GABA concentration by inhibiting the GABA shunt.     

Burn-induced lung damage in rat is mediated by a nitric oxide/cGMP system

This study was conducted to demonstrate the burn-induced lung neutrophil deposition and damage in rats is affected by the nitric oxide (NO)-dependent downstream cGMP signaling. In experiment 1, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one (ODQ) was given (20 mg/kg i.p.) to specific pathogen-free Sprague-Dawley rats immediately postburn to suppress the guanylate cyclase (GC) activity. At 8 h after burn, blood was assayed for the peroxynitrite-mediated dihydrorhodamine 123 (DHR 123) oxidation and lung tissues were harvested for myeloperoxidase (MPO) determination and histological studies. Pulmonary microvascular dysfunction was quantified by measuring the extravasations of Evans blue dye. In experiment 2, Sodium nitroprusside (SNP) was given (2 mM, i.p.) to elevate cGMP levels and ODQ (20 mg/kg, i.p.) or methylene blue (100 microM, i.p.) or saline was given. The animals were sacrificed 4 h after injection and lung tissues were harvested for iNOS mRNA study. The MPO activity in lung, blood DHR 123 oxidation level, and lung permeability increased up to 2-fold, 4-fold, and 2.5-fold after burn. Inhibition of GC by ODQ administration significantly decreased MPO activity, blood DHR 123 oxidation, and lung permeability by 55%, 66%, and 53%, respectively, and markedly decreased the thermal injury-induced perivascular and interstitial inflammatory cell infiltration and septum edema. The protective effects of ODQ were comparable to the use of selective iNOS inhibitor as demonstrated previously. Furthermore, ODQ decreased the burn or SNP-induced iNOS mRNA levels at 4 h after burn. These findings suggest that burn-induced lung dysfunction is mediated by the NO/cGMP system because it is abolished by application of either iNOS inhibitor or GC inhibitor. Also, the beneficial effect of ODQ is partly due to the attenuation of burn-induced iNOS expression by GC inhibition.     

Mortality among a cohort of female farm residents in New York State

A retrospective cohort study of mortality among 6,405 female farm residents who were New York Farm Bureau members, or spouses or relatives of members, was conducted from 1980 through 1993. Similar to previous findings for male farmers, the cohort experienced significantly lower mortality rates for all causes combined (including malignant neoplasms and cardiovascular disease), compared with rural nonfarm female residents. These findings suggest that farmers and farm residents of both genders have favorable habits with respect to several lifestyle factors. The results of this study were consistent with those from other studies of farm populations worldwide.     

Medicare breast surgery fees and treatment received by older women with localized breast cancer

OBJECTIVE: To determine whether area-level Medicare physician fees for mastectomy and breast conserving surgery were associated with treatment received by Medicare beneficiaries with localized breast cancer and to compare these results with an earlier analysis conducted using small areas (three-digit zip codes) as the unit of observation. DATA SOURCE: Medicare claims and physician survey data for a national sample of elderly (aged 67 or older) Medicare beneficiaries with localized breast cancer treated in 1994 (unweighted n = 1,787). STUDY DESIGN: Multinomial logistic regression analysis was used to estimate a model of treatment received as a function of Medicare fees, controlling for other area economic factors, patient demographic and clinical characteristics, physician experience, and region. PRINCIPAL FINDINGS: In 1994, average Medicare fees (adjusted for the effects of modifiers and procedure mix) for mastectomy (MST) and breast conserving surgery (BCS) were 904 dollars and 305 dollars, respectively. Holding other fees and factors fixed, a 10 percent increase in the BCS fee increased the odds of breast conserving surgery with radiation therapy relative to mastectomy to 1.34 (p = 0.02), while a 10 percent decrease in the MST fee increased the odds of breast conserving surgery with radiation therapy to 1.86 (p < 0.01). CONCLUSIONS: Among older women with localized breast cancer, financial incentives appear to influence the use of mastectomy and breast conserving surgery with radiation therapy. This finding is consistent with the hypothesis that physicians are responsive to financial incentives when the alternative procedures have clinically equivalent outcomes and the patient's clinical condition does not dominate the treatment choice. We also find that the fee effects derived from this analysis of individual data with more precise measurement of both diagnosis and treatment are qualitatively similar to the results of the small-area analysis. This suggests that the earlier study was not severely affected by ecological bias or other data limitations inherent in Medicare claims data.