The Geriatric Nutritional Risk Index is Independently Associated with Prognosis in Patients with Critical Limb Ischemia Following Endovascular Therapy.

OBJECTIVES: Patients with critical limb ischemia (CLI) have poor overall and limb prognosis. Although nutritional status influences overall prognosis, and the Geriatric Nutritional Risk Index (GNRI) is a widely used, simple and well established nutritional status screening method, the association between the GNRI and the overall and limb prognosis of patients with CLI following endovascular therapy (EVT) has not been explored. METHODS: Clinical outcomes were retrospectively evaluated in 473 consecutive patients (74 ± 10 years; 59% male) with CLI who underwent EVT. The GNRI on admission was calculated as follows: [14.89 × albumin (g/dL)] + [41.7 × (body weight/ideal body weight)]. Cox proportional hazard analysis was performed to explore the independent association between the GNRI and mortality and major amputation. RESULTS: Patients (53% ambulatory, 38% wheelchair bound, and 9% bedridden) were divided into two groups based on the median GNRI: the higher group (GNRI ≥ 91.2, n = 237) and the lower group (GNRI < 91.2, n = 236). Median follow up duration after EVT was 11.3 months. Three years after EVT, the survival rate (74% in the higher GNRI, and 48% in the lower GNRI, respectively), and limb salvage rate (92% in the higher GNRI, and 84% in the lower GNRI) were significantly lower in the lower GNRI group. GNRI (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.05), along with being wheelchair bound (HR, 1.87; 95% CI 1.17-2.97; vs. ambulatory status), being bedridden (HR, 3.10; 95% CI, 1.63-2.97; vs. ambulatory status), being on hemodialysis (HR, 2.33; 95% CI, 1.49-3.64), and having chronic heart failure (HR, 2.22; 95% CI, 1.44-3.43) were the independent predictors of mortality. The GNRI (HR, 1.04; 95% CI, 1.01-1.07), being bedridden (HR, 4.15; 95% CI, 1.67-10.3; vs. ambulatory status), isolated below knee disease (HR, 2.49; 95% CI, 1.30-4.77), and hemodialysis (HR, 2.44; 95% CI, 1.23-4.85) were independently associated with major amputation. CONCLUSIONS: The GNRI on admission was independently associated with mortality and major amputation after EVT in patients with CLI.

Impaired beta-adrenergic response and decreased L-type calcium current of hypertrophied left ventricular myocytes in postinfarction heart failure.

Infarct-induced heart failure is usually associated with cardiac hypertrophy and decreased -adrenergic responsiveness. However, conflicting results have been reported concerning the density of L-type calcium current (I Ca(L)), and the mechanisms underlying the decreased -adrenergic inotropic response. We determined I Ca(L) density, cytoplasmic calcium ([Ca2+]i) transients, and the effects of -adrenergic stimulation (isoproterenol) in a model of postinfarction heart failure in rats. Left ventricular myocytes were obtained by enzymatic digestion 8-10 weeks after infarction. Electrophysiological recordings were obtained using the patch-clamp technique. [Ca2+]i transients were investigated via fura-2 fluorescence. -Adrenergic receptor density was determined by [ H]-dihydroalprenolol binding to left ventricle homogenates. Postinfarction myocytes showed a significant 25% reduction in mean I Ca(L) density (5.7 0.28 vs 7.6 0.32 pA/pF) and a 19% reduction in mean peak [Ca2+]i transients (0.13 0.007 vs 0.16 0.009) compared to sham myocytes. The isoproterenol-stimulated increase in I Ca(L) was significantly smaller in postinfarction myocytes (Emax: 63.6 4.3 vs 123.3 0.9% in sham myocytes), but EC50 was not altered. The isoproterenol-stimulated peak amplitude of [Ca2+]i transients was also blunted in postinfarction myocytes. Adenylate cyclase activation through forskolin produced similar I Ca(L) increases in both groups. -Adrenergic receptor density was significantly reduced in homogenates from infarcted hearts (Bmax: 93.89 20.22 vs 271.5 31.43 fmol/mg protein in sham myocytes), while Kd values were similar. We conclude that postinfarction myocytes from large infarcts display reduced I Ca(L) density and peak [Ca2+]i transients. The response to -adrenergic stimulation was also reduced and was probably related to -adrenergic receptor down-regulation and not to changes in adenylate cyclase activity.

Cancer chemoprevention by ginseng in mouse liver and other organs.

Oral administration of red ginseng extracts (1% in diet for 40 weeks) resulted in the significant suppression of spontaneous liver tumor formation in C3H/He male mice. Average number of tumors per mouse in control group was 1.06, while that in red ginseng extracts-treated group was 0.33 (p<0.05). Incidence of liver tumor development was also lower in red ginseng extracts-treated group, although the difference from control group was not statistically significant. Anti-carcinogenic activity of white ginseng extracts, besides red ginseng extracts, was also investigated. In the present study, the administration of white ginseng extracts was proven to suppress tumor promoter-induced phenomena in vitro and in vivo. It is of interest that oral administration of the extracts of Ren-Shen-Yang- Rong-Tang, a white ginseng-containing Chinese medicinal prescription, resulted in the suppression of skin tumor promotion by 12-o-tetradecanoylphorbol-13-acetate in 7,12-dimethylbenz[a]anthracene-initiated CD-1 mice. These results suggest the usefulness of ginseng in the field of cancer prevention.

Increases of calcium and magnesium and decreases of phosphorus and iron with aging in human uterine tubes.

To elucidate compositional changes of the uterine tube by aging, the authors studied age-related changes of elements in human uterine tubes by inductively coupled plasma-atomic emission spectrometry. The uterine tubes were resected postmortem or surgically removed from patients with uterine myoma. It was found that the contents of calcium and magnesium increased progressively with aging in uterine tubes, whereas the contents of phosphorus and iron decreased gradually with aging. The sulfur content of uterine tubes remained constant and independent of aging. Regarding relationships between elements, significant relationships were found between calcium and magnesium contents, between phosphorus and iron contents, between phosphorus and sulfur contents, and between phosphorus and sodium contents in human uterine tubes.

Internucleobase-interaction-directed self-assembly of nanofibers from homo- and heteroditopic 1,omega-nucleobase bolaamphiphiles.

The complementary 1,omega-thymine, 1,omega-adenine, and 1,omega-(thymine, adenine) bolaamphiphiles, [N,N'-bis[3-(2,4-dihydroxy-5-methylpyrimidine-1-yl)propionyl]1,n-diaminoalkane [T-n-T (n = 10, 11, 12)], N, N'-bis[3-(6-aminopurine-9-yl)propionyl]1,n-diaminoalkane [A-n-A (n = 10, 11, 12)], and N-[3-(2,4-dihydroxy-5-methylpyrimidine-1-yl)propionyl], N'-[3-(6-aminopurine-9-yl)propionyl]1,n-diaminoalkane [T-n-A (n = 10, 11, 12)], respectively] have been synthesized. The spontaneous homo- and heteroassembly of these nucleobase-based bolaamphiphiles has been studied by light microscopy, energy-filtering transmission electron microscopy, FT-IR, and powder X-ray diffraction analyses. The achiral T-10-T bolaamphiphile produced in 10% ethanolic/aqueous solutions unprecedented double-helical ropes of 1-2 microm in widths and several hundred micrometers in length, whereas the complementary homologue A-10-A gave only microcrystalline solids of 1-10 microm in size. In contrast, an equimolar mixture of T-10-T and A-10-A yielded supramolecular fibers of 15-30 nm in width. (1)H NMR, CD, and UV studies of solution photoreactions of T-10-T suggested that under natural light the chiral rope formation is triggered by photodimerization of trace amounts of the thymine moieties in the T-10-T assemblies. Complementary hydrogen bond formation between the thymine-adenine heterobase pairs was found to prevent such a photoreaction and resulted in no chiral rope formation. The heteroditopic T-12-A bolaamphiphile self-assembled to form supramolecular fibers. Multilamellar organization was proposed for the homo- and heteroassemblies made of T-n-T and A-n-A.

Hepatocellular carcinoma: involvement of the internal mammary artery.

PURPOSE: To investigate factors related to the development of internal mammary arteries (IMAs) as feeding arteries of hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: In 30 patients with HCC located in ventral hepatic areas directly beneath the diaphragm, bilateral internal mammary arteriography was performed to explore involvement of the IMA with HCC. The number of previous transcatheter arterial embolizations (TAEs), tumor size, time from initial TAE to IMA angiography, inferior phrenic artery (IPA) involvement with tumor, presence of hepatic artery occlusion, and use of other treatments were compared in groups with and without involvement of the IMA. RESULTS: The group with IMA involvement included 10 patients; the group without involvement, 20 patients. TAE had been performed two to 12 times in the group with involvement and zero to six times in the group without involvement (P =.01). Mean tumor sizes in these two groups were 5.1 and 6.0 cm, respectively; hepatic artery occlusion was noted in nine and zero patients (P =.01) in the two groups. The time from initial TAE to IMA angiography ranged from 3 to 53 months (median, 31.5 months) and from zero to 89 months (median, 0 months) (P =.01). IPA involvement was observed in seven and four patients (P =.015). CONCLUSION: These results strongly suggest that, regardless of tumor size, when HCCs are located in the ventral hepatic areas directly beneath the diaphragm, the IMAs serve as feeding arteries in patients with hepatic artery occlusion caused by repeated TAE.

Serum-free coculture of stromal and epithelial cells from benign prostatic hyperplasia with keratinocyte growth factor.

We developed a serum-free coculture model of benign prostatic hyperplasia (BPH) to clarify whether stromal cells stimulate growth of epithelial cells from BPH tissues. Epithelial and stromal cells from freshly isolated BPH tissue were cultured separately in defined serum-free WAJC 404/RPMI 1640 medium supplemented with insulin, transferrin, selenium, hydrocortisone, bovine serum albumin, epidermal growth factor, basic fibroblast growth factor and keratinocyte growth factor. (3)H-Tdr incorporation into epithelial cells and stromal cells was used as a measure of proliferation. When epithelial cells were cocultured with stromal cells, (3)H-Tdr incorporation into epithelial cells was increased in comparison to that in epithelial cells cultured alone. Dihydrotestosterone significantly increased this effect. It is likely that the in vitro coculture model reported here will be useful for isolating and understanding stromal cell-derived paracrine growth factor(s).

High accumulation of calcium and phosphorus in human iliac arteries.

To elucidate accumulation of minerals in human iliac arteries with aging, the content of minerals was analyzed by inductively coupled plasma atomic emission spectrometry. Bilateral common, internal, and external iliac arteries of 16 men and 8 women, ranging ages from 65 to 93 yr, were examined. It was found that an extremely high accumulation of calcium and phosphorus occurred in the common iliac artery at old age, being higher than that of the internal and external iliac arteries. It should be noted that the accumulation of calcium and phosphorus is the highest in the common iliac artery among the human arteries examined to date. Regarding sexual differences, the content of calcium and phosphorus in the common and internal iliac arteries was higher in women than in men, whereas their content in the external iliac artery was lower in women than in men.

Suppression of lung and liver carcinogenesis in mice by oral administration of myo-inositol.

It has been reported that myo-inositol can inhibit carcinogenesis in various organs, such as the mammary gland, colon and lung. In the present study, at first, inhibitory effects of myo-inositol on lung carcinogenesis were confirmed. Then, the influence of myo-inositol on liver carcinogenesis in mice was investigated. In C3H/He male mice, the rate of spontaneous liver carcinogenesis is known to be high. Using this experimental model, the effects of oral administration of myo-inositol (added into the drinking water at the concentration of 1%) were assessed. Significant suppression of liver carcinogenesis was observed in mice treated with myo-inositol for 40 weeks. In the control group without myo-inositol administration, 88% of the animals developed liver tumors, whereas in the myo-inositol-supplemented group, the incidence of liver tumors was 38% (p < 0.05). The average number of liver tumors per mouse was also decreased significantly by myo-inositol treatment; from 7.8 in the control group to 0.8 in the myo-inositol-supplemented group (p < 0.01). Thus, myo-inositol may be useful for cancer chemoprevention in the liver, as well as the lung.

[Seasonal changes of laboratory data in patients with Japanese cedar pollinosis].

Japanese cedar pollen (JCP) causes a significant seasonal allergic rhinitis in Japan during the early spring. Blood samples were collected monthly from October 1993 through October 1994 from 11 patients with Japanese cedar pollinosis. The patients were segregated into two categories based on specific IgE (RAST): single positive RAST to JCP only and multiple positive RAST to JCP, house dust (H1) and mite (D1). These two populations differed in levels of total serum IgE, numbers of eosinophils, basophils and neutrophils in peripheral blood and clinical symptoms. Seasonal increase of JCP-specific IgE was observed after pollen season in both groups. In the single positive group, but not in the multiple positive group, seasonal increase of the number of eosinophils in peripheral blood was observed with post seasonal fall and the level of total serum IgE was increased in the same manner as that of the JCP specific IgE. Although it was not significant, there was a broad seasonal increase of serum nitrate anion, a metabolite of nitric oxide.

Prognostic significance of Ki-67 expression in transitional cell bladder carcinoma after radical cystectomy.

We evaluated the prognostic significance of the Ki-67 labeling index (Ki-67 LI) in 75 patients with transitional cell carcinoma of the bladder who underwent radical cystectomy. Immunohistochemical staining of archival material was performed by the streptavidin-biotin method. Univariate survival analysis showed that Ki-67 LI (p < 0.001), histologic grade (p < 0.05), tumor stage (p < 0.001) and the number of positive lymph nodes (p < 0.001) significantly correlated with prognosis. Multivariate survival analysis indicated that the Ki-67 LI (p < 0.05), histologic grade (p < 0.01), tumor stage (p < 0.01), presence of lymph node metastases (p < 0.05) and use of neo-adjuvant therapy (p < 0.05) had independent prognostic value. The Ki-67 LI is an independent prognostic factor for patients with transitional cell bladder cancer treated by radical cystectomy.

Effects of intracerebroventricular administration of 6-hydroxydopamine on ouabain-like immunoreactivity in plasma and the hypothalamo-pituitary axis in rats.

OBJECTIVE: To examine the role of central mechanisms on the production and release of an ouabain-like factor, the effects of intracerebroventricular injections of 6-hydroxydopamine on the tissue content and on the plasma level of the ouabain-like factor were determined in rats. METHODS: The vehicle (0.1% ascorbic acid in 0.9% saline) and 6- hydroxydopamine (250 micrograms/rat) were injected into the left lateral ventricle in ether-anaesthetized Wistar rats. Hypothalamus, pituitary, adrenal and venous blood was sampled 24h and 7 days later. The procedure was repeated using another rat group 7 days later. Characteristics of immunoreactive ouabain-like factor were determined by a combination of high-performance liquid chromatography and a highly sensitive enzyme-linked immunosorbent assay for ouabain. The level of the ouabain-like factor in these tissues and in plasma extracts measured by the enzyme-linked immunosorbent assay was compared between the two groups receiving 6-hydroxydopamine and the vehicle. RESULTS: Twenty-four hours after the intracerebroventricular injections of 6-hydroxydopamine, the ouabain-like factor level in the pituitary, hypothalamus and plasma had decreased significantly, whereas the ouabain-like factor level in the adrenal had not changed. The content of noradrenaline in the hypothalamus was also decreased markedly 7 days later and the content of ouabain-like factor in the pituitary remained low. On liquid chromatography the elution pattern of the ouabain-like factor in plasma and in tissue extracts coincided with that of authentic ouabain. CONCLUSIONS: Intracerebroventricular treatments with 6-hydroxydopamine elicited decreases in ouabain-like factor contents in the pituitary, the hypothalamus and the plasma. These results suggest that the production and release of ouabain-like factor are closely associated with the brain, particularly the hypothalamus-pituitary axis, and that noradrenergic or dopaminergic neurons, or both, play a key role in this mechanism.

Preoperative autologous blood donations in pediatric cardiac surgery.

BACKGROUND: Preoperative autologous blood donation is one of the most effective methods to avoid homologous blood transfusion in cardiac operations. However, there have been few reports about the safety and efficacy of autologous blood donation in children. METHODS: Since 1986, we have instituted a blood conservation program including preoperative autologous blood donations in children. Eighty children as young as 3 years old (mean +/- SD, 8.6 +/- 3.9 years) and weighing as little as 12.3 kg (29.2 +/- 14.5 kg) were enrolled in the program, and 735 +/- 388 mL of blood was donated during an average of 3.1 +/- 1.5 phlebotomies before the operations. RESULTS: Two episodes of mild vasovagal reaction were observed in 2 patients as a complication of the phlebotomy. Seventy-six percent of the collected blood was stored by cryopreservation; the remaining 24% was preserved by liquid storage. Seventy-eight of these patients (97.5%) underwent operations using cardiopulmonary bypass. Seventy-five patients (94%) were operated on successfully without the need for a homologous blood transfusion. As for the other 5 patients, 2 received only platelet concentrate. CONCLUSION: Preoperative autologous blood donation is a safe and effective method to avoid homologous blood transfusion in pediatric cardiac operations.

Mutagenicity studies with palm fruit carotene.

The mutagenicity of palm fruit carotene was examined using the reverse mutation test with bacteria, the chromosomal aberration test with mammalian cells and the micronucleus test in mice. The carotene induced neither reverse mutation in Salmonella typhimurium TA98, TA1537, TA100, TA1535 and in Escherichia coli WP2uvrA, nor structural and numerical (polyploidy) chromosomal aberrations in the Chinese hamster fibroblast cell line (CHL). In addition, no increase in micronucleated polychromatic erythrocytes was elicited in the micronucleus test in CD-1(ICR) male mice. It is concluded that palm fruit carotene had no mutagenic activity in these in vitro and in vivo tests.

Impaired release of cholecystokinin (CCK) from synaptosomes in old rats.

Cholecystokinin (CCK) is an abundant neurotransmitter peptide in the brain. CCK release from synaptosomes obtained from the cerebral cortex, the level of CCK mRNA and the tissue concentration of CCK were examined in young and old rats. CCK release stimulated by KCl was attenuated in old rats but that stimulated by calcium ionophore was comparable in animals at both ages. The CCK mRNA level in the cerebral cortex was decreased significantly in old rats despite the significant increase in CCK content. These results suggested that aging impaired CCK release, resulting in tissue accumulation and a decrease in the synthesis of CCK (the level of CCK mRNA).

Preservation of differentiated phenotypes in cultured aortic endothelial cells by malotilate and phosphoascorbic acid.

Confluent bovine aortic endothelial cells (BAECs) formed a cobblestone-shaped cell monolayer when cultured on a collagen gel in a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's-F12 supplemented with 5% newborn calf serum. Within a few days, however, they lost cell-cell attachment and became fibroblastic. When BAECs were cultured in the same culture medium but further supplemented with either 10 micrograms/ml malotilate or 1 mM phosphoascorbic acid, the monolayer organization and the cobblestone-like cell morphology were maintained for more than 2 weeks although many sprout cells were observed underneath the monolayer. In contrast, if both malotilate and phosphoascorbic acid were present in the culture medium, a tight monolayer without underlying sprout cells was maintained for at least 4 months and the cells expressed factor VIII-related antigens and massively internalized acetylated low density lipoprotein. By electron microscopy, we observed well-developed gap and adherence junctions, Golgi apparatuses and vesicles many of which were open to the outside by fusing with either the apical or the basal surface, indicating high metabolic activity of the cells cultured for weeks in the same dish. Although malotilate-treated BAEC monolayers secreted increased levels of prostacyclin (PGI2), the drug did not appear to directly affect the PGI2 production pathway since the similarly increased PGI2 production was noted in tight monolayers formed without the use of malotilate. Our results indicate that malotilate and phosphoascorbic acid together preserve differentiated phenotypes in cultured endothelial cells.

[Multicenter clinical evaluation of red cell concentrates stored up to 6 weeks in MAP, a new additive solution].

The clinical safety and efficacy of transfusion of red cell concentrates stored in MAP solution (MAP-CRC) containing mannitol, adenine, glucose, phosphate and citrate, into 39 anemic patients were evaluated. In 23 patients, infusion of MAP-CRC was alternated with infusion of ordinary CRC as a control. The MAP-CRC and CRC used in this study were stored at 4 degrees C for an average of 38.2 +/- 2.6 days (n = 52) and 18.1 +/- 2.2 days (n = 26), respectively. Red cell recovery was 77.5% for MAP-CRC and 82.5% for CRC, based on calculation of the increase in hemoglobin level one day after transfusion. There were no differences between patients transfused with MAP-CRC and those transfused with CRC in clinical findings or biochemical data. No major side-effects other than pyrexia associated with the underlying infections were seen in patients transfused with MAP-CRC. MAP-CRC stored up to 42 days is apparently as safe and effective as stored CRC. This new additive solution may therefore be useful for the future expansion of the indications for autologous blood transfusion by facilitating the collection and storage of more blood in the liquid state for a longer period, and may also be useful in obtaining more plasma from whole blood as source plasma.

Comparative study of cell saver and ultrafiltration nontransfusion in cardiac surgery.

Hemoconcentration for the establishment of no-donor blood transfusion in open heart surgery was assessed in regard to both the saving of protein and platelets and the exclusion of free hemoglobin. Two different types of hemoconcentrator were compared: the ultrafilter (group I, 6 patients) and the Cell Saver (group II, 6 patients). The total serum protein level, expressed as the percent recovery of the preoperative value, after hemoconcentration was significantly higher in group I (group I versus group II: total serum protein, 118% versus 87% [p less than 0.05]; fibrinogen, 77% versus 50% [p less than 0.01]; immunoglobulin, 83% versus 60% [p less than 0.01]). The platelets also seemed to be well preserved after hemoconcentration in group I. Although the exclusion of free hemoglobin from plasma was inferior in group I compared with group II, the postoperative plasma free hemoglobin level did not increase in group I. We conclude that use of the Cell Saver in nontransfusion cardiopulmonary bypass might cause a severe depletion of various proteins and that the ultrafilter is both safer and more useful if employed routinely.

Histopathological study on effects of potassium aspartate on the hypothalamus of rats.

Rats of various ages were treated orally or intraperitoneally with potassium aspartate. The dose required to induce hypothalamic lesion varied considerably by the age of animals and route of administration. Additional experiment, in which the animals were orally treated three times a day with potassium aspartate in dose levels between the maximum safety dose and minimum lesion-producing dose in the preceding single dose study, revealed no hypothalamic lesion at all in any animals of each age group. In this condition, the maximum safety dose was 3--5 times as large as that in single dosage administration experiment. Regarding the safety evaluation of potassium aspartate preparations, brief discussions on some points in extrapolation of the results of the present experimental study to the clinical use were made.