Estimated glomerular filtration rate and the risk-benefit profile of intensive blood pressure control amongst nondiabetic patients: a post hoc analysis of a randomized clinical trial.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT; ClinicalTrials.gov, NCT01206062) reported reduced cardiovascular events by intensive blood pressure (BP) control amongst hypertensive patients without diabetes. However, the risk-benefit profile of intensive BP control may differ across estimated glomerular filtration rate (eGFR) levels. METHODS: This is a post hoc analysis of the SPRINT. Nondiabetic hypertensive adults (n = 9361) with eGFR >20 mL per min per 1.73 m2 were enrolled from 102 US facilities between November 2010 and March 2013 and were followed up until August 2015 (median follow-up, 3.26 years). Patients were randomly assigned to either a systolic BP target of <120 or <140 mmHg (for intensive or standard treatment, respectively). The outcomes of interests were the development of (i) fatal and nonfatal major cardiovascular events and (ii) acute kidney injury (AKI). RESULTS: The cardiovascular benefit from intensive treatment was attenuated with lower eGFR (Pinteraction  = 0.019), whereas eGFR did not modify the adverse effect on AKI (Pinteraction  = 0.179). Amongst 891 participants with eGFR <45 mL per min per 1.73 m2 , intensive treatment did not reduce the cardiovascular outcome (54/446 vs. 54/445 events in the standard group, respectively; hazard ratio [HR], 0.92; 95% CI, 0.62-1.38) with an absolute rate difference (ARD) of -0.02 (95% CI, -0.07 to +0.03) per 100 patient-years, whereas it increased AKI (62/446 vs. 38/445 events in the standard group; HR, 1.73; 95% CI, 1.12-2.66) with an ARD of +1.93 (95% CI, +1.88 to +1.97) per 100 patient-years. CONCLUSIONS: Intensive BP control may provide little or no benefit and even be harmful for patients with moderate-to-advanced chronic kidney disease.

Post-Transplant Anemia Has Strong Influences on Renal and Patient Outcomes in Living Kidney Transplant Patients.

BACKGROUND: Post-transplant anemia (PTA) is a risk factor for mortality and graft loss in kidney transplant patients. METHODS: In all, 172 patients were included in this study. PTA was defined as hemoglobin <13.0 g/dL in men and 12.0 g/dL in women. The primary outcome of interest was the renal outcome, defined as a 50% increase in serum levels of creatinine, a return to chronic dialysis, and subsequent kidney transplantation (KTx). The secondary outcome was a composite of the primary outcome and death. RESULTS: At baseline, 75 patients (43.6%) had PTA. During follow-up of a median of 7.3 years, 52 patients (30.2%) had 2-fold higher creatinine levels than at baseline, 24 patients (14.0%) had to return to chronic dialysis or subsequent KTx, and 11 patients (6.4%) died; 8 (4.7%) of the deceased patients had functioning allografts. Univariate regression analyses showed that a lower hemoglobin level and positive proteinuria were significantly associated with both outcomes. After adjusting for important clinical variables, a lower hemoglobin level remained a strong predictor for both outcomes. Restricted cubic splines showed an almost linear inverse association with a hemoglobin level ≥12 g/dL. The risk of the outcomes increased with decreasing tertiles of the baseline hemoglobin level for both men and women, but the associations in women were much weaker than those in men, suggesting a different prognostic value of the hemoglobin level between men and women. CONCLUSIONS: PTA strongly influenced the renal and patient outcomes in living kidney transplant patients.

Diaphragmatic hernia resulting from injury during microwave-assisted laparoscopic hepatectomy.

A 31-year-old woman underwent microwave-assisted laparoscopic hepatectomy of the left lateral segment for focal nodular hyperplasia on January 14, 1998. On September 9, 1998, she felt continuous left abdominal pain and was admitted to our hospital for further examination. An upper gastrointestinal series showed converging folds of the greater curvature of the upper third of the stomach and craniad displacement of this portion. Thoracic magnetic resonance imaging showed herniation of the stomach into the pleural cavity. The patient was referred to our department, where she underwent surgery for a diaphragmatic hernia. The fundus of the stomach had escaped into the left pleural cavity through a defect in the diaphragm near where laparoscopic hepatectomy had been performed. The stomach was returned to the peritoneal cavity and the defect sutured. The patients postoperative course was uneventful. Although diaphragmatic hernia after laparoscopic surgery is a rare complication, with the performance of more advanced laparoscopic procedures and the use of higher-technology tissue-destruction/hemostatic devices such as the microwave coagulator, more caution should be observed to prevent injury to adjacent organs such as the diaphragm.

Dynemicins, new antibiotics with the 1,5-diyn-3-ene and anthraquinone subunit. II. Antitumor activity of dynemicin A and its triacetyl derivative.

Dynemicin A showed extremely potent in vitro cytotoxicity against a variety of murine and human tumor cells. In the experimental animal tumor models implanted ip with P388, L1210 leukemias and B16 melanoma cells, dynemicin A administered ip significantly prolonged life-span of tumor-bearing mice with the wide range of activity. This antibiotic administered iv was also active against iv implanted P388 and L1210 leukemias. In the macromolecule biosynthesis of B16 melanoma cells, dynemicin A inhibited DNA synthesis specifically. The triacetyl derivative exhibited similar in vitro and in vivo antitumor activities to those of the parent antibiotic.

Eurystatins A and B, new prolyl endopeptidase inhibitors. I. Taxonomy, production, isolation and biological activities.

Eurystatins A and B, were isolated from the cultured broth of Streptomyces eurythermus R353-21. They showed specific and potent inhibitory activity against prolyl endopeptidase and did not show antimicrobial activity. No lethal toxicity was observed for the two compounds after ip administration in mice at 200 mg/kg.

[Clinical evaluation of granisetron hydrochloride for nausea and vomiting induced by oral anticancer drugs].

We investigated the antiemetic effect, safety and usefulness of granisetron hydrochloride tablets on nausea and vomiting induced by oral anticancer drugs used in chemotherapy for gastric cancer and colorectal cancer. In the present trial, oral administration of granisetron hydrochloride was performed during 5 days after nausea or vomiting. 1) Clinically, the effective rate of granisetron hydrochloride (the percentage of cases in which the drug was assessed as "Remarkably effective" or "Effective") was more than 75% on each day of administration. There were no adverse events or abnormal laboratory tests. 2) In terms of usefulness, granisetron hydrochloride was rated "Extremely useful" or "Useful" in 17 out of 23 cases (78.2%). The above results have shown that granisetron hydrochloride tablets, administrated orally once daily at a dose of 2 mg, have an excellent antiemetic effect, and that this is a safe and useful drug.

[Analysis of immunological response of regional lymph node lymphocytes from patients with gastric cancer after endoscopic local injection of biological response modifier (BRM)].

Local injection of BRM (OK-432 or Lentinan) around the cancer lesions via endoscope was performed on 66 gastric cancer patients preoperatively, and the regional lymph node lymphocytes in the surgical specimens were examined on T-cell subset, production of IL-2, and responsiveness to IL-2. The results were as follows: 1) In the metastatic lymph nodes, proportions of T-lymphocyte subsets, production of IL-2 and responsiveness to IL-2 did not change after local administration of OK-432 or Lentinan. 2) In the non-metastatic lymph nodes, percentage of CD4+4B4+ cells were significantly increased and production of IL-2 was markedly augmented after local injection of OK-432. On the other hand, percentage of CD8+CD11- cells were significantly increased and production of IL-2 was markedly enhanced after the local injection of Lentinan. These data suggested that the antitumor response of the non-metastatic lymph node lymphocytes was augmented after the local injection of OK-432 or Lentinan.

[Preservation of anal transitional zone in restorative proctocolectomy].

Since 1980, restorative proctocolectomy has been established for surgical therapy to ulcerative colitis. The crucial points of this procedure are mucosectomy of the anorectal mucosa and pouch anal anastomosis. Mucosectomy is often difficult due to long standing acute and chronic inflammation and incomplete microscopically and leakage of pouch anal anastomosis is relatively high probably due to steroid given prior to surgery or direct effect of anorectal mucosal inflammation. Regards to postoperative bowel function, nocternal soiling is frequently recognized in the patients who received this operation. To overcome these technical and functional disadvantages, anal transitional zone preservation without mucosectomy and stapled anastomosis between pouch and the upper rim of the puborectalis muscle has been performed. Our series of 84 cases with this modified method, anastomotic leakage was significantly decreased and nocternal soiling was completely disappeared within 7 months postoperatively. And one stage procedure became possible unless severe, or high doses of steroid given prior to surgery. Only one case of mild dysplasia was experienced in the remaining rectal mucosa which was disappeared at the next examination. Medical treatment to the remaining lesion was not necessary in the most of cases. Anal canal preservation is superior to mucosectomy in the points of bowel function and minimizing postoperative complications.

Evidence for zero- and pi-phase order parameters of superconducting Nb/Co tri- and pentalayers from the oscillatory behavior of the transition temperature.

The oscillation behavior of the superconducting transition temperature Tc as a function of the ferromagnetic Co layer thickness (dCo) has been examined for Nb/Co superconductor(S)/ferromagnetic(F) trilayer series (F/S/F) and pentalayer series (F/S/F/S/F). Tc of the pentalayer series takes a local maximum between dCo=2.0-3.2 nm, where Tc of the trilayer shows a local minimum. This difference in the Tc versus dCo curves provides a clear evidence for the occurrence of the pi phase in the pentalayers, which has been theoretically predicted by Buzdin et al., Radovic et al., and Tagirov.

Studies on the Production of Digitalis Cardenolides by Plant Tissue Culture: II. EFFECT OF LIGHT AND PLANT GROWTH SUBSTANCES ON DIGITOXIN FORMATION BY UNDIFFERENTIATED CELLS AND SHOOT-FORMING CULTURES OF DIGITALIS PURPUREA L. GROWN IN LIQUID MEDIA.

Undifferentiated, highly chlorophyllous cell cultures; undifferentiated white cell cultures; green, shoot-forming cultures; and white, shoot-forming cultures of Digitalis purpurea L. were established and subcultured every 3 weeks in liquid media in the light or in the dark. The digitoxin content, the chlorophyll content, and the ribulose bisphosphate carboxylase activity of these cultures were assayed. The light-grown, green, shoot-forming cultures accumulated considerable amounts of digitoxin (about 20 to 40 micrograms per gram dry weight), and the white, shoot-forming cultures without chloroplasts accumulated about one-third that amount of digitoxin. The chlorophyll content and the ribulose bisphosphate carboxylase activity of the undifferentiated green cells were about the same as they were in the green, shoot-forming cultures, but the digitoxin content of the former was extremely low (about 0.05 to 0.2 microgram per gram dry weight), which is about the same as that in undifferentiated white cells without chloroplasts. Thus, it was concluded that the chloroplasts are not essential for the synthesis of digitoxin in Digitalis cells. The optimum concentrations of the tested compounds for accumulation of digitoxin were: benzyladenine, 0.01 to 1 milligram per liter; indoleacetic acid, 0.1 to 1 milligram per liter; alpha-naphthaleneacetic acid; 0.1 milligram per liter; and 2,4-dichlorophenoxyacetic acid, 0.01 milligram per liter.

Protective effect of eurystatins A and B, new prolyl endopeptidase inhibitors, on scopolamine-induced amnesia in rats.

Eurystatins A and B, which are produced by Streptomyces eurythermus R353-21, potently inhibited Flavobacterium prolyl endopeptidase (PED) with IC50 values of 0.004 and 0.002 micrograms/ml, respectively, while no inhibition was observed against another 5 proteases, even at 100 micrograms/ml. The protective effect of eurystatins A and B against scopolamine (3 mg/kg, i.p.)-induced amnesia in rats was evaluated by the step-through one-trial passive avoidance method. When administered i.p. 30 min prior to the acquisition trial, both eurystatins A, at 2-8 mg/kg, and B, at 4-8 mg/kg, significantly protected rats from the amnesic effect of scopolamine without behavioral side effects.

[Experimental study on the action mechanism of a new bronchodilator agent, BB-1502].

The action mechanism of the bronchodilator activity of BB-1502 was studied in comparison with aminophylline. Orally administered BB-1502 did not inhibit passive cutaneous anaphylaxis in rats, an immediate allergic reaction of Type I, but strongly protected the same antigen-mediated anaphylactic asthma by the intraduodenal route, the activity being approximately 13 times more potent than that of aminophylline. BB-1502 also inhibited IgG-mediated anaphylactic asthma in guinea pigs by the oral route. Both IgE- and IgG-mediated histamine releases from rat lung were similarly inhibited by BB-1502, the potency being 2--3 times that of aminophylline. Disodium cromoglycate showed specific inhibition of the IgE-mediated reaction. BB-1502 and aminophylline showed nonspecific inhibition of the spasms of guinea pig ileum elicited by histamine, acetylcholine and BaCl2. Both compounds inhibited cyclic AMP and cyclic GMP phosphodiesterases (PDEs) derived from guinea pig organs. BB-1502 specifically inhibited the cyclic AMP PDE of lung and brain origins, while aminophylline showed no such specificity. The results of the present study suggested that the bronchodilator and anti-asthmatic actions of BB-1502 might, at least in part, be due to the regulation of cyclic nucleotide PDEs.