Iron deficiency is associated with poor prognosis in idiopathic sudden sensorineural hearing loss.

OBJECTIVE: The effects of iron deficiency on the prognosis of idiopathic sudden sensorineural hearing loss are unclear. This study aimed to investigate the association between serum iron levels and idiopathic sudden sensorineural hearing loss prognosis and its usefulness as an independent prognostic marker for idiopathic sudden sensorineural hearing loss. METHODS: The audiological and haematological data, including hearing recovery and serum iron levels, of 103 patients with idiopathic sudden sensorineural hearing loss evaluated between 2015 and 2018 were retrospectively analysed. RESULTS: The overall complete recovery rate was 16.5 per cent. Initial higher hearing threshold was associated with poor idiopathic sudden sensorineural hearing loss prognosis. Serum iron levels were significantly higher in the complete recovery group than in the non-complete recovery group (p < 0.05). CONCLUSION: The possibility of complete recovery from idiopathic sudden sensorineural hearing loss was significantly lower with lower serum iron levels, suggesting that the serum iron level might be a novel prognostic marker for idiopathic sudden sensorineural hearing loss.

Hyaluronic acid pretreatment for Sendai virus-mediated cochlear gene transfer.

Gene therapy with viral vectors is one of the most promising strategies for sensorineural hearing loss. However, safe and effective administration of the viral vector into cochlear tissue is difficult because of the anatomical isolation of the cochlea. We investigated the efficiency and safety of round window membrane (RWM) application of Sendai virus, one of the most promising non-genotoxic vectors, after pretreatment with hyaluronic acid (HA) on the RWM to promote efficient viral translocation into the cochlea. Sendai virus expressing the green fluorescent protein reporter gene was detected throughout cochlear tissues following application combined with HA pretreatment. Quantitative analysis revealed that maximum expression was reached 3 days after treatment. The efficiency of transgene expression was several 100-fold greater with HA pretreatment than that without. Furthermore, unlike the conventional intracochlear delivery methods, this approach did not cause hearing loss. These findings reveal the potential utility of gene therapy with Sendai virus and HA for treatment of sensorineural hearing loss.

Pathogenic mechanism of mouse brain damage caused by oral infection with Shiga toxin-producing Escherichia coli O157:H7.

In a previous study, we showed that infection with Shiga toxin (Stx)-producing Escherichia coli O157:H7 (strain Sm(r)N-9) caused neurologic symptoms in malnourished mice with positive immunoreactions of Stx2 in brain tissues. The present study explores the mechanism of how Stx injures the vascular endothelium to enter the central nervous system in mice. Oral infection with strain Sm(r)N-9 elicited a tumor necrosis factor alpha (TNF-alpha) response in the blood as early as 2 days after infection, while Stx was first detected at 3 days postinfection. In the brain, TNF-alpha was detected at day 3, and its quantity was increased over the next 3 days. Frozen sections of the brains from moribound mice contained high numbers of apoptotic cells. Glycolipids recognized by an anti-Gb3 monoclonal antibody were extracted from the brain, and purified Stx2 was able to bind to the glycolipids. In human umbilical vascular endothelial cells (HUVEC) cultured with fluorescein-labeled Stx2 (100 ng/ml), TNF-alpha (20 U/ml) significantly facilitated the intracellular compartmentalization of fluorescence during 24 h of incubation, suggesting the enhanced intracellular processing of Stx2. Consequently, higher levels of apoptosis in HUVEC were found at 48 h. Short-term exposure of HUVEC to Stx2 abrogated their apoptotic response to subsequent incubation with TNF-alpha alone or TNF-alpha and Stx2. In contrast, primary exposure of HUVEC to TNF-alpha followed by exposure to Stx2 alone or TNF-alpha and Stx2 induced apoptosis at the same level as obtained after 48-h incubation with these two agents. These results suggest that the rapid production of circulating TNF-alpha after infection induces a state of competence in vascular endothelial cells to undergo apoptosis, which would be finally achieved by subsequent elevation of Stx in the blood. In this synergistic action, target cells must be first exposed to TNF-alpha. Such cell injury may be a prerequisite to brain damage after infection with Stx-producing E. coli O157:H7.

Adjuvant effect of clarithromycin on chemotherapy for murine lung cancer.

Clarithromycin (CAM) increased the median survival of patients with unresectable non-small-cell lung cancer who had received chemotherapy and/or radiotherapy [Chemotherapy 1997;43:288-296]. The present study was performed to ascertain whether CAM alone exhibits an antitumor effect against Lewis lung carcinoma (LLC) and to analyze the nature of its adjuvant effect on LLC-inoculated C57BL/6 mice. CAM at 10 mg/kg/day retarded the growth of subcutaneously inoculated LLC cells; consequently, the mean survival time of mice with LLC increased. This treatment was also effective in reducing the number of tumor nodules in the lung after intravenous inoculation with LLC cells. When tumor-bearing mice received an intravenous injection of vindesine sulfate (7 mg/kg) and cisplatin (6 mg/kg) 7 days after tumor inoculation, the chemotherapeutic effect was significantly enhanced by CAM treatment when it started 7 days after chemotherapy, but not when it started the day after chemotherapy. The delayed initiation of CAM treatment resulted in the enhancement of natural killer cell activity and CD8+ T cell cytotoxicity and increased the number of interferon-gamma-producing T cells and interleukin-4-producing T cells. These findings indicate that CAM can exhibit an antitumor effect by itself and also induce the well-balanced expansion of helper T cell subsets in tumor-bearing mice recovering from the immunosuppression caused by chemotherapy. CAM may therefore be a promising adjuvant drug in anticancer chemotherapy, and treatment with this macrolide should be initiated at some interval after basic cancer therapy.

Efficacy of antibiotic therapy for infection with Shiga-like toxin-producing Escherichia coli O157:H7 in mice with protein-calorie malnutrition.

Antibiotic therapy for infection with Shiga-toxin-producing Escherichia coli O157:H7 is controversial because of the possibility of its inducing hemolytic uremic syndrome and acute encephalopathy. In a previous study, mice with protein-calorie malnutrition were found to be highly susceptible to this pathogen. The efficacy of oral antibiotic therapy in malnourished mice infected with O157 organisms was assessed. Mice fed a low-protein calorie diet were infected intragastrically with 2 x 10(6) colony-forming units of a Shiga-toxin-producing strain of Escherichia coli O157:H7. Infected mice were orally given a therapeutic dose of an antibiotic, including norfloxacin, fosfomycin, kanamycin, ampicillin, clarithromycin or trimethoprim-sulfamethoxazole for 3 days: mice on protocol A received the antibiotic on days 1-3, starting on the day after infection, and mice on protocol B received the antibiotic on days 3-5. The duration of fecal pathogen excretion was shorter and the toxin level in the stool and blood lower in the mice that received protocol A than in untreated mice; all of the mice treated on protocol A survived the lethal infection. All antibiotics except trimethoprim-sulfamethoxazole, administered on protocol B, exhibited the same effect as that exhibited by the respective antibiotic administered on protocol A. Only the mice treated with protocol B of trimethoprim-sulfamethoxazole had a higher toxin level in the blood than untreated controls, resulting in 95% mortality. These results suggest that the antibiotics used in this study, except for trimethoprim-sulfamethoxazole, could reduce the risk of hemolytic uremic syndrome and acute encephalopathy following Escherichia coli O157:H7 infection in humans, and that fosfomycin, in particular, may be relevant for testing in humans.

Enhancement of susceptibility to Shiga toxin-producing Escherichia coli O157:H7 by protein calorie malnutrition in mice.

Infection with Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli is increasing among children. In this study, 5-week-old C57BL/6 mice with protein calorie malnutrition (PCM) that had been fed a 5% protein diet for 2 weeks since ablactation were inoculated intragastrically with 2 x 106 CFU of Stx-producing E. coli O157:H7. More than 75% of infected mice with PCM died by 10 days postinfection. Infected mice with PCM developed neurologic symptoms 5 days after infection, while well-nourished control mice receiving a 25% protein diet did not. In the intestinal tracts of infected mice with PCM, inoculated E. coli O157:H7 multiplied between days 2 and 4 of infection, with a peak of growth at day 4. Although the pathogens were not culturable from the stool after day 7, 0157 lipopolysaccharide was detectable in the stool by enzyme-linked immunosorbent assay even after day 8. Stx was detectable in the stool after day 2 of infection and increased in proportion to the growth of inoculated organisms. The maximal production of Stx occurred at 4 days postchallenge, and Stx was detectable in the blood on days 3 to 5. In contrast, well-nourished control mice survived the infection, and all of them remained well even after 3 weeks of infection. In these control mice, inoculated E. coli O157:H7 disappeared from the stool before day 3. Stx was not detectable in the stool and blood of infected control mice at any time from day 1 through day 8. Histologically, cerebral hemorrhages seemed to be the cause of acute death of infected mice with PCM. Immunocytochemical staining demonstrated the positive immunoreaction to Stx at the alveus and stratum pyramidale of the hippocampus and in renal tubules of infected malnourished mice. Such immunoreactions were not found in tissues from infected control mice. Histological study of the intestinal epithelium before infection showed that PCM severely affected the development of intestinal epithelia. These findings strongly indicate that PCM-induced nondevelopment of intestinal physical barrier is one of the predisposing factors for infection with Stx-producing E. coli O157:H7 in mice and suggest that our mouse model may explain the high incidence of infection with Stx-producing E. coli O157:H7 in the children whose intestinal epithelia have not yet completely developed.

Variant type of congenital stomatocytosis.

A 52-year-old female with congenital stomatocytosis showed hemolytic anemia, an increased mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC), reticulocytosis and an increased osmotic fragility. Lipid and protein content of membranes, the activities of membrane-associated enzymes in erythrocytes and the elution pattern of hemoglobin were normal. Erythrocyte Na+ influx was moderately increased and Na+ efflux, particularly ouabain-insensitive Na+ "leak-out" was also increased. K+ concentration of erythrocytes was abnormally low with a slightly increased Na+ content. These phenotypes are very rare, and should be classified as a variant type.

Endocrine and hemodynamic changes during liver surgery in patients with compensated liver cirrhosis.

The purpose of this study was to determine hormonal levels in compensated liver cirrhotic patients under general anesthesia before and after liver surgery. We measured plasma norepinephrine, epinephrine, arginine vasopressin, and aldosterone levels and renin activity in non-cirrhotic and compensated cirrhotic patients undergoing liver resection after induction of anesthesia but before skin incision and after the end of operation but before discontinuation of nitrous oxide. We simultaneously measured hemodynamic variables. Plasma levels of norepinephrine (P < 0.001), epinephrine (P < 0.001), arginine vasopressin (P < 0.05), renin (P < 0.05) and aldosterone (P < 0.001) significantly increased after completion of surgery compared with those before incision in both groups. There was a significant positive correlation between plasma renin and aldosterone (r = 0.56, P < 0.01) levels in non-cirrhotics, but no correlation was observed in cirrhotics; and there was a significant positive correlation between plasma norepinephrine and arginine vasopressin (r = 0.45, P < 0.05) levels in non-cirrhotics, but no correlation in cirrhotics. Cardiac index and arterial pressure increased after the end of operation (P < 0.05). This increase after the operation was the same between cirrhotic and non-cirrhotic groups. There were no changes in heart rate, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure after the end of operation. We conclude that hemodynamic and endocrinological changes were similar between compensated cirrhotic patients and non-cirrhotic patients during liver surgery. Endocrine changes might partly explain the hemodynamic changes during surgery.

Effect of combined infusion of nitroglycerin and nicardipine on femoral-to-radial arterial pressure gradient after cardiopulmonary bypass.

Nitrates and calcium channel blockers are frequently administered during cardiac surgery. We simultaneously measured femoral arterial pressure and radial arterial pressure to investigate whether nitrates, in conjunction with calcium channel blockers, would influence the central-to-peripheral arterial pressure gradient. Combined nitroglycerin and nicardipine infusion during cardiac surgery involving coronary artery bypass grafting or valve replacement resulted in a significant increase above baseline levels in the femoral-to-radial arterial pressure gradient at 60 min after cardiopulmonary bypass. In control patients there was no significant increase in the femoral-to-radial arterial pressure gradient at 60 min after completion of cardiopulmonary bypass. A subsequent study in patients given nitroglycerin and nicardipine identified that the difference in the systolic arterial pressure between femoral and radial arteries was observed 15, 60, and 120 min after completion of cardiopulmonary bypass. However, there was no difference in the mean arterial pressure between femoral and radial arteries throughout the same period. We conclude that combined infusion of nitroglycerin and nicardipine, a new calcium channel blocker, intensifies the magnitude and duration of the femoral-to-radial arterial pressure gradient after cardiopulmonary bypass.

Changes in serum glucose and serum growth hormone levels during pituitary surgery.

During transsphenoidal surgery, serum growth hormone (GH) and serum glucose levels were measured in five acromegalic patients with diabetes or glucose intolerance, three acromegalic patients without diabetes or glucose intolerance, and six patients with prolactinoma. Preoperative steroid administration produced a significant increase in serum glucose level in acromegalic patients with diabetes or glucose intolerance, whereas in the other two groups no significant change in serum glucose level was found. After surgery started, there was a statistically significant increase in serum glucose level above baseline levels in all three groups. Serum GH levels decreased after commencement of surgery in acromegalic patients, and tumor manipulation did not produce a statistically significant increase in serum GH levels. Simultaneous increases in serum glucose and serum GH levels upon tumor manipulation did not occur in any group. We conclude that preoperative steroid administration in patients with high serum levels of GH in association with diabetes or glucose intolerance increases serum glucose levels, and that, after commencement of surgery, GH has only a minor role in the changes of serum glucose levels.