Otoacoustic emissions as a screening test for hearing impairment in children recovering from acute bacterial meningitis

OBJECTIVES: To study the efficacy of otoacoustic emissions (OAEs) as a screening test for hearing impairment in children with acute bacterial meningitis. Hearing tests were performed before discharge from the hospital in an attempt to improve coverage and avoid delays in the diagnosis of postmeningitic hearing loss. METHODS: Children with bacterial meningitis were recruited from 21 centers. In the 48 hours before discharge from the hospital, all patients underwent a thorough audiologic assessment consisting of transient evoked OAEs, auditory brainstem responses (ABRs), otoscopy, and tympanometry. Hearing loss was defined as ABR threshold >/=30 dB. The results of OAE screening were compared with the gold standard of ABR threshold. RESULTS: Of 124 children recruited, we were able to perform both OAEs and ABRs on 110 children. Seven (6.3%) of the 110 children had ABR threshold >/=30 dB; 2 had sensorineural hearing loss and 5 had conductive hearing loss. At follow-up, hearing loss persisted in both cases of sensorineural hearing loss and no new cases were identified. All 7 children with hearing loss failed the OAE screening test. Ninety-four children with normal hearing thresholds passed the test, and 9 failed. Thus, the screening test had a sensitivity of 1.00 (95% confidence interval, 0.59 to 1.00), a specificity of 0.91 (0.85 to 0.97), a positive predictive value of 0. 44 (0.20 to 0.70), and a negative predictive value of 1.00 (0.96 to 1.00). CONCLUSIONS: OAE screening in children recovering from meningitis was found to be feasible and effective. The test was highly sensitive and reasonably specific. Inpatient OAE screening should allow early diagnosis of postmeningitic hearing loss and prompt auditory rehabilitation.     

Characterization of xenobiotic-metabolizing enzymes and nitrosamine metabolism in the human esophagus

Esophageal cancer has been associated with tobacco smoking, and nitrosamines are possible causative agents for this cancer. The present study investigated the metabolism of the tobacco carcinogens N'- nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK), and N-nitrosodimethylamine (NDMA), as well as the presence of xenobiotic-metabolizing enzymes in human esophageal tissues from individuals in the United States and Huixian, Henan Province, China (a high-risk area for esophageal cancer). All esophageal microsomal samples activated NNN and the metabolic rate was 2-fold higher in the esophageal samples from China than the USA. All microsomal samples activated NDMA. However, most of the microsomal samples did not activate NNK. Troleandomycin (an inhibitor of cytochrome P450 3A) decreased the formation of NNN-derived keto acid by 20-26% in the esophageal microsomes. The activities for NADPH: cytochrome c reductase, ethoxycoumarin O-deethylase, NAD(P)H: quinone oxidoreductase and glutathione S-transferase were present in the esophageal samples. Coumarin 7-hydroxylase (a representative activity for P450 2A6) activity was not detected in the esophageal microsomal samples. The activities for nitrosamine metabolism and xenobiotic- metabolizing enzymes were decreased (by 30-50%) in the squamous cell carcinomas compared with their corresponding non-cancerous mucosa. The presence of activation and detoxification enzymes in the esophagus may play an important role in determining the susceptibility of the esophagus to the carcinogenic effect of nitrosamines. Our results suggest that P450s 3A4 and 2E1 are involved in the activation of NNN and NDMA, respectively, in the human esophagus.      

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

Reduction of atherosclerosis in cholesterol-fed rabbits and decrease of expressions of intracellular adhesion molecule-1 and vascular endothelial growth factor in foam cells by a water-soluble fraction of Polygonum multiflorum

Polygonum multiflorum stilbeneglycoside （PMS） is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White （NZW） rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS （25, 50, or 100 mg/kg）. Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule （ICAM）-1 protein and the vascular endothelial growth factor （VEGF） protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells.     

Gastrointestinal haemorrhage due to erosion of the duodenal wall by a biliary stent

Complications from improperly placed biliary stents are not uncommon. Free loose wires from the ends of an uncovered stent can irritate and damage adjacent mucosal surfaces. Effective management can be achieved via percutaneous placement of a second stent to alter the orientation of the original stent.     

Coenzyme Q-10 treatment of patients with a 7445A--->G mitochondrial DNA mutation stops the progression of hearing loss

CONCLUSION: CoQ 10 may be helpful in delaying the progression of hearing loss in patients with the 7445A-->G mitochondrial mutation. Objective. To assess the effect of an antioxidant drug (Coenzyme Q-10) on the hearing level of patients with the mitochondrial DNA 7445A-->G mutation and associated sensorineural hearing loss (SNHL). Material and methods. We identified three patients with bilateral non-syndromic SNHL harboring the mitochondrial 7445A-->G mutation. Two patients had a family history of hearing loss with a strong matrilineal inheritance. The other patient did not have a family history of hearing loss. Two patients (1 with familial and 1 with sporadic SNHL) received treatment with 75 mg of Coenzyme Q-10 (CoQ10) twice a day for 1 year. The remaining patient with a familial form of hearing loss did not agree to take the treatment. Average bone conduction pure-tone thresholds for 0.5, 1, 2 and 4 kHz were obtained before and after diagnosis of mitochondrial hearing loss, and before and after treatment with CoQ10. Results. CoQ10-treated patients did not show any additional deterioration of their SNHL after 12 (familial case) and 13 months (sporadic case). The progression rate of SNHL was 6 dB/year in the 2 years prior to initiation of treatment in the familial case who received CoQ10 treatment. One year after being diagnosed with mitochondrial hearing loss, the patient who refused CoQ10 treatment exhibited an 11-dB deterioration of his hearing thresholds. There were no side-effects related to treatment with CoQ10.     

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.     

Interleukin-1-induced leukocyte extravasation across rat mesenteric microvessels is mediated by platelet-activating factor

Although our understanding of the molecular interactions that mediate the adhesion of leukocytes to venular endothelial cells has greatly expanded, very little is known about the mechanisms that mediate the passage of leukocytes across the vessel wall in vivo. The aim of the present study was to investigate the role of endogenously formed platelet-activating factor (PAF) in the process of leukocyte extravasation induced by interleukin-1 (IL-1). To determine at which stage of emigration PAF was involved, we studied the behavior of leukocytes within rat mesenteric microvessels by intravital microscopy. Rats were injected intraperitoneally with saline, recombinant rat IL-1 beta (IL-1 beta), or the peptide N-formyl-methionyl-leucyl- phenylalanine (FMLP) 4 hours before the exteriorization of the mesenteric tissue. In animals treated with IL-1 beta there was a significant increase in the number of rolling and adherent leukocytes within venules (20- to 40-micron diameter) and in the number of extravasated leukocytes in the tissue. Pretreatment of rats with the PAF receptor antagonist UK-74,505 had no effect on the leukocyte responses of rolling and adhesion, but significantly inhibited the migration of the leukocytes across the vessel wall induced by IL-1 beta (76% inhibition). A structurally unrelated PAF antagonist, WEB-2170, produced the same effect (64% inhibition). However, in contrast, UK- 74,505 had no effect on the leukocyte extravasation induced by FMLP, indicating selectivity for the response elicited by certain mediators. These results provide the first line of direct evidence for the involvement of endogenously formed PAF in the process of leukocyte extravasation induced by IL-1 in vivo.     

The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.