Vestibular and audiological findings in the Alport syndrome

Alport syndrome (AS) is caused by mutations in collagen IV, which is widespread in the basement membranes of many organs, including the kidneys, eyes, and ears. Whereas the effects of collagen IV changes in the cochlea are well known, no changes have been described in the posterior labyrinth. The aim of this study was to investigate both the auditory and the vestibular function of a group of individuals with AS. Seventeen patients, aged 9–52, underwent audiological tests including pure‐tone and speech audiometry, immittance test and otoacoustic emissions and vestibular tests including video head impulse test, rotatory test, and vestibular evoked myogenic potentials. Hearing loss affected 25% of the males and 27.3% of the females with X‐linked AS. It was sensorineural with a cochlear localization and a variable severity. 50% of the males and 45.4% of the females had a hearing impairment in the high‐frequency range. Otoacoustic emissions were absent in about one‐third of the individuals. A peripheral vestibular dysfunction was present in 75% of the males and 45.4% of the females, with no complaints of vertigo or dizziness. The vestibular impairment was compensated and the vestibulo‐ocular reflex asymmetry was more evident in rotatory tests carried out at lower than higher speeds; a vestibular hypofunction was present in all hearing impaired ears although it was also found in subjects with normal hearing. A posterior labyrinth injury should be hypothesized in AS even when the patient does not manifest hearing disorders or evident signs of renal failure.     

Effects of DFMO-induced polyamine depletion on human tumor cell sensitivity to antineoplastic DNA-crosslinking drugs

Summary We investigated the effect of pretreatment with difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, on the cytocidal responses of four human adenocarcinoma cell lines to two alkylating and crosslinking agents: chlorambucil and N,N,N-triethylenethio-phosphoramide (thiotepa). The cell lines studied included HuTu-80 (duodenum), HT-29 (colon), ME-180 (cervix), and A-427 (lung). A 48- to 72-h pretreatment with DFMO reduced intracellular putrescine and spermidine contents to <10% and <1% of control levels. This treatment also caused a 30%–70% decline in spermine content. Survival of control and DFMO-pretreated cells after treatment with chlorambucil or thiotepa was measured by a plating efficiency assy. For three of the four lines studied, the DFMO-induced partial polyamine depletion significantly protected cells from the lethal effects of chlorambucil. In ME-180 cultures alone, DFMO pretreatment did not alter the cytocidal efficacy of chlorambucil. Addition of exogenous putrescine to cultures of HuTu-80, HT-29, or A-427 24 h after DFMO addition but 24 h before treatment with chlorambucil reversed the polyamine depletion and its protective effects on chlorambucil-induced cell kill. In contrast to the above observations, DFMO and partial polyamine depletion had no effect on cell survival after thiotepa treatment for any of the cell lines investigated.Abbreviations BCNU 1,3-bis (2-chloroethyl)-1-nitrosourea - CENU chloroethylnitrosourea - cis-Pt (II) cis-diamminedichloroplatinum (II) - DFMO difluoromethylornithine - ODC ornithine decarboxylase - PU putrescine - SD spermidine - SP spermine thiotepa - N,N,N triethylenethiophosphoramide This investigation was supported in part by PHS grant no. CA-32758 awarded by the National Cancer Institute, DHHS; by grant no. 82-6 from the American Cancer Society, Ill. Div., Inc.; and by a Biomedical Research Support Grant to Northwestern University Medical School from the US PHS, NIH (RR-05370)     

Strand-Specific Reverse Transcription PCR for Detection of Replicating SARS-CoV-2

We developed an assay that detects minus-strand RNA as a surrogate for actively replicating severe acute respiratory syndrome coronavirus 2. We detected minus-strand RNA in 41 persons with coronavirus disease up to 30 days after symptom onset. This assay might inform clinical decision-making about patient infectiousness.     

How are bariatric patients coping during the coronavirus disease 2019 (COVID-19) pandemic? Analysis of factors known to cause weight regain among postoperative bariatric patients

BackgroundThe global coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc on society. Bariatric patients are more prone to severe infection due to their high body mass index (BMI) and are more vulnerable to the effects of isolation, such as depression or disruption of their health habits.ObjectivesTo quantify the impact of self-quarantine on bariatric patients and self-quarantine’s relationship with weight gain.SettingAcademic hospital, United States.MethodsA 30-item survey examining several known contributors to weight regain was distributed among the postoperative bariatric patients of our clinic. Changes in eating habits, exercise, depression, social support, loneliness, and anxiety were studied, among others.ResultsA total of 208 patients completed the survey (29.3% response rate). A large percentage of patients reported increases in their depression (44.2%), loneliness (36.2%), nervousness (54.7%), snacking (62.6%), loss of control when eating (48.2%), and binge eating (19.5%) and decreases in their social support (23.2%), healthy food eating (45.5%), and activity (55.2%). Difficulty in accessing vitamins was reported by 13%. Patients more than 18 months out of surgery regained more than 2 kg during an average of 47 days. Risk factors for weight regain were found to be loss of control when eating, increases in snacking and binge eating, reduced consumption of healthy food, and reduced physical activity.ConclusionBariatric patients are negatively affected by the COVID-19 pandemic and subsequent social isolation on many levels. This patient population is vulnerable to crisis situations; thus, additional intervention is needed to address behaviors that lead to weight regain.     

Pediatric Hand Injuries Requiring Closed Reduction at a Tertiary Pediatric Care Center

Background: Hand fractures and dislocations are common injuries in the pediatric population. This study aims to characterize the pediatric hand injuries that required closed reduction and identify those that required multiple reduction attempts. Methods: A retrospective cohort study was carried out in patients younger than 18 years of age with hand fractures or dislocations who underwent closed reduction in the emergency department (ED). Patients who ultimately required surgical reduction and fixation were not included. Results: Of the 310 hand injuries identified, 148 (114 fractures and 34 dislocations) underwent closed reduction in the ED; 7.4% of those required repeat reduction. Hand injuries that most often required repeat reduction included metacarpophalangeal joint dislocations (20.0%) and proximal phalanx neck (16.7%), metacarpal shaft (15.4%), metacarpal neck (6.2%), and proximal phalanx base (5.6%) fractures. No modifiable risk factors predicting the need for repeat reduction were identified. Conclusions: Some pediatric hand injuries are more likely to require repeat closed reduction by a hand surgeon. This retrospective study is the first step toward quality improvement as it provides opportunities for further research into the factors contributing to reductions that are unsuccessful at the first attempt. Identification of these factors and implementation of quality improvement measures are necessary to ensure the effective treatment of all pediatric hand injuries.     

Clinical pharmacokinetics of tacrolimus in heart transplant recipients

We report pharmacokinetic data on tacrolimus in 14 heart transplant patients (2 women, 12 men). The median age and the median body weight were 55.5 years (range, 23-61 years) and 67.0 kg (55-79 kg), respectively. All patients were maintained on a triple-drug protocol (tacrolimus, azathioprine, and prednisone), with a 7-day antithymocyte globuline induction. The first tacrolimus dose, administered orally 1 to 5 days posttransplant, ranged from 0.03 to 0.4 mg/kg (median = 0.052 mg/kg). The maintenance dose ranged from 0.03 to 0.13 mg/kg/day (administered in two equal doses) to achieve blood levels of 5 of 20 ng/ml, as determined by a microparticle enzyme immunoassay (MEIA). Whole blood samples were drawn just before, at 0.5 hour, and at 1, 2, 3, 4, 6, 8, 10, and 12 hours after the administration of the first dose; trough levels were measured thereafter.The mean oral clearance (CL/F) and apparent volume of distribution (Vd/F) averaged 0.21+/-0.08 L/hour/kg and 2.4+/-0.8 L/kg while the half-life averaged 8.7+/-3.5 hours. Tacrolimus accumulation index during chronic therapy (Rac = Cmin(steady state)/Cmin(first dose) normalized to the same dose) averaged 1.3. Eighty-eight percent of the trough blood levels measured in our patients were within 5 and 20 ng/ml. The incidence of rejection in the study population was extremely low: a prevalence of grade 2 rejection or more, of 0.4+/-0.8 episodes/ patient was observed after a follow-up period of 8.8+/-2.2 months. Only one patient experienced severe renal toxicity, probably because of his preoperative precarious hemodynamic status. Pharmacokinetic data suggest that maintenance tacrolimus daily dose should be equal to 0.1 mg/kg/day to obtain trough blood concentrations of approximately 10 ng/ml. Inter- and intra-patient variability of tacrolimus blood concentration should be expected and justify careful monitoring.