Optimum management of the discharging ear.

Discharge from the ear can be the result of many disease processes. The ear may discharge blood, pus, cerebrospinal fluid (CSF) or wax. Keratosis obturans, stenosis of the external meatus and benign tumours of the external meatus all lead to wax build-up, which may cause recurrent attacks of otitis externa. Malignant tumours, such as basal cell carcinoma, squamous cell carcinoma and tumours of ceruminous gland origin may also present with discharge. Tumours should be excluded by submitting all material removed from the external canal for histological examination. Single or multiple abscesses (known as furuncles) may occur in the hair follicles in the skin of the external acoustic meatus (EAM). Compulsive scratching, hearing aids and foreign bodies placed in the ear predispose to otitis externa, which is also often associated with infection by Pseudomonas aeruginosa, Staphylococcus aureus and faecal organisms. Management may be with aluminium acetate 14%, topical antibiotic/steroid drops, a gauze wick soaked with icthammol 10% in glycerin or polymyxin B sulphate--neomycin sulphate--hydrocortisone acetate cream placed into the EAM and replaced every 24 to 48 hours, or systemic antibiotics according to severity. Malignant (necrotising) otitis externa causes progressive destruction of the temporal bone, and cranial nerve palsies (usually facial first). Treatment is limited debridement of infected bone, accompanied by intravenous aminoglycosides, and local antibiotic treatment and aural cleanout or oral ciprofloxacin. Middle ear conditions causing discharge include acute otitis media, infected grommets, traumatic perforations and chronic suppurative otitis media, as well as tumours of the ear canal skin and middle ear, radiation-induced otitis externa and osteoradionecrosis of the temporal bone, tuberculosis, Langerhans cell histiocytosis, spontaneous or post-traumatic CSF leaks, Wegeners granulomatosis and immune deficiency states. Topical application of aminoglycoside antibiotics to the middle ear of laboratory animals such as rats, guinea pigs and chinchillas causes sensorineural hearing loss, an effect rarely seen clinically in humans. If the external acoustic meatus and tympanic membrane are obscured by discharge cotton buds, microsuction equipment or syringing are used to remove it. It is often useful to initiate treatment (usually with topical drops, wicks or an oral antibiotic) with a provisional diagnosis. A full examination and adequate visualisation of the tympanic membrane must eventually be performed, if necessary under anaesthesia, or else serious progressive conditions may be neglected. The most useful initial investigation is a swab sent for bacteriological assessment; other investigations are usually indicated by clinical findings and the provisional diagnosis.     

Laparoscopic management of ureteral endometriosis: our experience

STUDY OBJECTIVE: Ureteral endometriosis is rare, accounting for less than 0.3% of all endometriotic lesions. The aim of our study is to evaluate the prevalence of extrinsic ureteral endometriosis in women undergoing laparoscopic surgery for severe endometriosis and to suggest that laparoscopic ureterolysis represents a mandatory measure in all cases to avoid ureteral injury. METHODS: A retrospective analysis was performed of all cases of patients who underwent laparoscopic surgery for severe endometriosis at the departments of obstetrics and gynecology at CMCO-SIHCUS and Hautepierre Hospital, Strasbourg, from November 2004 through January 2006. MEASUREMENTS AND MAIN RESULTS: We recorded 54 patients with a mean age of 31 years and a mean body mass index of 21.9. Reported symptoms were dysmenorrhea (88%), severe dyspareunia (88%), severe pelvic pain (38.8%), and infertility (74%). Five women presented with dysuria, frequency, recurrent urinary tract infections, and pain in the renal angle, and 2 patients had hydronephrosis. We observed 3 patients (5.6%) with ureteral stenosis, 35 (64.8%) with adenomyotic tissue surrounding the ureter without stenosis, and 16 (29.6%) with adenomyotic tissue adjacent to the ureter. It was on the left side in 47.4% of cases, on the right side in 31.6% cases, and bilaterally in 21% of cases. In 9 patients, ureteral involvement was associated with bladder endometriosis (16.7%). In all patients, ureterolysis was performed. There was 1 case of ureteral injury during the procedure, 2 of transitory urinary retention, and 1 of uretero-vaginal fistula after surgery. During the first year of follow-up, the disease recurred in 4 patients, with no evidence of the disease in the urinary tract. CONCLUSION: Conservative laparoscopic surgery to relieve ureteral obstruction and remove pathologic tissue is the management of choice. Resection of part of the ureter should be performed only in exceptional cases. Ureterolysis should be performed in all patients before endometriotic nodule resection to recognize and prevent any ureteral damage.     

Chest pain in children. Follow-up of patients previously reported

During a 1-year period, 407 children with chest pain were seen in the Emergency Department of Children's Hospital of Philadelphia. Analysis of the clinical data of these children was reported previously. The authors successfully followed 149 of these children for 6 months or more, and 51 for 2 years or more. These patients returned for an average of 3.4 visits during the follow-up period. Thirty-four percent of the initial diagnoses were altered. Usually, during the follow-up period, the authors concluded that chest pain resulted from nonorganic causes. A new organic etiology was uncovered in only 12 of 149 cases. Only 1 child was found to have a heart abnormality (mitral valve prolapse), and 3 were found to have asthma. Chest pain did not resolve during the follow-up period in 43 percent of those followed. Children with chest pain should have follow-up care because of the persistence of symptoms, but serious disease is unlikely to be found over time.     

Measurement of both left ventricular function and regional myocardial perfusion with 133Xe in dogs

A technique to measure left ventricular (LV) function and myocardial perfusion was validated in 12 dogs. ¹³³Xe in saline was injected into the left atrium (LA) or LV and two data sets were obtained using gamma camera imaging: 1) A first pass gated scan for LV function; followed by 2) Sequential images for regional myocardial perfusion. LV ejection fraction and wall motion measurements from the ¹³³Xe blood pool images were compared to ejection fraction (r=0.88, P<0.01) and wall motion (r=0.83, P<0.01) data from ^99mTc labeled blood pool scans. The perfusion measurements obtained with the ¹³³Xe method were compared to microsphere data (r=0.79, P<0.01). Measurements after LV ¹³³Xe injection were similar to data following LA injection. Thus, quantitative assessment of global LV function, regional wall motion and myocardial perfusion is possible with LA or LV ¹³³Xe injection and gamma camera imaging.     

PROPERDIN FACTOR D: CHARACTERIZATION OF ITS ACTIVE SITE AND ISOLATION OF THE PRECURSOR FORM

The activity of properdin factor D was measured by the generation of the hemolytically active cellular intermediate, EAC43B(D), bearing the C3b-dependent alternate pathway C3 convertase. Treatment of factor D with DFP prevented formation of EAC43B(D); thus, a serine esterase is essential for the generation of the alternate pathway C3 convertase, a situation analogous to the role of C1 in the formation of the classical C3 convertase, C42. The definition of factor D as a serine esterase prompted a search for its proenzyme form, and resulted in the chromatographic isolation from plasma of a single peak of trypsin-inducible factor D activity, distinct from activated factor D. Analytical gel filtration indicated an apparent mol wt of 25,000. This protein from which trypsin elaborated factor D activity, as assessed by the formation of EAC43B(D), the generation of the CoVF-dependent C3 convertase, and the cleavage of factor B in the presence of C3b, was designated "precursor factor D." The DFP resistance of precursor factor D, and the susceptibility of its trypsin-activated form to inactivation by DFP is analogous to the behavior of other plasma serine esterases, including C1.     

Remote FEV1 Monitoring in Asthma Patients: A Pilot Study

Forced expiratory volume in one second (FEV₁) is a critical parameter for the assessment of lung function for both clinical care and research in patients with asthma. While asthma is defined by variable airflow obstruction, FEV₁ is typically assessed during clinic visits. Mobile spirometry (mSpirometry) allows more frequent measurements of FEV₁, resulting in a more continuous assessment of lung function over time and its variability. Twelve patients with moderate asthma were recruited in a single‐center study and were instructed to perform pulmonary function tests at home twice daily for 28 days and weekly in the clinic. Daily and mean subject compliances were summarized. The agreement between clinic and mobile FEV₁ was assessed using correlation and Bland‐Altman analyses. The test‐retest reliability for clinic and mSpirometry was assessed by interclass correlation coefficient (ICC). Simulation was conducted to explore if mSpirometry could improve statistical power over clinic counterparts. The mean subject compliance with mSpirometry was 70% for twice‐daily and 85% for at least once‐daily. The mSpirometry FEV₁ were highly correlated and agreed with clinic ones from the same morning (r = 0.993) and the same afternoon (r = 0.988) with smaller mean difference for the afternoon (0.0019 L) than morning (0.0126 L) measurements. The test‐retest reliability of mobile (ICC = 0.932) and clinic (ICC = 0.942) spirometry were comparable. Our simulation analysis indicated greater power using dense mSpirometry than sparse clinic measurements. Overall, we have demonstrated good compliance for repeated at‐home mSpirometry, high agreement and comparable test‐retest reliability with clinic counterparts, greater statistical power, suggesting a potential for use in asthma clinical research.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

☑ Forced expiratory volume in one second (FEV1) is the gold standard in clinical care and research practice for assessing patients with asthma. Mobile spirometry (mSpirometry) provides an opportunity to collect frequent repeated measures remotely with minimum disruption to everyday life.

• WHAT QUESTION DID THIS STUDY ADDRESS?

☑ We sought to estimate concordance of mobile and clinic measures, establish patient compliance, assess diurnal variation of FEV₁, and explore whether at‐home repeated FEV1 measures would improve statistical power over traditional clinic measures.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

☑ The mSpirometry FEV1 measurements were strongly correlated with clinic FEV1 from both the same morning (r = 0.993) and same afternoon/evening (r = 0.988). The mean subject compliance with mSpirometry was 85.3%. Our simulation analysis indicated a higher power using dense mSpirometry measurements.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

☑ Deploying mSpirometry in clinical trials is likely to improve statistical power.

Asthma is characterized by airway inflammation, airway hyper‐responsiveness, and variable airflow obstruction. ¹ Despite advances in our understanding of its pathophysiology, biomarker identification, and phenotyping, many patients remain poorly controlled. Asthma displays a strong circadian rhythm, which can cause symptom variability throughout a 24‐hour period. ² , ³ Clinical trials of novel drugs in asthma are faced with the challenge of measuring changes in lung function in this condition, which displays variable airflow obstruction, including diurnal fluctuations.Forced expiratory volume in 1 second (FEV₁) is the gold standard for monitoring lung function in clinical care and research. ⁴ Traditionally, measurements of lung function are performed during clinic visits. However, the frequency of measurements is often limited in clinical trials due to feasibility considerations for patients and cost. Asthma is characterized by airflow obstruction, which displays a diurnal pattern. Diurnal variation is observed in lung function in healthy individuals ⁵ and is greater in patients with asthma. ⁶ The lowest FEV₁ measurements are observed in early morning hours coinciding with increased symptoms and airway inflammation. ⁷ The requirement for clinic visits limits the ability to capture this variability. These limitations impose requirements of a relatively large sample size for drug development clinical trials to control for measurement variability. Furthermore, frequent clinic visits can limit patient participation.It is well known that multiple measures improve the accuracy of a measurement and therefore provide greater statistical power to detect a treatment difference in a measure with fewer patients. ⁸ The ability to monitor FEV₁ frequently may therefore be of benefit in clinical trials that evaluate treatment interventions in asthma. Frequent FEV₁ assessments can also help to account for diurnal variation. FEV₁ monitoring using mobile spirometers (mSpirometers) provides an opportunity to do at‐home monitoring, collect dense data, and minimize the effect of random anomalous tests results that may occur during sparse clinic visits. Although mSpirometers provide convenient means for collecting lung function data at home, a concern about this modality is related to patient compliance and willingness to put the best effort to perform expiratory maneuvers while unsupervised.The recent advances in remote FEV₁ monitoring demonstrated high correlation and small mean differences between at‐home mobile handheld and clinic‐based FEV₁ measurements in the context of randomized clinical trials in asthma ⁹ and chronic obstructive pulmonary disease (COPD). ¹⁰ However, the studies describing a comparison of clinic and mSpirometry data are limited, and study findings may be device‐specific. Moreover, patient compliance with mSpirometry was reported only in patients with COPD, ¹⁰ indicating a need to establish compliance data in different populations, including asthma. Additionally, to our knowledge, no study has investigated if FEV₁ repeated measurements at home can improve statistical power to detect a treatment effect. The aim of our study was to build on previous findings, by verifying agreement between clinic and mobile FEV₁ measurements using a different spirometer device, establishing patient compliance in patients with moderate asthma. Furthermore, we used the data to perform power simulation to estimate the effect sizes that can be detected from either weekly clinic measurements or daily measurements at home in clinical trials.