Quantitative analysis of hyperpolarized 3He ventilation changes in mice challenged with methacholine

The capability to use high‐resolution ³He MRI to depict regional ventilation changes and airway narrowing in mice challenged with methacholine (MCh) offers the opportunity to gain new insights into the study of asthma. However, to fully exploit the value of this novel technique, it is important to move beyond visual inspection of the images toward automated and quantitative analysis. To address this gap, we describe a postprocessing approach to create ventilation difference maps to better visualize and quantify regional ventilation changes before and after MCh challenge. We show that difference maps reveal subtle changes in airway caliber, and highlight both focal and diffuse regional alterations in ventilation. Ventilation changes include both hypoventilation and compensatory areas of hyperventilation. The difference maps can be quantified by a histogram plot of the ventilation changes, in which the standard deviation increases with MCh dose (R₂ = 0.89). This method of analysis is shown to be more sensitive than simple threshold‐based detection of gross ventilation defects. Magn Reson Med 63:658–666, 2010. © 2010 Wiley‐Liss, Inc.     

Rhinological, laryngological, oropharyngeal and other head and neck side effects of drugs

Following a previous paper in which we documented the otological side effects of drug therapy, we here review other drug side effects that ENT surgeons may encounter when dealing with patients. Although otological drug side effects such as hearing loss and tinnitus are well recognized there are many rhinological, laryngeal, oropharyngeal and other head and neck drug side effects. Our data were sourced from the British National Formulary and Electronic Medical Compendium websites.     

Sweets, snacking habits, and skipping meals in children and adolescents on intensive insulin treatment

Aim:  To examine the association between skipping meals and snacking events and dietary and clinical characteristics in children and adolescents using modern insulin treatment.
Methods:  Dietary intake was recorded for 4 d in food diaries in 655 young diabetic patients. Number of meals and snacking events was recorded in a separated questionnaire, while clinical data were obtained from case record forms. Skipping meals refer to consuming a main meal (e.g., breakfast) five times a week or less.
Results:  Modern insulin treatment may favor a more flexible lifestyle. This study shows that there are fewer young diabetic patients who skip meals than non-diabetic controls (p < 0.001) even when using modern intensified insulin treatment. However, skipping meals among young diabetic patients was associated with negative characteristics such as having suboptimal hemoglobin A1c (HbA1c) (OR 4.7, p = 0.02), higher low-density lipoprotein (LDL) cholesterol levels (OR 4.0, p < 0.001), watching more TV (OR 3.6, p < 0.001), being overweight (OR 2.8, p = 0.03), as well as having a higher intake of added sugar (OR 2.1, p = 0.01) and lower intake of fiber (OR 0.2, p = 0.04) compared with those not skipping meals. Having more than two snacking events during the day was associated with higher HbA1c, higher intake of added sugar and sweets, and spending more hours in front of the TV or personal computer.
Conclusions:  In general, fewer children and adolescents with type 1 diabetes skip meals compared with healthy peers. Those who skip meals and have more snacking events have poorer glycemic control and less healthy dietary and leisure habits.     

hsp70 synthesis in Schwann cells in response to heat shock and infection with Mycobacterium leprae.

Induction of heat shock protein synthesis was monitored in murine and monkey Schwann cells exposed to elevated temperatures. Synthesis of the stress-inducible 70-kDa heat shock protein (hsp70) was detected in both murine and primate Schwann cells by metabolic labelling and by immunoblotting with a specific monoclonal antibody. hsp70 synthesis was also induced in Schwann cells after infection with Mycobacterium leprae and was detected from 24 h to 1 week postinfection. These results are discussed with respect to the possible role of heat shock proteins in immunopathological events associated with the clinical manifestations of leprosy.     

Tyrosine phosphorylation of a 95 kDa protein and induction of the acrosome reaction in human spermatozoa by recombinant human zona pellucida glycoprotein 3

Protein tyrosine phosphorylation and induction of the acrosome reaction (AR) in non-capacitated and capacitated human spermatozoa was investigated in response to recombinant human zona pellucida glycoprotein (rhZP3) produced by Chinese hamster ovary cells transfected with a plasmid containing human ZP3 cDNA. rhZP3-containing medium promoted the AR in a high proportion of capacitated spermatozoa (48.6 +/- 3.2%; P < 0.01) compared with control (no rhZP3) samples (14.8 +/- 2.1%). However, rhZP3-containing medium did not cause increased acrosomal exocytosis in non-capacitated spermatozoa (16.8 +/- 3.0%). Induction of the AR was associated with increased tyrosine phosphorylation of a 95 +/- 5 kDa epitope only in capacitated spermatozoa. A dose-dependent increase in the protein phosphorylation of a 95 kDa epitope in response to rhZP3 was detected by [gamma-32P]- ATP labelling of detergent-solubilized sperm proteins. When spermatozoa were co-incubated with monoclonal antibody 97.25 (mAb 97.25) recognizing a 95 kDa tyrosine kinase epitope, there was no rhZP3 induction of tyrosine phosphorylation of the 95 kDa protein. Such co- incubation also markedly inhibited the AR (23.9 +/- 3.1%). These results support the model that initial interaction of the fertilizing spermatozoon with ZP3 involves the tyrosine phosphorylation of a 95 kDa tyrosine kinase protein and that this requires capacitation.      

Localization of oxytocin receptors in the human and macaque monkey male reproductive tracts: evidence for a physiological role of oxytocin in the male

The peptide oxytocin is present in tissues of the male reproductive tract from a variety of mammalian species. In the human, specific mRNA for oxytocin and the peptide itself have been identified in the testis, epididymis and prostate. The peptide has been shown to modulate both steroidogenesis and contractility in the male reproductive tract and may be involved in the pathogenesis of benign prostatic hyperplasia. We have performed Western blots and immunohistochemistry using a specific antibody to the human oxytocin receptor (OTR) to investigate the distribution and localization of the receptor in the human and macaque monkey (Macaca fasicularis). An immunoreactive band of approximately 55 kDa was detected in human and monkey uterine, testicular and prostatic tissues and in preparations of monkey caput and cauda epididymis. A second, less intense, band of 60 kDa was also seen in testicular and uterine tissue samples. No specific bands were detected in monkey muscle or in any tissue following incubation with mouse immunoglobulin (Ig)M. In the human and monkey testis staining for the OTR was present in the interstitial tissue and in Sertoli cells. Localization of the OTRs varied throughout the epididymis being expressed by epithelial cells proximally but confined to cells at the base of the epididymal ducts and to the surrounding smooth muscle layers distally. In the prostate OTR were localized to the stromal tissue surrounding the ducts. These findings correlate with sites of local production of the peptide and the observed biological actions of oxytocin, and thus support the evidence that oxytocin may play a physiological role in the male reproductive tract.      

Evaluation of the Reliability of the Challenge when used to Measure Advanced Motor Skills of Children with Cerebral Palsy

Aims: The Challenge was designed as an extension to the GMFM-66 to assess advanced motor skills of children with cerebral palsy (CP) who walk/run independently. This study evaluated the Challenge's inter-rater and test–retest reliability. Methods: Thirty children with CP (GMFCS level I [n = 24] and II [n = 6]) completed the Challenge, with re-testing one to two weeks later. Seven physiotherapist assessors passed the Challenge criterion test pre-administration. A single assessor administered and scored test and retest sessions (test–retest reliability). A second assessor independently scored one of these sessions (inter-rater reliability). Results: Inter-rater reliability was excellent (ICC = 0.97, 95%CI 0.94–0.99, CoV < 10%), with no bias (Bland-Altman plot). Test–retest ICC was excellent (ICC = 0.94, 95% CI 0.88–0.97. CoV < 10%, and Minimum Detectable Change (MDC₉₀) was 4.47 points. Many participants indicated practising at home pre-retest session. Conclusions: There was strong rating consistency between assessors. While test–retest ICC estimates were also high, Challenge scores were higher at retest. The MDC₉₀ was still in a range (>4.5 points) that seems clinically viable for change detection. Test–retest reliability could be reassessed with children instructed not to practice between assessments to determine the extent to which between-session practice influenced scores.     

Inside implant criteria or not? – Detection of non-organic hearing loss during cochlear implant assessment

Objectives: The diagnosis of non-organic hearing loss (NOHL) is a difficult but important issue during the assessment process for cochlear implantation (CI). We aim to identify the key factors in identifying patients with NOHL during CI assessment and present our local screening protocol for NOHL.

Methods: A retrospective review of patients referred to the Yorkshire Auditory Implant Service (YAIS) between 2003 and 2015 who were subsequently diagnosed with NOHL during the assessment. Patient demographic data, audiological and functional assessments were assessed.

Results: Thirty-two patients were included in the study. Mean age was 43 years (range 14–82 years). Male to female ratio was 1:1.7. Indicators of possible NOHL included a sudden deterioration in hearing (n?=?21; 66%), mismatches in observed behaviour and either pure-tone audiogram (PTA) (n?=?27; 84%) or functional testing (n?=?20; 80%) and stapedial reflexes below reported audiological thresholds (n?=?12; 46%). A mismatch in functional hearing and PTA was seen in 72% of patients. Patients with suspected NOHL were referred for further objective testing. All 23 patients who underwent objective testing had better hearing levels compared to reported hearing thresholds thus placing them outside of implant criteria. Five candidates were found to have normal hearing thresholds.

Discussion: NOHL can present a significant challenge to the implant team, particularly in the subgroup with a pre-existing organic hearing loss with non-organic overlay. We discuss the common features in this cohort of patients.

Conclusions: To facilitate the identification of patients with NOHL, the YAIS has developed a screening protocol.     

Separation of the masticator space from the parapharyngeal space

The separation of the masticator and parapharyngeal spaces is somewhat ambiguous. Anatomic specimens were dissected to define better the fascial layer representing the medial wall of the masticator space. A fascial layer was found extending from the medial pterygoid muscle to the skull base separating the masticator from the parapharyngeal space. The third branch of the trigeminal nerve was lateral to this fascial layer and thus passed through the masticator space. Clinical cases were reviewed. Tumors could be confidently assigned to the masticator, prestyloid, or poststyloid parapharyngeal spaces. Benign salivary gland tumors were found in the prestyloid parapharyngeal space only.     

Symptoms, spirometry, exhaled nitric oxide, and asthma exacerbations in clinical practice

BACKGROUND: Patient symptoms, spirometry measurements, exacerbation rates, and exhaled nitric oxide (FE(NO)) levels have all been used to quantify asthma severity. OBJECTIVE: To determine the relationships among these disease surrogates in clinical practice. METHODS: Data were collected from 5 primary care asthma clinics on patient symptoms, reliever use, spirometry measurements, maintenance pharmacotherapy, disease severity (British Thoracic Society treatment step), and FE(NO) level. Exacerbation data (asthma-related unscheduled health care contact or rescue oral corticosteroid therapy) for the 12 months before and 3 months after the clinic visit were then obtained. RESULTS: A total of 267 adult asthmatic patients (mean [SEM] age, 51.6 [1.1] years; forced expiratory volume in 1 second, 86.3% [1.2%] of predicted) participated, and 157 exacerbations were captured. For the 12 months before the clinic visit, exacerbation rate was positively correlated with dose of inhaled corticosteroid (P < .001), treatment step (P < .001), reliever use (P = .002), and symptom score (P < .001) but was negatively correlated with FE(NO) level (P = .04); only symptom scores correlated with exacerbation rate in the 3 months after the visit. Levels of FE(NO) were significantly lower in frequently exacerbating patients receiving higher doses of maintenance inhaled corticosteroids compared with patients with mild disease who were corticosteroid naive (19.7 vs 40.4 ppb, P < .001). Measurement of FE(NO) was an insensitive method (sensitivity, 66.7%; specificity, 51.9% at a cutoff value of 20 ppb) for identifying patients who subsequently exacerbated. CONCLUSION: Levels of FE(NO) are paradoxically decreased in patients with more severe asthma and frequent exacerbations and may, therefore, be of limited utility in primary care.