[Characteristics of low frequency repetitive nerve stimulation in patients with myasthenia gravis and its correlation with clinical features].

Objective: To investigate the characteristics of low frequency repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG) and analyze the correlation between RNS results and clinical characteristics. Methods: The clinical and electrophysiological data of 107 MG patients who were admitted to Guangdong Provincial People's Hospital and underwent electromyography (EMG) between September 2015 to September 2020 were retrospectively reviewed. The characteristics of low frequency RNS in ocular MG and generalized MG patients were analyzed. Patients were divided into RNS-negative group and RNS-positive group according to the RNS results. The clinical features, serological and thymic CT findings, thymic pathology were collected and compared. Binary logistic regression analysis was used to analyze the related factors of low frequency RNS. Results: Generalized MG (73.0%, 46/63) showed a lower positive rate of low frequency RNS compared to ocular MG (34.1%, 15/44) (P<0.001). In generalized MG, the positive rate of low frequency RNS in accessory nerve (68.3%, 43 cases) and facial nerve (52.4%, 33 cases) was higher than that in ulnar nerve (14.3%, 9 cases) (P<0.001). The decrease rate of compound muscle action potential (CMAP) in facial nerve (32%±11%) was higher than that in ocular muscle type (22%±7%) in RNS-positive group (P=0.011). Patients with positive facial nerve RNS were more likely to involve the throat muscles than those with negative result [22 cases (52.4%) compared with 17 cases (26.2%), P=0.006]. RNS-positive group showed a significantly higher quantitative myasthenia gravis (QMG) score than that of negative group (P<0.001). In ocular MG, patients with positive RNS showed a later onset (P=0.021), higher acetylcholine receptor (AChR) antibody-positive rate (P=0.03) and QMG score (P<0.001). Additionally, In generalized MG, patients with positive RNS showed a significantly higher AChR antibody-positive rate (P=0.023) and QMG score (P<0.001). The logistic regression analysis showed that QMG score [OR(95%CI)=1.66(1.36-2.03), P<0.001] and positive AChR antibody [OR(95%CI)=5.45(1.28-23.14), P=0.022] were independently related to abnormal RNS. Conclusions: Low frequency RNS is more sensitive in generalized MG. The stimulation of facial and accessory nerves increases the positive rate of RNS in MG patients. Abnormal results of low frequency RNS tend to be combined with positive AChR antibody and higher QMG score, reflecting the severity of muscle weakness. Therefore, serological examination and early intervention are required for those with abnormal RNS.

Quality of questionnaires for the assessment of otitis media with effusion in children.

OBJECTIVES: Audiometric tests provide information about hearing in otitis media with effusion (OME). Questionnaires can supplement this information by supporting clinical history-taking as well as potentially providing a standardized and comprehensive assessment of the impact of the disease on a child. There are many possible candidate questionnaires. This study aimed to assess the quality and usability of parent / child questionnaires in OME assessment. DESIGN AND MAIN OUTCOME MEASURES: Fifteen, published questionnaires, commonly used in audiological departments (Auditory Behaviour in Everyday Life (ABEL), Children's Auditory Performance Scale (CHAPS), Children's Home Inventory for Listening Difficulties (CHILD), Children's Outcome Worksheets (COW), Evaluation of Children's Listening and Processing Skills (ECLiPS), Early Listening Function (ELF), Fisher's Auditory Problem Checklist (FAPC), Hearing Loss 7 (HL-7), Listening Inventory for Education- Revised (LIFE-R Student), Listening Inventory for Education UK Individual Hearing Profile (LIFE-UK IHP), LittlEARS Auditory Questionnaire (LittlEARS), Listening Situations Questionnaire (LSQ), Otitis Media 6 (OM-6), Quality of Life in Children's Ear Problems (OMQ-14), Parents' Evaluation of Aural/Oral Performance of Children (PEACH) were assessed according to the following 8 criteria: conceptual clarity, respondent burden, reliability, validity, normative data, item bias, ceiling/ floor effects, and administrative burden. RESULTS: ECLiPS, LittlEARS and PEACH scored highest overall based on the assessment criteria established for this study. None of the questionnaires fully satisfied all 8 criteria. Although all questionnaires assessed issues considered to be of at least adequate relevance to OME, the majority had weaknesses with respect to the assessment of psychometric properties, such as item bias, floor/ceiling effects or measurement reliability and validity. Publications reporting on the evaluation of reliability, validity, normative data, item bias and ceiling/floor effects were not available for most of the questionnaires. CONCLUSIONS: This formal evaluation of questionnaires, currently available to clinicians, highlights three questionnaires as potentially offering a useful adjunct in the assessment of OME in clinical or research settings. These were the ECLiPS, which is suitable for children aged 6 years and older, and either the LittlEARS or the PEACH for younger children. The latter two are narrowly focused on hearing, whereas ECLiPS has a broader focus on listening, language and social difficulties.

A rare PAX6 mutation in a Chinese family with congenital aniridia.

Aniridia is an autosomal dominant disorder characterized by the complete or partial loss of the iris and is almost associated with mutations in the paired box gene 6 (PAX6). We examined three generations of a Chinese family with congenital aniridia and observed genetic defects. Exons of PAX6 from 12 family members were amplified by polymerase chain reaction, sequenced, and compared with reference sequences in NCBI reference sequence database (http://www.ncbi.nlm.nih.gov/nuccore/NG_008679.1?from=5001&to=38170&report=genbank). A rare mutation c.2T>A (M1K) in exon 4 of PAX6 was identified in all affected family members but not in unaffected family members. Our results suggest that the c.2T>A (M1K) mutation may be responsible for the pathogenesis of congenital aniridia in this family. To our knowledge, this is the first report of the M1K mutation in PAX6 in a Chinese family with this disease and the second report worldwide.

A novel mutation of PAX6 identified in a Chinese twin family with congenital aniridia complicated with nystagmus.

Genetic variations within the paired box gene 6 (PAX6) gene are associated with congenital aniridia. To detect the genetic defects in a Chinese twin family with congenital aniridia and nystagmus, exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Six members from the family of three generations were included in the study. The twins' father presented with congenital aniridia, nystagmus and cataract at birth, while the twins presented with congenital aniridia and nystagmus. A novel mutation c.888 insA in exon 10 of PAX6 was identified in all affected individuals. This study suggests that the novel mutation c.888 insA is likely responsible for the pathogenesis of the congenital aniridia and nystagmus in this pedigree. To the best of our knowledge, this is the first report of this mutation in PAX6 gene in pedigree with aniridia. Furthermore, no PAX6 gene defect was reported in twins with congenital aniridia.

Modified transseptal approach in endoscopic transsphenoidal pituitary surgery.

OBJECTIVE: Transsphenoidal pituitary surgery is commonly performed via a direct transostial approach with a posterior septectomy. However, a technique via an endoscopic transseptal route has been described that avoids a posterior septectomy, but it comes with its own disadvantages. METHODS: This paper describes a modification, and discusses its pros and cons. RESULTS: The initial incision in the mucosa is placed level with the anterior middle turbinate. The mucoperichondrial flap is raised ipsilaterally until the sphenoid sinus ostium. An incision is made at the osseocartilaginous junction, and the contralateral mucoperichondrial flap is raised. The bony septum and posterior aspect of this flap is excised. The size and position of this window can be adapted. At the end of the operation, the lateralised intact mucoperichondrial flap is moved back to the midline. CONCLUSION: Excision or deflection of the cartilaginous septum is not required. It maintains an intact septal mucosa on one side and avoids a septal perforation.

Effect of insulin infusion on electrocardiographic findings following acute myocardial infarction: importance of glycaemic control.

AIMS: To determine the effects of insulin infusion and blood glucose levels during acute myocardial infarction (AMI) on electrocardiographic (ECG) features of myocardial electrical activity. METHODS: ECGs at admission and 24 h were examined in a randomized study of insulin infusion vs. routine care for AMI patients with diabetes or hyperglycaemia. Results were analysed according to treatment allocation and also according to average blood glucose level. RESULTS: ECG characteristics were similar at admission in both groups. Patients allocated to conventional treatment had prolongation of the QT interval (QTc) after 24 h but those receiving infused insulin did not. In patients with a mean blood glucose in the first 24 h > 8.0 mmol/l, new ECG conduction abnormalities were significantly more common than in patients with mean blood glucose

Analgesia following adenotonsillar surgery in children: is Oramorph required in addition to paracetamol and ibuprofen?

BACKGROUND: Recent advice against codeine use in children prompted our unit to prescribe Oramorph as required, in addition to regular paracetamol and ibuprofen, as post-(adeno)tonsillectomy analgesia. This study investigated whether Oramorph was in fact required. METHODS: Following (adeno)tonsillectomy, parents were telephoned and asked whether they used Oramorph. RESULTS: Of 56 children studied, 41 (73.2%) were given Oramorph. In the 15 (26.8%) that were not, this was because parents felt it was not required in 14 children, and in 1 case, it was due to worries about side effects. Overall, 14 carers (25.0%) expressed concerns about Oramorph use, mostly over possible side effects. CONCLUSION: When regular paracetamol and ibuprofen are used post-(adeno)tonsillectomy, nearly three quarters of children require Oramorph as well. Prescribing Oramorph as required, in addition to regular paracetamol and ibuprofen, is appropriate following adenotonsillar surgery.

Downregulation of microRNA-21 expression restrains non-small cell lung cancer cell proliferation and migration through upregulation of programmed cell death 4.

Preliminary studies showed that miR-21 is overexpressed in some human cancers. However, the role of miR-21 in cancer is still unclear and even controversial. Our purpose was to investigate the biological effects of miR-21 on A549 non-small cell lung cancer (NSCLC) cells and the underlying mechanisms of those effects. The expression of miR-21 was quantified in serum samples from patients with NSCLC. A549 cells were transfected with miR-NC-sponge or miR-21-sponge only, or with miR-21-sponge plus PDCD4 small-interfering RNA (siRNA). The expression of miR-21 and PDCD4 mRNA in transfected cells was quantified by real-time polymerase chain reaction and the expression of PDCD4 protein by Western blot. Cell proliferation, apoptosis, migration, and invasion assays were performed to determine the biological effects of miR-21 expression and PDCD4 inhibition. miR-21 was overexpressed in serum from patients with NSCLC. Reduced miR-21 expression was observed following transfection with miR-21-sponge in A549 NSCLC cells. Co-transfection of miR-21-sponge with PDCD4 siRNA upregulated miR-21 expression in these cells. PDCD4 mRNA and protein levels were increased 2.14-fold and 2.16-fold, respectively, following inhibition of miR-21 expression. Inhibition of miR-21 expression following transfection of miR-21-sponge reduced cell proliferation, migration, and invasion of A549 cells. Depletion of PDCD4 by siRNA transfection reversed the reduction of cell proliferation, migration, and invasion induced by inhibition of miR-21 in A549 cells. It indicates that miR-21 is highly expressed in patients with NSCLC and inhibition of miR-21 expression reduces proliferation, migration, and invasion of A549 cells by upregulating PDCD4 expression. Modulation of miR-21 or PDCD4 expression may provide a potentially novel therapeutic approach for NSCLC.

Testing the validity of the lacunar hypothesis: the Northern Manhattan Stroke Study experience.

BACKGROUND/OBJECTIVE: Few studies have attempted to validate the "lacunar hypothesis." The accuracy of identifying lacunar and other nonlacunar mechanisms of infarction will be increasingly important in evaluating potential stroke treatments. The aim of this study was to determine the value of lacunar syndromes in predicting radiologic lacunes and the value of clinicoradiologic lacunes in predicting "lacunar infarction" as final stroke mechanism. METHODS: From 1990 to 1994, 591 patients with cerebral infarction, who were from northern Manhattan and over the age of 39, were prospectively examined. Data were collected on the admitting clinical syndrome (lacunar or nonlacunar) and brain imaging findings. Lacunar syndromes were categorized as pure motor hemiparesis (PMH), pure sensory syndrome (PSS), sensorimotor syndrome (SMS), ataxic-hemiparesis (A-H), and other lacunar syndromes. Brain imaging findings were classified as radiologic lacune or nonlacune. Positive predictive values, sensitivities, and specificities of lacunar syndromes for identifying radiologic lacunes were calculated. The final mechanism of infarction was determined after review of all the diagnostic tests and compared among the lacunar groups. RESULTS: Lacunar syndromes occurred in 225 cases. PMH was the most common lacunar syndrome, accounting for 45%, SMS 20%, A-H 18%, and PSS 7%. Lacunar syndromes had an overall positive predictive value (PPV) of 87% for detecting radiologic lacune: PSS 100%, A-H 95%, SMS 87%, and PMH 79%. Among the 195 patients who presented with a lacunar syndrome and had this condition confirmed radiologically, 147 were classified as having a final diagnosis of lacunar mechanism of infarction (PPV = 75%). Atherosclerosis accounted for 17 (9%), cardioembolism 10 (5%), cryptogenic 17 (9%), and other unusual causes 4 (2%). CONCLUSION: While lacunar syndromes, especially PSS and A-H, are highly predictive of lacune, in about one in four patients presenting with lacunar syndromes confirmed radiologically the condition is associated with nonlacunar mechanisms of infarction. Noninvasive neurovascular and cardiac evaluations are still warranted even among patients with lacunes.

Immunocytochemical localization of benzo(a)pyrene-DNA adducts in human tissue.

Specimens of human lung, uterine cervix, ovary, and placenta were studied for the presence of benzo(a)pyrene 7,8-diol 9,10 epoxide (BPDE)-DNA adducts by using rabbit anti-BPDE-DNA antibody and light microscopic immunocytochemistry. BPDE-DNA antigenicity was detected in the bronchial epithelial cells, cervical epithelium, oocytes, luteal cells, corpora albicans, and hyalinized media of arteries within the ovaries and trophoblastic cells of the placental villi. In conjunction with immunoassay detection of BPDE-DNA adducts in human peripheral blood lymphocytes, this study demonstrates that a variety of human tissues can metabolize and bind the ubiquitous carcinogen benzo(a)pyrene. The identification and localization of this carcinogen-DNA antigenicity in various tissues and cells may not only help in monitoring exposed persons but also give insight to organ site carcinogenesis, transplacental carcinogenesis, and teratogenesis.

Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms.

Previously we and others found that a majority of chronic fatigue syndrome (CFS) patients showed evidence of systemic mycoplasmal infections, and their blood tested positive using a polymerase chain reaction assay for at least one of the four following Mycoplasma species: M. fermentans, M. hominis, M. pneumoniae or M. penetrans. Consistent with previous results, patients in the current study (n=200) showed a high prevalence (overall 52%) of mycoplasmal infections. Using forensic polymerase chain reaction we also examined whether these same patients showed evidence of infections with Chlamydia pneumoniae (overall 7.5% positive) and/or active human herpes virus-6 (HHV-6, overall 30.5% positive). Since the presence of one or more infections may predispose patients to other infections, we examined the prevalence of C. pneumoniae and HHV-6 active infections in mycoplasma-positive and -negative patients. Unexpectedly, we found that the incidence of C. pneumoniae or HHV-6 was similar in Mycoplasma-positive and -negative patients, and the converse was also found in active HHV-6-positive and -negative patients. Control subjects (n=100) had low rates of mycoplasmal (6%), active HHV-6 (9%) or chlamydial (1%) infections, and there were no co-infections in control subjects. Differences in bacterial and/or viral infections in CFS patients compared to control subjects were significant. Severity and incidence of patients' signs and symptoms were compared within the above groups. Although there was a tendency for patients with multiple infections to have more severe signs and symptoms (p<0.01), the only significant differences found were in the incidence and severity of certain signs and symptoms in patients with multiple co-infections of any type compared to the other groups (p<0.01). There was no correlation between the type of co-infection and severity of signs and symptoms. The results indicate that a large subset of CFS patients show evidence of bacterial and/or viral infection(s), and these infections may contribute to the severity of signs and symptoms found in these patients.

Vascular impedance analysis in dog lung with detailed morphometric and elasticity data.

On the basis of experimentally measured morphometric and elasticity data and model-derived mean pressure-flow conditions, we attempt a theoretical modeling of pulsatile flow in the whole lung. In the model we use the "elastic tube" for arteries and veins, and the vascular impedance in arteries and veins follows Womersley's theory and electric analogue. We employ the "sheet-flow" theory to describe the flow in the capillaries and to obtain the microvascular impedance matrix. The characteristic impedance of each order along the vascular tree, the input impedance at the capillary entrance and exit, and the pulmonary arterial input impedance at the main pulmonary artery are computed under certain physiological conditions. Using the pulsatile flow model, we investigate the effects of arterial vascular obstruction on pulmonary vascular impedance. The model-derived data are compared with the available experimental results in the literature.

Morphometry of the dog pulmonary venous tree.

The biophysical approach to the study of blood flow in the pulmonary vasculature requires a detailed description of vascular geometry and branching pattern. The description of the pulmonary venous morphometry in the dog is the focus of this paper. Silicone elastomer casts of a dog lung were made and were used to measure the diameters, lengths, and branching pattern of the pulmonary venous vasculature. The anatomic data are presented statistically with a diameter-defined Strahler ordering scheme, a rule for assigning the order numbers of the vessels on the basis of a diameter criterion. The asymmetric branching pattern of the pulmonary venous vasculature is described with a connectivity matrix. Results show that for the dog's right pulmonary venous tree 1) a total of 11 orders of vessels lay between the left atrium and the capillary bed; 2) the average ratios of the diameter, length, and number of branches of successive orders of veins were 1.701, 1.556, and 3.762, respectively; and 3) a fractal description of the tree geometry resulted in diameter and length fractal dimensions of 2.49 and 2.99, respectively. The morphometric data were used to compute the cross-sectional area, vascular volume, and Poiseuillean resistance in the venous vessels.

Effect of chronic thromboembolism on the pulmonary artery pressure-flow relationship in dogs.

To understand the hemodynamic alterations associated with chronic thromboembolic pulmonary hypertension, the large pulmonary arteries of mongrel dogs were chronically obstructed with lysis-resistant thrombi. Pulmonary hemodynamics were experimentally measured and described by multipoint pulmonary arterial pressure (PAP) vs. flow plots. In nine anesthetized chronically embolized dogs, but not in six control dogs, the PAP-flow line shifted significantly upward in a parallel fashion by 4.2 +/- 0.7 mmHg. The postembolic pulmonary circulation was further characterized by predictions from a morphometric-based elastic tube and sheet flow model of the canine pulmonary circulation. After model validation with the preembolic PAP-flow data, the derived postembolic PAP matched the in vivo results to within 1 mmHg. A detailed analysis of the model-derived PAP drop revealed that the PAP-flow line shift can be accounted for by a novel fixed resistor in the largest obstructed pulmonary artery.

The medullary vascular syndromes revisited.

There are two major vascular syndromes of the medulla oblongata: the medial and the lateral. The medial medullary syndrome is characterized by the triad of ipsilateral hypoglossal nerve palsy with contralateral hemiparesis and loss of deep sensation. Lateral medullary infarction commonly presents with Horner's syndrome, ataxia, alternating thermoanalgesia, nystagmus, vertigo and hoarseness. Combinations of the two major syndromes occur as bilateral medial medullary, hemimedullary and bilateral lateral medullary syndromes. Each of these syndromes frequently manifests with incomplete or atypical findings depending on the extent of the lesion. Magnetic resonance imaging has been useful in the clinical diagnosis of medullary infarctions. The site of the lesion may help predict the arteries involved.

Rifampicin and sodium fusidate reduces the frequency of methicillin-resistant Staphylococcus aureus (MRSA) isolation in adults with cystic fibrosis and chronic MRSA infection.

Nosocomial transmission of methicillin-resistant Staphylococcus aureus (MRSA) to patients with cystic fibrosis (CF) frequently results in chronic respiratory tract carriage. This is an increasing problem, adds to the burden of glycopeptide antibiotic use in hospitals, and represents a relative contraindication to lung transplantation. The aim of this study was to determine whether it is possible to eradicate MRSA with prolonged oral combination antibiotics, and whether this treatment is associated with improved clinical status. Adult CF patients (six male, one female) with chronic MRSA infection were treated for six months with rifampicin and sodium fusidate. Outcome data were examined for six months before treatment, on treatment and after treatment. The patients had a mean age of 29.3 (standard deviation=6.3) years and FEV(1) of 36.1% (standard deviation=12.7) predicted. The mean duration of MRSA isolation was 31 months. MRSA isolates identified in these patients was of the same lineage as the known endemic strain at the hospital when assessed by pulsed-field gel electrophoresis. Five of the seven had no evidence of MRSA during and for at least six months after rifampicin and sodium fusidate. The proportion of sputum samples positive for MRSA was lower during the six months of treatment (0.13) and after treatment (0.19) compared with before treatment (0.85) (P<0.0001). There was a reduction in the number of days of intravenous antibiotics per six months with 20.3+/-17.6 on treatment compared with 50.7 before treatment and 33.0 after treatment (P=0.02). There was no change in lung function. Gastrointestinal side effects occurred in three, but led to therapy cessation in only one patient. Despite the use of antibiotics with anti-staphylococcal activity for treatment of respiratory exacerbation, MRSA infection persists. MRSA can be eradicated from the sputum of patients with CF and chronic MRSA carriage by using rifampicin and sodium fusidate for six months. This finding was associated with a significant reduction in the duration of intravenous antibiotic treatment during therapy.