bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIX1 Mutation Associated With Enlargement of the Vestibular Aqueduct in a Patient With Branchio‐Oto Syndrome
Authors: Ito Taku , Noguchi Yoshihiro , Yashima Takatoshi , Kitamura Ken 
Published: April 2006

AbstractObjectives: The objectives of this study were to identify SIX1 gene mutations in a patient with branchio‐oto syndrome (BO) and to clarify the relationship between SIX1 mutation and enlargement of the vestibular aqueduct (EVA).Methods: A genetic study and retrospective chart review for a patient in whom EYA1 mutation had already been excluded was conducted. We studied a Japanese patient who had autosomal‐dominant mixed hearing loss, a unilateral ear pit and unilateral EVA, and who was previously diagnosed as having BO. We searched for SIX1 and SLC26A4 mutations using polymerase chain reaction and direct gene sequencing.Results: The patient carried a heterozygous A→G mutation at nucleotide 386 within exon 1 of SIX1 that resulted in substitution of a cysteine for a tyrosine at codon 129 (Y129C) of the gene product. Y129C is a previously identified SIX1 mutation and was not detected in any of our 164 control chromosomes. No SLC26A4 mutations were identified.Conclusion: Y129C mutation in SIX1 may cause EVA as well as BO.
Human Cochleae With Three Turns: An Unreported Malformation
Authors: Tian Qing , Linthicum Fred H. , Fayad Jose N. 
Published: April 2006

AbstractObjective: The objective of this histologic study of archival temporal bone sections was to describe the morphology of human cochleae found with three turns, a previously unreported anomaly, found in three pairs of temporal bones.Methods: The authors conducted histopathologic processing and measurement of basilar membrane length. Basilar membrane length was compared with that found in six normal control bones.Results: Cochleae with three complete turns, rather than the usual two and a half turns, are described for the first time. All had longer than normal basilar membranes, with a mean length of 40.6 mm compared with a mean of 33.8 mm in the normal bones.Conclusions: Human cochleae with three turns exist as an unreported anomaly. This is a new category of anomaly, not likely based on interruption of development.
Everolimus (RAD) Inhibits In Vivo Growth of Murine Squamous Cell Carcinoma (SCC VII)
Authors: Khariwala Samir S. , Kjaergaard Jorgen , Lorenz Robert , Van Lente Frederick , Shu Suyu , Strome Marshall 
Published: April 2006

AbstractObjective: Everolimus (RAD) is an mTOR inhibitor closely related to rapamycin. A potent immunosuppressive agent, it has also shown evidence of antineoplastic properties. SCC VII is a spontaneously arising murine squamous cell carcinoma line. This study examines the effect of everolimus on SCC VII proliferation. The data may provide support for the use of everolimus in transplant recipients with a history of malignancy.Methods: A dose efficacy study was conducted that used a murine model of intradermal tumor growth and pulmonary metastases. The development of intradermal tumors and pulmonary metastases were studied. Of 80 total mice, 40 received intradermal injection of 1 × 105 SCC VII cells and 40 received intravenous injection of 1 × 105 cells to establish pulmonary metastases. Within each group, animals were subdivided into four subgroups that received 1) 1 mg/kg everolimus twice a day, 2) 0.5 mg/kg everolimus twice a day, 3) 7.5 mg/kg cyclosporine per day, and 4) no treatment. Intradermal tumors were measured three times per week. Animals receiving an intravenous tumor injection were killed after 17 days and pulmonary metastases were quantified. Medication trough levels were measured in all treated animals.Results: Everolimus showed statistically significant tumor inhibition at 1.0 mg/kg twice a day and 0.5 mg/kg twice a day when compared with animals treated with cyclosporine and with untreated animals (P < .0001). Tumor inhibition was evident in both models studied (intradermal tumors and pulmonary metastasis generation).Conclusions: Everolimus provides potent tumor inhibition in animals inoculated with SCC VII cells. Inhibition of both local and distant spread of disease is evident. Although most immunosuppressives are known to potentiate neoplastic disease, this study supports the use of everolimus immunosuppression in the face of prior malignancy. This data has significant implication for laryngeal transplantation after laryngectomy.
Patient‐Controlled Comparison of Flexible Endoscopic Evaluation of Swallowing With Sensory Testing (FEESST) and Videofluoroscopy
Authors: Tabaee Abtin , Johnson Paul E. , Gartner Carolyn J. , Kalwerisky Kevin , Desloge Rosemary B. , Stewart Michael G. 
Published: April 2006

AbstractObjective: The objective of this study was to compare the results of videofluoroscopy (VFS) with flexible endoscopic evaluation of swallowing with sensory testing (FEESST) in dysphagia testing.Methods: The authors conducted a retrospective review of data collected over a 4‐year period at a tertiary care medical center. The FEESST and VFS results for patients receiving both examinations within a 2‐week period were compared with respect to swallowing function. Comparisons were categorized as full agreement, minor disagreement that would not result in a significant difference in diet recommendations, and major disagreement that would result in a significant difference in diet recommendations. Kappa with quadratic weighting was calculated to evaluate the inter‐test agreement.Results: Fifty‐four patients met inclusion criteria and were reviewed. Forty‐one percent of patients were not eating by mouth at the time of FEESST and the mean interval between the two examinations was 5 days. Laryngeal examination revealed edema/erythema in 93%, impaired pharyngeal squeeze in 66%, decreased laryngopharyngeal sensation in 82%, and absent laryngeal adductor reflex in 30%. FEESST with all consistencies revealed pooling in 89%, penetration in 83%, and aspiration in 65% of patients. VFS revealed pooling in 65%, penetration in 67%, and aspiration in 54% of patients. Comparison of FEESST and VFS revealed full agreement in 52%, minor disagreement in 13%, and major disagreement in 35% of patients. A weighted kappa value of 0.324 signified only “fair” agreement between the two tests.Conclusions: FEESST and VFS may not represent comparable tests of dysphagia. Further comparative studies of tests of swallowing function are required to determine the ideal approach to dysphagia testing.
Treatment with botulinum toxin of octo‐nonagerians with oesophageal achalasia: a two‐year follow‐up study
Authors: BASSOTTI G. , D'ONOFRIO V. , BATTAGLIA E. , FIORELLA S. , DUGHERA L. , IAQUINTO G. , MAZZOCCHI A. , MORELLI A. , ANNESE V. 
Published: April 2006

SummaryBackgroundTreatment of oesophageal achalasia with intrasphincteric injections of botulinum toxin has proved to be a successful alternative treatment modality. However, little is known about its long‐term effects in very old patients.AimTo evaluate the effects of such treatment in octo‐nonagerians during a 2‐year follow‐up period.Patients and methodsThirty‐three patients with idiopathic oesophageal achalasia (range 81–94 years) entered the study. After basal evaluation and screening procedures, 100 U of botulinum toxin was injected at the lower oesophageal sphincter, and the procedure was repeated 1 month later. Data were collected at baseline and were compared after 1 and 2 years following the procedure.ResultsSeventy‐eight per cent of patients were considered responders at 1 year and 54% were considered responders at 2 years. The weight gain at the end of the follow‐up period was 2 (0–3) kg. No significant relationship was found between baseline lower oesophageal sphincter pressure and symptoms score after 1 and 2 years of follow‐up; moreover, no major complications of botulinum toxin therapy were reported.ConclusionTreatment of very old achalasic patients with botulinum toxin is safe, effective and yields good quality of life in a substantial proportion of these subjects.
Patients’ knowledge of adverse reactions to current medications
Authors: Cullen Garret , Kelly Emer , Murray Frank E. 
Published: April 2006

Aims  Adverse drug reactions (ADRs) account for 3.2–7% of acute hospital admissions. The aim of this study was to assess prospectively knowledge of ADRs in patients admitted through the emergency department of a teaching hospital.Methods  Three hundred and ninety‐nine patients were admitted on acute medical call during study periods in September 2002 and May 2003. One hundred gave their perception of the risk of ADRs using visual analogue scales, where 0 indicates minimum and 10 maximum risk. The medications studied were warfarin, proton pump inhibitors (PPIs), corticosteroids, nonsteroidal anti‐inflammatory drugs (NSAIDs) and aspirin. Responses are compared against a medical control group.Results  Corticosteroids were ranked most dangerous by patients (median score, 25th–75th centiles: 5.4, 2.9–8.7). Medical staff ranked NSAIDs as highest risk (6.2, 4.0–7.5). Patients identified NSAIDs as low risk (2.1, 0.7–4.9), perceiving the risk of cardiac arrhythmias and disturbance in liver biochemistry to be equivalent to risk of upper gastrointestinal ulceration and bleeding. Risk of haemorrhage was ranked as the most common ADR for warfarin by patients (8.6, 3.3–9.5) and medical staff (8.8, 7.6–9.3).Conclusions  Patients underrate the risk of ADRs of their medications. While there is a good level of knowledge of ADRs amongst warfarin and aspirin users, there is a clear lack of knowledge regarding the risk of upper GI bleeding in NSAID users. Increased education may reduce the incidence of ADRs but it is more likely that it will serve to meet increasing patient expectations.
Effects of the direct thrombin inhibitor dabigatran on ex vivo coagulation time in orthopaedic surgery patients: a population model analysis
Authors: Liesenfeld Karl‐Heinz , Schäfer Hans G. , Trocóniz Iñaki F. , Tillmann Christiane , Eriksson Bengt I. , Stangier Joachim 
Published: April 2006

AimsTo describe the pharmacokinetic–pharmacodynamic (PK–PD) characteristics of the direct thrombin inhibitor dabigatran in hip replacement patients by assessing coagulation parameters activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT), interindividual variability and factors affecting PD responses.MethodsBISTRO I patients received oral dabigatran etexilate postsurgery for 6–10 days. Dabigatran plasma concentrations and aPTT/ECT were measured on the day of surgery, on subsequent days and at steady state. PK–PD characteristics of the dabigatran–aPTT/ECT relationships were evaluated using NONMEM V.ResultsThe dabigatran concentration–aPTT relationship was described combining a linear and an Emax model. Mean baseline aPTT was 33.4 s and Emax (maximum increase in aPTT contributed by the Emax model) was 26.9 s. The dabigatran concentration needed to attain 50% of maximum effect (EC50) was 94.7 ng ml−1 and the mean slope of the linear concentration–response relationship (SLOP) was 0.0509 s ng−1 ml−1. Baseline aPTT and Emax were highest following surgery and declined with time. The dabigatran concentration–ECT relationship fitted a linear model. Mean baseline ECT was 28 s and decreased with time; 50% of the maximum effect was observed after 2.9 days. SLOP decreased from 0.38 to 0.27 s ng−1 ml−1 with a half‐life of 1.1 day, indicating greater PD effects on the day of surgery. Interindividual and residual variability was low. Covariates could not explain variability of this model.ConclusionsaPTT and ECT prolongation were directly correlated with dabigatran concentrations. Blood coagulation prolongation was most pronounced following surgery. Data suggest that ECT provides a more precise description of the anticoagulant effect than aPTT.
Detection of reaginic and short‐term sensitizing anaphylactic or anaphylactoid antibodies to milk in sera of allergic and normal persons
Authors: PARISH W. E. 
Published: April 2006

SummarySera of 50% of persons extremely sensitive and of 30% of persons moderately sensitive to milk had heat‐labile reaginic antibodies conferring passive cutaneous anaphylactic sensitivity on monkeys for 24 hr. More persons in each group had IgE antibodies that bound radio‐isotope labelled β‐lactoglobulin and passively sensitized monkey basophils for anaphylactic degranulation.These tests, however, are not certain evidence of clinical allergy, because of the sera of nineteen topic children, three mediated monkey PCA tests and five had γE anti‐$bt‐lactoglobulin antibodies detected by antigen binding or basophil degranulation, though the serum donors were not clinically allergic to milk. Similarly few normal, milk‐tolerant adults also had γE anti‐β‐lactoglobulin antibodies.Sera of nine children with milk‐induced gastroenteritis occurring 12–36 hr after exposure had no anti‐milk reagins, and only one had γE binding β‐lactoglobulin. This allergy may be mediated by heat‐stable IgG antibodies, because three sera conferred milk sensitivity on monkey skin for 4 hr and two others for 2 hr. The three sera had high titres of IgG agglutinins, one to β‐lactoglobulin, one to α‐lactalbumin and one to casein. All three fixed complement in the presence of milk, and one had precipitins. They did not passively sensitize human mast cells or monkey basophils for anaphylactic degranulation, but they prepared human lung for anaphylactic release of hist‐amine, though in small amounts compared to that released from lung prepared with reagins.The sera of two of three cases of cot death had IgG antibodies with similar properties.
Changes in nasal airways resistance on antigenic challenge in allergic rhinitis
Authors: TAYLOR GEOFFREY , SHIVALKAR P. R. 
Published: April 2006

SummaryThe nasal airways resistance changes occurring after challenge with graded doses of antigen have been measured in sixty‐five sensitive subjects. The degree of nasal sensitivity has been compared with skin sensitivity and no clear positive quantitative correlation was found. This lack of correlation is considered to indicate the importance of local IgE production in allergic rhinitis. Some subjects show evidence of local desensitization after several antigen challenges. Possible mechanisms are discussed.
Disodium cromoglycate: laboratory studies and clinical trial in allergic rhinitis
Authors: TAYLOR GEOFFREY , SHIVALKAR P. R. 
Published: April 2006

SummaryThe ability of disodium cromoglycate (DSCG) to block allergic responses in the nasal airways was investigated in two ways. The effect of DSCG on antigen‐induced airways resistance changes in sensitive subjects was investigated in the laboratory. DSCG in a dose of 10 mg applied to each nostril was shown to block the expected reaction in 71 % of subjects and a 1 mg dose in 47%. Protection was conferred against antigen challenge for a period of about 6 hr by the 10 mg dose. A clinical trial of DSCG (10 mg) in seasonal allergic rhinitis was carried out using a double‐blind cross‐over design. Analysis of the results showed significant DSCG protective effects against lower respiratory tract symptoms and a significant antihistamine sparing effect. Analysis of part of the trial period when antigen challenge was uniformly high showed significant DSCG protective effects against sneezing, nasal discharge and nasal obstruction. Nasal application of DSCG is considered to be a promising alternative therapeutic approach in allergic rhinitis.
The effect of disodium cromoglycate on pulmonary function in extrinsic bronchial asthma over 12 months
Authors: PATEL K.R. , KERR J. W. , WADE I. M. 
Published: April 2006

SummaryFourteen patients with extrinsic type bronchial asthma had pulmonary ventilation, lung volume and gas transfer measurements at rest and on exercise, carried out during a control period and again at 2 weeks and 12 months whilst on disodium cromoglycate. A significant improvement in forced expiratory volume, vital capacity and the ratio of residual volume to total lung capacity and in the exercise gas transfer, was observed at 12 months. The improved pulmonary function measurements agree with the clinical assessment of the improvement obtained in these patients whilst on disodium cromoglycate.
Hereditary angio‐oedema: a review with particular reference to pathogenesis and treatment
Authors: HADJIYANNAKI KATHERINE , LACHMANN P. J. 
Published: April 2006

SummaryHereditary angio‐oedema (HAE) is a rare disease associated with, and caused by, an inherited deficiency of the inhibitor of the activated first component of complement (C1‐inhibitor). The disease is readily diagnosed in the laboratory by measuring C1‐inhibitor levels.Very uncharacteristically for an inherited deficiency, genetic transmission is as an autosomal dominant. The patients are therefore heterozygotes and their deficiency is incomplete; many having up to 20% of the normal amount of inhibitor.It appears most probable that attacks are precipitated by exhaustion of local inhibitor as a result of its consumption by any of the plasma enzymes (plasmin. kininogenase, P.F./Dil as well as C1)with which the inhibitor can react. Thus, conditions associated with increased generation of any of these enzymes may predispose to relapse in HAE. In the absence of all inhibitor C1 activation proceeds autocatalytically and reacting with its substrates C4 and C2 produces a kinin‐like peptide from C2 which appears to be the main mediator of the disease.Attacks of the disease have been successfully treated by replacement of inhibitor using fresh frozen plasma as source. Effective prophylactic treatment has been obtained with ɛ‐aminocaproic acid and its derivatives. These drugs inhibit the activation of the plasma proteases with which the inhibitor reacts and will thus produce an ‘inhibitor sparing’ effect in addition to themselves inhibiting CT activation.
Exercise induced asthma: response to disodium cromoglycate in skin‐test positive and skin‐test negative subjects
Authors: SILVERMAN M. , TURNER‐WARWICK MARGARET 
Published: April 2006

SummaryThirty‐nine asthmatic subjects, aged 5‐50 and each with a history of exercise‐induced asthma, were classified according to their skin response to prick tests using nineteen common antigens. Ten had negative skin tests, four responded only to D. farinae and twenty‐five had multiple positive responses. Each patient then carried out three exercise tests on a treadmill, each test on a separate day. A control test was followed, in random order, by an exercise test after administration of disodium cromoglycate or of a placebo.In all groups, the mean fall in peak expiratory flow rate was less after disodium cromoglycate than after placebo, but the difference was significant only for the skin‐test positive groups. Similarly, positive skin‐test groups had a higher incidence of drug responders than did the negative skin‐test group.These observations are discussed.
Observations on the safety of disodium cromoglycate in long‐term use in children
Authors: SMITH JOHN MORRISON , PIZARRO YVONNE ARABELLA 
Published: April 2006

SummaryA group of eighty‐two children aged 6–18 years were investigated specifically for evidence of toxic or allergic effects from the use of disodium cromoglycate (‘Intal’) for 3 years or more by:

Radiological examination of the lungs.
Records of growth.
Haemoglobin estimations.
White blood counts.
Serum transaminase estimations.
Urine examinations.
Skin tests by the prick method.
Inhalation tests with disodium cromoglycate and lactose powder.

There was no evidence of drug‐induced toxic or allergic effects.Random urine samples from 186 patients on treatment with disodium cromoglycate were examined for the quantity of the drug excreted. These suggested that 13·4% were not taking the treatment as instructed and another 16% may not have been using the spinhaler effectively. The failure to take the treatment properly has been noted in other conditions requiring long continued treatment, such as tuberculosis, and must affect both the results and, to some extent, the possibility of toxic effects. It is concluded that disodium cromoglycate treatment is remarkably free of toxic or allergic effects but that an important problem in long‐term management is supervision of the patient's use of the treatment prescribed.
Asthma due to inhaled chemical agents—piperazine dihydrochloride
Authors: PEPYS J. , PICKERING C. A. C. , LOUDON H. W. G. 
Published: April 2006

SummaryAn occupational type exposure to the dust from a mixture of piperazine dihydrochloride and lactose provoked late (3–4hr) asthmatic reactions in two sensitized subjects. These reactions were completely inhibited by disodium cromoglycate.
Clinical significance of total IgE and of specific IgE to Dermatophagoides spp., grass pollen and other common allergens II. Relationship to clinical manifestations
Authors: STENIUS B. , WIDE L. , SEYMOUR W. M. 
Published: April 2006

SummaryThe relationships of total and specific IgE levels to the clinical manifestations and atopic status of ninety‐two subjects, suffering from asthma, rhinitis and infantile eczema in varying combinations, were examined. No significant correlations were found between specific IgE levels to Dermatophagoides spp. and grass pollen or between total IgE levels, and the age of the patient, nor the age of onset, duration, severity and frequency of symptoms. A highly significant correlation was found between total IgE levels and the numbers of skin test reactions to a battery of twenty routine tests and to the sum total of the graded sizes of the reactions in each subject.
Threadworms and IgE in allergic asthma
Authors: JARRETT ELLEN E. E. , KERR J. W. 
Published: April 2006

SummaryA high incidence of infection with the threadwormEnterobius vermicularishas been demonstrated in a group of children with allergic asthma, but also in a non‐allergic group. There was no evidence of infection with any other helminth parasites. Presence or absence of threadworm infection was not clearly correlated with differences in total serum IgE level in either allergic or non‐allergic children although levels of this immunoglobulin were raised in the former group. Some of the allergic children gave positive skin reactions following intradermal injection of an antigen extracted fromE. vermicularis.The suggestion is therefore put forward that hypersensitivity toE. vermicularisallergen absorbed from the bowel might contribute to the allergic symptoms. The results are also discussed in relation to recently discovered experimental evidence that helminth infection may non‐specifically potentiate unrelated IgE antibody responses.
Respiratory allergy to exotic wood dust
Authors: EATON K. K. 
Published: April 2006

SummaryThree cases are presented showing nasal and respiratory allergy to cocabolla (Dalbergia retusa) an exotic timber which is a member of the rosewood family, and also to other wood dusts. They gave positive immediate reactions on patch testing, which became negative after injections of aqueous extracts. There were suggestions in this limited study of clinical improvement.A possible relationship of this allergy to a quinone named dalbergiones present in cocabolla exists, but further work is necessary to confirm this.