Identification of functionally variant MDR1 alleles among European Americans and African Americans

MDR1 (P-glycoprotein) is an important factor in the disposition of many drugs, and the involved processes often exhibit considerable interindividual variability that may be genetically determined. Single-strand conformational polymorphism analysis and direct sequencing of exonic MDR1 deoxyribonucleic acid from 37 healthy European American and 23 healthy African American subjects identified 10 single nucleotide polymorphisms (SNPs), including 6 nonsynonymous variants, occurring in various allelic combinations. Population frequencies of the 15 identified alleles varied according to racial background. Two synonymous SNPs (C1236T in exon 12 and C3435T in exon 26) and a nonsynonymous SNP (G2677T, Ala893Ser) in exon 21 were found to be linked (MDR1*2 ) and occurred in 62% of European Americans and 13% of African Americans. In vitro expression of MDR1 encoding Ala893 (MDR1*1 ) or a site-directed Ser893 mutation (MDR1*2 ) indicated enhanced efflux of digoxin by cells expressing the MDR1-Ser893 variant. In vivo functional relevance of this SNP was assessed with the known P-glycoprotein drug substrate fexofenadine as a probe of the transporter's activity. In humans, MDR1*1 and MDR1*2 variants were associated with differences in fexofenadine levels, consistent with the in vitro data, with the area under the plasma level-time curve being almost 40% greater in the *1/*1 genotype compared with the *2/*2 and the *1/*2 heterozygotes having an intermediate value, suggesting enhanced in vivo P-glycoprotein activity among subjects with the MDR1*2 allele. Thus allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P-glycoprotein function.     

Is same-day discharge suitable following rigid esophagoscopy? Findings in a series of 655 cases

It has been suggested that more otolaryngologic procedures should be performed on an outpatient basis, and that rigid upper aerodigestive tract endoscopy might be a particularly suitable procedure in this regard. To determine if this is indeed the case, we retrospectively reviewed the records of 563 patients who had undergone 655 rigid esophagoscopies in our unit between Jan 1, 1991, and July 31, 1998. We ascertained the rate of complications (primarily esophageal perforation) following such procedures and, when they did occur, we determined the length of time between surgery and the onset of the complications' signs and symptoms. Our aims were to establish the minimum duration of postoperative observation that is required following esophagoscopy and to propose criteria for safe same-day discharge. We found that perforation rates were 4.5% following therapeutic procedures (dilation, biopsy, and foreign-body removal) and 1.2% following diagnostic procedures. In 40% of the patients who experienced perforations, no such signs or symptoms were noted within the first 8 hours following surgery. This finding has important implications for surgeons who wish to perform rigid esophagoscopy on an outpatient basis.     

Reading skills of otolaryngology outpatients: implications for information provision

The aim of this prospective observational study was to estimate the proportion of otolaryngology patients with poor reading skills, as a guide to information provision. The subjects were a consecutive series of 50 adult outpatients attending a general otolaryngology clinic at the Victoria Infirmary, Glasgow, and whose first language was English. Reading skills were estimated using the Rapid Estimate of Adult Literacy in Medicine. For comparison, the SMOG readability formula was used to estimate the reading skills required to understand the Department's 35 information leaflets, the standard elective admission notification letter and the surgical consent form. Fourteen (28 per cent) patients were found to have poor reading skills (8th grade or less). The surgical consent from required 11th grade reading ability, as did the standard admission letter, and the leaflets required 9th to 15th grade (graduate) reading ability (median 11th grade). Many patients could be expected to have difficulty understanding these written materials. Information must be written in plain English to be suitable for a wide range of patients, including those with poor reading skills.     

The role of fibreoptic laryngoscopy in infants with stridor

Stridor in infants may be potentially serious and would require further investigations in all cases. Laryngomalacia is the most common cause of congenital stridor. This is a self-limiting condition with a good prognosis but other causes of stridor should be excluded to enable the surgeon to plan further intervention if needed. Traditionally microlaryngoscopy and bronchoscopy under a general anaesthetic is performed to evaluate the airway. We have investigated the use of the flexible fibreoptic laryngoscope under local anaesthetics in infants with inspiratory stridor. The procedure was performed in the day surgery unit on a non-fasting, non-sedated child. A retrospective analysis of procedures performed between January 1998 and August 1999 was carried out. Of the 43 patients studied, laryngomalacia was diagnosed in 35, vocal cord palsies in six and two infants had a normal larynx. There were no complications during the procedure and only one child required further intervention. The results showed that the combination of fibreoptic laryngoscopy under local anaesthetic with follow-up is a safe, effective and cost effective method of assessing stridor in this group of patients.     

Aplastic anemia complicating systemic lupus erythematosus: successful management with cyclosporine

Anemia is common with connective tissue disorders, but pancytopenia is rare. We report a 22-year-old female who presented with menorrhagia, seizures, anemia, leukocytosis, thrombocytopenia, pericardial effusion, positive ANA, and evidence of vasculitis on CT head scan and was diagnosed with systemic lupus erythematosus (SLE). After 7 months of remission, she was readmitted with menorrhagia and pancytopenia. Investigations revealed aplastic anemia. She survived on transfusion support for 6 weeks, during which period she received methylprednisolone and cyclophosphamide pulses, and phenytoin was omitted but to no avail. Cyclosporine (300 mg/day) was started and the aplastic anemia responded. After 4 months of therapy, the cyclosporine was gradually tapered over the next 2 months. The patient has been on 10 mg/day of prednisolone for the last 6 months. Aplastic anemia is rare in SLE and the response to immunosuppressants is variable, but here is a success story.     

Laser division of congenital complete tracheal rings

Congenital complete tracheal rings are a rare and life threatening problem in young children and they are often challenging to manage. Whilst historically associated with high mortality rates increasing experience with this tracheal pathology has led to much improved survival rates and slide tracheoplasty has become the treatment of choice. We present 3 cases in which an open procedure was not deemed possible and they underwent laser division (CO2, KTP) of their complete rings. Two patients subsequently required stent insertion. All patients are alive and well at a mean follow up of 3 years and 5 months. Whilst laser division of complete tracheal rings has only been described in a small number of cases it may provide an alternative approach in patients who are not able to undergo an open procedure or in an emergency situation.     

How uncomfortable are the various positions recommended for the instillation of nose drops?

Nose drops are widely used in the topical treatment of nasal disorders. Their efficacy has previously been shown to depend on the position of the head adopted during instillation. All three of the commonly recommended head positions (head back, praying-to-Mecca, Mygind's) are uncomfortable, and this may affect patient compliance. As yet, no assessment has been made of the discomfort encountered by patients. Twenty adults from a general otolaryngology clinic were asked to adopt each of three positions and then rate the discomfort experienced on a 10 cm visual analogue scale. The results show that although Mygind's position is well tolerated, the praying-to-Mecca position was significantly more uncomfortable than any other. In the absence of any evidence that the praying-to-Mecca position is clinically more efficacious than Mygind's, it seems inappropriate to continue to advocate its use.