Development of a disease-specific health-related quality of life questionnaire for sleep apnea

The Calgary Sleep Apnea Quality of Life Index (SAQLI) was developed to record key elements of the disease that are important to patients. All items felt to influence the quality of life of these patients were identified. Final questionnaire items were selected by interviewing 113 patients with sleep apnea and 50 snorers who rated each item on whether it was a problem and the importance of it to their overall quality of life. Items for the final questionnaire were selected based on the rank order of the frequency ximportance product. The rank ordering was similar across strata of disease severity and between sexes. The Calgary SAQLI has 35 questions organized into four domains: daily functioning, social interactions, emotional functioning, and symptoms. A fifth domain, treatment-related symptoms, can be added for clinical intervention trials to record the possible negative impacts of treatment. The SAQLI has a high degree of internal consistency, face validity as judged by content experts and patients, and construct validity as shown by its positive correlations with the SF-36 and the improvement in scores in patients successfully completing a 4-wk trial of continuous positive airway pressure. It includes items shown to be important to patients with sleep apnea and is designed as a measure of outcome in clinical trials in sleep apnea. Flemons WW, Reimer MA. Development of a disease-specific health-related quality of life questionnaire for sleep apnea.     

Role of paired basic residues in the expression of active recombinant galactosyltransferases from the bacterial pathogen Neisseria meningitidis

The lgtB gene encoding a beta-1,4-galactosyltransferase gene and the lgtC gene encoding an alpha-1,4-galactosyltransferase from the bacterial pathogen Neisseria meningitidis were cloned into an expression vector and overexpressed in Escherichia coli. Both genes expressed very well, but problems with C-terminal proteolysis were encountered with both proteins. The lgtC protein was initially isolated from extracts of recombinant E.coli as a truncated species that retained enzymatic activity, and was subsequently shown by mass spectrometry to be 19 residues shorter than the expected protein. A specific set of engineered C-terminal deletions was constructed to investigate their effect on the expression of lgtC. As many as 28 residues could be deleted with little effect on activity, and with the concomitant improvement of the overall expression up to fivefold over the full length protein. The lgtB protein was also proteolysed in extracts of normal E.coli strains into enzymatically inactive fragments lacking 28 or 41 C-terminal residues. This degradation could be prevented by expression in an ompT protease deficient strain of E.coli. The full length lgtB protein was not stable in soluble protein extracts from all recombinant strains, however a stable enzyme preparation could be achieved with the membrane fraction from cells of the ompT deficient strain expressing lgtB. Specific deletions of lgtB were also constructed, and 15 residues could be removed without loss of enzyme activity and also with the concomitant improvement of the overall expression up to twofold over the full length protein. Longer deletions produced protein but activity could not be detected in these recombinant strains. Examination of the glycosyltransferase sequences from a wide range of bacteria showed their C-terminal segments of approximately 50 amino acids frequently contained paired basic residues. Engineering of these segments may therefore be required as a general practice to produce these enzymes for use in the large scale chemi-enzymatic synthesis of carbohydrate-based therapeutics.      

Comparative metabolism of bis(2-methoxyethyl)ether in isolated rat hepatocytes and in the intact rat: effects of ethanol on in vitro metabolism

The metabolism of the reproductive and developmental toxicant bis(2-methoxyethyl)ether (diglyme) was studied in isolated rat hepatocytes and in the intact rat. Male Sprague-Dawley rats (190-220 g) were used in both studies. Hepatocytes, isolated by a two-step in situ collagenase perfusion of the liver, were cultured as monolayers and incubated with [14C]diglyme at 1, 10, 30, and 50 microM for up to 48 h. For the in vivo study, rats were given single oral doses of [14C]diglyme at 5.1 mmol/kg body wt, and urine was collected for up to 96 h. Radioactive compounds in the culture medium or in the urine were separated by high performance liquid chromatography and quantified with an in-line radioactivity monitor. Metabolites were identified by comparison of their chromatographic retention times and their mass spectra with those of authentic compounds. The principal metabolite from hepatocytes and in the urine was (2-methoxyethoxy)acetic acid (MEAA). This metabolite accounted for approximately 36% of the radioactivity in the 48-h culture medium and about 67% of the administered dose in the 48-h urine. Other prominent metabolites common to both systems included 2-(2-methoxyethoxy)ethanol, methoxyacetic acid (MAA), 2-methoxyethanol, and diglycolic acid. The diglyme metabolite profiles from urine and from hepatocytes were qualitatively similar, demonstrating that, in the rat, hepatocytes serve as a good model system for predicting the urinary metabolites of diglyme. Moreover, MEAA was shown to be the metabolite best suited for use as a short-term biological marker of exposure to diglyme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of Frey's syndrome with botulinum A toxin

A 74-year-old woman suffered from severe gustatory sweating and flushing of the preauricular skin following parotidectomy (Frey's syndrome). She was treated with intracutaneous botulinum A toxin injections in the affected skin area. Minor's test was used to determine the extent of the affected area. Within one week, the symptoms disappeared. After three weeks, Minor's test was repeated and showed minimal residual hyperhidrosis. These small areas were treated again. No side effects were noted. At follow-up one year later, the patient was free of symptoms.     

The Index of Drug Involvement: a partial validation

Social workers often need a wider range of assessment scales that can be used in education, research, and practice. The Index of Drug Involvement (IDI) is a short-form assessment scale that may be of use to social work educators, researchers, and practitioners who work with clients with drug abuse or chemical dependency problems. This article describes the IDI; provides information about its administration, scoring, and interpretation; and describes the initial research conducted to validate the instrument. This article provides information about the reliability of the IDI; reports the standard error of measurement; and presents findings concerning the content, construct, and criterion validity of the instrument. Also presented is initial information about the development and use of a clinical cutting score that will help practitioners evaluate the clinical significance of a drug abuse problem and that can be a guide for establishing initial and final treatment goals.     

Optimal burr and adjunctive balloon sizing reduces the need for target artery revascularization after coronary mechanical rotational atherectomy

We analyzed the effect of differing burr and balloon sizes during mechanical rotational atherectomy on the need for target vessel revascularization at 6 months. The ideal burr/artery ratio and adjunctive balloon/artery ratio for optimizing acute luminal results and minimizing restenosis is unknown. Six-month clinical follow-up was obtained in 311 patients (339 lesions) treated with rotational atherectomy from August 1993 to September 1994, to determine whether procedural results or technique were related to the need for target vessel revascularization. Target vessel revascularization, defined as repeat percutaneous intervention or bypass surgery within 6 months after rotational atherectomy, occurred in 19% of patients. Larger burr/artery ratios, defined as the final burr size divided by the reference artery size, were correlated with decreased postatherectomy diameter stenosis (p <0.009) and decreased final diameter stenosis (p <0.03). However, there was no statistical association between postatherectomy or final diameter stenosis with need for revascularization (p = not significant [NS]). The need for revascularization was lowest for burr/artery ratio between 0.6 to 0.85 (15%) versus burr/artery <0.6 or >0.85 (25%) (p <0.04). Postatherectomy, smaller balloon/artery ratios, defined as the final balloon size divided by the reference artery size, were correlated with lower repeat revascularization rates. Balloon/artery ratios <0.95 (target vessel revascularization = 11% vs 25% in balloon/artery >0.95) were associated with the best luminal results and the least risk for clinical restenosis (p <0.006). For rotational atherectomy, despite improvement in acute luminal results with increased burr/artery ratio, the use of a moderate burr/artery ratio correlated with the lowest revascularization rates. There was no correlation between postatherectomy or final diameter stenosis and need for repeat interventions. However, the use of large balloon/artery ratios after rotablator was associated with higher target vessel revascularization rates.     

Sources of variability in data from a positive selection lacZ transgenic mouse mutation assay: an interlaboratory study

Experimental features of a positive selection transgenic mouse mutation assay based on a lambda lacZ transgene are considered in detail, with emphasis on results using germ cells as the target tissue. Sources of variability in the experimental protocol that can affect the statistical nature of the observations are examined, with the goal of identifying sources of excess variation in the observed mutant frequencies. The sources include plate-to-plate (within packages), package-to-package (within animals), and animal-to-animal variability. Data from five laboratories are evaluated in detail. Results suggest only scattered patterns of excess variability below the animal-to-animal level, but, generally, significant excess variability at the animal-to-animal level. Using source of variability analyses to guide the choice of statistical methods, control-vs-treatment comparisons are performed for assessing the male germ cell mutagenicity of ethylnitrosourea (ENU), isopropyl methanesulfonate (iPMS), and methyl methanesulfonate (MMS). Results on male germ cell mutagenesis of ethyl methanesulfonate (EMS) and methylnitrosourea (MNU) are also reported.     

A precondition prover for analogy

We describe here a prover PC (precondition) that normally acts as an ordinary theorem prover, but which returns a 'precondition' when it is unable to prove the given formula. If F is the formula attempted to be proved and PC returns the precondition Q, then (Q-->F) is a theorem (that PC can prove). This prover, PC, uses a proof-plan. In its simplest mode, when there is no proof-plan, it acts like ordinary abduction. We show here how this method can be used to derive certain proofs by analogy. To do this, it uses a proof-plan from a given guiding proof to help construct the proof of a similar theorem, by 'debugging' (automatically) that proof-plan. We show here the analogy proofs of a few simple example theorems and one hard pair, Ex4 and Ex4L. The given proof-plan for Ex4 is used by the system to prove automatically Ex4; and that same proof-plan is then used to prove Ex4L, during which the proof-plan is 'debugged' (automatically). These two examples are similar to two other, more difficult, theorems from the theory of resolution, namely GCR (the ground completeness of resolution) and GCLR (the ground completeness of lock resolution). GCR and GCLR have also been handled, in essence, by this system but not completed in all their details.