Awake fibrecapnic intubation.
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Biomedical subjects
Publications and source records attributed to N West.
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Previous research, mainly on enamel, supports a protective role for salivary pellicle against erosion. Pretreatments have tended to be lengthy (24 h or more) and of questionable relevance to the regular intake of acidic food and drink by many individuals. The aim of this study in vitro was to determine the protective effect of salivary pellicle formed on enamel and dentine over time periods up to 4 h. Flattened, polished human enamel and dentine specimens were pretreated with unstimulated human saliva from a single donor for 2 min, 30 min (enamel only), 1, 2, or 4 h. Controls were exposed to water for the same times. Specimens were then exposed to 0.3% citric acid, pH 3.2 for 10 min with stirring. This cycle was carried out 12 times. Tissue loss was measured by profilometry after 3, 6, 9 and 12 cycles. For enamel, statistically significant protection was found at >or=1 h. For dentine, significant protection was achieved at 2 min. Salivary pellicle offered proportionately greater protection to enamel than dentine. Cautiously extrapolating these in vitro data suggests that pellicle should offer erosion protection to individuals who imbibe acidic drinks at frequencies of 1 h or less.
BACKGROUND AND AIMS: The majority of patients with chronic pancreatitis are alcoholics. Our goal was to develop a mouse model of alcohol dependent chronic pancreatitis. METHODS: Mice were fed either the non-alcohol containing Lieber-DeCarli diet or the Lieber-DeCarli diet containing 24% of calories as ethanol. After eight weeks and while on their respective diets, mice were subjected to repeated episodes of acute pancreatitis elicited by administration of caerulein. They were sacrificed 1, 3, and 5 weeks after the last dose of caerulein. Pancreatic morphology and collagen deposition were evaluated in samples stained with haematoxylin-eosin and Sirius red. Collagen content was quantitated by measuring OH-proline. Gene expression was determined by quantitative polymerase chain reaction. RESULTS: Both groups of mice gained weight at the same rate. Those receiving the alcohol containing diet had serum alcohol levels of approximately 100 mM. No histological or gene expression differences were found in mice that were not subjected to acute pancreatitis, regardless of their diet. Necrosis, Sirius red staining, OH-proline content, and expression of alpha-1 collagen I, alpha-smooth muscle actin, transforming growth factor beta1, and tissue inhibitor of metalloproteinase 1 were all increased in mice fed the alcohol containing diet and given caerulein compared with those fed the control diet and given caerulein. Matrix metalloproteinase 9 expression was transiently decreased in mice fed ethanol and given caerulein compared with the group given caerulein but not fed ethanol. CONCLUSION: We have developed a mouse model of alcohol dependent chronic pancreatic fibrosis. This mouse model may be useful in studies examining the effects of genetic manipulation on chronic pancreatitis.
BACKGROUND: Limited access to exercise testing facilities means that the diagnosis of exercise induced asthma (EIA) is mainly based on self-reported respiratory symptoms. This is open to error since the correlation between exercise related symptoms and subsequent exercise testing has been shown to be poor. AIM: To study the accuracy of clinically diagnosed EIA among Vancouver schoolchildren. METHODS: Fifty two children referred for investigation of poorly controlled EIA were studied. Following a careful history and physical examination, children performed pulmonary function tests before, then 5 and 15 minutes after a standardised treadmill exercise test. Based on overall assessment, a diagnostic explanation for each child's respiratory complaints was provided as far as possible. RESULTS: Only eight children (15.4%) fulfilled diagnostic criteria for EIA (fall in FEV(1) > or =10%). Of the remainder: 12 (23.1%) were unfit, 14 (26.9%) had vocal cord dysfunction/sigh dyspnoea, 7 (13.5%) had a habit cough, and 11 (21.1%) had no abnormalities on clinical or laboratory testing, so were given no diagnosis. Initial reported symptoms of wheeze or cough often changed significantly following a careful history, particularly among the eight elite athletes. The final complaint was sometimes not respiratory, and, in a few cases, was not even associated with exercise. CONCLUSIONS: The clinical diagnosis of EIA is inaccurate among Vancouver schoolchildren, principally due to the unreliability of their initial exercise related complaints. Symptom exaggeration, familiarity with medical jargon, and psychogenic complaints are all common. A careful history is essential in this population before basing any diagnosis on self-reported respiratory symptoms.
BACKGROUND: The authors investigated the relationship between therapeutic blood transfusion before renal transplantation and rejection rates in cyclosporine- and tacrolimus-treated patients. METHODS: In one center, 265 consecutive recipients were studied. Protocol induction was with azathioprine, prednisolone, and cyclosporine or tacrolimus; 37% had biopsy-proven acute rejection in the first 6 months and 46% had received zero to two units of blood before transplantation. RESULTS: Lower risk of rejection was associated with tacrolimus induction (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.29-0.95; P=0.049), prior transfusion of three or more units of blood (OR, 0.54; 95% CI, 0.33-0.90; P=0.024), and older age at transplantation (mean, 44.23 +/- 12.56 [+/- SD] years vs. 38.96 +/- 12.37 years; P=0.001). Multiple logistic regression modeling showed the effect of three or more prior transfusions on acute rejection was as follows: OR, 0.49; 95% CI, 0.29 to 0.83; P=0.008. CONCLUSIONS: Induction immunosuppression should take account of the higher risk of rejection in patients coming to transplantation who have previously received zero to two units of blood.
Dose incurred with fluoroscopic procedures accounts for a significant proportion of medically induced diagnostic exposure. Children are particularly vulnerable and it is therefore important to minimize exposure where practicable. A recent theoretical study has highlighted the potential for X-ray equipment to produce significant dose savings during paediatric fluoroscopy without incurring loss of diagnostic image quality. This is achieved by hardening the beam with additional copper (Cu) filtration (approximately 0.2 mm Cu) and biasing exposure factors towards low tube potential, high tube current output. In practice, this method will have limited applicability because the high powered and programmable generator characteristics required are not commonly available in installations used for paediatric imaging. However, we describe a simple experiment in which our clinical equipment was modified to approximate desired low dose performance by altering the filtration and automatic exposure control characteristics of ordinary clinical equipment in the Sheffield Children's Hospital. This enabled us to obtain significant savings in dose. We performed a comparative study (normal dose vs low dose) using water phantoms to simulate patient attenuation in the age range 0-15 years. The Leeds N2 contrast sensitivity phantom was used to provide a measure of image quality. Dosimetric measurements recorded up to 40% reduction in dose rate with only marginal loss of image quality when 0.1-0.2 mm Cu filtration was used with the modified settings. This is a strong indication that significant dose reduction is achievable on routine clinical equipment without compromising image quality. Such simple and cost effective methods of dose reduction should be considered for wider implementation.
-Vein graft intimal hyperplasia, due to smooth muscle cell (SMC) proliferation, remains a limiting factor in long-term vein graft patency. Increased superoxide production regulates SMC mitogenesis and contributes to reduced NO bioactivity in systemic models of vascular disease. We compared superoxide production in experimental venous bypass grafts with ungrafted veins and determined its enzymatic sources and cellular localization. Vascular superoxide production was measured in vein grafts and control jugular veins obtained from normocholesterolemic rabbits undergoing jugular vein-carotid artery interposition bypass grafting. Surgical isolation of the contralateral jugular vein, without bypass grafting, provided an additional control for the effects of surgical manipulation. Superoxide production was increased 3-fold in vein grafts compared with control veins. Systematic stimulation and inhibition of specific oxidases revealed that the major source of increased vein graft superoxide production was a membrane-associated NAD(P)H-dependent oxidase. Western blotting of vascular homogenates demonstrated corresponding increases in NAD(P)H oxidase p22phox (membrane-associated) and p67phox (cytosolic) subunits in vein grafts compared with jugular veins. There was marked intimal hyperplasia in vein grafts, and immunohistochemical staining of vessel cryosections revealed increased p22phox-expressing cells in vein grafts that were predominantly intimal SMCs. Superoxide generation is increased in experimental vein grafts compared with ungrafted veins. The principal source of increased superoxide generation in vein grafts is an NAD(P)H oxidase, expressed by intimal SMCs. These findings suggest a role for NAD(P)H oxidase-mediated superoxide production in the proliferative response to vascular injury in vein grafts.
(6R)-5,6,7,8-Tetrahydro-biopterin (H(4)B) is essential for the catalytic activity of all NO synthases. The hyperphenylalaninemic mouse mutant (hph-1) displays 90% deficiency of the GTP cyclohydrolase I, the rate-limiting enzyme in H(4)B synthesis. A relative shortage of H(4)B may shift the balance between endothelial NO synthase (eNOS)-catalyzed generation of NO and reactive oxygen species. Therefore, the hph-1 mouse represents a unique model to assess the effect of chronic H(4)B deficiency on endothelial function. Aortas from 8-week-old hph-1 and wild-type mice (C57BLxCBA) were compared. H(4)B levels were determined by high-performance liquid chromatography and NO synthase activity by [(3)H]citrulline assay in homogenized tissue. Superoxide production by the chemiluminescence method was measured. Isometric tension was continuously recorded. The intracellular levels of H(4)B as well as constitutive NO synthase activity were significantly lower in hph-1 compared with wild-type mice. Systolic blood pressure was increased in hph-1 mice. However, endothelium-dependent relaxations to acetylcholine were present in both groups and abolished by inhibition of NO synthase with N(G)-nitro-L-arginine methyl ester as well. Only in hph-1 mice were the relaxations inhibited by catalase and enhanced by superoxide dismutase. After incubation with exogenous H(4)B, the differences between the 2 groups disappeared. Our findings demonstrate that H(4)B deficiency leads to eNOS dysfunction with the formation of reactive oxygen species, which become mediators of endothelium-dependent relaxations. A decreased availability of H(4)B may favor an impaired activity of eNOS and thus contribute to the development of vascular diseases.
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OBJECTIVE: To validate a neuropsychological algorithm for dementia diagnosis. METHODS: We developed a neuropsychological algorithm in a sample of 1,023 elderly residents of Cache County, UT. We compared algorithmic and clinical dementia diagnoses both based on DSM-III-R criteria. The algorithm diagnosed dementia when there was impairment in memory and at least one other cognitive domain. We also tested a variant of the algorithm that incorporated functional measures that were based on structured informant reports. RESULTS: Of 1,023 participants, 87% could be classified by the basic algorithm, 94% when functional measures were considered. There was good concordance between basic psychometric and clinical diagnoses (79% agreement, kappa = 0.57). This improved after incorporating functional measures (90% agreement, kappa = 0.76). CONCLUSIONS: Neuropsychological algorithms may reasonably classify individuals on dementia status across a range of severity levels and ages and may provide a useful adjunct to clinical diagnoses in population studies.
Epidermolysis bullosa simplex (EBS) is a blistering skin disease caused in most cases by mis-sense mutations in genes encoding the basal epidermal keratin (K) 5 and K14. The inheritance is usually autosomal dominant and the mutant keratin proteins appear to exert a dominant negative effect on the keratin intermediate filament cytoskeleton in basal keratinocytes. We report a child with a homozygous K14 mutation resulting in the complete absence of K14 protein in the epidermis; remarkably, he only had mild to moderate disease. Electron microscopy of a skin biopsy showed a marked reduction in numbers of keratin intermediate filaments in the basal keratinocytes. Immunofluorescence microscopy using monoclonal antibody LL001 against K14 showed no staining, suggesting a functional knockout of K14. Sequence analysis of genomic DNA revealed a homozygous mutation in codon 31 of K14 that resulted in a premature stop codon further downstream in exon 1. The child's mother, who is unaffected by the disease, is heterozygous for the mutation. The consanguineous father was unaffected and unavailable for testing. The resulting mRNA is predicted to encode a protein of 116 amino acids, of which the first 30 are identical to the normal K14 sequence, and the remaining 86 residues are mis-sense sequence. Four previously reported cases of autosomal recessive EBS with functional knockout of K14 were severely affected by blistering, in contrast to our patient in whom the predicted protein has only the first 30 amino acids of K14 and is therefore the closest to a true knockout of K14 protein yet identified.
OBJECTIVE: To examine the concurrent validity of a newly developed telephone adaptation of the Modified Mini-Mental State Exam. BACKGROUND: Longitudinal studies of cognition may be advantaged by availability of assessment instruments that can be used over the telephone, as well as in person. METHOD: Subjects were 263 noninstitutionalized elderly residents of a rural community in southern Idaho, aged 65 to 93, who had little or no cognitive difficulty. At an average interval of four weeks, we administered the Modified Mini-Mental State Exam (3MS) and the newly adapted Telephone Modified Mini-Mental State Exam (T3MS). Order of administration was randomly assigned. RESULTS: Agreement between scores on the two instruments was good (r = 0.82, p < 0.001). When we applied various cutoff scores to the instruments, thereby generating assignments of individuals to "screen positive" and "screen negative" groups, the percent agreement in screening results ranged from 80% to 96% as we reduced the cutoff scores from 90 to 74 (100 points possible). CONCLUSIONS: At least among subjects without major cognitive syndromes, the Telephone Modified Mini-Mental State Exam provides a reasonable substitute for the more costly in-person 3MS. The telephone instrument should now be tested over a broader range of cognitive abilities in order to assess its validity in more impaired subjects, e.g., by studying an institutionalized sample.
Dentine exhibiting symptoms of dentine hypersensitivity has tubules open at the dentine surface and patent to the pulp. The mechanisms whereby dentinal tubules are exposed is ill understood but probably involves a variety of abrasive and/or erosive agents. This study in vitro examined the quantitative and qualitative effects of toothpastes, their solid and liquid phases and detergents on dentine and acrylic. Abrasion of dentine and acrylic were measured by surfometry. Morphological changes to dentine were assessed by scanning electron microscopy. Abrasion of dentine and acrylic by toothpastes increased with increasing brushstrokes with marked differences in the extent of abrasion between different pastes. Brushing dentine with water or detergents produced progressive abrasion but which appeared to plateau around 2 microm loss. Water and detergents produced minimal effects on acrylic. At 5000 strokes dentine abrasion by solid phases was less than the parent toothpastes but the ranking order of abrasivity was the same as the parent toothpastes. Loss of dentine produced by liquid phases was minimal and in the order of 1-2 microm. Observationally, all toothpastes removed at least the dentine smear layer to expose many tubules; with one desensitizing product leaving a particulate deposit occluding most tubules. The solid phases of the toothpaste produced identical morphological changes to the parent paste. The liquid phases and detergents all exposed dentinal tubules by 5000 strokes. Water had little or no effect on the dentine smear layer. It is concluded that toothpastes, solid phase, liquid phase and detergents have the potential to abrade or erode dentine to a variable degree and result in tubule exposure. The effects of the liquid phases and detergents appear limited to the removal of the smear layer. Such detrimental effects seen in vitro could have relevance to the aetiology and management of dentine hypersensitivity. Toothpaste formulations which despite exposing tubules have ingredients capable of occluding tubules may be an area of development for such products.
Home-use studies on dentine hypersensitivity have most commonly involved toothpastes and rarely have mouthrinses been employed. Potassium and/or fluoride toothpastes have been shown effective in the treatment of dentine hypersensitivity. The aim of this study was to evaluate the effectiveness of a total formulation, containing potassium citrate, sodium fluoride, cetylpyridinium chloride mouthrinse compared to the base rinse minus actives in the reduction of dentine hypersensitivity. The study was a randomised placebo controlled, double blind parallel design. At a screening visit, 90 adult subjects were recruited who were suffering from dentine hypersensitivity from at least 1 tooth responding to tactile stimulation (45gm pressure) and had at least 2 teeth responding to evaporative stimulation (air blast). During a washout period of 28 days and throughout the 56-day study period, subjects used a soft filament toothbrush and standard fluoride toothpaste. At baseline (day 1), threshold sensitivities to incremental tactile (10 g to 70 g) and evaporative stimuli were determined. Gingival health was assessed by recording bleeding on probing at 25 g pressure at mesiobuccal and lingual sites. Plaque scores from buccal and lingual surfaces of disclosed teeth were also measured. Subjects then used the prescribed rinse, 10 ml for at least 30 s after brushing 2x per day returning on days 28 and 56 for rescoring of sensitivity, gingivitis and plaque. Data from 88 subjects were used with the intent to treat analyses and 83 in the completely evaluable analyses. Groups were well balanced for demographic data and product returns suggested good compliance. Both groups showed highly significant improvements in tooth sensitivity. The pattern was for greater improvement in the test compared to the control group (statistically significant for the plaque score), whereas bleeding scores, already low, showed no change in either group. By definition, the placebo rinse could not have exerted any therapeutic action; the study therefore provides clear direct evidence as to the magnitude (30%-40%) of the little studied, but assumed, placebo response in dentine hypersensitivity trials.
The expectation that cholecystectomy is effective treatment for symptomatic gallstones is not always achieved in surgical practice. The impact of cholecystectomy on the relief of gastrointestinal symptoms was evaluated in 92 patients followed up after surgery for a mean of 31.1 months (range 12-83 months). Abdominal pain continued to be present, or arose de novo, in 28 (30.4%) patients. Pain-free outcome after cholecystectomy was associated with a preoperative clinical diagnosis of biliary colic, fatty food intolerance, and a thick-walled gallbladder on ultrasound (P = 0.02). Logistic regression associated a thick-walled gallbladder, elevated gamma-glutamyl transpetidase, body mass index < 26, fat intolerance, and normal bowel habit with good postoperative results (P = 0.001). Application of each of these five factors to a clinical index failed to predict long-term pain-free outcome after cholecystectomy. Abdominal bloating (P = 0.03), dyspepsia (P < 0.001), heartburn (P < 0.007), fat intolerance (P < 0.001), nausea (P = 0.001) and vomiting (P < 0.001) were significantly improved after cholecystectomy, but diarrhoea, constipation and excessive flatus were not. Outcome benefit ratios confirmed that vomiting (0.96), nausea (0.87), dyspepsia (0.67), fat intolerance (0.57) and heartburn (0.51) were relieved by surgery. Cholecystectomy improved symptoms compared with a matched control group, suggesting that surgery remains the gold standard treatment of symptomatic gallstones.
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The predictive performance of estimating creatinine clearance (CrCl) with pediatric clearance models was evaluated. Thirty-two pediatric patients with stable renal function between the ages of 1 and 14 years about to undergo bone marrow transplantation (BMT) who had 12-24 h urine collections for measurement of CrCl were studied. The measured CrCl was compared to CrCls calculated from seven models used to estimate CrCl in the pediatric population. The models used were Traub and Johnson, Schwartz et al, Counahan et al, modified Counahan et al, Ghazali and Barratt, Shull et al and Dechaux et al. Coefficients of determination (r2) between measured and estimated CrCls from models 1 to 7 were 0.47, 0.47, 0.47, 0.49, 0.47, 0.52, 0.47. The mean absolute percent errors for the models were 23.2-45.2%. In the majority of children, models overestimated CrCl. The tested models did not accurately predict CrCl and did not provide a reliable alternative to measured CrCl.