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PubMed1988

Cholecystectomy and adenomatous polyps of the colon in women.

The relationship between prior cholecystectomy and colon cancer in women has been a subject of recent research interest. No study has yet reported on cholecystectomy and adenomatous polyps, a precursor lesion for most colon cancers. This pilot case-control study interviewed 245 women who had undergone colonoscopy between 1983 and 1985 at Columbia-Presbyterian Medical Center with a structured telephone-administered questionnaire. Fifty-six were colon cancer cases, 105 were adenomatous polyp (AP) cases, and 84 were controls (without colonic neoplasia). Adjusted for age and educational attainment, the odds ratio for prior cholecystectomy among colon cancer cases compared to controls was 1.79 (95% confidence limits, 0.59 to 5.44) and 2.26 for right-sided colon cancer cases (95% confidence limits, 0.61 to 8.42). Despite a lack of statistical power, these estimates are consistent with earlier reports. The odds ratio for adenomatous polyp cases was 1.02 (95% confidence limits, 0.40 to 2.64), suggesting no association between prior cholecystectomy and adenomatous polyps. These preliminary findings are currently being explored in a large-scale case-control study.

Aged↗
PubMed1987

Non-ocular cancer in retinoblastoma survivors.

The risk of non-ocular cancer has been investigated in 150 surviving Danish patients with retinoblastoma diagnosed in the period 1943-1984. None of the patients had been treated with chemotherapeutic drugs. The overall relative risk of non-ocular cancer was 4.2 (95% confidence limits, 1.1-11.5). In the subgroups of hereditary retinoblastoma, the relative risk was 15.4 (95% confidence limits, 2.6-50.8), and in the subgroups of non-hereditary retinoblastoma the relative risk was 1.7 (95% confidence limits (0.1-8.5). The risk of cancer among 267 parents of retinoblastoma children was not different from that of the general population.

Eye Neoplasms↗
PubMed1987

Case-control study of occupation and cancer of the prostate in New Zealand.

A New Zealand Cancer Registry based case-control study involved 617 male patients with prostate cancer registered during 1979 and aged 20 years or more at the time of registration. Controls were also males chosen from the Cancer Registry with two controls per case, matched on age and year of registration. There was an elevated risk in the upper social class groupings. The data did not support the findings, from other countries, of elevated risks in agricultural workers (odds ratio = 1.08, 90% confidence limits 0.86-1.36). The only occupational groups showing elevated risks were sales and service workers (odds ratio = 1.29, 90% confidence limits 0.99-1.69) and teachers (odds ratio = 2.44, 90% confidence limits 1.05-5.70). The New Zealand data do not in general suggest that occupational factors--or lifestyle factors associated with occupation--are of major direct importance in the aetiology of prostate cancer.

Humans↗
PubMed1997

Repair of complete common atrioventricular canal defects in patients younger than four months of age.

BACKGROUND: The purpose of this study was to evaluate the impact of age at repair and atrioventricular (AV) valve anatomy on preoperative and postoperative AV valve incompetence (AVVR) was done to test the hypothesis that early repair (less than 4 months of life) can be safely accomplished and not only control heart failure but also improve surgical results on AV valve reconstruction. METHODS AND RESULTS: One hundred patients, median age 6.1 months, underwent repair of the complete common AV canal defect (CAVC) between 1981 and 1996. Surgery was performed in 37 patients (37%) less than 4 months of age (Group 1) and in 63 patients (63%) more than 4 months of age (Group 2). Surgical correction included double patch septal reconstruction in all. Trifoliate reconstruction of the left AV valve was selected in 93 patients (93%). Parametric time-related predicted survival was 92.9% at 14 years in Group 1 (70% confidence limits, 87.6% to 96.1%) and 75.9% at 15.4 years in Group 2 (70% confidence limits, 70.08% to 81.02%) (P=.038). Multivariate analysis in hazard function domain shows early repair as a negative risk factor for death (P=.038). Ordinal logistic regression equation indicates a higher probability of preoperative AVVR with older age at operation (P=.019). Regression analysis demonstrates good correlation between annular size and age at repair (r=.87, P < .01) and between annular size and AVVR (r=0.68, P < .01). Parametric time-related predicted freedom from reoperation was 82.7% at 15.4 years (70% confidence limits, 76.9% to 88.5%). Multivariate analysis in hazard function domain demonstrated Down's syndrome as a negative risk factor for reoperation (P=.05), whereas annular dilation increased the risk of this event (P=.027). CONCLUSIONS: Early correction of CAVCs is safe and beneficial not only in controlling chronic heart failure, but also in preventing annular dilation secondary to large QP/QS, as a potential mechanism of preoperative AVVR. Annular dilation is an incremental risk factor for reoperation. Early correction according to the double patch technique and trifoliate approach to the left AV valve reconstruction allows respect of valvar and subvalvar apparatus architecture, with a low incidence of postoperative AVVR, excellent survival rate, and low reoperative rate for residual AVVR.

Age Factors↗
PubMed1989

Effect of indomethacin on adenosine-induced bronchoconstriction.

The exact mechanism of adenosine-induced bronchoconstriction in patients with asthma is unknown. Adenosine contraction of guinea pig trachea was antagonized by inhibitors of cyclooxygenase. The aim of this study was to investigate the effect of indomethacin (100 mg/day) on adenosine-induced bronchoconstriction in 14 asymptomatic patients with asthma. Airway response was evaluated as FEV1, and adenosine was administered as an aerosol diluted in 0.9% saline to produce a concentration range of 0.125 to 4 mg/ml. The dose of adenosine producing a 20% change in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curve; the results of PD20 were converted to log values for statistical analysis (Student's paired t test). The study was performed on 3 separate days. On the first day, the adenosine challenge was performed, and on subsequent days patients were pretreated with either placebo or indomethacin in a randomized, double-blind manner. Inhaled adenosine caused bronchoconstriction with a geometric mean PD20 of 0.71 mg (95% confidence limits, 0.44 to 1.16). After placebo, a geometric mean PD20 of 0.91 mg (95% confidence limits, 0.53 to 1.58) was obtained. Indomethacin pretreatment decreased adenosine hyperresponsiveness and shifted the dose-response curves of adenosine challenge to the right with a geometric mean PD20 of 1.28 mg (95% confidence limits, 0.64 to 2.56). The effect of indomethacin on adenosine bronchoconstriction (p less than 0.01 versus baseline; p less than 0.05 versus placebo) suggests an indirect mechanism of adenosine on inducing release of arachidonic acid derivatives. Inflammatory mediators inhibited by indomethacin may be involved in adenosine bronchoconstriction, even if this mechanism is not relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed2006

Inherent variability of CT lung nodule measurements in vivo using semiautomated volumetric measurements.

OBJECTIVE: The objective of our study was to evaluate repeatability and reproducibility of lung nodule volume measurements using volumetric nodule-sizing software. MATERIALS AND METHODS: Fifty nodules, less than 20 mm in diameter, in 29 patients were scanned with 1.25-mm collimation using MDCT (time 1 = T1). During the same session, two additional scans, using identical technique, were obtained through each nodule (T2, T3). Three observers working independently then obtained volumetric measurements using a semiautomated volumetric nodule-sizing software package. Qualitative nodule characterization was also performed. The Bland-Altman method for assessing measurement agreement was used to calculate the 95% limits for agreement for nodule volumes at T1, T2, and T3. RESULTS: Automated nodule segmentation was successful in 438 (97%) of 450 measurements. Forty-three nodules were available for final evaluation. Twenty-six nodules had well-defined edges, and 17 had irregular or spiculated margins. Seventeen were freestanding, 16 were juxtapleural, and 10 were juxtavascular in location. Average nodule volume was 345.5 mm(3) (range, 49.3-1,434 mm(3)). The mean interobserver variability (repeatability) was 0.018% (SD = 0.73%), and the SD of the mean for the three contemporaneous scans (reproducibility) was 13.1% (confidence limits, +/- 25.6%). SD and confidence limits narrowed as volumes increased. CONCLUSION: Volumetric measurements show minimal interobserver variability (0.018%) but an interscan SEM of 13.1% (confidence limits, +/- 25.6%). Repeatability and reproducibility of volumetric measurements are better than those of linear measurements reported in the literature.

Adult↗
PubMed1996

Congenital adrenal hyperplasia: neonatal mass screening compared with clinical diagnosis only in the Emilia-Romagna region of Italy, 1980-1995.

OBJECTIVE: Comparative study of the incidence of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (21ase-def CAH) and clinical findings of affected infants diagnosed via newborn screening versus case survey only in the Emilia-Romagna region of Italy. METHODS: Neonatal mass screening (from March 1980 to September 1983-Period A, and from March 1991 to August 1995-Period C) and case survey study (from 1980 to June 1995; case survey alone from October 1983 to February 1991--Period B) were performed by the Regional Referral Center for Neonatal Screening for Endocrine-Metabolic Disease with a laboratory (Central Laboratory, S. Orsola Hospital, Bologna) and clinical (First Pediatric Clinic, University of Bologna, S. Orsola Hospital, Bologna) component. A population-based sample of 420 960 newborns consecutively born in the Emilia-Romagna region from March 1980 to August 1995 were studied. Spot 17-OH-progesterone (nmol/L blood) was tested by the radioimmunoassay method after sample extraction during Period A and by fluoroimmunometric time resolved method without sample extraction during Period C. Serum 17-OH-progesterone (ng/dL or nmol/L) was tested by the radioimmunoassay method (Diagnostic Product Corporation Kit, Los Angeles, CA). The case survey was performed by means of a questionnaire sent to all regional centers dealing with pediatrics, neonatology, endocrinology, and pediatric surgery. RESULTS: Thirteen classic 21ase-def CAH were diagnosed by means of neonatal screening (combined A and C periods). One true and one questionable false-negative cases were identified. The incidence of classical 21-hydroxylase deficiency for the white population was 1:15 518 (95% confidence limits 1:9249-1:28 400) by neonatal screening plus case survey, 1:18 105 (95% confidence limits 1:10 365-1:35 041) by neonatal screening alone and 1:25 462 (95% confidence limits 1:12 925-1:59 043) by case survey alone. The sensitivity and specificity of screening for classic CAH were 83% and 99.8% for Period A and 90% and 99.2% for Period C, respectively. The percentage of salt-wasting forms and the male/female ratio were higher during the neonatal screening period than during the case survey only. Sixty-one percent of classic CAH patients benefited from a prompt diagnosis. Nonclassical 21ase-def CAH cases detected via screening and case survey were also reported. CONCLUSIONS: Even in a region with adequate neonatal services, clinical diagnosis alone of classic CAH might be delayed or misinterpreted and salt-wasting crises could cause neonatal deaths. CAH screening is thus an effective tool for diagnosing affected male infants without a family history of CAH and for preventing salt loss. However, to achieve maximal benefit from screening, quick procedures are necessary for notification of positive results and beginning prompt treatment. The possibility of false-negative cases indicates that clinical observation should never be abandoned, even with ongoing screening programs.

17-alpha-Hydroxyprogesterone↗
PubMed2004

Atrial septal defect in adults > or =40 years old: negative impact of low arterial oxygen saturation.

BACKGROUND: Although good prognosis and clinical long-term outcome have been commonly reported in minimally symptomatic adult patients with ASD, this information has been based on studies with a relatively small number of adult patients. We studied unoperated patients aged over 40 years to define the patterns of presentation, anatomical characteristics, outcome and predictive factors for free-event survival of major cardiovascular and pulmonary events. METHODS AND RESULTS: Two-hundred survivors of atrial septal defect aged over 40-yr attended from 1985 to 1998 were reviewed and followed-up from 1.6 to 22 years. Patients were classified in three groups according to age at entry: Group 1, between 40 and 49; Group 2; 50 and 59; and Group 3, > or =60 years old. The mean age at presentation was 48.8+/-9.2 years, and the most common clinical presentations were arrhythmia and dyspnea (51.4%). There were 37 (18.5%) events: 7 heart failure-related, 5 sudden death, 13 severe pulmonary infections, 5 embolisms, and 4 strokes. According to Cox's regression analysis, predictors of primary end point included age group at presentation (hazard ratio 1.71, 95% confidence limits 1.16 to 2.54), and either pulmonary hypertension (mean pulmonary pressure >35 mmHg; hazard ratio=0.65 (4.6, confidence limits 2.2 to 9.5) or, arterial oxygen saturation <80% (hazard ratio 1.71, 95% confidence limits 1.16 to 2.54). CONCLUSIONS: This study supports that long term outcome of patients aged >40 years with unoperated ASD is importantly determined by the mPAP (>35 mmHg), SaO2% (_80) and the age at diagnosis. Nevertheless we identified an inverse association between the mPAP level and SaO2% (interaction). The event-free survival expectancy may be estimated using the age at diagnosis and either SaO2% or mPAP. This prognostic stratification based on pathophysiological principles, may help in making decisions for therapeutic interventions. SaO2% should always be measured as a part of the initial clinical approach of those patients with atrial septal defect aged over 40 years.

Adult↗
PubMed2001

Physostigmine for Alzheimer's disease.

BACKGROUND: The main pharmacological approach for the treatment of Alzheimer's disease (AD) has been based on the use of agents potentiating cholinergic transmission, particularly by inhibiting acetylcholinesterase (AChE), the enzyme that destroys acetylcholine after it has been secreted into the synaptic clefts. Physostigmine is an AChE inhibitor originally extracted from calabar beans. It is licensed in many countries as an agent for reversing the effect of drugs and poisons causing the anticholinergic syndrome. Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Investigation of this property has been limited by the very short half-life of physostigmine. Various forms of administering the drug have been tried to overcome this problem, most recently a controlled-release (CR) oral formulation, and a skin patch. It has been proposed as a potential drug for the symptomatic treatment of AD. OBJECTIVES: To determine whether there is evidence of beneficial effects for the use of physostigmine in Alzheimer's disease. To assess the incidence and severity of adverse effects. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched using the following terms: 'physostigmine', 'physostigmine salicylate', 'Synapton' and 'Antilirium' in accordance with the Cochrane Dementia and Cognitive Improvement Group's search strategy. The pharmaceutical company was contacted. SELECTION CRITERIA: All relevant unconfounded, double-blind, randomized, placebo-controlled trials in which physostigmine was administered for more than one day to patients with dementia of Alzheimer type. Trials in which the allocation to the treatment was not randomized, or in which the allocation to the treatment was not concealed were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers (JMC & JB), pooled where appropriate and possible, and the weighted or standardized mean differences or Peto odds ratios (95% CI) were estimated. Where possible, intention-to-treat analysis was used. MAIN RESULTS: Fifteen studies were included using four different methods of administration of physostigmine. Four studies, involving 29 people in total, used intravenous infusion; seven, involving 131 people, used a conventional oral form; four, involving 1456 participants, used a controlled-release oral form, and one study of 181 people used a verum skin patch. There are no usable results from the intravenous infusion trials, and the few results from the conventional oral form showed no benefit of physostigmine compared with placebo. The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period. The best dose physostigmine (mean 25mg/day) was associated with a 1.75 point improvement on ADAS-Cog score (mean difference -1.75, 95% confidence interval -2.90, -0.60 on an intention-to-treat basis) and a 0.26 point improvement on the CGIC score (treated as a continuous scale) (mean difference -0.26, 95% confidence interval 0.06, 0.46 on an intention-to-treat basis) compared with placebo at 6 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial (22/183 vs 2/183)(OR 5.92, 95% confidence limits 2.59, 13.54) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, flatulence or sweating compared with placebo at 6 weeks. The best dose physostigmine (mean 27mg/day) was associated with a 2.0 point improvement on ADAS-Cog score (mean difference -2.02, 95% confidence interval -3.59, -0.45 on an intention to treat basis) compared with placebo at 12 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial due to adverse events (13/83 vs 5/93)(OR 3.05, 95% confidence limits 1.15, 8.07) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, tremor, asthenia or sweating compared with placebo at 12 weeks. When no attempt was made to identify responders and all relevant patients with Alzheimer's disease were randomized, fixed dose physostigmine (mean 33 mg/day) was associated with a statistically significantly higher number withdrawing (234/358 vs 31/117)(OR 4.82, 95% confidence limits 3.17, 7.33), withdrawing due to adverse events (196/358 vs 10/117) (OR 6.54, 95%confidence limits 4.29, 9.95) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, dyspepsia, sweating, asthenia, dyspnoea or abnormal dreaming compared with placebo at 24 weeks. The results from the study of the verum patch physostigmine show that the double dose (delivering mean dose 12mg/day) was associated with statistically significantly higher numbers suffering at least one adverse event of vomiting, nausea or abdominal cramps compared with placebo at 24 weeks, but placebo was associated with statistically significantly greater numbers of gastrointestinal complaints at 24 weeks compared with single-dose physostigmine. REVIEWERS' CONCLUSIONS: The evidence of effectiveness of physostigmine for the symptomatic treatment of Alzheimer's disease is limited. Even in a controlled release formulation designed to overcome the short half-life, physostigmine showed no convincing benefit and adverse effects remained common leading to a high rate of withdrawal.

Alzheimer Disease↗
PubMed2005

Cost utility analysis of co-prescribed heroin compared with methadone maintenance treatment in heroin addicts in two randomised trials.

OBJECTIVE: To determine the cost utility of medical co-prescription of heroin compared with methadone maintenance treatment for chronic, treatment resistant heroin addicts. DESIGN: Cost utility analysis of two pooled open label randomised controlled trials. SETTING: Methadone maintenance programmes in six cities in the Netherlands. PARTICIPANTS: 430 heroin addicts. INTERVENTIONS: Inhalable or injectable heroin prescribed over 12 months. Methadone (maximum 150 mg a day) plus heroin (maximum 1000 mg a day) compared with methadone alone (maximum 150 mg a day). Psychosocial treatment was offered throughout. MAIN OUTCOME MEASURES: One year costs estimated from a societal perspective. Quality adjusted life years (QALYs) based on responses to the EuroQol EQ-5D at baseline and during the treatment period. RESULTS: Co-prescription of heroin was associated with 0.058 more QALYs per patient per year (95% confidence interval 0.016 to 0.099) and a mean saving of 12,793 euros (8793 pounds sterling, 16,122 dollars) (1083 to 25,229 euros) per patient per year. The higher programme costs (16 222 euros; lower 95% confidence limit 15,084 euros) were compensated for by lower costs of law enforcement (- 4129 euros; upper 95% confidence limit - 486 euros) and damage to victims of crime (- 25,374 euros; upper 95% confidence limit - 16,625 euros). The results were robust for the use of national EQ-5D tariffs and for the exclusion of the initial implementation costs of heroin treatment. Completion of treatment is essential; having participated in any abstinence treatment in the past is not. CONCLUSIONS: Co-prescription of heroin is cost effective compared with treatment with methadone alone for chronic, treatment resistant heroin addicts.

Administration, Inhalation↗
PubMed1999

Risk of malformations and other outcomes in children exposed to fluconazole in utero.

AIM: Fluconazole is an active drug systematically used in the oral treatment of vaginal candidiasis and other fungal diseases. We examined the risk of malformations and other birth outcomes following pregnancy related exposures. METHOD: From 1 January 1991 to 31 December 1996 we identified 165 women who had taken fluconazole just before or during pregnancy in the Pregnancy Outcome Section of the North Jutland Pharmacoepidemiological Prescription Database, Denmark, which is linked to the Danish Medical Birth Registry. We compared their birth outcomes (malformation, low birth weight and preterm delivery) with the outcomes among 13 327 women who did not receive any prescriptions during their pregnancies. RESULTS: The prevalence of malformation was 3.3% (four cases) among the 121 women, who had used fluconazole in the first trimester, and 5.2% (697 cases) in offspring to controls (odds ratio: 0.65, 95% confidence limits: 0.24-1.77). Furthermore, we did not find any significantly elevated risk of preterm delivery (odds ratio: 1.17, 95% confidence limits: 0.63-2.17) and low birth weight (odds ratio: 1.19, 95% confidence limits: 0.37-3.79). CONCLUSION: The study showed no increased risk of congenital malformations, low birth weight or preterm birth in offspring to women who had used single dose fluconazole before conception or during pregnancy.

Abnormalities, Drug-Induced↗
PubMed1995

Mortality in recurrent mood disorders during periods on and off lithium. A complete population study in 362 patients.

Recent studies have suggested that long-term lithium treatment reduces the high mortality rates of recurrent mood disorders in patients selected for and compliant with treatment at specialized lithium clinics. Whether lithium also generally reduces mortality in this diagnostic category under less select treatment conditions is a question of vital public health interest. The impact of prophylactic lithium on mortality was studied in a complete population of 362 unselected patients with DSM-III-R diagnoses of mood disorders or schizoaffective disorder, hospitalized at least once between 1970 and 1977 and treated with lithium for a minimum of one year. The patients were followed until 1991 or until date of death. The final analyses included 3911 patient years with lithium and, because of temporary or permanent discontinuations, 1274 patient years without lithium prophylaxis. A total of 129 deaths were recorded, compared with the 60.7 deaths that would normally be expected in the general population, yielding a Standard Mortality Ratio (SMR) of 2.1, significantly different from 1.0 (p < 0.001, 95% confidence limits 1.8-2.5). The relative risk of death was 1.7 times higher (p < 0.01, 95% confidence limits 1.2-2.6) during periods off lithium than during periods on lithium. The relative risk of suicide was 4.8 times higher off lithium than on lithium (p < 0.02, 95% confidence limits 1.1-12.6). Suicide, pneumonia, pyelonephritis, and, unexpectedly, pulmonary embolism contributed to the excess mortality both on and off lithium.(ABSTRACT TRUNCATED AT 250 WORDS)

Affective Disorders, Psychotic↗
PubMed2006

Comparison of BACTEC 460 and MGIT 960 systems for the culture of Mycobacterium avium subsp. paratuberculosis S strain and observations on the effect of inclusion of ampicillin in culture media to reduce contamination.

To compare the utility and diagnostic accuracy of BACTEC and MGIT culture systems, a total of 41 pooled faecal samples, each containing faeces from one sheep infected with the S strain of Mycobacterium paratuberculosis and four uninfected sheep was cultured. The MGIT culture system did not support the growth of the S strain of M. paratuberculosis from faeces within the time frame of the experiments, although a laboratory adapted S strain grew slowly in MGIT provided that sufficient bacteria were inoculated. In contrast, C strain grew rapidly in MGIT. The sensitivity of culture was calculated relative to the infection status of the animals, none of which had clinical signs of ovine Johne's disease. The overall sensitivity of pooled faecal culture in the BACTEC culture system was 21.9% (95% confidence limits, 10.5-37.6), a figure dependant on the proportion of multibacillary cases. The sensitivities of the BACTEC culture system for pools containing animals with multibacillary and paucibacillary lesions were 100.0% (95% confidence limits, 47.2-100.0) and 17.8% (95% confidence limits 6.06-36.8), respectively. The contamination rate of BACTEC cultures was 9.7% compared to 14.3% for MGIT. The effect of 100 microg/ml ampicillin on the S strain of the M. paratuberculosis was examined and in both BACTEC and MGIT media it delayed growth by about 1 week. The composition of MGIT medium, particularly presence of vancomycin hydrochloride, slowed the growth of the S strain. The low content of egg yolk was considered to be another possible factor. The radiometric BACTEC culture system remains the best alternative for the culture of S strain and is recommended in circumstances where the genotype (s) of the strains present in a region/farm is either unknown or S strain.

Ampicillin↗
PubMed1998

Halothane requirement--a comparison between laryngeal mask airway insertion and endotracheal tube intubation in pediatric patients.

BACKGROUND: The present study was to determine the effective concentration of halothane for insertion of laryngeal mask airway (LMA) and for intubation of endotracheal tube (ETT) in pediatric patients. METHODS: Forty-eight ASA class 1 patients, aged from 10 months to 6 years, scheduled for minor elective surgery were randomly assigned to two groups i.e., LMA and ETT. The concentration of halothane effective in fifty percent of patients (EC50) was determined by the up-and-down method (with 0.5% as a step size). After the predetermined concentration of halothane delivered from a calibrated vaporizer was established and maintained for 20 min, LMA insertion or ETT intubation was attempted without the patient being curarized. The response of patient to LMA or ETT was reported either as "movement" or "non-movement". The effective concentration and associated 95% confidence limits were determined in each group. RESULTS: An effective concentration of halothane for LMA insertion was 1.5 +/- 0.4% (95% confidence limits 1.4-1.7%), whereas that for ETT intubation was 2.3 +/- 0.5% (95% confidence limits 2.1-2.5%). The difference between these two values was statistically significant (p < 0.01). Airway reflexes after LMA insertion were minimal. CONCLUSIONS: The insertion of LMA could be performed at a significantly less halothane concentration in comparison with ETT intubation in children.

Anesthetics, Inhalation↗
PubMed1988

Reproducibility study on the Scheimpflug Cataract Video Camera.

The Zeiss Scheimpflug Cataract Video Camera was designed to photograph, store and analyze cataracts in a semi-automated fashion for cross-sectional and longitudinal studies. We conducted a reproducibility study of this system. Twenty-four normal and 61 cataractous eyes were photographed twice by each of two of the authors in the 90 degree meridian and microdensitometry was performed on each of the stored images. Reproducibility was then determined using the intraclass correlation coefficient to determine whether or not the differences encountered were due to variability in the system or due to actual differences among the images. The intraclass correlation in the lens nucleus was 0.995 with 95% confidence limits of .992-.996. Therefore, reproducibility was 99.5%. In the anterior cortex, intraclass correlation was .941 with 95% confidence limits of .919-.959. In the posterior cortex intraclass correlation was .905 with 95% confidence limits of .870-.932. Reproducibility with this instrument was therefore excellent and with certain limitations, this may be a useful instrument in monitoring lens changes in certain diseases and the effects of anti-cataract agents.

Cataract↗
PubMed2000

Perspective: gene divergence, population divergence, and the variance in coalescence time in phylogeographic studies.

Molecular methods as applied to the biogeography of single species (phylogeography) or multiple codistributed species (comparative phylogeography) have been productively and extensively used to elucidate common historical features in the diversification of the Earth's biota. However, only recently have methods for estimating population divergence times or their confidence limits while taking into account the critical effects of genetic polymorphism in ancestral species become available, and earlier methods for doing so are underutilized. We review models that address the crucial distinction between the gene divergence, the parameter that is typically recovered in molecular phylogeographic studies, and the population divergence, which is in most cases the parameter of interest and will almost always postdate the gene divergence. Assuming that population sizes of ancestral species are distributed similarly to those of extant species, we show that phylogeographic studies in vertebrates suggest that divergence of alleles in ancestral species can comprise from less than 10% to over 50% of the total divergence between sister species, suggesting that the problem of ancestral polymorphism in dating population divergence can be substantial. The variance in the number of substitutions (among loci for a given species or among species for a given gene) resulting from the stochastic nature of DNA change is generally smaller than the variance due to substitutions along allelic lines whose coalescence times vary due to genetic drift in the ancestral population. Whereas the former variance can be reduced by further DNA sequencing at a single locus, the latter cannot. Contrary to phylogeographic intuition, dating population divergence times when allelic lines have achieved reciprocal monophyly is in some ways more challenging than when allelic lines have not achieved monophyly, because in the former case critical data on ancestral population size provided by residual ancestral polymorphism is lost. In the former case differences in coalescence time between species pairs can in principle be explained entirely by differences in ancestral population size without resorting to explanations involving differences in divergence time. Furthermore, the confidence limits on population divergence times are severely underestimated when those for number of substitutions per site in the DNA sequences examined are used as a proxy. This uncertainty highlights the importance of multilocus data in estimating population divergence times; multilocus data can in principle distinguish differences in coalescence time (T) resulting from differences in population divergence time and differences in T due to differences in ancestral population sizes and will reduce the confidence limits on the estimates. We analyze the contribution of ancestral population size (theta) to T and the effect of uncertainty in theta on estimates of population divergence (tau) for single loci under reciprocal monophyly using a simple Bayesian extension of Takahata and Satta's and Yang's recent coalescent methods. The confidence limits on tau decrease when the range over which ancestral population size theta is assumed to be distributed decreases and when tau increases; they generally exclude zero when tau/(4Ne) > 1. We also apply a maximum-likelihood method to several single and multilocus data sets. With multilocus data, the criterion for excluding tau = 0 is roughly that l tau/(4Ne) > 1, where l is the number of loci. Our analyses corroborate recent suggestions that increasing the number of loci is critical to decreasing the uncertainty in estimates of population divergence time.

Animals↗
PubMed1985

Reproducibility of left ventricular area and volume measurements using a computer endocardial edge-detection algorithm in normal subjects.

The variability of serially recorded 2-dimensional echocardiograms in normal subjects was determined. During a 2-week period, 10 normal subjects underwent echocardiography 5 times, in 2 laboratories, with use of different ultrasonographs. The video recordings were analyzed using a computer image analysis system (Quantic 1200) to provide standardized left ventricular short-axis areas and area ejection fraction (EF). Left ventricular volumes and volume EF were calculated. The 95% confidence limits of the percent difference for end-diastolic area and volume between 2 samples in a given subject were +/- 16.8 and +/- 16.7%, respectively. The limits for end-systolic area and volume were +/- 15.8 and +/- 17.0%, respectively. The 95% confidence limits for differences of area and volume EF between 2 recordings were +/- 12.8 and +/- 9.7%, respectively. No correlation was found between clinical grade (image quality) and the variability of area measurements. A good correlation (r = 0.98) was found between area and volume EF for any given subject over the 5 observations. These confidence limits are narrower than those previously recorded.

Adult↗
PubMed1994

Determination of end-tidal sevoflurane concentration for tracheal intubation and minimum alveolar anesthetic concentration in adults.

The purpose of this study was to determine both the concentration of sevoflurane required for tracheal intubation (MACEI) and its minimum alveolar anesthetic concentration (MAC) in adults. The study group consisted of 86 elective surgical patients, ASA physical status I or II, aged 16-59 yr. There was no premedication administered. For MACEI determination, after establishing and maintaining the predetermined end-tidal concentration for 20 min, tracheal intubation was attempted using a cuffed tracheal tube without muscle relaxant or other adjuvants. Each concentration at which tracheal intubation was attempted was predetermined as follows: 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, and 7.0%. For MAC determination, the patients examined were basically the same as those for MACEI determination, except for those who received muscle relaxant or other adjuvants because they were "not intubated smoothly." After establishing and maintaining the predetermined end-tidal concentration for 20 min, skin incision was attempted. Each concentration at which skin incision was attempted was predetermined as follows: 0.5%, 1.0%, 1.5%, 2.0%, 2.5%, and 3.0%. The MACEI of sevoflurane was 4.52% (95% confidence limits, 3.91%-5.21%), and the ED95 for tracheal intubation was 8.07%. The MAC of sevoflurane was 1.58% (95% confidence limits, 1.14%-1.98%), and the AD95 (anesthetic ED95) was 2.96%. The MACEI/MAC ratio was 2.86 (95% confidence limits, 2.63-3.43). Anesthesia induction followed by tracheal intubation can be accomplished in adults when sevoflurane is administered as a sole anesthetic, but in excess of 8% end-tidal concentration.

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