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PubMed1999

Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model.

OBJECTIVE: The relative analgesic potency of single doses of oral controlled-release oxycodone and oral controlled-release morphine were compared in a randomized, double-blind trial using a postoperative pain model. METHODS: Women (n = 169) with moderate to severe pain following abdominal hysterectomy received single oral doses of controlled-release oxycodone, 20 mg or 40 mg, or controlled-release morphine, 45 mg or 90 mg. Assessments were made at 30 min, 60 min, then hourly after dosing for 12 h or until remedication. RESULTS: The most precise estimates of relative potency showed that controlled-release oxycodone was 1.8 times more potent than controlled-release morphine for total effect (95% confidence limits 1.09-2.42; lambda 0.44) and 2.2 times more potent for peak effect (95% confidence limits 0.96-4.59; lambda 0.71). Controlled-release oxycodone at doses of 20 mg or 40 mg was comparable with controlled-release morphine at doses of 45 mg or 90 mg, respectively, for total and peak analgesic effects. For the two higher doses, time to peak relief was approximately 1 h shorter with controlled-release oxycodone than with controlled-release morphine. Most patients reported onset of analgesia within 1 h with all doses. Side effects were similar with the two opioids. CONCLUSION: Oral controlled-release oxycodone was twice as potent as oral controlled-release morphine in this single-dose, relative potency assay. When converting patients from oral morphine to oral oxycodone, an initial oral oxycodone dose of one-half the oral morphine dose is recommended.

Administration, Oral↗
PubMed1988

Gout and coronary heart disease: the Framingham Study.

The relationship between gout, not associated with the use of diuretics, and the development of coronary heart disease was examined in 5209 subjects originally enrolled in the Framingham Study. Based on 32 years of follow-up, the two year incidence of gout was six times greater in men (3.2/1000) as compared to women (0.5/1000). For both sexes, the incidence of gout showed no clear relationship with age. Among men who never received diuretics, those afflicted by gout, as compared to those without gout, experienced a 60% excess of coronary heart disease (95% confidence limits, 1.1-2.2), primarily attributed to a two fold excess of angina pectoris (95% confidence limits, 1.2-3.1). Although gout was usually associated with other atherogenic risk factors, control of systolic blood pressure, total cholesterol, alcohol intake, body mass index, and diabetes failed to alter the effect of gout on the preceding coronary events in men. For women, there were no significant associations between gout and coronary heart disease. We conclude that gout, unrelated to the intake of diuretics, imparts an additional risk of coronary heart disease in men, unexplained by clinically measured risk factors.

Adult↗
PubMed2004

Is female sex associated with increased survival after out-of-hospital cardiac arrest?

AIM: To evaluate survival after out-of-hospital cardiac arrest in relation to sex. METHODS: All patients with out-of-hospital cardiac arrest included in the Swedish Cardiac Arrest Registry between 1990 and 2000 in whom cardiopulmonary resuscitation (CPR) was attempted and who did not have a crew witnessed arrest were included. The registry covers 85% of the inhabitants of Sweden (approximately 8 million inhabitants). P-values were adjusted to differences in age. Survival was defined as patients being hospitalised alive and being alive one month after cardiac arrest. In all, 23,797 patients participated in the survey of which 27.9% were women. RESULTS: Among women 16.4% were hospitalised alive versus 13.2% among men ( P<0.001). After one month 3.0% among women were alive versus 3.4% among men (NS). In a multivariate analysis considering differences in age and various factors at resuscitation female sex was an independent predictor for patients being hospitalised alive (odds ratio 1.66; 95% confidence limits 1.49-1.84) and for being alive after one month (odds ratio 1.27; 95% confidence limits 1.03-1.56). Women differed from men as they were older ( P<0.001 ), had a lower prevalence of witnessed cardiac arrest ( P=0.01), a lower occurrence of bystander CPR (P<0.001), a lower occurrence of ventricular fibrillation as initial arrhythmia (P<0.001) and a lower occurrence of cardiac disease judged to be the cause of cardiac arrest ( P<0.0001 ). On the other hand they had a cardiac arrest at home more frequently ( P<0.001 ). CONCLUSION: Among patients suffering out-of-hospital cardiac arrest in Sweden which was not crew witnessed and in whom resuscitation efforts were attempted, female sex was associated with an increased survival.

Adolescent↗
PubMed1998

Mediastinitis after cardiovascular operations: a case-control study of risk factors.

BACKGROUND: An analysis of risk factors for postoperative mediastinitis can lead to a better understanding of the pathogenesis of this complication and to more effective preventive measures. METHODS: This case-control study of 37 patients and 74 matched controls evaluated 54 potential risk factors. RESULTS: Nine variables were significantly associated with increased risk of postoperative mediastinitis: total operation time (p = 0.0013), high body-mass index (p = 0.0033), use of beta-adrenergic drugs before the onset of infection (p = 0.0037), long cardiopulmonary bypass time (p = 0.0072), long aortic cross-clamp time (p = 0.0075), presence of diabetes (p = 0.0122), high body weight (p = 0.0130), and use and duration of temporary pacing wires (p = 0.0293 and p = 0.0241 respectively). In a conditional logistic regression analysis, use of beta-adrenergic drugs before the onset of infection (p = 0.0058; odds ratio 19.7; 95% confidence limits, 2.37 and 163.7) and body mass index (p = 0.0082; odds ratio 1.27; 95% confidence limits, 1.06 and 1.52) were independently associated with a significantly increased risk of postoperative mediastinitis. CONCLUSIONS: Obesity and use of beta-adrenergic drugs, which is indicative of obstructive respiratory problems, were the most important risk factors suggesting that mechanical strain on the sternotomy and sternal instability may precede infection. Targeted preventive measures for these groups could be justified.

Adrenergic beta-Agonists↗
PubMed1999

Sero-epidemiology of measles antibodies in the Netherlands, a cross-sectional study in a national sample and in communities with low vaccine coverage.

Serum antibodies against measles were measured in the Dutch general population and in municipalities with low vaccine coverage, where religious groups that refuse vaccination are clustered sociogeographically. The results suggest that wild measles virus may still circulate in municipalities with low vaccine coverage; the circulation in the general population seems to have decreased significantly right after the introduction of mass vaccination. The overall prevalence in the general population was high (95.7%, 95% confidence limits 95.3-96.2%); the seroprevalence in the age groups offered two vaccinations (91.7%, 95% confidence limits 89.4-94.0%) was lower than the level believed to be necessary for the elimination of measles. Protective levels of maternal antibodies in newborns have waned several months before the first vaccination is scheduled.

Adolescent↗
PubMed1990

Background gamma radiation and childhood cancers within ten miles of a US nuclear plant.

In light of some recent reports concerning childhood leukaemia near nuclear installations, we examined rates of cancer in children in relation to background gamma ray exposure. Data from a national monitoring programme around nuclear facilities were used to map the distribution of background gamma radiation for 69 small geographical subunits (average population 2300) within ten miles of one US nuclear plant. An association was found for incidence of childhood cancers as a whole (odds ratio (OR) = 2.4; 95% confidence limits (CL) 1.2, 4.6). For leukaemias specifically, the odds ratio was also elevated but confidence limits were very wide (OR = 2.4; 95% CL 0.5, 12.9). Analyses adjusting for sociodemographic characteristics of study tracts (population density and income) gave similar results; data on other risk factors were unavailable. Conventional risk models would not predict a detectable increase in childhood cancer from background gamma radiation, particularly not an increase of this magnitude. The large effect for solid tumours as well as leukaemias is also somewhat counter to expectation. Since a priori the association we observed was unlikely, it is important to know if similar trends in childhood cancer with background radiation are seen in other areas before rejecting chance or bias as an explanation for the result.

Accidents↗
PubMed1999

A double-blind, randomized study assessing the equivalence of valacyclovir 1000 mg once daily versus 500 mg twice daily in the episodic treatment of recurrent genital herpes. Genival Study Group.

Valaciclovir is a prodrug of acyclovir with more favourable bioavailability. Twice daily oral administration of valacyclovir is recommended in patients with genital herpes. A double-blind, randomized, controlled, multicriteria equivalence trial was conducted to determine whether od treatment with valacyclovir 1000 mg is as effective as bd treatment with 500 mg in patients with recurrent genital herpes. A total of 922 immunocompetent outpatients were treated with either regimen for 5 days; treatment was self-initiated at the first symptoms of the next recurrence. The principal outcome measures were the percentage of lesions healed at day 6, time to healing, time to cessation of pain, discomfort or itching, the percentage of abortive episodes and safety. Equivalence was assessed by comparison of 80% confidence limits for each measure; the two regimens were regarded as equivalent if the lower confidence limit was higher than a pre-determined equivalence limit calculated to show a maximum 10% inferiority of valacyclovir 1000 mg od against valaciclovir 500 mg bd. Intention-to-treat analysis showed that the two treatments were equivalent for each outcome measure. Hence, it is concluded that valacyclovir 1000 mg od is as effective as 500 mg bd. as self-initiated therapy in patients with recurrent genital herpes.

Acyclovir↗
PubMed1998

The normal kidney growth rate during year 1 of life is variable and age dependent.

PURPOSE: The concept of normal contralateral kidney growth rate was introduced as a parameter to consider in conjunction with others in the evaluation of unilateral hydronephrosis in asymptomatic neonates and infants. Historically measurements of renal size obtained at different times from different patients have been relied on to construct normal renal growth charts. We report normal kidney growth rates in year 1 of life derived from interval ultrasound measurements of renal size in the same newborns and infants longitudinally with time. MATERIALS AND METHODS: We reviewed 333 normal renal ultrasound studies performed between 1991 and 1995 in 55 patients during year 1 of life. These longitudinal measurements were made bilaterally 2 to 8 times (median 3) per patient. Growth curve models that consider random patient effects were used to estimate the mean growth curve and ascertain its form. We also reviewed an additional 91 ultrasound studies in 10 patients with myelomeningocele without hydronephrosis or reflux. We analyzed the kidney growth rate in a similar manner and compared the results with those in the normal patients. RESULTS: Analysis of the normal cases revealed a changing growth rate during year 1 of life estimated to be 3.1 mm. per month at birth, decreasing gradually during the first 7 months of life to 0.25 mm. per month and remaining constant thereafter (p = 0.0064). Mean kidney size at birth was estimated to be 42.8 mm. (95% confidence limits 27.0 to 58.5). At age 7 months mean size was 60.7 mm. (95% confidence limits 40.1 to 81.3). CONCLUSIONS: These data demonstrate that normal kidney growth is age dependent. A rapid but slowly decreasing growth rate during the first 7 months of life is followed by a more constant and lower rate. The data also suggest that unusually rapid growth, such as that which may occur in the normal contralateral kidney in unilateral obstruction, may also be age dependent, exceeding 5.0 mm. per month during the first 7 months of life and 2.0 mm. per month thereafter.

Age Factors↗
PubMed1994

The Ullanlinna Narcolepsy Scale: validation of a measure of symptoms in the narcoleptic syndrome.

The Ullanlinna Narcolepsy Scale (UNS) is a simple questionnaire-based method used to measure the symptoms of the narcoleptic syndrome. The 11-item scale (range 0-44) assesses the two main features of the narcoleptic syndrome, the abnormal sleeping tendency and cataplexy. The UNS sum score reliably distinguishes patients with the narcoleptic syndrome from patients with sleep apnoea, multiple sclerosis, and epilepsy. The mean score in patients with the narcoleptic syndrome was 27.3 (95% confidence limits 24.4-33.1); the sleep apnoea group with a mean score of 9.6 (95% confidence limits 7.2-12.0) came closest to this. Validation data were also selected from a large survey of non-institutionalized adults in Finland including groups with insomnia, excessive daytime sleepiness, sleep deprivation, sciatica, alcohol abuse, and high scores on a depression scale and on a scale of neurovegetative symptoms. With the lowest UNS score in the narcoleptic syndrome group (= 14) as the cutpoint, the sensitivity is 100% and the specificity is 98.8% in the subjects studied. The accurate assessment of the symptoms of the narcoleptic syndrome in a format suitable for questionnaire studies is essential.

Journal Article↗
PubMed1989

Genetic linkage between Huntington's disease and D4S10 (G8) in Scottish families.

Genetic linkage between Huntington's disease (HD) and polymorphic DNA markers at the D4S10 locus has been investigated in 16 Scottish families. A maximum lod score of 3.499 at a recombination fraction of 0.07 was found, with 95% confidence limits of 0.02 and 0.22. Only one obvious recombinant was detected, and the wide confidence limits probably reflect the large number of unaffected individuals whose risk could only be estimated empirically.

Chromosomes, Human, Pair 4↗
PubMed1977

Liver biopsies from psoriatics related to methotrexate therapy. 3. Findings in post-methotrexate liver biopsies from 160 psoriatics.

The purpose of this paper is to report findings in post-MTX liver biopsies from 160 psoriatics treated with Methotrexate (MTX) in single biopsy and B. 68 patients with serial biopsies. At the time of liver biopsy the 92 patients had received a mehosis and six patients had fibrosis. Comparing these 7 patients with patients having normal liver histology (13 patients) revealed no statistically significant difference in cumulative doses of MTX, but a statistically significant higher admitted alcohol intake during MTX therapy (p less than 0.002) and an older age (p less than 0.01) in the patients with cirrhosis or fibrosis. in the 68 patients MTX had accumulated to a mean dose of 3940 mg (range 32k-8355 mg) at the time the latest liver biopsies were taken. Among the latest liver biopsies were 14 cirrhosis (21 per cent, 95 per cent confidence limits: 12-32 per cent) and 16 fibrosis (24 per cent, 95 per cent confidence limits: 14-35 per cent). The 14 patients with cirrhosis when compared to patients with normal histology (9 patients), had taken an equal total dose of MTX at the latest liver biopsy, but had consumed a statistically significant higher amount of alcohol (p less than 0.05) during MTX therapy and also tended to be older (p less than 0.006). Comparison of a material A and B indicates that the prevalence of cirrhosis and fibrosis among MTX treated psoriatics increases rapidly beyond a cumultative dose of two to four grams of MTX. No MTX treated psoriatics should thus be allowed to pass this dosage range without having a liver biopsy performed.

Adult↗
PubMed2002

Outcome of Burkholderia cepacia colonisation in an adult cystic fibrosis centre.

BACKGROUND: Colonisation with Burkholderia cepacia is a poor prognostic indicator in subjects with cystic fibrosis (CF), but outcome prediction is impossible since patients are colonised by different strains with differing pathogenicity. The clinical course of a large cohort of CF patients colonised with UK epidemic (ET12) B cepacia was followed for 5 years and compared with that of the remaining patients in the clinic. METHODS: Pulmonary function, nutritional state, and lung pathogen colonisation were recorded for 5 years before December 1997 or death for all 107 patients who had attended the Liverpool adult CF clinic since 1993. For each patient a time line from study entry to date of death or 1997 was constructed. In 1993 potential risk factors including age and sex were subjected to Cox proportional hazards analysis using the end point of mortality as the outcome variable. The analysis was supplemented by time varying covariables that described the change in FEV(1), BMI, and colonisation status across time, and the excess risk associated with B cepacia colonisation was calculated. Subsequently, in those patients who died between 1993 and 1997, predictive factors for death were compared within groups using complete 5 year data. RESULTS: Thirty seven patients had been colonised by epidemic B cepacia and these patients had four times the mortality of the remainder (p<0.01). In 1993 univariate predictors of mortality were age (alive 19.6 (0.64) v dead 23.8 (1.44); p<0.005) and baseline FEV(1) (alive 68.6 (2.5)% predicted v dead 43.2 (4.8)%; p<0.001) with a trend for BMI (p=0.07). However, following time varying covariate Cox proportional hazards analysis, only lower FEV(1) (hazards ratio 1.1, 95% confidence limits 1.06 to 1.14; p<0.001) and colonisation with B cepacia (hazards ratio 7.92, confidence limits 2.65 to 23.69; p<0.001) were identified as significant factors for death. Surviving B cepacia patients had similar initial lung function to the remaining surviving patients but had an accelerated loss of lung function over the study period (colonised -1.9% predicted per year v non-colonised -0.3% predicted per year; p<0.05). Deceased patients colonised with B cepacia had better spirometric results than the remaining deceased patients 5 years before death (p<0.05) but lost lung function at a greater rate than non-colonised patients (colonised -6.2% predicted per year v non-colonised -1.9% predicted per year; p<0.05). CONCLUSIONS: This study confirms the excess mortality associated with epidemic B cepacia colonisation and shows that those with poor spirometric values are at the greatest risk.

Adolescent↗
PubMed1989

Amino acid exchange between plasma and erythrocytes in vivo in humans.

To study amino acid exchange between plasma and erythrocytes in vivo, 4-h primed, continuous intravenous infusions of L-[1-13C]leucine, [15N]glycine, and L-[15N]alanine were administered to five healthy young men in the postabsorptive state. Stable isotope enrichments and amino acid levels were determined by gas chromatography-mass spectrometry in both plasma and whole blood and estimated (using hematocrit) in erythrocytes. A high concentration gradient across the erythrocyte membrane was consistently found for glycine (552 +/- 268 microM in erythrocytes vs. 155 +/- 35 microM in plasma), but not for leucine or alanine. A steady-state isotopic enrichment was observed in whole blood as well as plasma for each amino acid in every subject. Steady-state [13C]leucine enrichment in erythrocytes did not differ from plasma enrichment at steady state, the ratio of erythrocyte to plasma enrichment being 1.03 +/- 0.20 (95% confidence limits = 0.78-1.28); in contrast, this ratio reached only 0.23 +/- 0.04 and 0.59 +/- 0.09 (confidence limits 0.18-0.28 and 0.48-0.70) for [15N]glycine and [15N]alanine at steady state, respectively. These results suggest that most of erythrocyte leucine is exchangeable with plasma, whereas only a fraction of erythrocyte glycine and alanine is involved in exchange with plasma in vivo.

Adult↗
PubMedDate not supplied

Decreased plasma phosphatidylcholine/free cholesterol ratio as an indicator of risk for ischemic vascular disease.

As part of a population survey and a follow-up study of plasma lipid profiles by high temperature gas-liquid chromatography, we have determined the quantities and relative proportions of all major chemical classes and molecular species of lipids of plasma from 1200 subjects at Visit 2 of the Toronto-McMaster Lipid Research Clinic Prevalence Study. We have compared these values between our 24 subjects with ischemic vascular disease and 73 control subjects matched for age, sex, and plasma total cholesterol and triacylglycerols. The phosphatidylcholine/free cholesterol ratio showed the highest association with ischemic vascular disease of any of over 10 other lipid parameters and all the common risk indicators except high density lipoprotein cholesterol. The phosphatidylcholine/free cholesterol ratio had a relative risk ratio of 20/4 (95% confidence limits, 15/9, 23/1) and high density lipoprotein cholesterol, a risk ratio of 23/1 (95% confidence limits, 24/0, 19/5) for ischemic vascular disease. The average ratio of phosphatidylcholine/free cholesterol for the ischemic vascular disease group was 1.36 and for the controls 1.51, the population average being 1.50. Plasma high density lipoprotein cholesterol had a significant correlation (R = 0.15) with the phosphatidylcholine/free cholesterol ratio in the total population sample. The increased risk for ischemic vascular disease from a lower phosphatidylcholine/free cholesterol ratio may possibly be explained on the basis of decreased fluidity and stability of the lipoproteins due to a relative oversaturation with free cholesterol.

Adult↗
PubMed1990

Intravenous thrombolytic therapy with a combination of single-chain urokinase-type plasminogen activator and recombinant tissue-type plasminogen activator in acute myocardial infarction.

The effects of simultaneous intravenous infusions of 12 mg recombinant tissue-type plasminogen activator (rt-PA) over 30 minutes and 48 mg single-chain urokinase-type plasminogen activator (scuPA) over 40 minutes were studied in 38 patients with acute myocardial infarction. Coronary arterial patency was assessed angiographically 60 minutes and 90 minutes after initiation of treatment. Patency was achieved in 19 of 31 patients (61.3%) (95% confidence limits, 42-78%) at 60 minutes and in 27 of 33 patients (81.8%) (95% confidence limits, 65-93%) at 90 minutes. Nonspecific plasminogen activation was monitored by measuring relevant plasma parameters. At 60 minutes and 120 minutes, the fibrinogen concentration decreased slightly to 82.8 +/- 24.3% and 91.2 +/- 17.4% of the preinfusion level, and the plasminogen concentration to 66.3 +/- 15.2% and 65.3 +/- 13.4%, respectively. A greater consumption of alpha 2-antiplasmin was observed, which decreased to 30.7 +/- 22.8% and 32.2 +/- 21.2% of the preinfusion level at 60 and 120 minutes, respectively. No bleeding necessitating transfusion was observed. Two patients (5.3%) died during hospitalization. The findings suggest that the combined intravenous infusion of rt-PA and scuPA at appropriate doses induces highly effective coronary thrombolysis equal to the best results obtained with either rt-PA or scuPA alone. This efficacy is coupled with high specificity. Thus, the data support the potential use of combinations of rt-PA and scuPA in place of monotherapy.

Drug Therapy, Combination↗
PubMed1991

Reliability of hypocycloidal tomography for the evaluation of the distance from the alveolar crest to the mandibular canal.

When implants are to be inserted in the mandible posterior to the mental foramen, tomography is required to determine the exact location of the mandibular canal and assess the dimensions of the body and alveolar process. Previous studies have shown discrepancies between the true distance between the alveolar crest and the upper border of the mandibular canal and that measured from computed tomograms. This study evaluates the reliability of such measurements made from hypocycloidal tomograms. Six examiners, three radiologists and three oral surgeons, independently measured the distance from the alveolar crest to the upper border of the mandibular canal in transverse hypocycloidal tomograms of the mandible. Analysis of variance showed an average standard deviation between observers of 1.33 mm. This variation, which is the total of inter- and intra-observer variation conditional upon patient and radiograph, was mainly due to the latter which amounted to a mean of 1.04 mm. Calculation of lower confidence limits showed that these could be decreased by the use of several observers. Various confidence levels, equal to the probabilities of obtaining lower confidence limits which are below the true values, can be used to choose acceptable levels of risk in overestimating the true distance.

Alveolar Process↗
PubMed2001

Measurement accuracy in congenital scoliosis.

BACKGROUND: The accuracy of measurement of curves in idiopathic scoliosis has been extensively studied; however, we know of only one article in the literature concerning the accuracy of measurement of curves in congenital scoliosis. That article stated that intraobserver variability was +/- 9.6 degrees and interobserver variability was +/- 11.8 degrees. METHODS: Sixty-nine curves in fifty patients with congenital scoliosis were measured on two separate occasions by seven different observers with varying experience in curve measurement. RESULTS: Mean intraobserver variance ranged from 1.9 degrees to 5.0 degrees, with an average of 2.8 degrees (95% confidence limit, +/- 3 degrees) for the seven observers. The interobserver variance was 3.35 degrees (95% confidence limit, 7.86 degrees). CONCLUSIONS: It is possible to measure curves in congenital scoliosis with much greater accuracy than previously reported. In the clinical situation in which a skilled observer can measure two radiographs at the same time, an accuracy of +/- 3 degrees can be expected 95% of the time.

History, Modern 1601-↗
PubMed1989

Propranolol in prevention of rebleeding from oesophageal varices during the course of endoscopic sclerotherapy.

Thirty-one patients admitted with the first bleeding episode from oesophageal varices were randomized in a double-blind manner to receive oral propranolol, 160 mg daily, for 6 months (n = 15) or matching placebo (n = 16) for the same period. Endoscopy was performed each month during the 6 months and additionally after a further 3 months. The oesophageal varices were injected paravariceally with 2% aethoxysclerol until obliteration. If rebleeding occurred, additional sclerotherapy was performed. In the group treated with sclerotherapy and propranolol 3 patients rebled (20%; 95% confidence limits, 4%-48%), whereas 12 patients treated with sclerotherapy and placebo rebled (75%; 95% confidence limits, 48%-93%; p less than 0.05). There were no side effects to treatment in either of the groups, and it is concluded that administration of propranolol reduces the frequency of variceal rebleeding before variceal obliteration during a course of endoscopic sclerotherapy.

Adult↗