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Repair of tetralogy of Fallot after Waterston anastomosis.

Sixty-three corrective operations have been performed in patients with Tetralogy of Fallot and a previously constructed Waterston shunt. The patients were from 1.4 to 8 years of age (median 4.3 years), and the mean interval between the Waterston shunt and the repair was 39.3 +/- 16.05 months. Three patients developed pulmonary atresia and six required a second anastomosis prior to intracardiac repair. Kinking and stenosis of the right pulmonary artery at the site of the Waterston anastomosis occurred in 12 (19 percent; 70 percent confidence limits 14 to 26 percent) patients who required patch enlargement of the right pulmonary artery at repair. Seven (11 percent; 70 percent confidence limits 7 to 17 percent) patients died in the hospital and three (5 percent; 70 percent confidence limits 2 to 11 percent) during the period of late follow-up. None of the early or late deaths was specifically related to the presence of the previously performed Waterston anastomosis.

Age Factors↗

Long-term follow-up of extended aortoplasty for supravalvular aortic stenosis.

Extended aortoplasty is an operation that was designed to provide a symmetric reconstruction of the aortic root in patients with supravalvular aortic stenosis. The aim of this report is to provide long-term follow-up of the original cohort of 15 patients who underwent extended aortoplasty between 1975 and 1983. Follow-up was obtained in 14 patients. One patient was lost to follow-up 3 years after operation; he was included in this report. An echocardiogram, chest radiograph, and electrocardiogram were obtained for each surviving patient. The median length of follow-up was 141 months (range 36 to 238). The median preoperative gradient was 90 mm Hg (range 55 to 150). The median immediate postoperative gradient was 20 mm Hg (range 0 to 50, p < 0.05 compared with preoperative gradient) and the median long-term gradient was 32 mm Hg (range 6 to 96, p < 0.05 compared with preoperative gradient; p = not significant compared with immediate postoperative gradient). Two patients died: one of left ventricular failure after a subsequent aortic valve replacement and one of chronic left ventricular failure. The Kaplan-Meier estimate of survival at 218 months for all patients was 77.4% (70% confidence limits 62% to 93%). The estimated freedom from reoperation for all patients was 69% at 218 months (70% confidence limits 56% to 82%). Univariate analysis revealed that the presence of a bicuspid valve is a significant risk factor for reoperation (p = 0.038), but not for death (p = 0.51). The Kaplan-Meier estimate of freedom from reoperation for patients with a bicuspid aortic valve was 42.9% at 141 months (70% confidence limits 21% to 65%). Extended aortoplasty provides effective long-term relief of the pressure gradient across the supravalvular ridge. However, a significant number of patients require subsequent operations, particularly those with a bicuspid aortic valve.

Adolescent↗

Risk of colorectal cancer among automotive pattern and model makers.

Twofold to threefold increases in risk for colorectal cancer associated with pattern and model making in the automobile industry have been suggested by several reports. This paper reports the investigation of a cohort of 7545 General Motors pattern and model makers originally defined for the purpose of cancer screening. All-cause mortality for this cohort was lower than that of the US population (standardized mortality ratio [SMR] = 0.7; 95% confidence limits 0.6, 0.8). There were 22 colon cancer deaths v 10.9 expected, resulting in a significantly elevated SMR of 2.0 (95% confidence limits of 1.3, 3.0), consistent with previous studies. The colon cancer SMR for nonparticipants in the screening programs was 4.0 (95% confidence limits of 2.2, 6.7), emphasizing the importance of complete follow-up for all members of a defined cohort.

Adult↗

Heat resistance in liquids of Enterococcus spp., Listeria spp., Escherichia coli, Yersinia enterocolitica, Salmonella spp. and Campylobacter spp.

The aim of the work was to collect, evaluate, summarize and compare heat resistance data reported for Campylobacter, Enterococcus, Escherichia, Listeria, Salmonella and Yersinia spp. The work was limited to resistance in liquids with pH values 6-8. Results obtained under similar experimental conditions were sought. Thermal destruction lines for the various bacterial groups studied were constructed using log10 D values and treatment temperatures. There was a good linear relationship between log10 D and temperature with Escherichia coli, listerias and salmonellas. For campylobacters, enterococci and yersinias the relationships were weaker but, nevertheless, present. Using the slopes of the lines and their 95% confidence limits, z values and their 95% confidence limits were calculated. z values were compared with z values obtained from reports. The equations for the lines were also used for calculation of predicted means of D values at various treatment temperatures. 95% confidence limits on predicted means of D values and on predicted individual D values were also calculated. Lines and values are shown in figures and tables. Differences in heat resistance noted between and within the bacterial groups studied are discussed.

Bacteria↗

A new noninvasive management strategy for patients with suspected pulmonary embolism.

Pulmonary embolism is associated strongly with proximal-vein thrombosis. We tested the hypothesis that recurrent venous thromboembolism is unlikely in the absence of proximal-vein thrombosis. We performed a prospective cohort study in 874 patients with suspected pulmonary embolism. On long-term follow-up of 371 patients with the following characteristics: (1) abnormal, non-high-probability lung scans, (2) off anticoagulant therapy, and (3) serial noninvasive test results negative for proximal-vein thrombosis, only 10 (2.7%; 95% confidence limits, 1.3% to 4.9%) had venous thromboembolism. By comparison, venous thromboembolism on follow-up occurred in 3 (1%) of 315 patients (95% confidence limits, 0.2% to 2.8%) with normal lung scans, and in 5 (7%) of 66 patients (95% confidence limits, 2.5% to 16.8%) with high-probability lung scans. Patients whose serial noninvasive test results were negative for proximal-vein thrombosis have a good prognosis without anticoagulant therapy.

Adult↗

Early morning off-medication dyskinesias, dystonia, and choreic subtypes.

BACKGROUND: Abnormal involuntary movements (dyskinesias) are common in patients with Parkinson disease (PD) as a consequence of the disease and dopaminergic replacement therapy. Early morning off-medication choreic dyskinesias have been recently reported after fetal dopaminergic cell transplantations in patients with advanced PD. OBJECTIVE: To determine the frequency and severity of the early morning off-medication dyskinesias in consecutive patients with advanced PD and an insufficient response to medical management before they undergo neurosurgery. METHODS: Consecutive patients with advanced idiopathic PD were examined and videotaped before undergoing neurosurgery that included pallidotomy, fetal transplantation, or deep brain stimulation. The examination took place in the morning in the practically defined off state, at least 12 hours after the last dose of dopaminergic drugs. Parkinson disease was characterized using the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stage. Dyskinesias were rated with the Abnormal Involuntary Movements Scale and the Rush Dyskinesia Rating Scale. Patients' characteristics and medications were compared using the Wilcoxon rank sum and the Fisher exact tests. RESULTS: Of 68 consecutive patients (44 [65%] men and 24 [35%] women), 11 (16%) had early morning off-medication dyskinesia, with a 95% upper confidence limit of 24%. Focal dystonia was the most common off-medication dyskinesia, and occurred in 10 patients (15%), with a 95% upper confidence limit of 22%; and off-choreic dyskinesia occurred in 1 patient (1.5%), with a 95% upper confidence limit of 4%. There was no difference in PD medications between the patients with and those without dyskinesias. CONCLUSIONS: The most common form of off-medication dyskinesia seen in patients with advanced PD is dystonia. Early morning off-medication choreic dyskinesias are rare but do occur in patients with advanced PD before surgical intervention. The presence and type of off-medication dyskinesias should be monitored in clinical and surgical studies in patients with PD as part of the safety and evaluation of clinical benefits.

Adult↗

Age-dependent growth rate of primary breast cancer.

BACKGROUND: Currently, there have been no reports of clear-cut beneficial effects of regular screening with mammography at a mean screening interval of 2 years in women younger than 50 years of age. It may be that, because of a higher growth rate of breast cancer, more frequent screening is necessary if any effect is to be observed in this age group. However, good quantitative estimates for the growth rate in different age groups are lacking. METHODS: The study group consisted of cancers diagnosed in women who participated in a screening program with serial mammography available. The growth rate, expressed as the tumor volume doubling time, was calculated on the assumption of exponential growth. The analysis was based, not only on the increase in tumor volume for cancers with at least two mammograms showing a measurable tumor nucleus shadow (n = 85), but also on censored values, calculated for cancers showing no growth (n = 6) and for cancers showing only a measurable tumor nucleus shadow on the mammogram at diagnosis (n = 109). In calculating these latter growth rates, the density of the breast parenchyma was taken into account. RESULTS: The median volume doubling time of the primary breast cancers diagnosed in women aged 50-70 years was 157 days (95% confidence limits, 121-204 days). This was significantly longer than in women younger than 50 years of age at diagnosis (80 days; 95% confidence limits, 44-147 days). Primary breast cancer in women older than 70 years of age at diagnosis grew even more slowly (median, 188 days; 95% confidence limits, 120-295). CONCLUSIONS: To observe a beneficial effect of screening, if any, for women younger than age 50 years, more frequent screening than in the older age group is necessary.

Age Factors↗

Plasma deoxyribonucleic acid concentrations of women in labor and umbilical cords.

The concentration of deoxyribonucleic acid (DNA) in plasma from 30 women in labor and plasma from the umbilical cords was determined with a rapid, inexpensive, and simple fluorometric method. These concentrations of DNA were compared to the plasma DNA concentrations of nonpregnant women. The mean plasma DNA concentration of women in labor was significantly lower than the mean plasma DNA concentration of nonpregnant women in the use of 99 per cent confidence limits. The mean plasma DNA concentration of umbilical cords during the third stage of labor was significantly lower than the mean plasma DNA concentrations of women in labor with the use of 99 per cent confidence limits and of nonpregnant women using 99.9 per cent confidence limits.

Blood Specimen Collection↗

No change in repair capacity of mouse lung irradiated three months after a single dose of cyclophosphamide.

The repair capacity of mouse lung was determined at 3 months after a single i.p. injection of cyclophosphamide (Cy) at a maximally tolerated dose of 275 mg/kg. Mice were irradiated to the whole thorax only with 1, 2, 9, or 15 fractions of X-rays using doses/fraction ranging from 1.2 to 11 Gy. Breathing rate (breaths per minute), histology and pulmonary mortality were used to assess lung damage. Raw breathing rate data were converted to quantal response data by scoring the number of mice in each dose group in each fractionation schedule with a breathing rate 1.3 times the breathing rate of control mice. Dose-response curves of mortality and the converted breathing rate data were constructed at 15 weeks after irradiation (approximately 28 weeks after drug treatment) fitted by logit analysis and 50% effective doses with 95% confidence limits obtained. Values of alpha/beta were obtained by using the direct analysis method of H. D. Thames et al. (Int. J. Radiat. Biol., 49:999-1009, 1986). The alpha/beta for mice given Cy 3 months before radiation was 3.69 Gy (95% confidence limits, 2.83, 4.69 Gy) and 3.06 Gy (95% confidence limits, 2.31, 3.99 Gy) for the lethality data and breathing rate data, respectively. These alpha/beta values are in good agreement with the previously published ranges of alpha/beta of 3 to 4 Gy for mouse lung not given Cy previously. Because the repair capacity of the target cells of a tissue govern the fractionation response and choice of fractionation regimen in clinical radiotherapy, these data indicate that the fractionation regimen used can remain the same as that used in non-drug-treated lungs when the lung is irradiated 3 months after exposure to Cy.

Animals↗

Anti-inflammatory effects of peripheral benzodiazepine receptor ligands in two mouse models of inflammation.

In vivo treatment of mice with peripheral benzodiazepine receptor ligands exerts an inhibitory effect on the inflammatory response in two models of acute inflammation. In the first model, pretreatment of the animals (24 h) with 1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide (PK11195) and 7-chloro-5-(4-Chlorophenyl)-1, 3-dihydro-1-methyl-2-H-1,4-benzodiazepin-2 (Ro5-4864), at different doses (0.00001-10 mg/kg, i.p.) dose dependently inhibited the formation of mouse paw oedema induced by carrageenan with mean ID(50s) of 0.009 (95% confidence limits=0.0076-0.013) and 0.04 (95% confidence limits=0.025-0.0086) mg/kg, respectively. Both ligands (0. 1 mg/kg, i.p.) inhibited in the same way the mouse paw oedema induced by carrageenan in animals with and without adrenal glands. PK11195 and Ro5-4864 (0.1 mg/kg, i.p.) inhibited the mouse paw oedema induced by several inflammatory mediators. In the second model, the pretreatment (24 h) with peripheral benzodiazepine receptor ligands (0.1 mg/kg, i.p.) exerted an inhibitory effect on neutrophil influx and produce a marked inhibition of carrageenan-produced interleukin-13 and interleukin-6 in pleural exudation. Our results extend previous findings that peripheral benzodiazepine receptor is involved in the inflammatory response, and suggest that this action may be linked to the action of different inflammatory mediators, probably mainly by the inhibition of the release of pro-inflammatory cytokines.

Animals↗

Apolipoprotein E polymorphism and gallstones.

BACKGROUND & AIMS: Apolipoprotein (apo) E is a genetically polymorphic protein influencing lipoprotein metabolism and the risk of both atherosclerosis and Alzheimer's disease. As opposed to common apo E3, apo E2 decreases and apo E4 increases hepatic lipoprotein uptake; hence, apo E4 could promote gallstone formation by increasing hepatic and biliary cholesterol concentrations. This study was designed to evaluate whether apo E polymorphism is related to gallstone risk. METHODS: apo E phenotype was determined in subjects older than 40 years of age (160 with and 125 without gallstones) and in 61 patients with cholesterol gallstones who underwent cholecystectomy. Bile composition, nucleation time, and gallstone features were analyzed in surgical patients. RESULTS: The E4/3 phenotype was enriched in both patients with gallstones and those who underwent cholecystectomy, with significantly (P < 0.006) higher epsilon 4 allele frequencies than in gallstone-free subjects (odds ratio, 2.67 [95% confidence limits, 1.23-5.93] and 3.62 [95% confidence limits, 1.49-8.91], respectively); women, but not men, accounted for these differences. The prevalence of the epsilon 4 allele increased with age in patients with gallstones, whereas the opposite occurred in gallstone-free subjects. Biliary lipid and gallstone cholesterol content tended to increase in the sequence E4 > E3 > E2 in patients who underwent cholecystectomy. CONCLUSIONS: Carrying the apo E4 isoform is a genetic risk factor for cholelithiasis in humans, thus adding another adverse effect of apo E polymorphism on health.

Adult↗

Changes in attitudes and practices of optometrists in their management of diabetic retinopathy after the release of NHMRC guidelines. National Health and Medical Research Council.

The purpose of this study was to document attitudes and practices of Australian optometrists in their management of diabetic retinopathy prior to the release of the National Health and Medical Research Council (NHMRC) Clinical Practice Guidelines for the Management of Diabetic Retinopathy and at two time points following their release. A self-administered questionnaire was mailed to a stratified random sample of 500 Australian optometrists at the three time points. The same sample was used for the first two surveys and a new random sample was drawn for the second follow-up survey. The response to the three questionnaires was 86%, 80% and 84%, respectively. More than 90% of optometrists reported receiving a copy of the guidelines and 82% reported receiving the supplementary Retinopathy Chart. Fifty-seven per cent reported having read the guidelines at least once in entirety and 65% reported that they refer to the Retinopathy Chart at least monthly in their clinical practice. There was a significant decrease in the number of optometrists who reported that patient unwillingness to be dilated and their fear of precipitating angle closure glaucoma were moderate or major barriers to performing dilated ophthalmoscopy. Concomitantly, the percentage of optometrists who reported that they often or always perform dilated ophthalmoscopy on new patients with diabetes increased significantly from 74.5% (95% confidence limit = 70.2, 78.8) to 81.5% (95% confidence limit = 77.5, 85.5). There have been some significant changes in the self-reported management practices of optometrists in relation to diabetic retinopathy since the release of the NHMRC guidelines and Retinopathy Chart.

Attitude to Health↗

Risk factors for thyroid cancer in northern Italy.

We conducted a hospital based case-control study of 245 cases of thyroid cancer (62 males and 183 females) and 411 controls in three areas of Northern Italy. Subjects with thyroid cancer more often had a history of benign thyroid nodules (18 cases versus 0 controls, lower 95% confidence limit = 7.84), goitre (RR = 5.61, 95% confidence interval (CI): 2.13-14.77) and residence in endemic goitre areas (RR for residence longer than 20 years = 2.29, 95% CI: 1.23-4.29). Heavy (greater than 1000 rads) irradiation of the neck was reported only by seven cases (lower 95% confidence limit: 2.45). Among 31 food items considered, a few showed direct association, including starchy foods and various sources of animal fats or proteins, whereas frequent consumption of other foods, including major sources of dietary iodine (such as fish, green vegetables and fruit) gave significant protection. When analysis was restricted to various subgroups of patients (ie, different histological types, sexes and major groups of hospital controls), it yielded similar results.

Adult↗

Health experiences of operating room personnel.

In an attempt to evaluate health experiences of operating room personnel using previously published reports, the authors calculated summary relative risks (RRs) for each outcome under investigation by combining data from six studies. For each summary RR, they also calculated 95% confidence limits; when the range of the confidence interval excludes 1.0, the increased risk is statistically significant at the 0.05 level. The most consistent evidence was for spontaneous abortion among pregnant physicians and nurses who work in operating rooms, where the RR was 1.3 (95% confidence limits from 1.2 to 1.4). For liver disease there were statistically significant increased RRs among both men (1.6, 1.3-1.9) and women (1.5, 1.2-1.9), but these were based on smaller numbers of studies. Although the results of pooled analyses are suggestive, most studies of this issue have relied on voluntary responses and self-reported outcomes, so that response and/or recall bias could explain these findings. In addition, these investigations generally have examined working in operating rooms rather than actual exposure to anesthetic gases. Finally, there have been considerable improvements in operating room scavenging systems during the last decade. Thus, prospective cohort studies are needed to determine whether there is a relationship between current levels of occupational exposure to anesthetic gases and adverse outcomes, particularly spontaneous abortion and liver disease.

Abortion, Spontaneous↗

Multiplicity-adjusted inferences in risk assessment: benchmark analysis with quantal response data.

A primary objective in quantitative risk or safety assessment is characterization of the severity and likelihood of an adverse effect caused by a chemical toxin or pharmaceutical agent. In many cases data are not available at low doses or low exposures to the agent, and inferences at those doses must be based on the high-dose data. A modern method for making low-dose inferences is known as benchmark analysis, where attention centers on the dose at which a fixed benchmark level of risk is achieved. Both upper confidence limits on the risk and lower confidence limits on the "benchmark dose" are of interest. In practice, a number of possible benchmark risks may be under study; if so, corrections must be applied to adjust the limits for multiplicity. In this short note, we discuss approaches for doing so with quantal response data.

Biometry↗

The day-to-day variation in serum digoxin concentration. The Hørsholm digoxin study.

Serum digoxin concentration was measured in 70 medical patients 7 and 8 days after admission to hospital. The digoxin treatment taken at home was continued in hospital. There was no statistically significant difference between mean digoxin concentrations in samples taken at day 7 (1.52 nmol/l) and day 8 (1.48 nmol/l). The variation in serum digoxin concentration from day to day expressed as SD was 0.25 nmol/l; 95% confidence limits were +/- 0.51 nmol/l, and 99% confidence limits +/- 0.67 nmol/l. Variations in serum digoxin concentration were not correlated to age, sex, body weight, serum creatinine and the oral dose of digoxin.

Aged↗

Consanguinity and prereproductive mortality in the Utah Mormon population.

To test the effects of parental consanguinity on mortality among offspring, inbreeding coefficients were estimated for 303,675 members of the Utah Mormon population who were born between 1847 and 1945. Although consanguinity has been relatively rare in this population, the large sample size permitted the identification of more than 3,500 inbred offspring. Among the offspring of unrelated parents, 13.2% died before the age of 16. Significant elevations in prereproductive mortality were seen among the offspring of first-cousin marriages (22%) and among the offspring of closer unions (32%). The cor- responding relative risks are 1.70 (95% confidence limits = 1.52, 1.91) and 2.41 (95% confidence limits = 1.59, 3.41), respectively. Other categories of relationship did not produce significant elevations in offspring mortality. Similar results were obtained when a case-control approach was used to remove the effects of socioeconomic variation. Consistent with many other studies of populations with low consanguinity rates, this population experienced a relatively high absolute increase in mortality among the offspring of first-cousin marriages (9%). Preliminary evidence is offered for the hypothesis that mortality differentials are larger in populations with low inbreeding and low mortality because nongenetic causes of death do not obscure the effects of consanguinity.

Christianity↗

Albumin excretion rate increases during acute myocardial infarction and strongly predicts early mortality.

BACKGROUND: This study was undertaken to assess whether albumin excretion rate (AER) increases during acute myocardial infarction (AMI) and whether it predicts in-hospital mortality. METHODS AND RESULTS: The study was carried out in 496 subjects admitted to hospital for suspected AMI. Of these, 360 had evidence of AMI. The other 136 were studied as control subjects. AER was assessed by radioimmunoassay in three 24-hour urine collections performed on the first, third, and seventh days after admission. Left ventricular ejection fraction was measured by two-dimensional echocardiography in 254 subjects. AER adjusted for several confounders was higher in the AMI than the non-AMI group on the first (69.2+/-5.2 versus 27.3+/-8.5 mg/24 h, P<.0001) and third (30.3+/-2.7 versus 12.5+/-4.4 mg/24 h, P=.001) days, whereas no difference was present on the seventh day. When the subjects with heart failure were excluded, the difference between the two groups remained significant (first day, P<.0001; third day, P=.001). On the basis of classification of the 26 AMI patients who died in hospital according to whether they had normal AER, microalbuminuria, or overt albuminuria, mortality rate progressively increased with increasing levels of AER (P<.0001). In a Cox's proportional hazards model, AER was a better predictor of in-hospital mortality than Killip class or echocardiographic left ventricular ejection fraction. A cutoff value of 50 mg/24 h for first-day AER and 30 mg/24 h for third-day AER yielded a sensitivity of 92.3% and of 88.5% and a specificity of 72.4% and of 79.3%, respectively, for mortality. Adjusted relative risks for the two cutoff values were 17.3 (confidence limits, 4.6 to 112.7) and 8.4 (confidence limits, 2.4 to 39.3), respectively. CONCLUSIONS: These data show that AER increases during AMI and that it yields prognostic information additional to that provided by clinical or echocardiographic evaluation of left ventricular performance.

Aged↗