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PubMed1981

Oral contraceptives and risk of ovarian cancer.

Among a large cohort of married, female, registered nurses under 55 years of age, oral contraceptive (OC) use was examined in women with ovarian cancer and 470 age-matched controls. Use of OCs before the diagnosis of cancer was reported by 28% of the women with ovarian cancer and 33% of the controls, yielding a relative risk of 0.8 (95% confidence limits 0.4-1.5). This apparent inverse relationship was attributable to a large effect in women 35 years of age or younger (relative risk = 0.2, 95% confidence limits 0.1-1.0). Patients with ovarian cancer were 2.2 times more likely than controls to be nulliparous. These data provide reassurance that OC use is not likely to be associated with any major increase in risk of ovarian cancer, but suggest that future studies of this relationship need to consider the possible confounding effect of infertility.

Adult↗
PubMed1987

Anterograde transsynaptic degeneration in the deep cerebellar nuclei of Purkinje cell degeneration (pcd) mutant mice.

The genetically-determined loss of Purkinje cells (PCs) in 'Purkinje cell degeneration' (pcd) mutant mice results in the loss of presynaptic afferents to the deep cerebellar nuclei (DCN). This deafferentation takes place between postnatal day (P)17 and P45, i.e. after the maturation of cerebellar circuitry. We examined the DCN of normal and pcd mutant mice by quantitative light microscopic methods to determine whether neuronal atrophy or loss in the DCN take place during and after the loss of their input from the PCs. Neuronal diameters in control mice were 16.4 +/- 0.72 microns (mean +/- S.D.) at P23 and 15.6 +/- 0.64 microns at P300. The respective values in pcd mutant mice were 15.7 +/- 0.58 microns and 13.5 +/- 0.24 microns. Diameters in 300-day-old mutants were significantly smaller than those in both age-matched controls and 23-day-old mutants (P less than 0.001). Neuronal populations in the DCN of control mice were 10,167 +/- 949 at P23 and 10,429 +/- 728 at P300. The respective values in mutants were 9,436 +/- 1,366 and 7,424 +/- 1,324. There was a significant difference of 29% [95% confidence limits: 9-45%] between 300-day-old mutants and age-matched controls (P less than 0.01), and a significant loss of 21% [95% confidence limits: 4-36%] in 300-day-old mutants with respect to 23-day-old mutants (P less than 0.05). The total volume of the DCN was 22% less in 300-day-old mutants in relation to 23-day-old mutants (P less than 0.05). These findings support the idea that the stability of DCN neurons in the mature cerebellum depends in part on the synaptic input from PCs.

Animals↗
PubMed1985

Retinal blood flow in the cat following periods of light and darkness.

Estimates of flow velocity in retinal arterioles of seven cat eyes were obtained using high-speed cine Indocyanine Green absorption angiography in the near-infra-red waveband, following alternate 30 min periods of light and darkness. Simultaneous estimates of vessel calibre were obtained by micrometry of the cine image. Comparisons of values obtained after periods of light adaptation with the preceeding and subsequent periods of darkness show no significant changes in vessel calibre (at P greater than 0.95 level, confidence limits +/- 17% of the mean) while three of 14 comparisons show significant but inconsistent changes in linear flow velocity (at P greater than 0.95 level, confidence limits +/- 22% of the mean). A significant decrease (41%) in b-wave amplitude was seen in six of seven experiments after dark adaptation subsequent to exposure to light for a total of 60 min.

Animals↗
PubMed1995

Pulmonary interstitial pressure in premature rabbits.

By micropuncture technique we measured pulmonary interstitial pressure (Pip) from birth up to 6 h postnatal age in anesthetized and paralyzed cesarian delivered term (31 days gestation) and premature (27 to 30 days gestation) rabbits. In term cesarian delivered rabbits Pip followed the time course of vaginally delivered rabbits, namely, it increased from about zero at birth up to about 5 cmH2O at 2 h, as a result of alveolar fluid reabsorption, subsequently it decreased becoming subatmospheric due to progressive interstitial fluid drainage. In ventilated lung regions of premature rabbits, Pip also peaked to about 5 cmH2O at 2 h but its subsequent decrease was markedly slowed down while in atelectatic regions of premature rabbits Pip remained slightly subatmospheric. Up to 6 h, the wet/dry weight ratio of the lung was higher in premature relative to vaginally and cesarian delivered term rabbits (at birth 8.4 +/- 0.9 vs. 7.5 +/- 0.8). In 29-31 days rabbits, plasma protein concentration at birth was 3.6 +/- 0.5 g/dl (within 95% confidence limits for vaginally delivered rabbits, considered as control) while in 27-28 days rabbit it was 3.1 +/- 0.4 g/dl (at the lower edge of control confidence limits). In the first postnatal hours, the increase in Pip favoured fluid reabsorption into pulmonary microcirculation in term cesarian delivered rabbits and in ventilated regions of premature rabbits. Conversely, in the atelectatic regions of premature rabbits the unchanged Pip value in the postnatal hours favours fluid filtration from microcirculation into lung interstitium.

Age Factors↗
PubMed2005

Absorption of urea through the oral mucosa and estimation of the percentage of secreted whole saliva inadvertently swallowed during saliva collection.

OBJECTIVE: To determine whether some of the urea added to certain chewing gums may be absorbed through the oral mucosa and whether some saliva is inadvertently swallowed during the collection of saliva elicited by the chewing of gum. DESIGN: On two occasions, 10 experienced saliva collectors made a 5 min collection of unstimulated whole saliva and then chewed gum for 10 min and during this time collected their saliva. On one occasion, they chewed one tablet of gum containing 0.5 mg of Phenol Red, a non-absorbable substance, and one tablet of a gum containing 27.3 mg of urea. On another occasion, they chewed two tablets of the Phenol Red gum. Their saliva and the chewed gum were assayed for their Phenol Red and urea contents and the totals calculated. Since saliva normally contains urea, the recovery of urea was calculated as the difference between the amounts recovered in the two collection sessions. RESULTS: The mean recovery of Phenol Red was 96.7%, but in three participants the amount recovered was less than the 95% confidence limits for assay error. The mean recovery of urea was 85.7% and in nine of the 10 participants, the amount recovered was less than the confidence limits for assay error. In all participants, the percentage urea recovery was less than that of Phenol Red. CONCLUSION: The results showed: (1) that Phenol Red appears to be a useful, non-absorbed marker for studies of drug absorption through the oral mucosa, (2) that when the salivary urea concentration is higher than that in plasma, urea may be absorbed through the oral mucosa, (3) that even experienced saliva collectors may inadvertently swallow some of the saliva they produce. This latter finding has implications for all clinical studies of saliva.

Absorption↗
PubMed2000

Long-term mortality after acute myocardial infarction in relation to prescribed dosages of a beta-blocker at hospital discharge.

This study was designed to describe the 5-year mortality rate in relation to the dose of metoprolol prescribed at hospital discharge after hospitalisation for acute myocardial infarction (AMI). All patients discharged alive after being hospitalized for AMI at Sahlgrenska Hospital (covering half of the community of Göteborg, with 500,000 inhabitants) during 1986-1987 (period I) and all patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital and Ostra Hospital (covering the whole area of the community of Göteborg) in 1990-1991 (period II) were included. Overall mortality was retrospectively evaluated over 5 years of follow-up. In all there were 2161 patients who were discharged after AMI. Seventy-three percent of these patients were prescribed a beta-blocker and 59% were prescribed metoprolol. Of the patients prescribed metoprolol, 34% were on 200 mg, 46% on 100 mg, and 20% on 50 mg or less. Information on 5-year mortality was available for 2142 of the 2161 patients (99.1%). The 5-year mortality was 24% among patients prescribed 200 mg, 33% among patients prescribed 100 mg, and 43% among patients prescribed 50 mg (P < 0.0001). Patients prescribed another beta-blocker had a 5-year mortality of 39%, and patients prescribed no beta-blocker at all had a 5-year mortality of 61%. When correcting for dissimilarities at baseline, patients who were prescribed < or =100 mg had an adjusted risk ratio for death of 0.79 (95% confidence limit 0.64-0.96; P = 0.021) as compared with patients not prescribed a beta blocker. The corresponding figure for patients prescribed >100 mg was 0.63 (95% confidence limit 0.48-0.84; P = 0.001). Both patients prescribed high and low doses of metoprolol after AMI appeared to benefit from treatment. There was a trend indicating more benefit when larger doses were prescribed.

Acute Disease↗
PubMed1984

Case mix, costs, and outcomes. Differences between faculty and community services in a university hospital.

To gain insight into the possible consequences of prospective payment for university hospitals, we studied 2025 admissions to the faculty and community services of a university hospital, measuring differences in case mix, costs, and mortality in the hospital. The faculty service had more of the patients with costly diagnoses, but even after adjustment for diagnosis-related groups (DRGs), costs were 11 per cent higher on the faculty service (95 per cent confidence limits, 4 to 18 per cent). The percentage differential was greatest for diagnostic costs. The differential was particularly large--70 per cent (95 per cent confidence limits, 33 to 107 per cent)--for patients with a predicted probability of death of 0.25 or greater. The in-hospital mortality rate was significantly lower on the faculty service after adjustment for case mix and patient characteristics (P less than 0.05); the difference was particularly large for patients in the high-death-risk category. Comparison of a matched sample of 51 pairs of admissions from the high-death-risk category confirmed the above results with respect to costs and in-hospital mortality, but follow-up revealed that the survival rates were equal for the two services at nine months after discharge. The effect of prospective payment on the cost of care will be closely watched; we conclude that is will also be important to monitor the effect on outcomes, including hospital mortality rates.

Aged↗
PubMed1995

Geographical clustering of human T-cell lymphotropic virus type 1 infection in Honduras.

Geographical clustering of human T-cell lymphotropic virus type 1 (HTLV-1) infection has been identified in the nonmestizo communities in several cities along the Atlantic coast of Honduras. Of the 2,651 serum samples tested, 122 samples were repeatedly reactive for HTLV-1 antibodies in two different enzyme immunoassays and 3 were indeterminate. These sera did not react in the HTLV-2-specific antibody tests. The presence of HTLV-1 antibodies was confirmed by HTLV-1 immunoblots or Western blots (immunoblots), and the infection was verified by the detection of HTLV-1-specific genetic sequences in the cellular DNA by PCR. Genomic DNA from the peripheral blood mononuclear cells was first tested with generic primers and probes that identified both HTLV-1 and HTLV-2. Next, all DNA samples that showed HTLV reactivity were tested by PCR with specific primers and probes that distinguished HTLV-1 sequences from those of HTLV-2. Our results indicate that only HTLV-1 infection was present in the blood of both mestizo and nonmestizo residents of 15 cities in the Republic of Honduras. The overall prevalence of HTLV-1 infection in the nonmestizo population was 8.1% (95% confidence limit, 6.6 to 9.7%). The mestizo population residing in the same geographical vicinities showed a HTLV-1 antibodies in 0.5% of serum samples tested (95% confidence limit, 0.6 to 1.7%), indicating a significantly greater prevalence of HTLV-1 infection in the nonmestizo population than in the mestizo ethnic groups living in Honduras (P = 0.0001). Since no HTLV-2 antibody reactivity or HTLV-2-specific genetic sequences were detected by PCR with different primers and probes, it was concluded that HTLV-2 infection was not present in the Honduran population groups we tested. Our study also suggested an endemic nature for this virus because there was no difference in the prevalence rate of HTLV-1 antibodies in the nonmestizo community living in the coastal towns of Honduras between 1989 and 1993. This is the first report of HTLV-1 cluster identification in Honduras, Central America.

Adolescent↗
PubMed1984

Statistical approaches to the analysis of receiver operating characteristic (ROC) curves.

In this article we review published and some unpublished work in statistical analyses of ROC curves. We describe both single and joint indices and indicate the approaches that have been taken to consider between-reader variations and correlations, within-reader variations, and variations and correlations between cases. We then discuss in detail a single index, the TP ratio at a fixed FP ratio (designated TPFP), or the FP ratio at a fixed TP ratio (designated FPTP). We show how to calculate confidence limits around any point on the curve; we further show, using the conventional Dorfman and Alf program and the jackknifing technique, how to calculate these confidence limits for multiple curves derived from the same sample of patients.

Diagnosis↗
PubMed1998

Inhibitory effects of ginkgolides on nitric oxide production in neonatal rat microglia in vitro.

AIM: To study the effects of ginkgolide A (GA) and B (GB), apafant (Apa), and N omega-nitro-L-arginine (L-NA) on nitric oxide (NO) production in cultured neonatal rat microglia. METHODS: NO concentration was represented by nitrite which was determined by Griess reaction. RESULTS: In resting microglia, no inhibitory effects of GA, GB, and Apa were observed. L-NA inhibited NO production, its IC50 value (95% confidence limits) being 3.4 (0.8-14.9) mumol.L-1. GA, GB, and L-NA inhibited NO production in LPS-stimulated microglia, and their IC50 values (95% confidence limits) were 5.7 (1.8-18.1), 1.1 (0.3-4.4), and 0.5 (0.1-2.8) mumol.L-1, respectively. Apa did not inhibit NO production. CONCLUSION: GA and GB inhibited NO production in LPS-stimulated microglia.

Animals↗
PubMed1994

Effect of verapamil on reinfarction and cardiovascular events in patients with arterial hypertension included in the Danish Verapamil Infarction Trial II. The Danish Study Group on Verapamil in Myocardial Infarction.

An increased incidence of reinfarction and cardiovascular events has been reported in patients with hypertension recovering from acute myocardial infarction. We studied the effect of intervention with verapamil on the development of myocardial infarction and cardiovascular events in 301 patients with hypertension enrolled in the Danish Verapamil Infarction Trial II. During the second week after the index infarct, patients were randomly assigned to treatment with verapamil 360 mg per day (n = 149) or placebo (n = 152) and followed-up to 18 months (mean 16 months). The 18 months first reinfarction rates were 12.5% in verapamil and 19.8% in placebo treated patients (hazard ratio 0.53, 95% confidence limits 0.28-1.00, P = 0.04). The first cardiovascular event rates were 21.8% in the verapamil and 29.3% in the placebo group (hazard ratio 0.66, 95% confidence limits 0.41-1.06, P = 0.07). In this retrospective analysis of patients with hypertension included in the Danish Verapamil Infarction Trial II, intervention with verapamil reduced cardiovascular events primarily due to a substantial reduction in reinfarctions.

Aged↗
PubMed1996

Effects of methylflavonolamine on free intracellular calcium in isolated embryonic rat brain cells.

AIM: To observe the effects of methylflavonolamine (MFA) on free intracellular calcium concentration ([Ca2+]i) of isolated embryonic rat brain cells in presence and absence of high extracellular potassium and L-glutamate. METHODS: [Ca2+]i was measured in a spectrofluorophotometer by preloading the cells with calcium sensitive fluorescent indicator Fura 2-AM. RESULTS: Resting [Ca2+]i was 197 +/- 20 nmol.L-1 (n = 44) in the presence of Ca2+ 1.3 mmol.L-1 in Hanks' solution. MFA 0.15 mmol.L-1 had no effect on the resting [Ca2+]i. When extracellular Ca2+ was 1.3 mmol.L-1, MFA (0.03-0.3 mmol.L-1) concentration-dependently inhibited the [Ca2+]i elevation induced by high extracellular potassium, with an IC50 value of 0.14 (95% confidence limits: 0.05-0.42) mmol.L-1. At higher concentration (0.15-0.30 mmol.L-1), MFA decreased L-glutamate-induced [Ca2+]i elevation, with an IC50 of 0.20 (95% confidence limits: 0.01-3.40) mmol.L-1. CONCLUSION: MFA inhibited Ca2+ influx through voltage-dependent calcium channel and, at higher concentration, through receptor-operated calcium channel in the embryonic rat brain cells.

Animals↗
PubMed2000

Regrowth delay analysis of irradiated tumors in the curative dose region.

PURPOSE: To develop a method to analyze regrowth delay times, including cured tumors. METHODS AND MATERIALS: Regrowth delay measured in the in vitro squamous cell carcinoma megacolony system following fractionated irradiation was analyzed using two different approaches. A conventional regrowth delay analysis based on means or medians of dose groups was contrasted with a one-step procedure using the inverse of individual regrowth delay times, where cured tumors are represented by an infinite delay time. Two data sets with different proportions of cured tumors were compared in this way. In addition, for both approaches, confidence limits were also generated by the bootstrap technique. RESULTS: The parameter estimated was the alpha/beta ratio. The inverse analysis yielded similar results as the conventional analysis, but with much smaller confidence limits. When the dataset was stripped by stepwise removal of lower dose groups with no cures, the estimates of the alpha/beta ratio remained definitely more robust in inverse analysis. Results of the bootstrap procedure confirmed the accuracy of the calculated confidence intervals. CONCLUSION: Regrowth delay analysis using reciprocal regrowth delay times is a useful tool, especially when the data shows large variations, or a substantial fraction of the dataset falls into the curative dose region.

Animals↗
PubMed2000

Incorporating model uncertainties along with data uncertainties in microbial risk assessment.

Much research on food safety has been conducted since the National Food Safety Initiative of 1997. Risk assessment plays an important role in food safety practices and programs, and various dose-response models for estimating microbial risks have been investigated. Several dose-response models can provide reasonably good fits to the data in the experimental dose range, but yield risk estimates that differ by orders of magnitude in the low-dose range. Hence, model uncertainty can be just important as data uncertainty (experimental variation) in risk assessment. Although it is common in risk assessment to account for data uncertainty, it is uncommon to account for model uncertainties. In this paper we incorporate data uncertainties with confidence limits and model uncertainties with a weighted average of an estimate from each of various models. A numerical tool to compute the maximum likelihood estimates and confidence limits is addressed. The proposed method for incorporating model uncertainties is illustrated with real data sets.

Colony Count, Microbial↗
PubMed1986

Stroke and migraine in the Oxfordshire Community Stroke Project.

A total of 323 cases of first-ever stroke were registered in the first 2 years of the Oxfordshire Community Stroke Project. Of these patients, 244 (76%) had a stroke due to cerebral infarction. There was a past history of migraine headaches in 56 (17%) of the 323 cases of stroke and in 44 (18%) of the 244 cases of cerebral infarction. A past history of migraine headaches was no commoner in patients with stroke due to cerebral infarction than in those with stroke due to intracranial haemorrhage. One hundred and seventy-three (71%) patients with cerebral infarction had at least one risk factor for ischaemic stroke; the frequency of such risk factors was similar in patients with and without a history of migraine. In 7 (3%) of the 244 patients the cerebral infarction was presumed to be "migrainous"; however, only 3 of these 7 (1.2% of the 24) were free of risk factors for ischaemic stroke. If all 7 cases were considered migrainous, the incidence rate of first migrainous cerebral infarction was 3.36 per 100,000 per year (95% confidence limits 0.87-5.86). If only the 3 patients who were free of risk factors were included, the incidence was 1.44 per 100,000 per year (95% confidence limits 0-3.07).

Adult↗
PubMed1995

Percutaneous central venous catheter use in the very low birth weight neonate.

UNLABELLED: A retrospective study was carried out comparing 61 very low birth weight infants (VLBW) with percutaneous central venous catheters with 92 infants managed with peripheral cannulae. Eighteen infants developed one or more episodes of catheter-associated bacteraemia. In 70% of cases the infection was successfully treated with the line in situ. Logistic regression analysis was performed to examine risk factors for bacteraemia. The duration of intravenous fluids and of intermittent positive pressure ventilation were both significant risks for infection (odds ratios and 95% confidence limits 4.4, 2.7-12.0 and 2.5, 1.0-6.1 respectively), but the presence of a silastic catheter was not an independent risk factor (odds ratio 0.6, 95% confidence limits 0.1-3.0). CONCLUSION: Percutaneous central venous catheters provide a satisfactory means of delivering parenteral nutrition with minimal disturbance to ill VLBW infants.

Bacteremia↗
PubMed1993

Staged conversion to arterial switch for late failure of the systemic right ventricle.

Late failure of the systemic right ventricle is seen in up to 10% of patients after atrial switch for transposition of the great arteries and in patients with atrioventricular and ventriculoarterial discordance. Since 1981, 24 such patients have entered a program to achieve conversion to arterial switch. The primary diagnoses were transposition of the great arteries with ventricular septal defect (n = 10), transposition of the great arteries with intact ventricular septum (n = 5), Taussig-Bing anomaly (n = 4), and atrioventricular and ventriculoarterial discordance (n = 5). The mean interval from atrial switch to right ventricular failure was 7 years. Four patients underwent direct conversion to arterial switch, with one operative death. In 3 of these patients the initial left ventricular pressure was high. The fourth patient was too sick to undergo banding, and he required left ventricular assist device support after switch conversion. The other 20 patients underwent 34 procedures to place or tighten a pulmonary artery band to prepare the left ventricle to tolerate systemic pressure. There was one band-related operative death. Twelve patients have thus far gone on to switch conversion 13 days to 5 years (mean, 26 months) after banding. In total, therefore, 16 patients have had an arterial switch with atrial reconstruction. The early mortality for switch conversion was 2 of 16 (12.5%; 70% confidence limits, 4% and 27%), with one late death 12 months after operation. Including operative mortality, the 1-year actuarial survival probability after conversion was 80% (70% confidence limits, 62% and 92%). All survivors are asymptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2002

Monitoring xenon in the breathing circuit with a thermal conductivity sensor. Comparison with a mass spectrometer and implications on monitoring other gases.

OBJECTIVE: To test the accuracy of a thermal conductivity xenon sensor in vitro and in vivo and to test the effect of xenon on other anesthetic gas analyzers as determined by a mass spectrometry gold standard. METHODS: The xenon concentration was measured with a prototype of a thermal conductivity sensor and a mass spectrometer in vitro and in 6 patients. Further in vitro experiments determined the impact of xenon on the measurements of oxygen, carbon dioxide and desflurane with three commercially available anesthesia gas monitors. RESULTS: In vitro the thermal conductivity sensor and an associated computer, when calibrated against a mass spectrometer using a third order polynomial calibration curve measured the xenon concentration to a 95% confidence limit of -1.2 to +1.8 vol% compared to mass spectrometry. In vivo and under clinical conditions with a mixture of xenon, O2 and CO2 the 95% confidence limit was -2.5 to +1.6 vol% with a mean bias of -0.5 vol% over a concentration range of 20 to 70 vol%. Xenon induced a clinically relevant bias on the measurements of oxygen (up to 5 vol%), carbon dioxide and desflurane (both twofold overestimation) in a Hewlett-Packard M1025B monitor. In contrast there was only a small bias on the measurements of a Drager PM8060 and a Datex AS3 compact monitor, which was statistically significant (oxygen and desflurane) but clinically irrelevant. CONCLUSION: Thermal conductivity is a clinically useful technique to measure xenon in the breathing circuit despite its statistically significant but clinically irrelevant error compared to mass spectrometry. Other gases of interest have to be measured with selected monitors explicitly approved or tested for use with xenon.

Anesthesiology↗