Early changes in tests of peripheral nerve function during oxaliplatin treatment and their correlation with chemotherapy-induced polyneuropathy symptoms and signs.

BACKGROUND AND PURPOSE: Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. METHODS: Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison. RESULTS: Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. CONCLUSIONS: Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.

The volitional travel speed varies with reproductive state in mature female brown trout Salmo trutta.

This study tested the effect of reproduction on the volitional travel speed of mature female brown trout Salmo trutta L. The downstream travel speed in the pre-spawning state was 0.25 m s(-1) (95% CI : 0.19, 0.34) while it increased significantly to 0.65 m s(-1) (95% CI: 0.49, 0.87) in the post-spawning state. The results suggest state-dependent travel speed in S. trutta.

Phagocyte-derived lactate stimulates oxygen consumption by Neisseria gonorrhoeae. An unrecognized aspect of the oxygen metabolism of phagocytosis.

O2 consumption resulting from interaction of Neisseria gonorrhoeae and human neutrophils represents a composite of O2 consumed by the two cell systems. Experiments studying the relative contribution of each system suggested the possibility that gonococci increased their metabolic activity in response to interaction with neutrophils. This hypothesis was confirmed by demonstrating that undifferentiated HL-60 cells, which are unable to undergo a respiratory burst, induce a two- to three-fold increase in gonococcal O2 consumption. Gonococcal capacity to adhere to HL-60 cells did not correlate with extent of metabolic stimulation. Stimulatory activity was demonstrable in cell-free supernatant from neutrophils or HL-60 cells, and increased with duration of incubation. Supernatant applied to a G-15 Sephadex column yielded fractions that stimulated gonococcal O2 consumption. Elution profiles were similar for HL-60 cells, neutrophils, and a stimulatory factor previously isolated from pooled human serum. This stimulatory factor(s) failed to adhere to DEAE or C-18 HPLC columns. Stimulatory activity release from myeloid cells was inhibited by incubation at 4 degrees C or in the presence of NaF, indicating a critical role for glucose metabolism. Lactate, the principal product of resting neutrophil glucose catabolism, was demonstrable in cell-free supernatants after incubation at 37 degrees C. Lactate accumulation was inhibited by NaF and decreased temperature of incubation. Lactate at levels present in cell-free supernatant increased gonococcal O2 consumption twofold and restored stimulatory activity to dialyzed serum. Live, but not heat-killed gonococci eliminated lactate released from neutrophils during phagocytosis. Gonococci are able to utilize host-derived lactate to enhance their rate of O2 metabolism.

On the mechanisms of blunted nocturnal decline in arterial blood pressure in NIDDM patients with diabetic nephropathy.

Nondiabetic hypertensive patients lacking the normal nocturnal decline in arterial blood pressure have enhanced cardiovascular complications. Since cardiovascular morbidity and mortality are increased in non-insulin-dependent diabetes mellitus (NIDDM), we performed a prospective cross-sectional case-controlled study comparing the diurnal variation in arterial blood pressure, prevalence of dippers, cardiac autonomic nervous function (beat-to-beat variation during deep breathing), and extracellular fluid volume (51Cr-labeled EDTA) in 55 NIDDM patients with diabetic nephropathy (group 1), 55 NIDDM patients with normoalbuminuria (group 2), and 22 nondiabetic control subjects (group 3). All antihypertensive treatments were withdrawn at least 2 weeks before the study. The nocturnal blood pressure reduction (daytime-to-nighttime)/daytime (mean +/- SE) was impaired in group 1 (6.6 +/- 1.5%) and group 2 (11.1 +/- 1.4%) as compared with group 3 (17.6 +/- 1.7%), and it was impaired in group 1 as compared with group 2 (P < 0.05 for each comparison). The prevalence of dippers (95% confidence interval) was lower in group 1 (42% [29-56]) as compared with group 2 (58% [44-71]; P = 0.08) and group 3 (86% [65-97]; P < 0.001) and in group 2 as compared with group 3 (P < 0.01). Abolished beat-to-beat variation was more prevalent in group 1 (63% [50-76]) as compared with group 2 (15% [7-27]) and with group 3 (5% [0-23]) (P < 0.001). Nocturnal blood pressure reduction was associated with beat-to-beat variation during deep breathing (r = 0.22, P < 0.01). Extracellular fluid volume (mean +/- SE) was higher in group 1 (15.9 +/- 0.5 l/m2) as compared with group 3 (14.1 +/- 0.8 l/m2) (P < 0.05) with group 2 between the two (15.1 +/- 0.4 l/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Microvascular right-to-left pulmonary shunt demonstrated by a radionuclide method.

A 37-yr-old man with angiolymphoid hyperplasia (Kimura's syndrome), who had been treated unsuccessfully for suspected asthma, was investigated due to a decrease in arterial oxygen saturation (86%). Right heart catheterization and angiography of the pulmonary artery failed to demonstrate any right-to-left shunts. However, simultaneous scintigraphy over the lungs, kidneys, and head after injection of 150 MBq technetium-99m-labeled macroaggregated albumin i.v. and inhalation of 150 MBq krypton-81m demonstrated a right-to-left shunt in the lungs probably caused by precapillary pulmonary arteriovenous shunts.

Gender differences in systolic left ventricular function in hypertensive patients with electrocardiographic left ventricular hypertrophy (the LIFE study).

Echocardiography was performed in 944 untreated hypertensive patients (391 women and 553 men, mean age 66 years) who had electrocardiographic left ventricular (LV) hypertrophy at baseline in the Losartan Intervention For End point reduction in hypertension (LIFE) study to evaluate gender-associated differences in systolic LV function. Women had significantly lower diastolic blood pressure (175/97 vs 173/99 mm Hg) and body surface area and a higher body mass index (all p < 0.01). Women also had higher LV ejection fraction (EF), endocardial and midwall fractional shortening (63% vs 60%, 35% and 33%, and 16% vs 15%, respectively, all p < 0.01), higher stress-corrected midwall fractional shortening (98% vs 96%, p < 0.05), and lower circumferential end-systolic wall stress (178 vs 187 kdynes/cm(2), p < 0.01). There was no difference in age or LV mass indexed for height(2.7), but relative wall thickness was higher in women (0.42 vs 0.41, p < 0.05). In multiple regression analyses: (1) EF and endocardial fractional shortening were 2% to 3% higher in women than men, independent of the effects of LV stress, body mass index, and height (multiple r = 0.77 and 0.75, respectively, gender p < 0.02 in both models); (2) midwall fractional shortening was 0.5% higher in women, independent of the effects of age, body mass index, circumferential end-systolic stress, and absence of diabetes (multiple r = 0.36, p = 0.014 for gender); and (3) stress-corrected LV midwall fractional shortening was 2% higher (p = 0.004) in women, independent of the effects of age, height, heart rate, body mass index, and diabetes (multiple r = 0.33). Thus, female gender is an independent predictor of higher systolic LV function in hypertensive patients with electrocardiographic LV hypertrophy.

Retinol-binding protein and transferrin in urine. New markers of renal function in essential hypertension and white coat hypertension?

We studied the 24 h urinary excretion of albumin, transferrin, immunoglobulin G, and retinol-binding protein in individuals with essential hypertension, white coat hypertension, and normotension. In 56 individuals, we measured the 24 h ambulatory blood pressure (AMBP). The individuals could be divided into three groups: 26 hypertensives, 14 white coat hypertensives, and 16 normotensives. Daytime AMBP values were (median values with range in parentheses, mm Hg): hypertensives 158/105 (198 to 121/95 to 120), white coat hypertensives 141/83 (161 to 129/72 to 90), and normotensives 123/75 (148 to 102/63 to 86). We determined with immunochemical methods the 24 h urinary excretions of albumin, transferrin, and immunoglobulin G, all markers of glomerular dysfunction, and retinol-binding protein, a marker of impaired proximal tubular function. We found a significantly higher excretion of albumin and transferrin in hypertensives (P < .0000/P < .0001) and in white coat hypertensives (P < .003/P < .02) compared to normotensives. Out of 26 hypertensives, seven had microalbuminuria (> or = 30 to < 300 mg albumin/ 24 h). Two cases of microalbuminuria were found among the 14 white coat hypertensives. Immunoglobulin G excretion was not significantly increased in any of the hypertensive groups. Retinol-binding protein excretion was significantly higher in hypertensive patients (P < .007), whereas no elevation was observed in persons with white coat hypertension. In hypertensives, a significant correlation was found between urinary excretion of albumin and transferrin and office blood pressure and systolic AMBP. There was no significant correlation between the urinary excretions of IgG and retinol-binding protein and blood pressures in any of the three groups. Our findings indicate that patients with white coat hypertension, like hypertensives, have a selective type of glomerular dysfunction. However, proximal tubular dysfunction was seen only in hypertensives. Urinary excretions of albumin, transferrin, and retinol-binding protein may be useful as markers of glomerular and tubular dysfunction in essential hypertension.

White coat hypertension diagnosed by 24-h ambulatory monitoring. Examination of 159 newly diagnosed hypertensive patients.

The study was conducted to estimate the frequency of white coat hypertension, ie, hypertension when in contact with the doctor only, in patients with newly diagnosed hypertension. We studied 159 consecutive patients (median age 47 years, 86 women) referred from primary health care to a hypertension clinic. For all patients, their general practitioner had decided to treat the hypertension pharmacologically, but the treatment had not yet begun. The blood pressure measurements reported from the referring doctors were 164.1 +/- 18.1/104.3 +/- 7.1 mm Hg (mean +/- SD). Measured at the hypertension clinic with random zero sphygmomanometer the pressures were 156.8 +/- 22.5/99.8 +/- 11.7 mm Hg. The indirectly measured day-time ambulatory blood pressures were 145.2 +/- 18.1/95.9 +/- 11.5 mm Hg. When a cut-off level of 90 mm Hg diastolic was applied, all patients were considered hypertensive by the referring doctors' measurements; the random zero office measurements regarded 18.3% of the patients as normotensive. The ambulatory measurements regarded a further 24.8% as normotensive (white coat hypertensive), whereas five patients considered normotensive by office measurements were hypertensive when evaluated by ambulatory monitoring (reverse white coat phenomenon). The difference between systolic office measurements and the daytime ambulatory blood pressures was significantly larger for female patients; age was positively correlated and weight negatively correlated to this difference. No significant difference was found for the diastolic measurements. It is concluded that white coat hypertension is present in approximately a quarter of the patients with newly diagnosed hypertension. By implementing ambulatory monitoring in clinical practice some of the overdiagnosing will possibly be avoided, but further studies on the subject are needed.

Smoking related to 24-h ambulatory blood pressure and heart rate: a study in 352 normotensive Danish subjects.

This study shows the association between smoking and both office and ambulatory blood pressure. By means of stratification, a uniform number of subjects of both sexes and spanning 6 decades (aged 20 to 79 years) were recruited randomly from the local community register. A total of 352 subjects participated, including 161 smokers. Smokers (both sexes and all age groups summed), as compared with nonsmokers had statistically significant lower office blood pressure as follows (mean systolic +/- SED/mean diastolic +/- SED): (systolic and diastolic, -6.8 +/- 2.1/-3.9 +/- 1.3); day ambulatory blood pressure (diastolic, /-2.8 +/- 1.0); and night ambulatory blood pressure (systolic and diastolic, -4.2 +/- 1.8/-3.9 +/- 1.1). The intraperson variability of the day ambulatory blood pressure (as measured every 15 min) was identical for the smokers and the nonsmokers. Smokers were found to have a diminished "white coat" effect; this diminished white coat effect has not previously been described. The major white coat effect was seen in the older nonsmokers, whereas the diminished white coat effect was most pronounced in the older male smokers and in the younger female smokers. Smokers seem to have a diminished white coat effect, as well as a lower ambulatory blood pressure throughout the day (diastolic) and at night (systolic and diastolic). The similar intraperson variability found in the smokers' and nonsmokers' blood pressure further speaks for a consistently lower blood pressure in smokers as compared with nonsmokers.

24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender.

UNLABELLED: The study was conducted to determine age and sex stratified normal values for 24-h ambulatory blood pressure. A sample of 352 healthy subjects (all white) were randomly selected from the community register and stratified by sex and age groups in decades from 20 to 79 years of age. Persons with a history of hypertension, cerebral apoplexy, diabetes, myocardial or renal disease, and who were taking blood pressure-influencing medication were excluded. Ambulatory blood pressure was recorded over 24 h, with measurements taken every 15 min from 07:00 to 22:59, and every 30 min from 23:00 to 6:59. Systolic blood pressure increased only slightly with age and was significantly higher in men than in women. The diastolic blood pressure increased only slightly with age in both sexes until the 50 to 59 years age group and declined thereafter. The diastolic blood pressure was not different for the two sexes. Both systolic and diastolic blood pressure were approximately 15% lower during the night regardless of age or sex. Ambulatory blood pressure during the daytime was on an average of 5 mm Hg lower than office blood pressure, but the mean difference between the two measurements increased with age. The variability of the difference also increased with age. IN CONCLUSION: Normal values for ambulatory blood pressure are presented in a randomly selected age- and gender-stratified population. Differences between office blood pressure and ambulatory blood pressure increased with age suggesting that the previously observed higher blood pressure seen in the elderly partly might be explained by a greater impact of white coat hypertension in older people.

The incidence of multiple gestations after in vitro fertilization is dependent on the number of embryos transferred and maternal age.

OBJECTIVE: To determine if the incidence of multiple gestations after IVF differs significantly depending on the number of embryos transferred and maternal age. DESIGN: Retrospective analysis of IVF database. SETTING: Tertiary care academic center. PATIENTS: One thousand eight hundred sixty-seven patients undergoing IVF with up to four embryos transferred during 1986 through 1993. MAIN OUTCOME MEASURES: The rate of singleton and multiple gestations > 20 weeks estimated gestational age (EGA). RESULTS: The incidence of triplet gestations > 20 weeks EGA among patients < or = 34 years of age with three versus four embryos transferred was 0.3% (1/335) versus 2.4% (15/662), respectively. The incidence of twin gestations > 20 weeks EGA among patients < or = 34 years of age with two versus four embryos transferred was 1.3% (3/234) versus 7.4% (46/622), respectively. Also among patients < or = 34 years of age, the incidence of singleton gestations > 20 weeks EGA with two versus three embryos transferred was 12.8% (30/234) versus 15.8% (53/335); with two versus four embryos was 12.8% (30/234) versus 17.2% (107/622); and with three versus four embryos was 15.8% (53/335) versus 17.2% (107/622), respectively. CONCLUSIONS: In women < or = 34 years of age undergoing IVF-ET, the transfer of four versus three and four versus two embryos significantly increased the incidence of triplet and twin gestations, respectively, without significantly improving the chance of singleton conception. This implies that a policy of transferring only three embryos should be considered in this age group (realizing that such a policy may merit modulation if pretransfer embryo selection is used.).

Xamoterol in severe congestive heart failure: long-term oral treatment, a double-blind randomised study.

Twelve patients in severe congestive heart failure were given placebo, 100 mg xamoterol (Corwin) twice daily and 200 mg xamoterol twice daily, respectively, in 3 two-week periods in a double-blind randomised study. At the end of each treatment period the patients were evaluated. No differences were found between placebo and xamoterol in the following parameters: New York Heart Association function group index, heart volume, body weight, exercise duration on bicycle and treadmill, heart rate and systolic and diastolic blood pressure at rest. However, during exercise we found significantly lower heart rate and rate-pressure product during xamoterol treatment. This reduction is probably indicating occupation of beta-adrenoreceptors with concomitant reduced oxygen consumption during exercise.

Do we undertreat hypertensive smokers? A comparison between smoking and non-smoking hypertensives.

The acute effect of smoking is a rise in blood pressure and heart rate. Nevertheless, in several epidemiologic studies, smokers tend to have a slightly lower office blood pressure than non-smokers. We studied the 24 h ambulatory blood pressure consecutively in hypertensive smokers (> or = 10 cigarettes per day, n = 26) and hypertensive non-smokers (n = 26) to test the hypothesis that smoking is associated with a rise in ambulatory blood pressure. There was no difference between smokers and non-smokers in office blood pressure (153.8 +/- 22.2/98.5 +/- 10.6 vs 149.0 +/- 16.1/96.9 +/- 11.6 mmHg). However, we found a statistically significant higher daytime systolic and diastolic blood pressure in smokers (153.7 +/- 16.2/96.1 +/- 9.5 vs 145.0 +/- 12.1/90.1 +/- 10.0 mmHg) than in non-smokers. Differences were also found for office-daytime differences and when studying patients on pharmacological antihypertensive treatment separately. Daytime heart rate was also significantly higher in smokers (86.6 +/- 9.4 vs 76.0 +/- 10.9). We conclude that smokers tend to be undertreated in that they have a higher daytime blood pressure than do non-smokers, a difference that is not recognized by measuring office blood pressure alone. We therefore recommend 24h ambulatory blood pressure measurement in smokers with essential hypertension.

Multivariate prognostic index in acute myocardial infarction for individual duration of hospitalization.

To estimate the feasibility of an early and individualized discharge of acute myocardial infarction patients, a new prognostic index was constructed from Cox's regression model for survival analysis. From the first 5 d in the coronary care unit the significant prognostic variables in the index were heart failure (definite objective signs of congestive heart failure and/or definite cardiomegaly and/or pulmonary vascular enlargement on chest x ray in upright position), cardiogenic shock, atrioventricular block, and age. From the index the individual patient's probability of survival up to day 36 after admission could be directly predicted. The more positive the index, the higher was the probability of death. The prognostic efficacy was good, with two unexpected deaths from 149 patients in the lowest risk group. With a selected mortality risk of 5% from the day of discharge until day 30 after admission, 134 patients (52%) could be discharged on day 6. To have the risk of less than or equal to 5% after discharge another 54 patients (21%) would have to stay in the hospital for 24 d. Following this system of early and individualized discharge there were few serious post-discharge complications (one cardiac arrest and one ventricular tachycardia). Reinfarctions could not be predicted. This model could save around 2000 hospitalization days per year in this hospital.

Intention to stop smoking among Norwegian smokers: the role of nicotine dependence, type of cigarettes, and age at onset of daily smoking.

This study is a report on the data of psychological nicotine dependence among Norwegian daily smokers. Nicotine dependence was higher among smokers smoking hand-rolled cigarettes than smokers smoking manufactured cigarettes in spite of the fact that the average number of cigarettes smoked per day was the same for both groups. The dependence also increased as the starting age of daily smoking decreased. Nicotine dependence was higher among daily smokers of low education compared to smokers of higher education. This was explained by a difference in the proportion of smokers of hand-rolled cigarettes in the two groups. The data are discussed in light of Norwegian research showing that hand-rolled cigarettes can contain two to three times as much nicotine and tar as manufactured cigarettes. The differences in dependence levels among smokers of hand-rolled and manufactured cigarettes suggest that the smokers are also exposed to different amounts of other harmful substances present in tobacco. Moreover, smokers of hand-rolled cigarettes were less motivated to quit, which implies that these smokers are exposed to greater health damage compared to smokers of manufactured cigarettes. These findings are discussed with regard to Norwegian taxing policy, which appears to encourage the consumer to smoke the more harmful product. Furthermore, the research findings are discussed in light of the fact that Norway has neither set a maximum limit of poisonous substances in rolling tobacco nor required that packs of rolling tobacco be labeled with a declaration of contents.

[A comparative study of atenolol (Tenormin) and the combined preparation atenolol/chlorthalidone (Tenoretic Mite) in essential hypertension. A randomized double-blind study from general practice]. / En sammenlignende undersøgelse af atenolol (Tenormoin) og kombinationspraeparatet atenolol/klortalidon (Tenoretic Mite) ved essentiel hypertension. En randomiseret dobbeltblind undersøgelse fra almen praksis.

Two hundred and ninety-two hypertensive patients from general practice who had previously been treated with a diuretic with insufficient effect participated in a randomised trial for a period of three months. A total of 115 patients completed treatment with 50 mg atenolol (Tanormin) and 121 were treated with the combined preparation consisting of 50 mg atenolol and 12.5 mg chlothalidone (Tenoretic Mite) while 56 patients defected from the trial. In both of the groups, the average blood pressure was reduced significantly already after treatment for one month. A significantly greater number of patients receiving combined treatment achieved satisfactory diastolic blood pressures (less than 90 mmHg), the proportions being 78% and 54%, respectively. Better effects from combined treatment were found particularly in patients over 60 years of age and in females. No significant differences were observed between the side-effects of the regimes nor in the laboratory values registered during treatment.

[Is Letigen contraindicated in hypertension? A double-blind, placebo controlled multipractice study of Letigen administered to normotensive and adequately treated patients with hypersensitivity]. / Er Letigen kontraindiceret ved hypertension? En dobbeltblindet, placebokontrolleret multipraksisundersøgelse af Letigen givet til normotensive og velbehandlede hypertensive patienter.

The aim of this study was to study how the slimming drug, Letigen, containing ephedrine (E) 20 mg and caffeine (C) 200 mg (E + C) affects blood pressure in normotensive and hypertensive patients treated with adrenergic beta-receptor blocking drugs and/or other antihypertensive agents, during a period of six weeks. We followed 136 patients in a double blind, randomised, placebo controlled study of five parallel groups of overweight patients from general practices. The systolic blood pressure was reduced significantly (5.5 mmHg) in the patients treated with antihypertensive agents other than betablockers, plus E + C. In normotensive patients treated with E + C the systolic and diastolic blood pressure declined significantly (4.4/3.9 mmHg). A mean loss of weight of 4 kg over six weeks was significant for all groups. This study does not support the assumption that E + C should cause rises in blood pressure in either normotensive or hypertensive obese patients. The antihypertensive effect of the betablockers was not reversed by E + C.

[Isolated systolic hypertension in the elderly]. / Isoleret systolisk hypertension hos aeldre.

This review article examines the essential literature concerning isolated systolic hypertension in the elderly (ISH). The prevalence of ISH rises curvilinearly with age from approximately 3% at 30 years of age to 25% at 80 years of age, and is more common in women. The pathophysiology of ISH is not yet completely investigated. It seems that the haemodynamics of ISH differ from those of essential hypertension by showing considerably decreased arterial compliance and lack of elevated peripheral resistance. Humoral changes seem very insufficiently investigated. Several studies have shown that ISH is difficult to diagnose because of a high prevalence of white coat hypertension, perhaps in the area of 40%. The treatment of ISH has formerly been debated. Recently published studies have shown beneficial effects of medical antihypertensive treatment in ISH. First choice drugs should be low-dose thiazides and beta-blockers.

[What do we know about consultation hypertension?]. / Hvad ved vi om konsultationshypertension?

This review article examines the essential literature concerning "white coat" hypertension. It is stated that "white coat" hypertension is present in approximately 20% of patients with diagnosed mild to moderate hypertension. It is concluded that the pathophysiology of "white coat" hypertension is incompletely investigated; that the prognosis for untreated "white coat" hypertension seems fair; medical treatment being scarcely required. It is concluded further that more accurate diagnosis of mild to moderate hypertension, including the use of ambulatory blood pressure monitoring, will reduce the overall expenses by approximately million Danish crowns annually (approximately 2,000,000 pounds).

[Standardized prothrombin time determinations and optimal anticoagulant therapy]. / Den standardiserede protrombintidsbestemmelse og optimal antikoagulansbehandling.

WHO and other international organizations have recommended the introduction of a standardized prothrombin time determination. This would allow a universal scale for the intensity of oral anticoagulation therapy to be used. A prerequisite is the use of thromboplastin, calibrated against the international reference thromboplastin, standardized methodology etc. This permits every prothrombin time determination to be expressed as International Normalized Ratio (INR). The introduction of INR facilitates the implementation of optimal oral anticoagulation as defined by larged international studies.