Rising erythrocyte sedimentation rate during several years before diagnosis can be a predictive factor in 70% of renal cell carcinoma patients. The benefit of knowing subject-based reference values

Objectives. A diagnosis of renal cell carcinoma (RCC) early enough for potentially curative surgery is difficult. We wanted to establish whether the erythrocyte sedimentation rate (ESR) in RCC patients had begun to rise before the appearance of any symptoms or signs and, if so, when.
Design. A retrospective study of the evolution of the ESR in 236 randomly selected RCC patients during several years before diagnosis, comparing the results with previously obtained population-based control values.
Results. It is generally held that RCC patients have a high ESR at diagnosis. In our material, however, 29.7% of the RCC cases had an ESR that at this time was at or below the population-based upper reference limit; it had not increased significantly, neither with time before diagnosis, nor with age. In 70.3% of RCC patients the ESR was increased and had been significantly rising for up to 6 years or more before diagnosis. This had not been adequately responded to, probably because the physicians lacked knowledge of the patients' baseline ESR, and because none of the prediagnostic readings had been above the population-based reference limit.
Conclusions. Systematic ESR graphic recordings over time will enable a physician to determine each individual's baseline value, and hence note any continuously rising trend, which should lead to further investigations, e.g. an ultrasound kidney examination. This may provide an early clue to many otherwise non-symptomatic RCC cases. It is time for a reappraisal of the predictive value of the ESR to discover early RCC, and possibly other diseases as well.     

Daytime sleepiness and napping amongst the elderly in relation to somatic health and medical treatment

Objectives. To investigate daytime sleepiness and napping in relation to age, health and nocturnal sleep.
Design. An epidemiological survey by means of a questionnaire.
Setting. The counties of Västerbotten and Norrbotten in northern Sweden.
Subjects. All 10216 members of the pensioners' association SPF.
Main outcome measures. Daytime sleep, daytime sleepiness, health, night sleep, somatic diseases and medication.
Results. Daytime sleepiness was 4.9 (3.7–6.4) and 5.1 (4.2–6.1) times more common in men and women, respectively, in poor health than in those in good health. It was also more common in subjects suffering from cardiac diseases, diabetes and musculo-skeletal diseases, urological symptoms, and diseases with sensory and neurological impairments, compared with symptomless subjects. Stepwise regression analysis showed an increase in daytime sleepiness in men in association with impaired general health ( r ²=0.067), frequent awakenings ( r ² =0.098), higher age ( r ²=0.109) and difficulty in falling asleep again after nocturnal awakening ( r ²= 0.115), and in the women, in association with impaired health ( r ²=0.118), difficulty in falling asleep again ( r ²=0.149), frequent awakenings (r ²=0.160) and higher age ( r ²=0.171). There was no further increase in r ²=either for men or women in relation to use of hypnotics.
Conclusion. Age, poor health and different somatic diseases, but not hypnotics, are associated with daytime sleepiness in elderly persons.     

Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries

Objective. Haemostatic imbalance may be an aetiological factor in the development of acute coronary syndromes. Inherited resistance to activated protein C (APC) is a common disorder associated with hypercoagulability and lifelong risk of venous thrombosis. APC resistance is due to a single mutation in the gene coding for coagulation factor V (FV:Q⁵⁰⁶). To test the importance of the FV:Q⁵⁰⁶ mutation in premature myocardial infarction (MI), its prevalence was investigated in Swedish patients with MI before the age of 50 years.
Design, setting and subjects. In a retrospective case-control study, the FV:Q⁵⁰⁶ mutation was investigated in 101 survivors of MI (79 men, 22 women) and in 101 healthy sex- and age-matched controls.
Main outcome measure. The prevalence of FV:Q⁵⁰⁶ mutation.
Results. The FV:Q⁵⁰⁶ mutation was found in 18% of patients versus 11% of controls ( P =0.16). The mutation was significantly more frequent amongst male patients than amongst controls (23 vs. 10%; P =0.03), the calculated odds ratio being 2.6 (95% CI, 1.1–6.4).
Conclusion. The high prevalence of the FV:Q⁵⁰⁶ mutation found amongst Swedish MI patients, especially amongst men, is noteworthy, and calls for further studies on the outcome of MI in APC-resistant patients. The prevalence of the FV:Q⁵⁰⁶ mutation in controls is higher than figures reported from other countries, suggesting that at least 10% of the Swedish population are carriers of a congenital prothrombotic disorder.     

Chronic consumers of boiled coffee have elevated serum levels of lipoprotein(a)

Objectives. Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boiled coffee and serum levels of lipoprotein(a).
Design, setting and subjects. Healthy Norwegians 40–42 years of age, who habitually consumed five or more cups of boiled coffee per day ( n =150) were compared with matched filter coffee consumers ( n =159) in a cross-sectional study, as part of the Norwegian National Health Screening in 1992.
Results. The median lipoprotein(a) level was 13.0 mg  dL⁻¹ (10th and 90th percentile: 2.5 and 75.0 mg  dL⁻¹, respectively) on boiled and 7.9 mg dL^-1 (10th and 90th percentile: 1.9 and 62.5 mg dL⁻¹, respectively) on filter coffee ( P =0.048). Means±SE were 25.8±2.4 mg dL⁻¹ and 19.6±2.0 mg dL⁻¹, respectively ( P =0.04). Although not statistically significant, subjects consuming nine or more cups of coffee per day had higher lipoprotein(a) levels than those drinking five to eight cups per day in both coffee groups.
Conclusion. Chronic consumers of unfiltered, boiled coffee have higher serum levels of lipoprotein(a) than filter coffee drinkers.     

Dissociation between urinary albumin excretion and variables associated with insulin resistance in a healthy population

Objectives. To see if the cluster of metabolic and haemodynamic variables defined as comprising Syndrome X varied as a function of urinary albumin excretion (UAE) rate in a healthy population.
Design. A cross-sectional, population-based study.
Setting. A factory in Italy.
Subjects. Two hundred and twenty-five healthy volunteers, 115 men and 110 women.
Outcome measures. Measurements were made of the plasma glucose and insulin responses to oral glucose, fasting triglyceride (TG) and high density lipoprotein (HDL)-cholesterol concentrations, blood pressure, and UAE rates.
Results. Only five of the 225 volunteers had microalbuminuria, defined as a UAE rate >2 μg min^-1, and the UAE rate was <5 μg min^-1 in 80% of the volunteers. Significant variations in the metabolic and haemodynamic variables measured were not associated with any differences in UAE. Finally, significant relationships were found between various measures of plasma insulin concentration and plasma glucose response to oral glucose, plasma TG and HDL-cholesterol concentrations, and mean arterial blood pressure, independent of variations in age, body mass index, ratio of waist-to-hip girth, and UAE rates.
Conclusion. The widespread variability in plasma glucose and insulin responses, plasma TG and HDL-cholesterol concentrations, and blood pressure that are seen in the population at large cannot be attributed to variations in UAE rate.     

Gender crossover of lung function

Background:  Although standard values of lung function are used for screening pulmonary diseases, only a few studies have been reported in the elderly.
Methods:  In this study, lung function in subjects below and above 65 years of age was analysed and the decline in lung function was compared according to age, between those below and those above 65 years.
Results:  Lung function below 65 years declined more in males than in females in both vital capacity (VC) and forced expiratory volume in 1 s (FEV₁). The decline in lung function was greater in females more than 65 years of age, compared with those less than 65 years. In males, the decline in FEV₁ was less for those more than 65 years than for those below 65 years, although the decline in VC showed a similar tendency to that of females.
Conclusions:  Selective survival may influence lung function more in men than in women. The gender difference of survival should be considered when estimating standard values, such as lung function, in the elderly.     

Disarticulation of a knee joint in a haemophiliac with high inhibitor titre

Summary. Disarticulation of a knee joint in an 8-year-old haemophilia A patient with high inhibitor of 3450 Bethesda units (BU) is described. He had an infected compound fracture of the tibia and fibula. Surgery was successfully performed after extensive plasma exchange; administration of immunosuppressive agents such as cyclophosphamide, methylprednisolone, intravenous immunoglobulin and cyclosporine were combined with a loading dose of 100 units kg^-1 of factor VIII concentrate, followed by continuous infusion of 16 units kg^-1 h^-1 of factor VIII in the form of factor VIII concentrate and cryoprecipitate for 7 days and decreased to 8 units kg^-1 h^-1 in the form of cryoprecipitate for 19 more days. During the 1st to 7th post-operative days, the lowest factor VIII inhibitor was 18 BU and the factor VIII level ranged from < 1–2.1 IU dL^-1. On the 9th and 13th post-operative day, although the inhibitor rose to 330 and 2700 BU, respectively, there was no serious bleeding. The suture was removed on the 21st post-operative day. The inhibitor spontaneously decreased to 550, 232 and 14 BU at 1, 7 and 10 months, respectively.     

Plateletpheresis with the IBM Model 2997

Abstract. 9 healthy subjects dosed with acid-citrate-dextrose, NIH formula B (ACD-B) while undergoing plateletpheresis with the continuous-flow IBM Model 2997 centrifuge, received on average 59.5 ± (SD) 3.2 mg Na₃ citrate-kg^-1. h^-1. This rate of infusion of Na₃ citrate resulted in a maximum 12-fold rise in the concentration of citrate in serum (plasma) following the processing of 10 litres of whole blood, and subsequently reduced the level of total calcium in serum (plasma) by 9%. This dose of Na₃ citrate produced no clinical symptoms suggestive of hypocalcaemia in these subjects, even though the use of acid-citrate-dextrose, NIH formula A (ACD-A) under identical conditions has been reported to reduce significantly the level of total calcium in serum, and concomitantly increase the number or reactions occurring in donors. From previous studies employing the intermittent-flow centrifugation system of plateletpheresis, a rate of infusion of Na₃ citrate below 65 mg.kg^-1. h^-1 can insure maximum donor safety and this rate can be achieved with the IBM Model 2997 by the utilisation of ACD-B.     

Choice of spirometric reference values for compensation assessment

Background and objective:   Two sets of local reference values are available for spirometry in Hong Kong, but it is uncertain how well they work in the assessment of occupational lung diseases. This study examined their relative performance in the compensational assessment of silicosis.
Methods:   Local reference values published in 1982 and 2006 were compared in two different populations comprising normal construction/quarry workers and silicosis patients. Only men aged 20–74 years were included.
Results:   The FVC results of 93 normal workers were significantly higher than those predicted by either the 1982 or the 2006 reference values. Compared with the 1982 reference values, the mean FEV₁% or FVC% was age-dependent and 5.2% higher in the normal workers. Smoking decreased the forced expiratory ratio, but did not show a major effect on FEV₁ or FVC among asymptomatic subjects. Despite their derivation largely from never-smokers, the 2006 reference values better predicted FEV₁ and FVC among all smoking categories. Among the 357 silicosis patients, the 1982 reference values also gave 8.8% higher FEV₁% and 7.4% higher FVC%. These spirometric values differed by more than 10% in patients aged 60 years or more. Despite the presence of disease, the mean FVC% was still significantly above 100%.
Conclusions:   Both the 1982 and 2006 local reference values underestimated the FVC of normal construction and quarry workers, reflecting possible occupational selection factors. The 2006 reference values outperformed the 1982 ones, especially among older subjects. Careful calibration with similar occupational groups in the same laboratory is highly desirable in the choice of spirometric reference values for compensation assessment. Smoking does not appear to affect this choice.     

Functional impact of relative versus absolute sarcopenia in healthy older women

OBJECTIVES: To determine whether adjustment of muscle mass for height² or for body mass represents a more-relevant predictor of physical performance.
DESIGN: Cross-sectional study, using baseline data from a trial comparing upper- and lower-body training.
SETTING: Women recruited from the community and gynecological practices in Connecticut.
PARTICIPANTS: One hundred eighty-nine healthy older (aged 67.5 ± 4.8), active women receiving estrogen for osteoporosis over 2 years.
MEASUREMENTS: Total and appendicular skeletal muscle (ASM) and fat mass (AFM) were determined using dual x-ray absorptiometry. Physical performance, muscle strength, and fitness measures were obtained at baseline.
RESULTS: Adjusting ASM for height² identifies lean women who are sarcopenic according to published standards yet fails to identify overweight and obese women whose ASM adjusted for body mass is low. ASM divided by body mass (ASM/body mass) is a stronger physical performance predictor, explaining 32.5%, 13.5%, 11.6%, 6.3%, and 6.8% of the variance in maximum time on treadmill, 6-minute walk, gait speed, 8-foot walk, and single leg stance, respectively, whereas ASM divided by height in m² (ASM/height²) explained only 2.9%, 0.2%, 2.0%, 0.04%, and 0.1%. Multivariate modeling demonstrated considerable overlap in aspects of ASM/body mass and AFM/body mass associated with performance, with ASM/body mass dominant. In contrast, ASM/height² is a much stronger predictor of leg press 1 repetition maximum and maximum power.
CONCLUSION: The results suggest that relative sarcopenia with ASM adjusted for body mass is a better mobility predictor, with absolute sarcopenia a better indicator of isolated muscle group function in healthy postmenopausal women receiving estrogen replacement.     

Insulin-like factor 3 as a marker of testicular function in obese men

Objectives  Testicular function declines with obesity as a result of central and peripheral mechanisms, including a primary dysfunction of the Leydig cells. The levels of insulin-like factor 3 (INSL3), a sensitive marker of Leydig cell impairment, have never been evaluated in obese men. To better evaluate the hormonal function of the testis in obese men, we analysed their INSL3 plasma levels and compared them with the obesity status and the other reproductive hormones.
Design  Cross-sectional study.
Patients  Thirty-one obese men [body mass index (BMI) >30 kg/m²) aged 22–49 years and 64 age-matched nonobese men.
Measurements  Plasma concentrations of INSL3, testosterone (T), sex hormone-binding globulin (SHBG), oestradiol (E₂), LH, FSH. Free testosterone (FT) levels were calculated.
Results  Obese men had significantly lower plasma concentrations of total T, SHBG, FT and INSL3, and higher levels of E₂ with respect to nonobese men. LH and FSH values were not different from controls. In obese men, we found a significant negative correlation between BMI and INSL3, and a positive correlation between INSL3 and T. Only one (1/31, 3·2%) obese man had subnormal T levels. On the contrary, 10/31 (32·3%) obese men had low INSL3 values.
Conclusions  This study showed for the first time that INSL3 levels decrease with obesity, probably as a result of a primary dysfunction of the Leydig cells. INSL3 is a reliable marker of Leydig cell general impairment, whereas T mainly reflects the steroidogenic activity of these cells.     

Twenty-four hour ambulatory blood pressure in the population

Objectives. To establish a population-based 24-h ambulatory blood pressure (ABP) reference material with day/night mean BP calculated by standardized and true bedtimes.
Design. A cross-sectional study of 200 randomly selected subjects (20 men and 20 women in each 10-year age interval 20–70 years) in Linköping, Sweden.
Setting. University Hospital of Linköping, Sweden.
Results. Participation rate was 67%. Mean supine clinic BP (CBP) and 24-h-ABP values for the whole material were 123±13/79±8 mmHg and 120± 10/73±7 mmHg, respectively. White coat BP phenomenon increased with age (systolic CBP/ABP ratio versus age, r =0.35, P <0.0001). Seventeen participants had a night/day mean arterial blood pressure ratio >0.9 (non-dipper) when calculated from their own time-notations. If standardized day (06.00–23.00) and night (23.00–06.00) limits were used, 24 subjects were non-dippers. Of these, only eight were 'true'. 'True' non-dippers had a similar day-time mean arterial ABP as 'true' dippers (92.4±11 mmHg versus 91.9±13 mmHg, P = 0.92) while night-time BP was higher (89.9± 13 mmHg versus 74.1±7 mmHg, P <0.0001).
Conclusion. Population-based ABP reference values have been defined. We found 9% non-dippers and that standardized day/night-time limits may lead to misclassification. This could be due to gender- and age-differences in sleeping habits, which was also shown in this study. The frequency of white coat BP phenomenon increases with age.     

Prediction of iron deficiency in chronic inflammatory rheumatic disease anaemia

Summary. We prospectively studied 45 anaemic patients (3 7 women, 8 men) with chronic inflammatory rheumatic diseases. The combination of serum ferritin and CRP (as well as ESR) in its predictive capacity for bone marrow iron stores was examined. The relationship between other iron-related measurements (transferrin, transferrin saturation, soluble transferrin receptor, erythrocyte porphyrins and percentage of hypochromic/microcytic erythrocytes) and bone marrow iron stores was also investigated. Stainable bone marrow iron was taken as the most suitable standard to separate iron-deficient from iron-replete patients. 14 patients (31%) were lacking bone marrow iron. Regression analysis showed a good correlation between ferritin and bone marrow iron (adjusted R ²=0.721, P<00001). The combination of ferritin and CRP (ESR) did not improve the predictive power for bone marrow iron (adjusted R ²=0.715) in this cohort of patients with low systemic inflammatory activity. With respect to the bone marrow iron content the best predictive cut-off value of ferritin was 30μg/l (86% sensitivity, 90% specificity). The other iron-related parameters both individually and when combined were less powerful in predicting bone marrow iron than ferritin alone. Only zinc bound erythrocyte protoporphyrin in combination with ferritin slightly improved prediction (adjusted R ²=0.731). A cut-off point of 11% hypochromic erythrocytes reached a high specificity (90%), but was less sensitive (77%).     

Comparison of the Effects of Regional Ischemia and Hyperkalemia on the Membrane Action Potentials of the In Situ Pig Heart

APD During Ischemia. Introduction: This study was designed to determine the role of increased extracellular potassium [K⁺]_e on action potential duration (APD) in the in situ porcine heart during acute regional no-flow ischemia.
Methods and Results: In open chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise [K⁺]_e, Myocardial [K⁺]_e, was determined by potassium-sensitive electrodes, and transmembrane action potential was recorded by floating glass microelectrode. During the first 2 minutes of ischemia, APD at 90% repolarization (APD₉₀) lengthened by 31.2 ± 1.1 msec (P < 0.05). The comparable increase in [K⁺]_e alone shortened APD₉₀, During the next 6 minutes of ischemia. [K⁺]_e, rose to 11.3 ± 0.3 mM and APD₉₀, showed a decrease. However, the comparable increase in |K⁺]_e, by infusion of KCl caused further shortening of APD₉₀, at similar levels of [K⁺]_e.
Conclusions: Acutely ischemic myocardium showed a brief increase in APD₉₀, during the first 2 minutes of ischemia, followed by a fall in APD₉₀, after 2 minutes of ischemia, but the shortening is less than anticipated by the rise in [K⁺]_e. Thus, we hypothesize that other component(s) of ischemia may inhibit action potential repolarization.     

Fasting and post-methionine homocysteine levels in a healthy Australian population

Abstract Background: Plasma homocysteine (H[e]) is frequently measured in patients with occlusive vascular disease, but levels vary between populations and between laboratories.
Aims: We sought to derive reference values for an Australian population over a wide age range.
Methods: We measured plasma H(e) in the fasting state and after methionine loading in 116 volunteers selected at random from the Hunter districts of the New South Wales electoral roll and in 49 apparently healthy, active subjects recruited from the region's lawn bowling clubs. Reference ranges were derived for born sexes, in three age strata. We collaborated with two international laboratories in standardising our results.
Results: Mean fasting H(e) levels were approximately 2.7 μ.mol/L higher in men than women, at all ages (95% CI for the difference, 1.2 to 4.1 μmol/L). Levels increased with age (approximately 1.0 μmol/L/decade, 95% CI 0.5 to 1.5) and were correlated with serum creatine (r=0.48), serum folate (r=−0.30), red cell folate (r=−0.25) and serum B₁₂ (r=−0.31) (all p <0.001). These results are similar to those reported in other populations.
Conclusions: We have defined reference ranges for a typical Australian population, following careful laboratory standardisation. H(e) levels must be interpreted with regard to age, sex, renal function and vitamin B₁₂ and folate status.     

ESR or CRP? A comparison of their clinical utility

Objective: To review the normal reference values for erythrocyte sedimentation rate (ESR) and the significance of high values in the elderly, to re-examine the correlation, if any, between ESR and C-reactive protein (CRP) and to compare their utility and limitations for both health screening and clinical management of patients.

Methods: CRP and ESR were measured in 295 blood samples from male and female subjects in whom their family doctors had found no clinically significant symptoms nor abnormal physical sign and in whom all other pathology tests gave normal results. None had been hospitalised during at least a six-week period prior to the study.

Results: The results showed a mean ESR of 10 mm/1 h (range 0–25) in both males and females below the age of 40 yrs; this increased with age, to a mean of 18 mm (range 0–35) by 60 yrs in both men and women. In the CRP test, 95% of the samples in the >40 yrs group had CRP range of 0–18 mg/l compared with 0–10 mg/l in the younger subjects. The distribution plot of CRP results showed a left skew with mode at about 2 mg/l, whereas the equivalent ESR distribution shows a broad plateau with less skew. Thus, there was more overlapping of the numerical values for ESR and CRP in subjects younger than 40 yrs, as compared with those over 40 yrs old in whom the two sets of measurements were well separated.

The relative utility of the two tests in clinical management of patients was also discussed. Different rates of increase and subsequent fall in the test results were shown over several weeks on a patient with an acute infection. Initially, both tests were increased, but after antibiotic therapy the CRP returned to normal indicating that remission had occurred, whereas the ESR remained high, indicating persistence of the infection. A subsequent dramatic increase in CRP to 180 mg/l confirmed the reinfection that had been indicated earlier by the ESR. After further antibiotic therapy CRP fell to normal, followed later by a slower reduction in ESR to a normal value for the patient's age.

Conclusion: This study confirms that after the age of 40, there is an age-related elevation of ESR, increasing steadily, especially after age 60 yrs. CRP is also affected by age, but to a much less extent. ESR and CRP appear to be equally useful and reliable as a screening test. Accordingly, in deciding which test should be carried out account must be taken of their relative convenience and cost. However, when required as a clinical test in the management of patients with specific diseases both tests should be carried out in tandem.     

Polymorphism of Tumor Necrosis Factor-β and Alcohol Dehydrogenase Genes and Alcoholic Brain Atrophy in Japanese Patients

Background: Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. Many inflammatory cytokines such as tumor necrosis factor (TNF) are produced rapidly in the brain by experimental or clinical injury.
Method: To investigate whether genetic polymorphism of TNF was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the TNF-β genes in 72 male alcoholics. Computed tomography was used to determine the severity of brain atrophy.
Results: Digestion with Nco I and Msp I after polymerase chain reaction amplification showed that the TNFB¹ allele frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (χ²= 10.20, p = 0.0034). A multivariate analysis that included age, total alcohol intake, ADH2 genotype, and TNF-β genotype showed that the ADH2¹/2¹ genotype and TNFB¹/B¹ genotype are independently associated with alcoholic brain atrophy. These findings suggest that the TNFB¹ allele may be associated with alcoholic brain atrophy.     

Electrocardiographic left ventricular hypertrophy has low diagnostic accuracy in middle-aged subjects

Objective. To evaluate the usefulness of electrocardiographic left ventricular hypertrophy (ECG LVH) as a marker of LVH in middle-aged subjects. Methods. LVH was determined by cardiovascular magnetic resonance imaging (MRI) in 188 apparently healthy middle-aged [97 men (45±7 years) and 91 women (47±6 years)]. Receiver operating characteristic (ROC) curves, test sensitivity, specificity, positive and negative predictive values for identifying LVH at different ECG criteria were calculated. Results. Systolic and diastolic blood pressures were 142±13 mmHg and 90±8 mmHg in men and 139±10 mmHg and 90±8 mmHg in women, respectively. LVMI was 78±17 g/m² in men and 67±12 g/m² in women, and 14% of men and 22% of women had LVH in cardiac MRI. Only Sokolow-Lyon and Sokolow-Lyon product had the area under the ROC curve over 0.70. Sokolow-Lyon product had the highest sensitivity (47%). All ECG criteria had high negative predictive values, but the positive predictive values were below 46%. Conclusions. Commonly used ECG criteria of LVH have low discrimination ability in middle-aged subjects. ECG LVH alone should not be used as a marker of target organ damage in middle-aged, never treated and apparently healthy hypertensives.     

In-vitro stability of porcine factor VIII (Hyate:C®)

The stability of porcine factor VIII (Hyate:C^®) 30 units mL^–1, 15 units mL^–1 and 5 units mL^–1 prepared aseptically in 0.9% sodium chloride injection was studied. Solutions were stored in plastic syringes at room temperature and ambient light, and at body temperature protected from light. Samples obtained immediately after mixing and at 4, 24, 48 and 72 h were assayed for FVIII activity using a one-stage FVIII assay. Samples were considered stable if FVIII activity did not decline more than 10% compared with baseline values.
Hyate:C^® 5 units mL^–1 stored at room temperature retained FVIII activity within 90% of baseline values for at least 24 h. When stored at body temperature, FVIII activity of Hyate:C^® 5 units mL^–1 declined to less than 90% of baseline values within 4 h. Stability of Hyate:C^® 15 units mL^–1 and 30 units mL^–1 stored at room temperature was retained for at least 72 h. When Hyate:C^® 15 units mL^–1 and 30 units mL^–1 were stored at body temperature, stability was retained for 24 h. Results of this study will permit further evaluation of Hyate:C^® stability when administered by ambulatory infusion pumps.     

I(Ks) block by HMR 1556 lowers ventricular defibrillation threshold and reverses the repolarization shortening by isoproterenol without rate-dependence in rabbits

Introduction: The slow delayed rectifier K⁺ current (I_Ks) contributes little to ventricular repolarization at rest. It is unclear whether I_Ks plays a role during ventricular fibrillation (VF) or ventricular repolarization at rapid rates during β-adrenergic stimulation.
Methods and Results: In an in vivo rabbit model, we evaluated the effects of HMR 1556 (1 mg Kg⁻¹+ 1 mg kg ⁻¹ hr ⁻¹ i.v.), a selective I_Ks blocker, on monophasic action potential duration at 90% repolarization (MAPD₉₀), ventricular effective refractory period (VERP), and defibrillation threshold (DFT). In perfused rabbit hearts, the effects of HMR 1556 (10 and 100 nM) in the presence of isoproterenol (5 nM) on MAPD₉₀ and VERP were studied at cycle lengths (CLs) 200–500 msec. In vivo , HMR 1556 prolonged MAPD₉₀ by 6 ± 1 msec at CL 200 msec (P < 0.01, n = 6), lowered DFT from 558 ± 46 V to 417 ± 31 V (P < 0.01), and decreased the coefficient of variation in the VF inter-beat deflection intervals from 8.9 ± 0.6% to 6.5 ± 0.4% (P < 0.05) compared with control. In perfused rabbit hearts, isoproterenol shortened MAPD₉₀ by 5 ± 1 msec at CL 200 msec and 11 ± 4 msec at CL 500 msec (P < 0.05, n = 7). This shortening was reversed by HMR 1556 (P < 0.05), and both effects were rate-independent.
Conclusion: I_Ks block increases VF temporal organization and lowers DFT, and I_Ks that is activated following β-adrenergic stimulation contributes to ventricular repolarization without rate dependence.