Pain and quality of life for patients with venous leg ulcers: proof of concept of the efficacy of Biatain®-Ibu, a new pain reducing wound dressing

Wound pain is a serious problem for elderly patients suffering from chronic leg ulcers, and it may lead to reduced wound healing rates and reduced quality of life. Biatain-Ibu Non-adhesive (Coloplast A/S), a new pain-reducing moist wound healing dressing containing ibuprofen was tested for pain reduction, safety, and efficacy on 10+2 patients in a single-blinded crossover study against Biatain Non-adhesive (Coloplast A/S). Pain was measured with a Numeric Box Scale before, during, and after dressing change. Quality of life was measured using the World Health Organization-5 Well-Being Index. Dressing moist wound healing properties such as absorption capacity and leakage were tested together with assessment of wound exudate and blood plasma content of ibuprofen. Use of the Biatain-Ibu foam dressing correlated with a decrease in pain intensity scores from 7 in the run-in period to approximately 2.5 in the Biatain-Ibu treatment phase. Quality of life measures were improved which together with the reduced pain could contribute to faster wound healing. The moist wound healing properties of Biatain-Ibu were similar to that of the Biatain Non-adhesive and ulcer size was reduced by 24% during the treatment period. Neither side effects nor systemic plasma concentrations of ibuprofen were observed. These data indicate that Biatain-Ibu could reduce persistent and temporary wound pain, increase Quality of life, was found safe to use, and had excellent moist wound healing properties.     

Lactate/H+ transport kinetics in rat skeletal muscle related to fibre type and changes in transport capacity

 Lactate/H⁺ transport kinetics were determined by means of the pH-sensitive probe BCECF in sarcolemmal giant vesicles, obtained from rat skeletal muscle, and related to variations in lactate/H⁺ transport capacity. Vesicle preparations were made from red and white muscles, mixed muscles, denervated muscles, muscles of old rats and rats that had been subjected to high-intensity training, endurance training, repeated exposure to hypoxia, and hypothyroid or hyperthyroid treatments. The lactate/H⁺ transport capacity of red muscles was greater than that of white muscles, and this difference was associated with a higher maximal transport rate (V _max) in red muscles, whereas the K _m was similar in the two muscle types. High-intensity training and hyperthyroidism increased the lactate/H⁺ transport capacity by enhancing V _max without affecting K _m. Similarly, a reduced transport capacity with old age and hypothyroidism was due to a decrease in V _max. The denervation-induced decline in lactate/H⁺ transport capacity resulted from both an increased K _m and a reduced V _max. The present data show that muscle type differences and most changes in the lactate/H⁺ transport capacity are mediated by modifications in V _max, which is expected to represent the number of membrane transporter molecules. K _m is unaffected by most treatments and appears to be independent of fibre type. Received: 10 February 1998 / Received after revision: 21 April 1998 / Accepted: 24 April 1998     

Expression of Na+/HCO3− co‐transporter proteins (NBCs) in rat and human skeletal muscle

Aim: Sodium/bicarbonate co‐transport (NBC) has been suggested to have a role in muscle pH regulation. We investigated the presence of NBC proteins in rat and human muscle samples and the fibre type distribution of the identified NBCs. Methods and results: Western blotting of muscle homogenates and sarcolemmal membranes (sarcolemmal giant vesicles) were used to screen for the presence of NBCs. Immunohistochemistry was used for the subcellular localization. The functional test revealed that approximately half of the pH recovery in sarcolemmal vesicles produced from rat muscle is mediated by bicarbonate‐dependent transport. This indicates that the NBCs are preserved in the vesicles. The western blotting experiments demonstrated the existence of at least two NBC proteins in skeletal muscle. One NBC protein (approximately 150 kDa) seems to be related to the kidney/pancreas/heart isoform NBC1, whereas the other protein (approximately 200 kDa) is related to the NBC4 isoform. The two NBC proteins represent the electrogenic isoforms named NBCe1 and NBCe2. Membrane fractionation and immunofluorescence techniques confirmed that the two NBCs are located in the sarcolemmal membrane as well as in some internal membranes, probably the T‐tubules. The two NBCs localized in muscle have distinct fibre type distributions. Conclusions: Skeletal muscle possesses two variants of the sodium/bicarbonate co‐transporter (NBC) isoforms, which have been called NBCe1 and NBCe2.     

Increasing asthma mortality in Denmark 1969-88 not a result of a changed coding practice.

We have studied asthma mortality in Denmark from 1969 to 1988. Age standardized mortality rates calculated in three age groups, 10-34, 35-59, and greater than or equal to 60 years, disclosed similar trends. Increasing mortality from asthma in the mid-1970s to 1988 was seen in all three age groups with higher mortality in 1979-88 as compared with 1969-78 of 95%, 55%, and 69%, respectively. Since the eighth revision of the International Classification of Diseases (ICD8) was used in Denmark over the entire 20-year period, changes in coding practice due to change of classification system cannot explain the findings.     

Impact of work-related and psychosocial factors on the development of ischemic heart disease among urban bus drivers in Denmark

From 1978 to 1985, 2,465 male bus drivers in the three major cities in Denmark were followed with regard to hospital admission due to myocardial infarction (MI) and death due to ischemic heart disease (IHD). In all 2,045 (83%) of these men responded in 1978 to a questionnaire on psychosocial well-being and work conditions. The respondents did not differ from the nonrespondents regarding hospital admissions and death in the follow-up period (1978-1984). Sixty-two cases of MI were registered among the 2,045 bus drivers in 1978-1984. On this basis relative risk for MI was calculated with a multiple regression model for independent variables regarding psychosocial well-being and work conditions. High work load (driving in heavy traffic) was significantly associated with the occurrence of MI. Of the psychosocial factors "no social contact with colleagues" and "increased work pace" were also significantly associated with the occurrence of MI. Smoking habits tended to be associated with the occurrence of MI, while stress symptoms and job dissatisfaction did not. The mental burden on bus drivers working in heavy traffic seems a possible explanation for the findings.     

Potassium and sodium shifts during in vitro isometric muscle contraction,and the time course of the ion-gradient recovery

Intracellular potassium ([K⁺]_i), interstitial potassium ([K⁺]_inter), intracellular sodium ([Na⁺]_i), and resting membrane potential (RMP) were measured before and after repetitive stimulation of mouse soleus and EDL (extensor digitorum longus) muscles. At rest, RMP was –69.8 mV for soleus and –74.9 mV for EDL (37°C). [K⁺]_i was 168 mM and 182 mM, respectively. In soleus, free [Na⁺]_i was 12.7 mM. After repetitive stimulation (960 stimuli) RMP had decreased by 11.9 mV for soleus and by 18.2 mV for EDL. [K⁺]_i was reduced by 32 mM and 48 mM, respectively, whereas [K⁺]_inter was doubled. In soleus [Na⁺]_i had increased by 10.6 mM, demonstrating that the [K⁺]_i-decrease is three times higher than the [Na⁺]_i-increase. It is concluded that this difference reflects different activity induced movements of Na and K, and that the difference is not due to the Na/K pumping ratio. The possible involvement of the potassium loss in muscle fatigue is discussed. After stimulation RMP recovered with a time constant of 0.9 min for soleus and 1.5 min for EDL. Within the first minutes after stimulation the intracellular potassium concentration increased by 20.4 mM/min for soleus and 21.7 mM/min for EDL. Free [Na⁺]_i decreased with less than 10 mM/min. The mechanisms underlying the different rate of changes are discussed.Parts of this work have been published in preliminary form (Juel and Sjøgaard 1984)     

Lactate transport in isolated mouse muscles studied with a tracer technique--kinetics, stereospecificity, pH dependency and maximal capacity

Lactate transport across the sarcolemma of isolated mouse muscles was studied with a 14C tracer technique. The cellular tracer uptake could be inhibited by unlabelled L-lactate (and pyruvate) and to a lesser extent by D-lactase. The stereospecific fraction had a Km of 3.5 mM, and made up 50% of the total transport. The tracer uptake was unaffected by 0.05 mM DIDS and 0.2 mM amiloride, but was inhibited by cinnamate (Ki = 8 mM) and PCMBS (Ki = 0.8 mM). With high concentrations of the latter inhibitor compounds or with high concentrations of unlabelled L-lactate, the tracer uptake was inhibited 80%, which indicates that the main part of the transport involves facilitated diffusion. The remaining fraction (20%) was non-saturable, reduced at high pH, and could not be inhibited; it is probably mediated by diffusion of undissociated lactic acid. Lactate transport was pH-dependent, which is consistent with a lactate-H+ symport. The maximal transport capacity, as calculated from the pH changes measured with pH-sensitive micro-electrodes while the lactate gradient was 30 mM, was 11.8 mmol kg-1 min-1 (pH 6.2).     

Diurnal variations of serum erythropoietin at sea level and altitude

This study tested the hypothesis that the diurnal variations of serum-erythropoietin concentration (serum-EPO) observed in normoxia also exist in hypoxia. The study also attempted to investigate the regulation of EPO production during sustained hypoxia. Nine subjects were investigated at sea level and during 4 days at an altitude of 4350 m. Median sea level serum-EPO concentration was 6 (range 6–13) U·l^–1. Serum-EPO concentration increased after 18 and 42 h at altitude, [58 (range 39–240) and 54 (range 36–340) U·l^–1, respectively], and then decreased after 64 and 88 h at altitude [34 (range 18–290) and 31 (range 17–104) U·l^–1, respectively]. These changes of serum-EPO concentration were correlated to the changes in arterial blood oxygen saturation (r = –0.60,P = 0.0009), pH (r = 0.67,P = 0.003), and in-vivo venous blood oxygen half saturation tension (r = –0.68,P = 0.004) but not to the changes in 2, 3 diphosphoglycerate. After 64 h at altitude, six of the nine subjects had down-regulated their serum-EPO concentrations so that median values were three times above those at sea level. These six subjects had significant diurnal variations of serum-EPO concentration at sea level; the nadir occurred between 0800–1600 hours [6 (range 4–13) U·l^–1], and peak concentrations occurred at 0400 hours [9 (range 8–14) U·l^–1,P = 0.02]. After 64 h at altitude, the subjects had significant diurnal variations of serum-EPO concentration; the nadir occurred at 1600 hours [20 (range 16–26) U·l^–1], and peak concentrations occurred at 0400 hours [31 (range 20–38) U·l^–1,P = 0.02]. This study demonstrated diurnal variations of serum-EPO concentration in normoxia and hypoxia, with comparable time courses of median values. The results also suggested that EPO production at altitude is influenced by changes in pH and haemoglobin oxygen affinity.