Socioeconomic position, treatment, and survival of non-Hodgkin lymphoma in Denmark--a nationwide study.

BACKGROUND: Not all patients have benefited equally from the advances in non-Hodgkin lymphoma (NHL) survival. This study investigates several individual-level markers of socioeconomic position (SEP) in relation to NHL survival, and explores whether any social differences could be attributed to comorbidity, disease and prognostic factors, or the treatment given. METHODS: This registry-based cohort study links clinical data on prognostic factors and treatment from the national Danish lymphoma database to individual socioeconomic information in Statistics Denmark including 6234 patients diagnosed with NHL in 2000-2008. RESULTS: All-cause mortality was 40% higher in NHL patients with short vs higher education diagnosed in the period 2000-2004 (hazard ratio (HR)=1.40 (1.27-1.54)), and 63% higher in the period 2005-2008 (HR=1.63 (1.40-1.90)). Further, mortality was increased in unemployed and disability pensioners, those with low income, and singles. Clinical prognostic factors attenuated, but did not eliminate the association between education and mortality. Radiotherapy was less frequently given to those with a short education (odds ratio (OR)= 0.84 (0.77-0.92)), low income (OR=0.80 (0.70-0.91)), and less frequent to singles (OR=0.79 (0.64-0.96)). Patients living alone were less likely to receive all treatment modalities. CONCLUSION: Patients with low SEP have an elevated mortality rate after a NHL diagnosis, and more advanced disease at the time of diagnosis explained a part of this disparity. Thus, socioeconomic disparities in NHL survival might be reduced by improving early detection among patients of low SEP.

Socioeconomic position, stage of lung cancer and time between referral and diagnosis in Denmark, 2001-2008.

INTRODUCTION: We investigated the association between socioeconomic position, stage at diagnosis, and length of period between referral and diagnosis in a nationwide cohort of lung cancer patients. METHODS: Through the Danish Lung Cancer Register, we identified 18,103 persons diagnosed with lung cancer (small cell and non-small cell) in Denmark, 2001-2008, and obtained information on socioeconomic position and comorbidity from nationwide administrative registries. The odds ratio (OR) for a diagnosis of advanced-stage lung cancer (stages IIIB-IV) and for a diagnosis >28 days after referral were analysed by multivariate logistic regression models. RESULTS: The adjusted OR for advanced-stage lung cancer was reduced among persons with higher education (OR, 0.92; 95% confidence interval (CI), 0.84-0.99), was increased in persons living alone (OR, 1.06; 95% CI, 1.01-1.13) and decreased stepwise with increasing comorbidity. Higher education was associated with a reduced OR for >28 days between referral and diagnosis as was high income in early-stage patients. Male gender, age and severe comorbidity were associated with increased ORs in advanced-stage patients. INTERPRETATION: Differences by socioeconomic position in stage at diagnosis and in the period between referral and diagnosis indicate that vulnerable patients presenting with lung cancer symptoms require special attention.

Socioeconomic position and participation in colorectal cancer screening.

BACKGROUND: Colorectal cancer (CRC) screening with faecal occult blood test (FOBT) has the potential to reduce the incidence and mortality of CRC. Screening uptake is known to be inferior in people with low socioeconomic position (SEP) when compared with those with high position; however, the results of most previous studies have limited value because they are based on recall or area-based measures of socioeconomic position, and might thus be subject to selective participation and misclassification. In this study we investigated differences in CRC screening participation using register-based individual information on education, employment, and income to encompass different but related aspects of socioeconomic stratification. Also, the impact of ethnicity and cohabiting status was analysed. METHODS: A feasibility study on CRC screening was conducted in two Danish counties in 2005 and 2006. Screening consisted of a self-administered FOBT kit mailed to 177 114 inhabitants aged 50-74 years. Information on individual socioeconomic status was obtained from Statistics Denmark. RESULTS: A total of 85 374 (48%) of the invited returned the FOBT kits. Participation was significantly higher in women than in men (OR=1.58 (1.55-1.61)), when all socioeconomic and demographic variables were included in the statistical model. Participation also increased with increasing level of education, with OR=1.38 (1.33-1.43) in those with a higher education compared with short education. Also, participation increased with increasing income levels, with OR=1.94 (1.87-2.01) in the highest vs lowest quintile. Individuals with a disability pension, the unemployed and self-employed people were significantly less likely to participate (OR=0.77 (0.74-0.80), OR=0.83 (0.80-0.87), and OR=0.85 (0.81-0.89), respectively). Non-western immigrants were less likely to participate (OR=0.62 (0.59-0.66)) in a model controlling for age, sex, and county; however, this difference might be attributed to low SEP in these ethnic groups ((OR=0.93 (0.87-0.99), when adjusting for SEP indicators). CONCLUSION: This study based on individual information on several socioeconomic dimensions in a large, unselected population allowed for identification of several specific subgroups within the population with low CRC screening participation. Improved understanding is needed on the effect of targeted information and other strategies in order to reduce socioeconomic inequalities in screening.

Procedural pain of an ultrasound-guided brachial plexus block: a comparison of axillary and infraclavicular approaches.

BACKGROUND: Ultrasound (US)-guided infraclavicular (IC) and axillary (AX) blocks have similar effectiveness. Therefore, limiting procedural pain may help to choose a standard approach. The primary aims of this randomized study were to assess patient's pain during the block and to recognize its cause. METHODS: Eighty patients were randomly allocated to the IC or the AX group. A blinded investigator asked the patients to quantify block pain on a Visual Analogue Scale (VAS 0-100) and to indicate the most unpleasant component (needle passes, paraesthesie or local anaesthetics injection). Sensory block was assessed every 10 min. After 30 min, the unblocked nerves were supplemented. Patients were ready for surgery when they had analgesia or anaesthesia of the five nerves distal to the elbow. Preliminary scan time, block performance and latency times, readiness for surgery, adverse events and patient's acceptance were recorded. RESULTS: The axillary approach resulted in lower maximum VAS scores (median 12) than the infraclavicular approach (median 21). This difference was not statistically significant (P=0.07). Numbers of patients indicating the most painful component were similar in both groups. Patients in either group were ready for surgery after 25 min. Two patients in the IC group and seven in the AX group needed block supplementation (n.s.). Block performance times and number of needle passes were significantly lower in the IC group. Patients' acceptance was 98% in both groups. CONCLUSIONS: We did not find significant differences between the two approaches in procedural pain and patient's acceptance. The choice of approach may depend on the anaesthesiologist's experience and the patient's preferences.

A comparison of ultrasound-guided supraclavicular and infraclavicular blocks for upper extremity surgery.

BACKGROUND: Ultrasound (US)-guided supraclavicular or infraclavicular blocks are commonly used for upper extremity surgery. The aims of this randomized study were to compare the block performance and onset times, effectiveness, incidence of adverse events and patient's acceptance of US-guided supraclavicular or infraclavicular blocks. We hypothesized that the supraclavicular approach, being more superficial and easier to visualize using a 10 MHz transducer, will produce a faster and a more extensive sensory block. METHODS: One hundred and twenty patients were randomized to two equal groups: supraclavicular (S) and infraclavicular (I). Each patient received a mixture containing equal volumes of ropivacaine 7.5 mg/ml and mepivacaine 20 mg/ml with adrenaline 5 microg/ml, 0.5 ml/kg body weight (minimum 30 ml, maximum 50 ml). The sensory score (anaesthesia--2 points, analgesia--1 point and pain--0 point) of the seven terminal nerves was assessed every 10 min. Patients were declared ready for surgery when they had an effective surgical block--anaesthesia or analgesia of the five nerves below the elbow. Thirty minutes after the block, the unblocked nerves were supplemented. The block performance and latency times, surgical effectiveness, adverse events and patient's acceptance were recorded. RESULTS: Significantly more patients in the I group were ready for surgery 20 and 30 min after the block. The mean block performance time was 5.7 min in the S group and 5.0 min in the I group (NS). Block effectiveness was superior in the I group: 93% vs. 78% in the S group (P=0.017). The S group patients had a significantly poorer block of the median and ulnar nerves, but a better block of the axillary nerve. Sensory scores at 10, 20 and 30 min were not significantly different. Thirty-two patients in the S group vs. nine patients in the I group experienced transient adverse events (P<0.0001). Patients' acceptance of the block was similar in both groups. CONCLUSIONS: Infraclavicular block had a faster onset, better surgical effectiveness and fewer adverse events. Block performance time and patients' acceptance of the procedure were similar in both groups.

Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis.

Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung infections are the leading cause of morbidity and mortality in cystic fibrosis (CF). Accordingly, we investigated whether MBL variant alleles, which are associated with recurrent infections, might be risk factors for CF patients. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology, and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers of MBL variant alleles when compared with normal homozygotes. The negative impact of variant alleles on lung function was especially confined to patients with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infection was significantly more frequent in carriers of variant alleles than in homozygotes. The risk of end-stage CF among carriers of variant alleles increased 3-fold, and the survival time decreased over a 10-year follow-up period. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele carriers when compared with normal homozygotes. Presence of MBL variant alleles is therefore associated with poor prognosis and early death in patients with CF.

Eradication of early Pseudomonas aeruginosa infection.

Chronic pulmonary infection with Pseudomonas aeruginosa is responsible for most of the morbidity and mortality in cystic fibrosis (CF). Once established as a biofilm, chronic P. aeruginosa infection caused by the mucoid phenotype cannot be eradicated. However, a period of intermittent colonization with P. aeruginosa precedes the establishment of the chronic infection. This window of opportunity can be utilized to eradicate P. aeruginosa from the respiratory tract of CF patients by means of oral ciprofloxacin in combination with nebulized colistin for 3 weeks or, even better, for 3 months or by means of inhaled tobramycin as monotherapy for 4 weeks or longer. This early, aggressive eradication therapy has now been used for 15 years without giving rise to resistance to the antibiotics and without serious side effects. The therapeutic results have been very successful and have completely changed the epidemiology in the Danish Cystic Fibrosis Center and a few other centers which have used this strategy for several years. The chronic P. aeruginosa lung infection is not seen in CF infants and children anymore due to the aggressive therapy, and no other bacteria have replaced P. aeruginosa in these young patients. The aggressive therapy has been shown to very cost-effective, and a European Consensus report recommends this approach.

Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence.

We conducted a 1000 Genomes-imputed genome-wide association study (GWAS) meta-analysis for nicotine dependence, defined by the Fagerström Test for Nicotine Dependence in 17 074 ever smokers from five European-ancestry samples. We followed up novel variants in 7469 ever smokers from five independent European-ancestry samples. We identified genome-wide significant association in the alpha-4 nicotinic receptor subunit (CHRNA4) gene on chromosome 20q13: lowest P=8.0 × 10(-9) across all the samples for rs2273500-C (frequency=0.15; odds ratio=1.12 and 95% confidence interval=1.08-1.17 for severe vs mild dependence). rs2273500-C, a splice site acceptor variant resulting in an alternate CHRNA4 transcript predicted to be targeted for nonsense-mediated decay, was associated with decreased CHRNA4 expression in physiologically normal human brains (lowest P=7.3 × 10(-4)). Importantly, rs2273500-C was associated with increased lung cancer risk (N=28 998, odds ratio=1.06 and 95% confidence interval=1.00-1.12), likely through its effect on smoking, as rs2273500-C was no longer associated with lung cancer after adjustment for smoking. Using criteria for smoking behavior that encompass more than the single 'cigarettes per day' item, we identified a common CHRNA4 variant with important regulatory properties that contributes to nicotine dependence and smoking-related consequences.

Detection of antibodies to human immunodeficiency virus (HIV) in eluates from whole blood impregnated filter paper discs.

A method for elution of HIV antibodies from whole blood or serum impregnated filter paper discs was developed. The results from testing of 73 eluates in an enzyme linked immunosorbent assay and the immunoblotting test agreed with the results obtained by ordinary serum testing. Significant loss of antibody activity was not observed, neither in the eluates after storage for 1 mth at -20 degrees C nor in the filter paper discs after storage for 3 mths at +4 degrees C. This technique may be useful in facilitating sample collection and transportation, particularly in remote areas of the world.

Intermittent topical treatment of psoriasis with clobetasol propionate ("Dermovate").

In an open multi-centre trial, 316 psoriasis patients were treated with clobetasol propionate intermittently over a 14-day period. The treatment gave rapid clinical healing of the psoriasis infiltration in 62% of the patients. A total of 132 of these patients was subsequently put on maintenance treatment with two applications per week. This regimen kept the disease in remission throughout the observation period, which exceeded 4 months on average, in 75% of the patients. Only 5 patients experienced side-effects.

Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis.

Chronic pulmonary infection with Pseudomonas aeruginosa (PA) develops in most patients with cystic fibrosis (CF) and is associated with a poor prognosis. Much effort has been directed toward treating the chronic infection, but it is almost impossible to eradicate it once established; therefore, prevention is preferable. Since 1989 CF patients at the Danish CF Center in Copenhagen have been treated with an intensive three-step-protocol consisting of colistin inhalations and oral ciprofloxacin at the time of initial PA colonization. This study compares 48 patients treated according to this intensive protocol with 43 historic controls. The study was carried out over 44 months and included 218 patient-years. Only 16% of the treated patients developed chronic PA infection after 3 1/2 years compared with 72% of the control patients (Kaplan Meier estimate, P < 0.005, log rank test). This indicates that aggressive treatment prevented or delayed chronic PA infection in 78% of the patients for 3 1/2 years. Furthermore, aggressive treatment maintained or increased pulmonary function (forced vital capacity and forced expiratory volume in 1 second in percent of predicted values) during the year after inclusion compared with the control group, in which pulmonary function declined (P < 0.01, Mann-Whitney test). Although some of the treated patients eventually developed chronic PA infection, these patients had significantly better pulmonary function at the onset of chronic PA infection compared with control patients (P < 0.001, Mann-Whitney test). When the different steps in the intensive three-step-protocol were analyzed, there was a trend suggesting that 3 months of high-dose treatment with colistin inhalation and oral ciprofloxacin produced the best results in terms of postponement or prevention of chronic PA infection (P < 0.05).

Pseudomonas aeruginosa cross-infection among patients with cystic fibrosis during a winter camp.

Twenty-seven patients with cystic fibrosis from our Danish Cystic Fibrosis Center went to a winter camp for 1 week in November of 1990. This study is based on 22 of these patients. Prior to attending camp, 17 out of 22 patients harbored Pseudomonas aeruginosa in their sputum, but 5 patients did not. After returning from camp, all 22 patients harbored P. aeruginosa in the sputum, including the 5 patients whose sputum was free of P. aeruginosa before they went. Epidemiological typing used pulsed-field gel electrophoresis of the P. aeruginosa isolates was performed. The typing results showed that the 5 cystic fibrosis patients who were free of P. aeruginosa in their sputum prior to the winter camp had acquired P. aeruginosa isolates identical to the P. aeruginosa strains isolated from the other 17 cystic fibrosis patients. This constitutes a cross-colonization rate of 100%, the highest rate ever detected among patients with cystic fibrosis. We conclude that separate holiday camps based on the infection status of the patients with cystic fibrosis are necessary to avoid cross-infection of patients not infected with P. aeruginosa.

Changing epidemiology of Pseudomonas aeruginosa infection in Danish cystic fibrosis patients (1974-1995).

Recurrent and chronic lower airway infection with Pseudomonas aeruginosa (PA) is an important component of cystic fibrosis (CF) pulmonary disease. Different modes of treatment and control of CF patients have been introduced at the Copenhagen CF Centre over the past 20 years and have been associated with improved survival. Treatment consisted of: 1) elective antibiotics for 14 days every 3 months to patients with chronic PA infection (started in 1976), 2) cohort isolation to prevent cross-infection (patients with PA were separated from patients without PA, starting in 1981); and 3) early intensive treatment with inhaled colistin and oral ciprofloxacin from time of initial PA colonization (started in 1989). The aim of the present study was to evaluate the impact of each of these interventions on the changes in the epidemiology of PA. Based on monthly cultures of lower airway secretions in each CF patient seen during 1974-1995, significant changes in the incidence and prevalence of the PA infection were found. The monthly prevalence of chronic PA increased significantly (P < 0.0001) from below 40% before 1976 to above 60% in 1980, which was found to be due to cross-infection among the CF patients after introduction of elective antibiotic courses in 1976. To deal with this problem, cohort isolation was introduced in 1981, and since then the monthly point prevalence of chronic PA decreased slowly until 1989 (P < 0.0001), when early intensive treatment from initial PA colonization was introduced; this was associated with a further decrease in point prevalence to 45% in 1995 (P < 0.005). The annual incidence of chronic PA infection also decreased significantly (P < 0.01) from 16% to below 2% after introduction of cohort isolation and early intensive treatment from initial PA isolation. Furthermore, the time from acquisition of first PA to development of chronic PA infection increased significantly, from approximately 1 year to almost 4 years after introduction of cohort isolation (P < 0.0001). After introduction of early intensive treatment, the probability of still not having developed chronic PA infection 7 years after the first isolation of PA was above 80% (P < 0.0001). In conclusion, the introduction of cohort isolation and early intensive treatment following the initial isolation of PA resulted in a reduced incidence and prevalence of chronic PA infection. We are not aware of other studies showing a decreasing prevalence of chronic PA infection, as survival of CF patients has increased.

Improved survival in the Danish center-treated cystic fibrosis patients: results of aggressive treatment.

We report survival data for Danish center-treated cystic fibrosis (CF) patients, covering the period 1974-1993 and using cross-sectional cumulative survival probability based on annual age-specific mortality rates. Analyses by age and by years after diagnosis were made. No significant differences were noted in the survival probability when patients were grouped according to sex or absence/presence of meconium ileus. The annual mortality rate for 1989-1993 was 0-1.2%. Using the age-specific mortality rate for 1989-1993, we were unable to calculate the median survival probability because the curve did not fall below 50% (age up to 45 years); however, it was possible to show that the survival probability for a newborn CF child to reach his 45th birthday was 80.4%(confidence interval 76.5-84.6%). The median age at diagnosis was 0.63 years with no sex difference. The probability of surviving 40 years after the diagnosis of CF was made was 83.3% (confidence interval 80.1-86.6%). This is considerably higher than any other published survival probability. An early anti-Pseudomonas aeruginosa treatment regimen seemed important in achieving the observed improved survival.

Feto-maternal listeriosis in Denmark 1981-1988.

We collected clinical information about 30 cases of Listeria monocytogenes infections in pregnancy, which occurred in Denmark between 1981 and 1988. The incidence of feto-maternal listeriosis was approximately one case per 100,000 live births in the early 1980s but increased to 25.3 cases per 100,000 live births in 1986. Listeriosis in Denmark occurred in two different patterns: endemic, in which the feto-maternal cases were a small proportion of the total, and epidemic: cases due to strains which were indistinguishable by phage-typing, and having a higher proportion of feto-maternal cases, as was seen in the outbreak of 1985-1987. The study group comprised 11 cases of intra-uterine death, three of maternal septicaemia without infection of the fetus and 16 cases of neonatal infection. Most neonates were ill at birth or became so within the first 24 h. The overall mortality rate among liveborn infants was 10.5% (2/19).

Epidemiologic, bacteriologic, and long-term follow-up data of children with acute hematogenous osteomyelitis and septic arthritis: a ten-year review.

A total of 69 children with acute hematogenous osteomyelitis and 48 with septic arthritis admitted in the period 1978 through 1987 were included in a retrospective review. Epidemiologic and bacteriologic data were analyzed and compared with those of an earlier study (1965 through 1975), confined to the same geographic area. Long-term outcome was evaluated by a questionnaire and clinical and radiographic follow-up. A significant increase in the admission rate for both disorders was observed. The long-term outcome was favorable: major sequelae were found in three patients (3%), minor sequelae in two patients (2%). The benign long-term outcome may well be related to rapid hospital admission and appropriate long-lasting antibiotic treatment.

[Familial infection caused by Haemophilus influenzae]. / Familiaer infektion med Haemophilus influenzae.

A three-year-old girl developed purulent arthritis and her nine-month-old younger brother meningitis with Haemophilus influenzae type b, after an interval of 43 days. Attention should be drawn to the spread of Haemophilus disease other than meningitis.

[Improved prognosis for patients with cystic fibrosis. A result of aggressive center-based treatment]. / Forbedret prognose for patienter med cystisk fibrose. Et resultat of aggressiv centerbehandling.

We report survival data for Danish centre-treated cystic fibrosis (CF) patients, covering the period 1974-1993 using cross-sectional cumulative survival probability based on annual age-specific mortality rates. No significant differences were noted in the survival probability when patients were grouped according to sex or absence/presence of meconium ileus. The annual mortality rate for 1989-1993 was 0-1.2%. Using the age-specific mortality rate for 1989-1993, we were unable to calculate the median survival probability because the curve did not fall below 50% (age up to 45 years). It was, however, possible to show that the survival probability for a CF child born after 1989 to reach his or hers 45th birthday was 80.4% (95% confidence interval 76.5-84.6%). The probability of surviving 40 years after the diagnosis of CF is made was 83.3% (95% confidence interval 80.1%-86.6%). This is considerably higher than any other published survival probability. An aggressive anti-Pseudomonas aeruginosa treatment regimen seemed important in achieving the observed improved survival.

Investigation of the vitamin D receptor gene (VDR) and its interaction with protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2) on risk of islet autoimmunity and type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY).

The present study investigated the association between variants in the vitamin D receptor gene (VDR) and protein tyrosine phosphatase, non-receptor type 2 gene (PTPN2), as well as an interaction between VDR and PTPN2 and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D). The Diabetes Autoimmunity Study in the Young (DAISY) has followed children at increased risk of T1D since 1993. Of the 1692 DAISY children genotyped for VDR rs1544410, VDR rs2228570, VDR rs11568820, PTPN2 rs1893217, and PTPN2 rs478582, 111 developed IA, defined as positivity for GAD, insulin or IA-2 autoantibodies on 2 or more consecutive visits, and 38 IA positive children progressed to T1D. Proportional hazards regression analyses were conducted. There was no association between IA development and any of the gene variants, nor was there evidence of a VDR*PTPN2 interaction. Progression to T1D in IA positive children was associated with the VDR rs2228570 GG genotype (HR: 0.49, 95% CI: 0.26-0.92) and there was an interaction between VDR rs1544410 and PTPN2 rs1893217 (p(interaction)=0.02). In children with the PTPN2 rs1893217 AA genotype, the VDR rs1544410 AA/AG genotype was associated with a decreased risk of T1D (HR: 0.24, 95% CI: 0.11-0.53, p=0.0004), while in children with the PTPN2 rs1893217 GG/GA genotype, the VDR rs1544410 AA/AG genotype was not associated with T1D (HR: 1.32, 95% CI: 0.43-4.06, p=0.62). These findings should be replicated in larger cohorts for confirmation. The interaction between VDR and PTPN2 polymorphisms in the risk of progression to T1D offers insight concerning the role of vitamin D in the etiology of T1D.

Mechanisms of renal NaCl retention in proteinuric disease.

In diseases with proteinuria, for example nephrotic syndrome and pre-eclampsia, there often are suppression of plasma renin-angiotensin-aldosterone system components, expansion of extracellular volume and avid renal sodium retention. Mechanisms of sodium retention in proteinuria are reviewed. In animal models of nephrotic syndrome, the amiloride-sensitive epithelial sodium channel ENaC is activated while more proximal renal Na(+) transporters are down-regulated. With suppressed plasma aldosterone concentration and little change in ENaC abundance in nephrotic syndrome, the alternative modality of proteolytic activation of ENaC has been explored. Proteolysis leads to putative release of an inhibitory peptide from the extracellular domain of the γ ENaC subunit. This leads to full activation of the channel. Plasminogen has been demonstrated in urine from patients with nephrotic syndrome and pre-eclampsia. Urine plasminogen correlates with urine albumin and is activated to plasmin within the urinary space by urokinase-type plasminogen activator. This agrees with aberrant filtration across an injured glomerular barrier independent of the primary disease. Pure plasmin and urine samples containing plasmin activate inward current in single murine collecting duct cells. In this study, it is shown that human lymphocytes may be used to uncover the effect of urine plasmin on amiloride- and aprotinin-sensitive inward currents. Data from hypertensive rat models show that protease inhibitors may attenuate blood pressure. Aberrant filtration of plasminogen and conversion within the urinary space to plasmin may activate γ ENaC proteolytically and contribute to inappropriate NaCl retention and oedema in acute proteinuric conditions and to hypertension in diseases with chronic microalbuminuria/proteinuria.