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In this study, we identified all adults living in Denmark diagnosed with common variable immunodeficiency (CVID) and characterized them according to clinical presentation and EUROclass classification. Using a retrospective, cross-sectional design, possible CVID patients were identified in the Danish National Patient Register and Centers in Denmark treating patients with primary immunodeficiencies. The CVID diagnosis was verified by review of medical records. One-hundred-seventy-nine adults with CVID were identified. This corresponds to a prevalence of 1:26,000. The median age at onset of symptoms was 29 years with no sex difference. The median age at diagnosis was 40 years. Males were diagnosed earlier with a peak in the fourth decade of life, whereas females were diagnosed later with a peak in the sixth decade. The median diagnostic delay was seven years. Recurrent sinopulmonary infections were seen in 92.7% of the patients. The prevalence of non-infectious complications was similar to that of previously reported cohorts: bronchiectasis (35.8%), splenomegaly (22.4%), lymphadenopathy (26.3%), granulomatous inflammation (3.9%) and idiopathic thrombocytopenic purpura (14.5%). Non-infectious complications were strongly associated with B cell phenotype, with all having a reduced number of isotype-switched memory B cells. One-hundred-seventy (95%) were treated with immunoglobulin replacement therapy, primarily administered subcutaneously. According to international guidelines, diagnostic evaluation was inadequate in most cases. This study emphasizes the need for improved diagnostic criteria and more awareness of CVID as a differential diagnosis. Diagnosis and management of CVID patients is a challenge requiring specialists with experience in the field of PID.

Both animal and human studies have associated the endocannabinoid system with obesity and markers of metabolic dysfunction. Blockade of the cannabinoid receptor 1 (CB1) caused weight loss and reduction in waist size in both obese and type II diabetics. Recent studies on common variants of the CB1 receptor gene (CNR1) and the link to obesity have been conflicting. The aim of the present study was to evaluate whether selected common variants of the CNR1 are associated with measures of obesity and fat distribution.

Adiponectin, a protein classically known to be secreted by adipocytes, is also secreted by bone-forming cells. Results of previous studies have been contradictory as to whether serum adiponectin and bone mineral density (BMD) are associated. The aim of this study was to investigate a possible association between serum adiponectin and BMD in young, healthy men at a time of peak bone mass. BMD in the femoral neck, total hip, and lumbar spine were measured in this population-based cross-sectional study of 700 men aged 20-29 years participating in the Odense Androgen Study. Magnetic resonance imaging of femoral cortical thickness and bone marrow size was performed in a subsample of 363 participants. The associations between serum adiponectin and various bone measures were investigated by means of regression analyses with adjustment for potential confounding variables. An inverse association was found between serum adiponectin and total hip BMD and a direct between adiponectin and femoral bone marrow size (r = -0.092; P = 0.036 and r = 0.164; P = 0.003, respectively). Femoral muscle size may, at least in part, explain the association between adiponectin and total hip BMD. Serum adiponectin was inversely associated with total hip BMD in men at the time of peak bone mass, but this association may be explained by factors related to muscle size and function. The observed association between adiponectin and femoral bone marrow size was retained even after adjustment for potential covariates.

Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross-sectional study in young men and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function.

Population-based reference values for peak bone mass density in Danish men. BMD of total hip (1.078 +/- 0,14 g/cm2) differed significantly from values from National Health and Nutrition Examination Survey III and of total lumbar spine ((1.073 +/- 0.125 g/cm2) differed significantly from Hologic values.

To investigate the impact of the Ala1330Val (rs3736228, exon 18) and Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene on peak bone mass in young men.

In a nation-wide questionnaire survey, the incidence and risk factors of percutaneous (PCE) and mucocutaneous (MCE) blood exposure among doctors in Denmark were studied. Of 9375 doctors, 6256 (67%) responded and 6005 were included for analysis. The highest incidence per person-risk-year (pry) was found in General Surgery, Neurosurgery, Obstetrics-Gynaecology and Orthopaedic Surgery (6.2-8.5 PCE/pry and 7.3-8.8 MCE/pry) followed by Anaesthesiology and Oto-rhinolaryngology (2.6-3.1 PCE/pry and 6.0-6.9 MCE/pry) and Pathology, Internal medicine, Radiology and Paediatrics (0.8-1.3 PCE/pry and 1.3-2.9 MCE/pry). Employment as senior as compared to junior doctor was associated with a higher risk of PCE and MCE among surgeons and a higher risk of PCE in anaesthetists, but a lower risk of PCE and MCE in Internal Medicine, Radiology and Paediatrics. Only 35% adhered to the basic principles of universal precautions and non-compliance was associated with a considerably increased risk of exposures, especially in non-surgical specialties. In conclusion, we found an unacceptably high incidence of occupational blood exposures among Danish doctors and preventive measures to reduce the incidence are strongly needed.

Occupational blood exposures involves a risk of transmission of serious infections. We performed a nation-wide survey, to describe the incidence and risk factors of percutaneous (PCE) and mucocutaneous (MCE) blood exposures among hospital employed doctors in Denmark. Of 9,374 questionnaires, 6,256 (67%) were returned and 6,005 were eligible for analysis. The highest risk per person-risk-year (pry) was found in General surgery, Neurosurgery, Obstetrics-Gynaecology and Orthopaedic surgery (6.2-8.5 PCE/pry and 7.3-8.8 MCE/pry). The second risk group Anaesthesiology and Oto-rhino-laryngology (2.6-3.1 PCE/pry and 6.0-6.9 MCE/pry). Finally Pathology, Internal medicine, Radiology and Paediatrics had a considerable risk (0.8-1.3 PCE/pry and 1.3-2.9 MCE/pry). Potential risk factors were examined by Poisson regression. Employment as senior as compared to junior doctor was associated with a higher risk of PCE (RR 2.2) and MCE (RR up to 2.7 depending on experience) among surgeons and an increased risk of PCE in anaesthetists (RR 1.7). In contrast, senior physicians in Internal medicine, Radiology and Paediatrics had a several fold lower risk of PCE (RR 0.6) and MCE (RR 0.6 in males, 0.3 in females). Only 35% adhered to the basic principles of universal precautions (UP) and non-compliance was associated with a considerably increased risk of both MCE and PCE, especially in non-surgical specialties. In conclusion, we found an unacceptably high incidence of occupational blood exposures among Danish doctors. Non-compliance with UP was associated with an increased risk of exposure and efforts to improve compliance with UP as well as implementation and evaluation of other preventive measures are needed.

Occupational blood exposures involves a risk of transmission of serious infections. We performed a nation-wide survey, to describe the incidence and risk factors of percutaneous (PCE) and mucocutaneous (MCE) blood exposures among hospital employed doctors in Denmark. Of 9,374 questionnaires, 6,256 (67%) were returned and 6,005 were eligible for analysis. The highest risk per person-risk-year (pry) was found in General surgery, Neurosurgery, Obstetrics-Gynaecology and Orthopaedic surgery (6.2-8.5 PCE/pry and 7.3-8.8 MCE/pry). The second risk group Anaesthesiology and Oto-rhino-laryngology (2.6-3.1 PCE/pry and 6.0-6.9 MCE/pry). Finally Pathology, Internal medicine, Radiology and Paediatrics had a considerable risk (0.8-1.3 PCE/pry and 1.3-2.9 MCE/pry). Potential risk factors were examined by Poisson regression. Employment as senior as compared to junior doctor was associated with a higher risk of PCE (RR 2.2) and MCE (RR up to 2.7 depending on experience) among surgeons and an increased risk of PCE in anaesthetists (RR 1.7). In contrast, senior physicians in Internal medicine, Radiology and Paediatrics had a several fold lower risk of PCE (RR 0.6) and MCE (RR 0.6 in males, 0.3 in females). Only 35% adhered to the basic principles of universal precautions (UP) and non-compliance was associated with a considerably increased risk of both MCE and PCE, especially in non-surgical specialties. In conclusion, we found an unacceptably high incidence of occupational blood exposures among Danish doctors. Non-compliance with UP was associated with an increased risk of exposure and efforts to improve compliance with UP as well as implementation and evaluation of other preventive measures are needed.

The objective of this study was to describe the mechanisms of percutaneous blood exposure (PCE) among doctors and discuss rational strategies for prevention. Data were obtained as part of a nation-wide questionnaire survey of occupational blood exposure among hospital employed doctors in Denmark. The doctors were asked to describe their most recent PCE, if any, within the previous 3 months. Detailed information on the instruments, procedures, circumstances and mechanisms that caused the PCE was obtained. Of 9375 doctors, 6256 (67%) responded, and 6005 questionnaires were eligible for analysis. Of 971 described PCE the majority were caused by suture needles (n = 483), i.v.-catheter-stylets (n = 94), injection needles (n = 75), phlebotomy needles (n = 53), scalpels (n = 45), arterial blood sample needles (n = 41) and bone fragments (n = 23). Inattentiveness was the most common cause, contributing to 30.5% of all PCE. Use of fingers rather than instruments was a major cause of injury in surgical specialities and was a contributing cause of 36.9% PCE on suture needles. Common contributing causes when fingers were used (n = 199) were poor space in (30.2%) or view of (18.6%) the operation field. It was often argued that instruments were not practical to use or might harm the tissue. Of 689 PCE in surgical specialties, 17.4% were inflicted by colleagues. Up to 53.3% of PCE on hollow-bore needles could be attributed to unsafe routines like recapping only, but other mechanisms like sudden patient movements and 'acute situation' were common, especially in the case of PCE on i.v.-catheter-stylets. It is concluded that the exposure mechanisms of PCE reflect both unsafe routines, difficult working conditions and unsafe devices. Education in safer working routines are needed in all specialties. Introduction of safer devices should have a high priority in surgical specialties, and should be considered in non-surgical specialties too.

OBJECTIVE: To study the compliance, and reasons for noncompliance, with Universal Precautions and the associated circumstances of mucocutaneous blood exposure (MCE) among Danish physicians. DESIGN: A nationwide questionnaire survey. SETTING: All Danish hospitals. PARTICIPANTS: All hospital-employed physicians. RESULTS: Of 9,384 questionnaires, 6,256 (67%) were returned, and 6,005 were eligible for analysis. Only 35% of respondents were compliant with the basic principle of Universal Precautions. Compliance with specific barriers in the preceding week among "surgeons and pathologists" and "other physicians" was as follows: gloves, 63.0% and 23.4%; masks, 55.2% and 17.6%; and protective eyewear, 11.5% and 4.0%, respectively. Common arguments for non-compliance were "interferes with working skills," "forget," "wear spectacles," "not available," "too much trouble to get," or "gloves do not fit." Detailed descriptions of 741 MCEs were obtained. Blood splashes in the eyes (n = 320) was the most common MCE in surgical specialties and pathology, whereas blood on the hands (n = 290) was most common in other specialties. In 20% of MCEs of the eyes, the exposure occurred despite the use of spectacles. An estimated 84% to 98% of MCEs potentially would have been preventable had appropriate barriers been worn. More than one half of MCEs were preventable by two interventions only: compulsory use of protective eyewear during operations and use of gloves during insertion of peripheral intravenous catheters. CONCLUSION: Compliance with Universal Precautions is unacceptably low, as reflected by the circumstances of MCE. Increased efforts to ensure education in Universal Precautions, easy accessibility of protective barriers, and improved design of the barriers are necessary to improve compliance and reduce the risk of MCE.

Health care workers are at risk of acquiring blood-borne infections. To assess the risk of exposure to hepatitis B or C in the case of occupational blood exposure, we determined the seroprevalence of these infections in 466 patients admitted to a Copenhagen university hospital. Serological markers for hepatitis B or C were detected in 56 patients (12.0%). The seroprevalence of HBsAg and anti-HCV was 0.9% and 1.5% respectively. HCV RNA, indicating ongoing hepatitis C, was found in five of seven anti-HCV-positive patients by polymerase chain reaction. The serological findings had not previously been diagnosed in 4 of 10 potentially infectious patients and only 6 of 10 patients belonged to high-risk groups. In conclusion, health care workers should be aware of the potential the occupational risk of hepatitis B and C even in a low-prevalence country like Denmark. Management of health care workers after blood exposure should include serological testing for both hepatitis B and C. Strict adherence to universal precautions is recommended and vaccination against hepatitis B should be encouraged.

OBJECTIVE: To examine the importance of cytomegalovirus (CMV) in bronchoalveolar lavage (BAL) fluid of patients with HIV-associated Pneumocystis carinii pneumonia (PCP) treated with adjunctive corticosteroids (CS). DESIGN: Analysis of clinical data during a 5-year period. SETTING: Department of infectious diseases where clinical and paraclinical data on patients suspected of having PCP have been sampled prospectively. PATIENTS: 148 consecutive patients with a first episode of PCP in a 5-year period. MAIN OUTCOME MEASURE: Vital status 3 months after diagnosis of PCP. RESULTS: Patients with PCP treated with adjunctive CS who had CMV cultured from BAL fluid had a two times higher mortality within 3 months from bronchoscopy than others (p = 0.08). This difference could not be explained by differences in CD4 count, PO2 or PCO2 at time of bronchoscopy. CONCLUSION: With the accepted usage of adjunctive CS in severe PCP, the role of CMV as a pulmonary copathogen may have changed. Active CMV infection may be an important cause of failing treatment of severe PCP in those treated with adjunctive CS.

Pneumocystis carinii pneumonia (PCP) may cause severe respiratory distress. This is believed to be partly caused by the accumulation of neutrophils in the lung. Interleukin-8 (IL-8) and leukotriene B4 (LTB4) are potent neutrophil chemo-attractants and activators. Eicosanoids [i.e. prostaglandins (PG) and leukotrienes (LT)] are pro-inflammatory mediators released from arachidonic acid by action of phospholipase A2 (PLA2) and have been implicated in the host response to micro-organisms. Bronchoalveolar lavage (BAL) was performed on patients with PCP as part of a randomized study of adjuvant corticosteroids vs. placebo, in addition to standard antimicrobial therapy. Re-bronchoscopy was offered at day 10. BAL fluid was available for 26 patients who had follow-up bronchoscopy performed. At diagnosis, IL-8 levels were elevated in patients with PCP, compared to healthy controls, and correlated with relative BAL neutrophilia and P(A-a)O2. LTB4 was also elevated in PCP, but failed to correlate with either BAL neutrophilia or P(A-a)O2. PLA2 activity in patients correlated with IL-8 levels and BAL neutrophilia, but not with P(A-a)O2. A trend towards a decrease in IL-8 levels in BAL fluid was detected in the corticosteroid-treated patients from days 0-10, whereas no change was detected in the placebo group. No change in levels of LTB4, LTC4, PGE2, PGF2a and PLA2 were detected cover time in either treatment group. This study establishes a correlation between IL-8, BAL neutrophilia and P(A-a)O2, and suggests a role of IL-8 as a mediator in the pathogenesis of PCP, whereas the role of eicosanoids seems less clear.

Forty-three human immunodeficiency virus-infected patients with Pneumocystis carinii pneumonia (PCP) were enrolled in a study of adjunctive corticosteroid treatment for 10 days versus placebo, in addition to antimicrobial treatment. Levels of neopterin and beta 2-microglobulin (beta 2M) were determined in consecutive serum samples. Initiation of antimicrobial treatment resulted in significantly increased neopterin levels, whereas beta 2M levels slightly decreased from pretreatment levels. In patients treated with corticosteroid, both neopterin and beta 2M decreased, by approximately 50% and approximately 30%, respectively, and returned to baseline after discontinuation of corticosteroid treatment. Antimicrobial treatment alone did not affect either neopterin or beta 2M in healthy controls. Results indicate that treatment has a differential effect on the immune response: increased macrophage activation leading to neopterin production and decreased production of beta 2M by lymphocytes. Further, addition of corticosteroids modified and decreased this immune activation and may explain the earlier demonstrated beneficial effect of corticosteroids in PCP treatment.

The frequency and reporting rate concerning occupational blood exposure were investigated among former and currently employed medical staff at a Department of Infectious Diseases (DID) having a high prevalence of HIV-positive patients. Subjects were asked to complete an anonymous questionnaire describing occupational percutaneous exposure (PCE) and mucocutaneous exposure (MCE) to blood, experienced during their employment at the DID. 135 out of 168 (80%) subjects responded. 45 subjects described 37 incidents of PCE and 15 of MCE. 44 of the exposures (85%) involved HIV-positive blood and 6 (11.5%) involved blood from a patient with hepatitis B. Annual incidence rates of PCE and MCE were: for A) interns and residents, 0.51 PCE/year and 0.17 MCE/year; B) for senior residents and senior physicians, 0.13 PCE/year and 0.21 MCE/year; C) for registered nurses, 0.11 PCE/year and 0.03 MCE/year; D) for auxiliary nurses, 0.09 PCE/year and 0.11 MCE/year. 35% of PCE and 87% of MCE were not reported to the security representative, the major reason being that the subject felt it to be unnecessary. We conclude that medical employment, especially as interns and residents at clinics for infectious diseases, carries a real and serious risk of contracting infectious diseases due to occupational exposure to blood. The importance of reporting needs to be emphasized.

Correlations between semiquantitative amounts of Pneumocystis carinii (PC), the degree of inflammation, and the severity of pneumonia were analyzed in 58 patients with PC pneumonia (PCP). Material from both transbronchial biopsies (TBBs; n = 39) and bronchoalveolar lavage fluid (BALF; n = 57) was examined. In the TBB the amount of PC correlated strongly with overall inflammation in the interstitium (Kendall correlation coefficient [Kcc] = 0.59; p < 0.0001), type 2 pneumocyte proliferation, and edema formation. The amount of PC in the TBB also correlated with interstitial accumulation of neutrophils (Kcc = 0.54; p = 0.0001), lymphocytes, and macrophages. In BALF the amount of PC correlated with edema formation and type 2 pneumocyte proliferation in the TBB but not with the percentage of neutrophils, lymphocytes, or macrophages in BALF. The amount of PC in the BALF and the percentage of neutrophils in the BALF correlated significantly with Po2 and the serum lactate dehydrogenase (LDH) level. Neither short-term nor long-term survival was affected by the amount of PC, inflammatory markers in the TBB, inflammatory cells in BALF, Po2, or the serum LDH levels. In conclusion, the amount of PC is associated with the extent of the acute inflammatory reaction in the lung in PCP associated with human immunodeficiency virus (HIV).

We investigated mechanisms of mucocutaneous exposure (MCE) and percutaneous exposure (PCE) to blood, and compliance with protective barriers among all former and presently employed medical staff at a Danish Department of Infectious Diseases. All subjects were asked to complete an anonymous questionnaire. 135 out of 168 (80%) subjects responded. 37 incidents of PCE and 15 MCE were described. More than 50% of PCE had occurred without obvious explanation during medical procedures, or were caused by unexpected patient movement, while only 1 PCE was caused by recapping. 35% of PCE occurred during drawing of venous blood samples. Compliance with usage of gloves was high (70-100%), depending on the procedure, and 72% of the subjects claimed to have sufficient knowledge of the risk of blood exposure and how to prevent it. Yet 11 (73%) out of 15 MCE might have been prevented by appropriate use of protective barriers. To further reduce the frequency of blood exposure, the development of safer instruments and unceasing education in safer technique and use of protective barriers are of major importance.

The effectiveness and tolerability of Sulfamethoxazole with Trimethoprim (SMX-TMP), a dose of 400mg/80mg given twice a day as secondary prophylaxis (SP) against Pneumocystis carinii pneumonia (PCP) was assessed retrospectively in 166 AIDS patients. The mean observation period was 9.7 months (range 1.0-1.4). Relapse of PCP occurred in eight patients; four episodes were histologically verified and four episodes were clinically assumed. The relapse rate after one year of prophylaxis was 5.1% (95% CI 0.0%-11.0%) using the log-rank test. Intolerance of secondary prophylaxis, defined as adverse effects necessitating cessation of SP with SMX-TMP, was reported in eight patients (5%) (95% CI 2.1%-9.3%).

Inflammation may play a central role in the pathogenesis of HIV-related Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in granulation tissue and in chronic rheumatic and liver disorders. To investigate changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive serum samples were taken from 48 HIV-infected patients with PCP in a randomized, placebo-controlled study of the effect of adjunctive methylprednisolone therapy (26 in corticosteroid [CS] group and 22 in control group). All patients were treated with co-trimoxazole. In the control group, PIIINP serum levels at day of initiation of therapy (Day 0) were significantly higher in patients requiring mechanical ventilation and/or dying during the course of the pneumonia, and serum levels of PIIINP higher than 5 ng/ml were associated with a higher mortality than levels below 5 ng/ml. The level of PIIINP increased from Day 0 to Day 5. There was a significant correlation between changes in PIIINP levels and changes in the alveolar-arterial oxygen gradient from Day 0 to Day 5. In the CS group, the PIIINP levels decreased while steroid was administered. At Days 21 to 28 there were no difference in the levels of PIIINP between the two groups. PIIINP serum levels may predict the clinical outcome of PCP. The antimicrobial therapy may exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory failure. CS prevents this increased inflammatory activity.

Fifty-nine human immunodeficiency virus type-1-infected patients with a microscopically proven first episode of moderate to severe Pneumocystis carinii pneumonia (PCP) were enrolled into a randomized European multicenter study. The effect of adjunctive corticosteroid (CS) therapy was assessed on (a) survival to discharge, (b) need for mechanical ventilation, and (c) survival at day 90. CS was given within 24 h of standard therapy as intravenous methylprednisolone 2 mg/kg body weight daily for 10 days. All patients received cotrimoxazole as standard treatment. Inclusion criteria were a PaO2 less than 9.0 kPa (67.5 mm Hg) and/or a PaCO2 less than 4.0 kPa (30.0 mm Hg) while breathing room air. During the acute episode of PCP, 9 (31%) of the 29 control patients died versus 3 (10%) of the 30 CS patients; p = 0.01. Mechanical ventilation was necessary in 15 patients; 12 (41%) in the control group and 3 (10%) in the CS group; p = 0.01. The 90-day survival was 69% in controls versus 87% in CS patients; p = 0.07. Based on these data we conclude that adjunctive CS therapy for moderate to severe PCP in AIDS patients reduces the acute mortality and the need for mechanical ventilation.

The diagnostic value of the CD4 cell counts and the HIV p24 antigen were evaluated in a consecutive series of 105 HIV-infected patients experiencing 128 episodes of pulmonary symptoms which required bronchoscopy. One-third of patients with opportunistic infection (OI) had CD4 counts greater than 0.200 x 10(9)/l, and 60% of patients without OI had CD4 counts less than 0.200 x 10(9)/l; 47 and 42% of patients with and without OI, respectively, had detectable p24 antigen in serum. Only 36% of the patients with OI presented the combination of CD4 cells less than 0.200 x 10(9)/l and p24 in serum. In conclusion, the CD4 cell counts and the presence of p24 antigen in serum had a very limited predictive value for the presence of OI in HIV-infected patients with pulmonary symptoms.

During a six-month period, 40 consecutive fiberoptic bronchoscopic procedures including bronchoalveolar lavage, bronchial brushing and forceps biopsy were performed in local anaesthesia on 34 HIV-infected males presenting symptoms compatible with Pneumocystis carinii pneumonia. In 23 examinations, P. carinii was found. Sixteen examinations were non-diagnostic and one was unsuccessful. The clinical course confirmed the diagnoses of the P. carinii positive as well as the P. carinii negative patients. Except for a lower total lymphocyte count in the patients harbouring P. carinii, the two groups did not differ with regard to history, clinical examination, immunology, serology or chest radiograph. We conclude that fiberoptic bronchoscopy should be performed on wide indications in HIV-infected patients with symptoms compatible with P. carinii pneumonia. The procedure is easily performed, it is safe, and it is highly sensitive. The advantage of an early diagnosis compensates for a rather high frequency of negative examinations.