Longitudinal changes of serum cytokines in patients with chronic low back pain and Modic changes.

OBJECTIVES: To explore serum cytokine levels over time in patients with chronic low back pain (cLBP) and Modic changes (MCs), difference in change between treatment groups in the Antibiotics in Modic Changes (AIM) study and associations between change in cytokines and low back pain. METHODS: Serum concentrations of 39 cytokines were measured at baseline and 1 year from 73 participants in the AIM study; 30 randomized to placebo, 43 to Amoxicillin. Low back pain intensity was measured by numeric rating scale. Change in cytokine levels over time were assessed by paired t-tests. Difference in change in cytokine levels between treatment groups and associations between changes in LBP and cytokine levels were assessed by linear regression models. Networks of cytokine changes in each treatment groups were explored by Pearson's correlations. RESULTS: Five cytokines changed from baseline to 1 year, (mean change, log transformed values with CI) C-X-C motif chemokine ligand (CXCL) 10 (IP-10) (0.11 (0.01-0.20)), CXCL13 (0.61 (0.00-0.12)), C-C motif chemokine ligand (CCL)26 (0.05 (0.01-0.1)), granulocyte macrophage-colony stimulating factor (GM-CSF) (-0.12 (-0.23 to 0.00)) and CXCL11 (0.12 (0.03-0.22)). Treatment group only influenced change in CCL21 (ß 0.07 (0.01-0.12)), and IL-6 (ß -0.17 (-0.30 to -0.03)). Change in CXCL13 (ß 2.43 (0.49-4.38)), CCL27 (ß 3.07 (0.46-5.69)), IL-8 (ß 1.83 (0.08-3.58)) and CCL19 (ß 3.10 (0.86-5.43)) were associated with change in LBP. The correlation networks of cytokine changes demonstrate small differences between treatment groups. CONCLUSIONS: Cytokine levels are relatively stable over time in our sample, with little difference between treatment groups. Some cytokines may be associated with LBP intensity. The differences between the correlation networks suggest that long-term Amoxicillin-treatment may have longstanding effects to be further explored.

Research protocol of two concurrent cluster-randomized trials: Real-life Effect of a CAMPaign with Measles Vaccination (RECAMP-MV) and Real-life Effect of a CAMPaign with Oral Polio Vaccination (RECAMP-OPV) on mortality and morbidity among children in rural Guinea-Bissau.

BACKGROUND: Measles and oral polio vaccinations may reduce child mortality to an extent that cannot be explained by prevention of measles and polio infections; these vaccines seem to have beneficial non-specific effects. In the last decades, billions of children worldwide have received measles vaccine (MV) and oral polio vaccine (OPV) through campaigns. Meanwhile the under-five child mortality has declined. Past MV and OPV campaigns may have contributed to this decline, even in the absence of measles and polio infections. However, cessation of these campaigns, once their targeted infections are eradicated, may reverse the decline in the under-five child mortality. No randomized trial has assessed the real-life effect of either campaign on child mortality and morbidity. We present the research protocol of two concurrent trials: RECAMP-MV and RECAMP-OPV. METHODS: Both trials are cluster-randomized trials among children registered in Bandim Health Project's rural health and demographic surveillance system throughout Guinea-Bissau. RECAMP-MV is conducted among children aged 9-59 months and RECAMP-OPV is conducted among children aged 0-8 months. We randomized 222 geographical clusters to intervention or control clusters. In intervention clusters, children are offered MV or OPV (according to age at enrolment) and a health check-up. In control clusters, children are offered only a health check-up. Enrolments began in November 2016 (RECAMP-MV) and March 2017 (RECAMP-OPV). We plan 18,000 enrolments for RECAMP-MV with an average follow-up period of 18 months and 10,000 enrolments for RECAMP-OPV with an average follow-up period of 10 months. Data collection is ongoing. The primary outcome in both trials is non-accidental death or non-accidental first non-fatal hospitalization with overnight stay (composite outcome). Secondary outcomes are: non-accidental death, repeated non-fatal hospitalizations with overnight stay, cause-specific primary outcome, outpatient visit, and illness. We obtained ethical approval from Guinea-Bissau and consultative approval from Denmark. DISCUSSION: Cluster randomization and minimum risk of loss to follow-up are strengths, and no placebo a limitation. Our trials challenge the understanding that MV and OPV only prevent measles and polio, and that once both infections are eradicated, campaigns with MV and OPV can be phased out without negative implications on child health and survival. TRIAL REGISTRATION: NCT03460002.

The causal role of smoking on the risk of headache. A Mendelian randomization analysis in the HUNT study.

BACKGROUND AND PURPOSE: Headache has been associated with various lifestyle and psychosocial factors, one of which is smoking. The aim of the present study was to investigate whether the association between smoking intensity and headache is likely to be causal. METHOD: A total of 58 316 participants from the Nord-Trøndelag Health (HUNT) study with information on headache status were genotyped for the rs1051730 C>T single-nucleotide polymorphism (SNP). The SNP was used as an instrument for smoking intensity in a Mendelian randomization analysis. The association between rs1051730 T alleles and headache was estimated by odds ratios with 95% confidence intervals. Additionally, the association between the SNP and migraine or non-migrainous headache versus no headache was investigated. All analyses were adjusted for age and sex. RESULTS: There was no strong evidence that the rs1051730 T allele was associated with headache in ever smokers (odds ratio 0.99, 95% confidence interval 0.95-1.02). Similarly, there was no association between the rs1051730 T allele and migraine or non-migrainous headache versus no headache. CONCLUSION: The findings from this study do not support that there is a strong causal relationship between smoking intensity and any type of headache. Larger Mendelian randomization studies are required to examine whether higher smoking quantity can lead to a moderate increase in the risk of headache subtypes.

Cerebral oximetry during preoperative resuscitation in elderly patients with hip fracture: a prospective observational study.

This study explores the association between postadmission and intraoperative cerebral oxygenation (ScO2), reflecting systemic perfusion, and postoperative mortality and delirium. Forty elderly (age > 65 years) patients with hip fractures were included in this prospective observational study. The ScO2 was determined using near-infrared spectroscopy at initial resuscitation after patients were admitted to the hospital and during surgery. Postoperative delirium was assessed up to seven days after surgery using the memorial delirium assessment scale and the confusion assessment method. Ten patients (25%) developed postoperative delirium within the first seven postoperative days. At initial resuscitation ScO2 was lower in patients that later developed delirium, but the difference was not significant (p = 0.331). Intraoperative ScO2 values remained similar in the two groups. Mortality regardless of cause was 10% (4 out of 40 patients) after 30 days. At initial resuscitation ScO2 was significant lower in the mortality group than in the surviving group (p = 0.042), and the ScO2 nadir values were also significant lower (p = 0.047). Low ScO2 during initial resuscitation (defined as ScO2 < 55 for a minimum of two consecutive minutes) was also significantly associated with 30-day mortality (p = 0.015). There were no associations between low blood pressure and postoperative delirium or 30-day mortality. We found that low preoperative ScO2 was better associated with 30-day all-cause mortality in elderly patients undergoing surgery for hip fracture than blood pressure measurements. Future studies in preoperative resuscitation of hip fracture patients should focus on perfusion measures as opposed to conventional haemodynamic.

The causal role of smoking on the risk of hip or knee replacement due to primary osteoarthritis: a Mendelian randomisation analysis of the HUNT study.

OBJECTIVE: Smoking has been associated with a reduced risk of hip and knee osteoarthritis (OA) and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal. METHOD: 55,745 participants of a population-based cohort were genotyped for the rs1051730 C > T single-nucleotide polymorphism (SNP), a proxy for smoking quantity among smokers. A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR)). Association between rs1051730 T alleles and TJR was estimated by hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were adjusted for age and sex. RESULTS: Smoking quantity (no. of cigarettes) was inversely associated with TJR (HR 0.97, 95% CI 0.97-0.98). In the Mendelian randomization analysis, rs1051730 T alleles were associated with reduced risk of TJR among current smokers (HR 0.84, 95% CI 0.76-0.98, per T allele), however we found no evidence of association among former (HR 0.97, 95% CI 0.88-1.07) and never smokers (HR 0.97, 95% CI 0.89-1.06). Neither adjusting for body mass index (BMI), cardiovascular disease (CVD) nor accounting for the competing risk of mortality substantially changed the results. CONCLUSION: This study suggests that smoking may be causally associated with the reduced risk of TJR. Our findings add support to the inverse association found in previous observational studies. More research is needed to further elucidate the underlying mechanisms of this causal association.

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Impact of chemotherapy regimen and rituximab in adult Burkitt lymphoma: a retrospective population-based study from the Nordic Lymphoma Group.

BACKGROUND: Standard treatment of adult Burkitt lymphoma is not defined due to the lack of randomised trials. In this situation, population-based data may represent a useful contribution in order to identify an optimal treatment strategy. PATIENTS AND METHODS: The aims of this study were to investigate the outcome for adult HIV-negative BL with different chemotherapy regimens, and to assess possible improvement within the time frame of the study. The study population was identified through the Swedish and Danish lymphoma registries 2000-2009. RESULTS: A total of 258 patients were identified. Since 2000, overall survival (OS) improved significantly only for younger patients (<65 years). Intensive regimens such as the Berlin-Frankfurt-Münster, hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and cyclophosphamide, vincristine, doxorubicin, methotrexate, ifosfamide, etoposide, and cytarabine (CODOX-M/IVAC) were associated with a favourable 2-year OS of 82%, 83%, and 69%, respectively. The low-intensive CHOP/CHOEP regimens achieved a 2-year OS of 38.8%, confirming their inadequacy for the treatment of BL. In a multivariate analysis, rituximab was not significantly associated with improved OS. CONCLUSIONS: In this population-based retrospective series of adult BL, intensive chemotherapy regimens were associated with favourable outcome. The impact of the addition of rituximab remains uncertain and warrants further investigation.

Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study.

BACKGROUND: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. RESULTS: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. CONCLUSIONS: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov. identifier NCT01502982.

Middle cerebral artery blood velocity during running.

Running induces characteristic fluctuations in blood pressure (BP) of unknown consequence for organ blood flow. We hypothesized that running-induced BP oscillations are transferred to the cerebral vasculature. In 15 healthy volunteers, transcranial Doppler-determined middle cerebral artery (MCA) blood flow velocity, photoplethysmographic finger BP, and step frequency were measured continuously during three consecutive 5-min intervals of treadmill running at increasing running intensities. Data were analysed in the time and frequency domains. BP data for seven subjects and MCA velocity data for eight subjects, respectively, were excluded from analysis because of insufficient signal quality. Running increased mean arterial pressure and mean MCA velocity and induced rhythmic oscillations in BP and in MCA velocity corresponding to the difference between step rate and heart rate (HR) frequencies. During running, rhythmic oscillations in arterial BP induced by interference between HR and step frequency impact on cerebral blood velocity. For the exercise as a whole, average MCA velocity becomes elevated. These results suggest that running not only induces an increase in regional cerebral blood flow but also challenges cerebral autoregulation.

R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-14. A population-based investigation from the Danish Lymphoma Group.

BACKGROUND: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18-60 years with two or more risk factors (stage III-IV, elevated lactate dehydrogenase levels, performance status 2-4). To our knowledge, this is the first study comparing these two regimens in this patient group. METHODS: We obtained data for the period 2004-2009 from the Danish Lymphoma Database. One hundred and fifty-nine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety. RESULTS: Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P=0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P=0.02). CONCLUSION: R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14.

FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas.

The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (P<0.05). FOXP1 knockdown in ABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL patients (n=150), reduced HLA-DRA (<90% frequency) expression correlated with inferior overall survival (P=0.0003) and progression-free survival (P=0.0012) and with non-GCB subtype stratified by the Hans, Choi or Visco-Young algorithms (all P<0.01). In non-GCB DLBCL cases with <90% HLA-DRA, there was an inverse correlation with the frequency (P=0.0456) and intensity (P=0.0349) of FOXP1 expression. We propose that FOXP1 represents a novel regulator of genes targeted by the class II MHC transactivator CIITA (MHC II and CD74) and therapeutically targeting the FOXP1 pathway may improve antigen presentation and immune surveillance in high-risk DLBCL patients.

Microalbuminuria in patients with lung cancer.

In a prospective study of 102 outpatients with histologically proven lung cancer, the prevalence and prognostic significance of microalbuminuria (urinary albumin excretion > 20 micrograms/min) were analysed. 65 consecutive outpatients with benign lung disorders served as controls. An immunoturbidimetric assay, sensitive at low concentrations, was used to quantify the albumin excretion rate in timed overnight urine samples. Patients with malignancies had a significantly higher frequency of microalbuminuria (32.4% compared with controls, 13.8%, P < 0.01) and median urinary albumin excretion rate (13.4 versus controls, 8.9 micrograms/min, P < 0.003). Urinary albumin excretion was significantly higher in lung cancer patients with TNM stage III and IV. Patients with malignancies and microalbuminuria had a significantly lower survival rate than patients with normoalbuminuria (probability of survival 1 and 3 years after diagnosis 66% and 16% versus controls, 22% and 4%, P < 0.00001). In a multivariate model, which adjusted for age, sex, performance status, histological type and TNM stage, microalbuminuria continued to be a significant predictor of survival. In conclusion, an increased prevalence of microalbuminuria has been demonstrated in patients with lung cancer. The presence of microalbuminuria was associated with advanced disease stage and poor survival.

Production of hyaluronan and chondroitin sulphate proteoglycans from human arterial smooth muscle--the effect of glucose, insulin, IGF-I or growth hormone.

BACKGROUND: Although it is recognized that the extracellular matrix is important for cell proliferation, migration and metabolism of growth factors, the regulation of the synthesis of hyaluronan and chondroitin sulphate proteoglycan (CSPG) in the vessel wall is poorly understood. OBJECTIVE: To examine the role of glucose, insulin, IGF-I and human growth hormone (hGH) on the accumulation of hyaluronan and CSPG using cultures of human aortic smooth muscle cells. METHODS: The cultures were exposed for 36 h. The CSPG content in the incubation medium was measured by a combination of digestion with testicular hyaluronidase and precipitation of [35SO4(2-)]-labelled material with ethanol and trichloroacetic acid. Hyaluronan was estimated using a radiometric assay. RESULTS: Glucose and insulin reduced the amount of synthesized hyaluronan (2P<0.01). Stimulation of synthesis was seen with hGH (2P<0.01), whereas no effect was observed with IGF-I. The production of CSPG was increased with glucose and hGH (2P<0.01), but showed no change with insulin. CONCLUSIONS: The present data obtained with human arterial smooth muscle cells in vitro showed that glucose, insulin and hGH can influence the accumulation of hyaluronan and CSPG. These observations may be relevant for an understanding of diabetic macroangiopathy.

Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly.

The aim was to evaluate, markers of disease activity in acromegaly in relation to perceived disease activity. Thirty-seven consecutively treated, acromegalic patients, classified by clinical symptoms as inactive (n=16), slightly active (n=10) and active (n=11), entered the study. When evaluating the inactive and the active groups, we found that positive and negative predictive values (PV(pos), PV(neg)) for clinical disease activity of total and free insulin-like growth factor-I (IGF-I) were 0.59, 0.90 and 1.00, 0.82 respectively. Acid-labile subunit (ALS) showed diagnostic merit similar to insulin-like growth factor binding protein-3 (IGFBP-3) with PV(pos) of 0.69 and 0.71 and PV(neg) of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease activity. Total IGF-I, IGFBP-3 and ALS possess a higher PV(neg) for the clinical disease activity. None of the parameters can at present be claimed to be superior to the others and thus all the measured parameters are recommended to be part of the evaluation of acromegalic patients.

Urinary albumin excretion and transcapillary escape rate of albumin in malignancies.

Transcapillary escape rate of albumin was determined in 22 patients with different malignancies. In addition, urinary albumin excretion rate was measured in 24-h urine samples using a sensitive immunoassay. Increased urinary albumin excretion was defined as >/=20 microg/min according to conventional standards. Renal glomerular filtration and tubular function was estimated by 51Cr-EDTA plasma clearance and urinary beta 2-microglobulin, respectively. Median urinary albumin excretion rate was 15.0 microg/min (range 6-510 microg/min) and the frequency of increased urinary albumin excretion was 41%. This agrees with other studies showing increased albuminuria in several types of malignant diseases. Patients with advanced disease (tumour, node, metastasis (TNM) stage II-IV) had a significantly higher urinary albumin excretion rate than patients with localized disease (TNM stage I). Serum creatinine, glomerular filtration rate and urinary beta 2-microglobulin were all within normal limits. Median transcapillary escape rate of albumin was 5.5 %/h (range 2-8 %/h) and this level is comparable with values in healthy subjects. There was no significant difference in transcapillary escape rate between patients with elevated urinary albumin excretion and the normoalbuminuric group. Median value of the absolut outflux of albumin was 10.6 g/h with similar levels in patients with increased urinary albumin excretion and patients with normoalbuminuria. Our results indicate a high prevalence of minor glomerular dysfunction with a slightly elevated urinary albumin excretion in patients with malignancies. The normal endothelial function, as estimated by the transcapillary escape rate of albumin, suggests an overall unaffected capillary permeability and increased urinary albumin loss appears to be an isolated renal phenomenon in cancer patients.

[The clinical impact of gestational diabetes mellitus]. / Den kliniske betydning af gestationel diabetes mellitus.

In Denmark, gestational diabetes mellitus (GDM) develops in about 2% of all pregnant women. The discussion of GDM is complicated by lack of consensus regarding screening methods, diagnosis and treatment. Observational studies indicate that untreated GDM is associated with an increased risk of maternal and perinatal morbidity, and that the offspring of GDM mothers tend to be at increased risk of developing diabetes and adiposity as a result of an abnormal intrauterine environment. Several follow-up studies have shown that women with previous GDM run a considerable risk of developing diabetes (especially type 2 diabetes) later in life. Intervention strategies for this high risk group are suggested.

[Oral contraceptives and diabetes mellitus]. / P-piller og diabetes mellitus.

PIP: The author reviews studies on the adverse effects of oral contraceptives (OCs) on insulin response and blood lipids in diabetes mellitus. The mechanisms of OCs and their diabetogenic effects are not well understood. The effect is dose-dependent on the estrogen and progestin content of the individual pill. Low doses of the new triphasic preparations appear to have a minimal effect on carbohydrate and lipid metabolism. Disorders of diabetic metabolism in insulin-dependent diabetics and a possible deterioration of noninsulin-dependent diabetics or potential diabetics have been attributed to earlier types of contraceptive pills with a higher steroid content. Whether the adverse effects can be avoided by taking low-dose or triphasic contraceptive preparations is yet unknown. In a recent study 120 patients, 3 women suffered temporary cerebral thrombosis and one a myocardial infarction. A comparative study found no cardiovascular complications in a control group of 156 insulin-dependent diabetics who were not on contraceptives. Whether contraceptives have an effect on existing diabetic retinopathy is not yet known. Since diabetic women already have a higher risk of cardiovascular complications, women who had diabetes in pregnancy should undergo a glucose tolerance test once a year while on contraceptives. It is very important to find a safe contraceptive method for diabetics. At the present time mini-pills or IUDs seem to have the fewest side effects.^ieng

[Angiofollicular lymph node hyperplasia (Castleman disease)]. / Angiofollikulaer lymfeknudehyperplasi (mb. Castleman).

Angiofollicular lymph node hyperplasia (Castleman's disease) is a relatively rare disease of differential diagnostic interest in patients with lymphadenopathy. The etiology and pathogenesis are still not elucidated. The disease is classified into localized and systemic types. The localized form is divided histologically into hyaline-vascular type and plasma cell types. The former is usually demonstrated incidentally as a widening of the mediastinum in otherwise asymptomatic patients. The plasma cell type usually presents in the abdominal lymph nodes and is accompanied by fever, loss of weight, anemia and hypergammaglobulinemia. Surgical treatment is curative in the localized disease. The systemic disease involves multiple lymph nodes, and multiple organs are affected. The prognosis is dubious, and frequently the patients rapidly die from septicemia or other infectious complications. Some patients develop malignancies. Treatment with glucocorticosteroids and chemotherapy has only demonstrated a limited effect. The diagnosis requires both a characteristic histopathology and typical clinical symptoms. A current illustrative case report is presented.

[The prognostic value of thrombocytosis in patients with primary lung cancer]. / Den prognostiske vaerdi af trombocytose hos patienter med primaer lungecancer.

The prognostic information provided by platelet counts was studied in 1115 patients with primary lung cancer and in 550 control patients with benign lung disorders. Patient records were retrospectively reviewed regarding histological tumour type, TNM stage, thromboembolic episodes and survival. The prevalence of thrombocytosis (platelet count > 400 x 10(9)/l) in patients with lung cancer was 32.1% vs. 6.4% in controls (p < 0.0001). Platelet counts increased with TNM stage (p < 0.0001). Patients with thrombocytosis had a shorter survival than patients with normal platelet count (p < 0.0001). Thrombocytosis was a predictor of short survival also when adjusted for tumour type, sex, age, and TNM stage (p < 0.001). The platelet count and the frequency of thrombocytosis declined after tumour resection (p < 0.0001). Thrombocytosis was not associated with thromboembolism. In conclusion, thrombocytosis is a clinically significant prognostic indicator regarding survival in patients with primary lung cancer.

[Kidney function problems in rheumatoid arthritis]. / Nyrefunktionsproblemer ved reumatoid arthritis.

Rheumatoid arthritis is a systemic, disabling disease with significant excess mortality which is partly caused by renal disease, infection and renal insufficiency being the main contributors. The bulk of renal problems in reumatoid arthritis are related to complications such as vasculitis and amyloidosis, and complications to the medical treatment of the disease, the main offenders being gold salts, penicillamine and cyclosporine. Also, there is increasing evidence that reumatoid arthritis per se can cause subclinical renal dysfunction with microalbuminuria as well as clinical disease, caused by immune-complex mediated glomerulonephritis and interstitial tubular fibrosis. In reumatoid arthritis serum creatinine can overestimate renal function by as much as 30% and it is suggested that more sensitive methods such as measuring urinary albumin excretion and glomerular filtration rate should be used for monitoring renal function.