[A refugee with inguinal lymfadenopathy and skin lesions]. / Een vluchteling met lymfadenopathie en huiduitslag.

We present a 30-years-old man with lymphadenopathy and itchy skin lesions. One lymphoblast and atypical lymphocytes were found in the peripheral blood. Histopathologic examination of a skin punch biopsy revealed scabies. Lymphadenopathy is normally only seen in patients with widespread long-lasting scabies crustosa. However, this case illustrates that scabies should also be included in the differential diagnosis of patients with lymphadenopathy and only a few itchy skin lesions.

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial.

AIM: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. MATERIAL AND METHODS: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. RESULTS: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. CONCLUSIONS: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.

Enterovirus Exposure Uniquely Discriminates Type 1 Diabetes Patients with a Homozygous from a Heterozygous Melanoma Differentiation-Associated Protein 5/Interferon Induced with Helicase C Domain 1 A946T Genotype.

In children at risk for type 1 diabetes, innate immune activity is detected before seroconversion. Enterovirus infections have been linked to diabetes development, and a polymorphism (A946T) in the innate immune sensor recognizing enterovirus RNA, interferon-induced with helicase C domain 1/melanoma differentiation-associated protein 5, predisposes to disease. We hypothesized that the strength of innate antienteroviral responses is affected in autoimmune type 1 diabetes patients and linked to the A946T polymorphism. We compared induction of interferon-stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) in healthy individuals and diabetes patients upon stimulation with enterovirus, enterovirus-antibody complexes, or ligands mimicking infection in relation to the A946T polymorphism. Overall, PBMCs of diabetes patients and healthy donors showed comparable ISG induction upon stimulation. No differences were observed in DCs. Interestingly, the data imply that the magnitude of responses to enterovirus and enterovirus-antibody complexes in PBMCs is critically influenced by the A946T polymorphism and elevated in heterozygotes compared to TT homozygous individuals in autoimmune diabetes patients, but not healthy controls. These data imply an intrinsic difference in the responses to enterovirus and enterovirus-antibody complexes in diabetes patients carrying a TT risk genotype compared to heterozygotes that may influence control of enterovirus clearance.

Humoral and cellular immune responses after influenza vaccination in patients with chronic fatigue syndrome.

BACKGROUND: Chronic fatigue syndrome (CFS) is a clinical condition characterized by severe and disabling fatigue that is medically unexplained and lasts longer than 6 months. Although it is possible to effectively treat CFS, the nature of the underlying physiology remains unclear. Various studies have sought evidence for an underlying disturbance in immunity. The aim of this study was to compare the humoral and cellular immune responses upon influenza vaccination in CFS patients and healthy controls. RESULTS: Identical antibody titers were observed in CFS patients and healthy controls. Patients and controls demonstrated similar seroprotection rates against all three virus-strains of the influenza vaccine, both pre- and post-vaccination. Functional T cell reactivity was observed in both CFS patients and healthy controls. CFS patients showed a non-significant, numerically lower cellular proliferation at baseline compared to controls. Vaccination induced a significant increase in cellular proliferation in CFS patients, but not in healthy controls. Cytokine production and the number of regulatory T cells were comparable in patients and controls. CONCLUSIONS: The humoral and cellular immune responses upon influenza vaccination were comparable in CFS patients and healthy controls. Putative aberrations in immune responses in CFS patients were not evident for immunity towards influenza. Standard seasonal influenza vaccination is thus justified and, when indicated, should be recommended for patients suffering from CFS.

[Reimbursement for alternative medical treatment in the Netherlands, incomprehensible]. / Vergoeding van alternatieve geneeswijzen in Nederland: onbegrijpelijk.

It is remarkable that, at a time when not only doctors but also the Health Care Inspectorate (IGZ) and the health insurance companies are paying increasing attention to the quality of conventional medicine, many alternative methods of treatments without a scientific basis are accepted in the Netherlands. Even though it has been conclusively demonstrated that most alternative therapies do not work and despite the absence of scientific proof of the safety and efficacy of alternative treatments, health insurance companies do often reimburse the incurred costs. Because the safety of alternative therapies is not guaranteed, these are neither in the interest of the patient nor of society. Moreover, they are associated with considerable costs for the individual patient. By reimbursing the costs of insufficiently proven treatments, the health insurance companies are applying double standards. Reimbursement for these therapies is made at the expense of other effective and proven treatments. This can be changed through the concerted efforts of policy-makers, doctors, the IGZ, and health insurance companies.

Urinary heparanase activity in patients with Type 1 and Type 2 diabetes.

BACKGROUND: A reduced heparan sulphate (HS) expression in the glomerular basement membrane of patients with overt diabetic nephropathy is associated with an increased glomerular heparanase expression. We investigated the possible association of urinary heparanase activity with the development of proteinuria in patients with Type 1 diabetes (T1D), Type 2 diabetes (T2D), or membranous glomerulopathy (MGP) as non-diabetic disease controls. METHODS: Heparanase activity, albumin, HS and creatinine were measured in the urine of patients with T1D (n=58) or T2D (n=31), in patients with MGP (n=52) and in healthy controls (n=10). Heparanase messenger RNA (mRNA) expression in leukocytes was determined in a subgroup of patients with T1D (n=19). RESULTS: Urinary heparanase activity was increased in patients with T1D and T2D, which was more prominent in patients with macroalbuminuria, whereas no activity could be detected in healthy controls. Albuminuria levels were associated with increased urinary heparanase activity in diabetic patients (r=0.20; P<0.05) but not in patients with MGP (r=0.11; P=0.43). A lower urinary heparanase activity was observed in diabetic patients treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS), when compared to diabetic patients treated with other anti-hypertensives. Additionally, urinary heparanase activity was associated with age in T1D and MGP. In MGP, heparanase activity and ß2-microglobulin excretion correlated. In patients with T1D, no differences in heparanase mRNA expression in leukocytes could be observed. CONCLUSIONS: Urinary heparanase activity is increased in diabetic patients with proteinuria. However, whether increased heparanase activity is a cause or consequence of proteinuria requires additional research.

The effect of crossing legs on blood pressure.

OBJECTIVE: To determine whether crossing of the legs at the knee or at the ankles during blood pressure measurement in sitting position has an effect on blood pressure. METHODS: One hundred and eleven patients, 60 women, mean age 52+/-17 years (19-80): 49 chronically treated hypertensives, 28 treated diabetics and 34 normotensives were measured by one trained investigator, with an oscillometric device (Omron 705CP) on the left arm. We looked for the difference of blood pressure with the ankle or the knee crossed versus the uncrossed position. RESULTS: Leg crossing at the knee during blood pressure measurement increased systolic blood pressure significantly by 6.7 (95% confidence interval 5.0-8.4) mmHg in the hypertensives and 7.9 (4.0-11.8) mmHg in the treated diabetics. Diastolic blood pressure increased by 2.3 (0.8-3.8) mmHg in the hypertensives and 1.7 (0.1-3.4) mmHg for the treated diabetics. Normotensive participants showed a smaller, though significant, increase of systolic blood pressure 2.7 (1.2-4.2) mmHg, but not significant for diastolic blood pressure, -0.1 (-1.5-1.3) mmHg, respectively. In all groups there was no effect of crossing the ankles on blood pressure. No differences were found between men and women. No significant correlation between the increase of the blood pressure when the knees were crossed and BMI, age or baseline blood pressure was present. CONCLUSIONS: Blood pressure increased when legs were crossed at the knee in the sitting position. No significant increase of blood pressure was found when crossing the legs at the ankles. Leg position during measurement of blood pressure should be standardized and mentioned in publications.

A brief behavioral feedback intervention in hospital outpatients with a high cardiovascular risk.

OBJECTIVE: Examining the prevalence of risk behavior and motivation to change among hospital outpatients with a high cardiovascular risk, and the implementation and results of a brief behavioral feedback intervention by internists. METHODS: One hundred and sixty-one patients completed a lifestyle questionnaire and were given personalized feedback on the results by their internists. The delivery of the feedback was monitored. In an ad hoc non randomized comparison after four months, 68 patients who received an intervention were compared with 40 who did not receive it. RESULTS: Ninety-six percent of the patients demonstrated at least one risk behavior and 73% were not contemplating change. The intervention was correctly given to 62%. The patients who received the intervention reported more lifestyle changes and altered their motivation to change more often. DISCUSSION: Given the prevalence of risk behavior lifestyle interventions are worthwhile. Internists delivered the intervention to most patients. Small effects of the intervention were found, but the non-experimental nature of the study should be taken into account. CONCLUSION: Implementation of a behavioral feedback intervention seems to be feasible and can lead to worthwhile lifestyle changes for patients at risk for cardiovascular disease. PRACTICE IMPLICATIONS: Training and education can improve the intervention. Also a nurse practitioner can perform part of it.

Theophylline improves hypoglycemia unawareness in type 1 diabetes.

Iatrogenic hypoglycemias and the subsequent occurrence of hypoglycemia unawareness are well-known complications of intensive insulin therapy in type 1 diabetic patients that limit glycemic management. From a pharmacological point of view, the adenosine-receptor antagonist theophylline might be beneficial in the management of hypoglycemia unawareness. Theophylline stimulates the release of catecholamines and reduces cerebral blood flow, thereby facilitating stronger metabolic responses to and a prompter perception of decreasing glucose levels. To test the effect of theophylline on responses to hypoglycemia, we performed paired hyperinsulinemic-hypoglycemic clamp studies in 15 diabetic patients with hypoglycemia unawareness and 15 matched healthy control subjects. In random order, we concurrently infused either theophylline or placebo. Measurements included counterregulatory hormones, symptoms, hemodynamic parameters, and sweat detection using a dew-point electrode. Additionally, middle cerebral artery velocities (V(MCA)) using transcranial Doppler were monitored as an estimate of cerebral blood flow. When compared with placebo, theophylline significantly enhanced responses of plasma epinephrine, norepinephrine, and cortisol levels in both diabetic patients and control subjects. Because of the theophylline, sweat production started at approximately 0.3 mmol/l higher glucose levels in both groups (P < 0.01), and symptom scores in diabetic patients approached those in control subjects. Theophylline decreased V(MCA) in both groups (P < 0.001), but significantly greater in diabetic patients (P < 0.01), and prevented the hypoglycemia-induced increase of V(MCA) that occurred during the placebo studies. We conclude that theophylline improves counterregulatory responses to and perception of hypoglycemia in diabetic patients with impaired awareness of hypoglycemia.