Primary CNS lymphoma with bilateral symmetric hypothalamic lesions presenting with panhypopituitarism and diabetes insipidus

We present an unusual case of primary central nervous system (CNS) lymphoma presenting with bilateral symmetric hypothalamic lesions causing diabetes insipidus and hypopituitarism. A 50-year-old male presented initially with mental status changes, polyuria and polydipsia. The patient was determined to have diabetes insipidus (DI) and significant anterior pituitary deficiencies resulting in symptomatic pleural and pericardial effusions. Brain MRI with contrast demonstrated bilateral enhancement of his hypothalamus extending to the optic tract. The extensive diagnostic workup that ensued on his initial presentation was non-diagnostic as he had no obvious site of involvement that was easily accessible to biopsy. With close follow-up, the patient had rapid radiographic progression of his disease to his cerebral hemispheres. He therefore underwent brain biopsy and was diagnosed with primary CNS large B cell lymphoma. Chemotherapy has resulted in disease remission with resolution of MRI findings, but the patient has not had resolution of the hypopituitarism or DI. This case highlights the unique diagnostic challenge of patients with isolated hypothalamic lesions.     

The association between active and passive smoking and frequent pain in a general population

Background: It is controversial whether the association between back pain, and other types of chronic pain, and smoking is causal or not. Aim: To examine the relationship between frequent pain and smoking, and between frequent pain and exposure to environmental tobacco smoke (ETS) in smokers and non‐smokers. Methods: A randomised population‐based study, Inter99 (1999–2006), Denmark. Subjects in the intervention groups (N=6784; participation rate=52.5%) completed self‐report questionnaires. Cross‐sectional data from baseline were analysed in adjusted logistic regression analyses to investigate the relationship between active and passive smoking and frequent pain in the back, abdomen, joints and head. Results: Daily smokers reported significantly more frequent pain in every of the six locations, and in several, minimum three, locations (OR=1.98 (95%CI=1.6–2.4)) than never smokers. We found a dose–response relationship between frequent pain and intensity of both active and passive smoking (test‐for‐trend p<0.001). Those exposed to 5h or more of ETS reported significantly more frequent pain than those almost never exposed to ETS (non‐smokers: OR=1.46 (95%CI=1.2–1.8), and smokers: OR=2.04(95%CI=1.4–3.0)). Also, an earlier smoking debut and an increasing number of pack‐years increased the probability of frequent pain in daily smokers (test‐for‐trend p<0.05). Conclusion: We found significant association, dose–response and reversibility between active smoking and frequent pain in all six locations. Furthermore, we found that increasing intensity of ETS increased the probability of frequent pain in non‐smokers, which has not been shown before. In conclusion, several findings in this study indicate a causal link between tobacco smoke and pain, which is supported by recent prospective studies.     

Haemodynamic and respiratory effects of an abdominal compression binder

In order to elucidate the circulatory and respiratory effects of a newly developed abdominal compression binder 25 healthy, normal weight subjects were studied. In supine position the central haemodynamics were measured and estimated with a Finapress device. Lower extremity venous haemodynamics were measured in supine position with venous occlusion plethysmography. In an upright-seated position arterial oxygen saturation was measured by a pulseoxymeter for 1 h before spirometry was performed with a turbine flow measurement device. All the tests were performed in a randomized order with or without the abdominal compression binder. The results show that the compression binder significantly increases the venous volume in the lower extremities as showed by a reduction in the venous capacitance in the lower extremities and a reduction in the stroke volume and cardiac output, while it does not influence the pulmonary volumes. It is concluded that the applied abdominal binder significantly affects peripheral and central haemodynamics. It should therefore be used with caution when in the supine position for longer periods, as the pooling of blood it induces in the lower extremities may have implications for the risk of deep venous thrombosis formation.     

T wave morphology analysis distinguishes between KvLQT1 and HERG mutations in long QT syndrome

OBJECTIVES: The aim of this study was to develop an objective method to distinguish between HERG and KvLQT1 genotypes on the surface ECG. BACKGROUND: The two most prevalent genes affected in long QT syndrome (LQTS) are KvLQT1 (KCNQ1) and HERG (KCNH2), which are mutated in >90% of patients with a reported LQTS genotype. It is known that T waves have lower amplitude and more notches in HERG patients than T waves in KvLQT1 patients, but this semiquantitative method lacks the discriminative power to be used in a clinical setting. We developed a simple mathematical method that allowed us to quantify T wave shape in LQTS mutations for clinical use. METHODS: ECGs from 24 HERG patients, 13 KvLQT1 LQTS patients, and 13 healthy relatives were examined. The repolarizing integral (RI) was constructed from the T wave. The resulting RI is sigmoid and was modeled using the Hill equation as (RI(t) = V(max)*[t(n)/[K(m)(n) + t(n)]]). V(max) is equivalent to the total T wave area, K(m) is the time when 50% of the T wave area is reached, and n is a measure of the slope of the sigmoid RI. RESULTS: The RI correlated nearly perfectly to the fitted sigmoid, r = 0.99. In lead V(2), V(max) was larger in KvLQT1 (0.148 +/- 0.021) (mean +/- SE) compared to HERG (0.080 +/- 0.012) and controls (0.067 +/- 0.021). The Hill coefficient n of the RI discriminated perfectly between HERG (2.00 +/- 0.11) and KvLQT1 (4.11 +/- 0.15). CONCLUSIONS: RI allows distinguishing between HERG and KvLQT1 mutations based solely on the T wave morphology in the present LQTS population.     

Sirolimus-eluting stents inhibit neointimal hyperplasia in diabetic patients. Insights from the RAVEL Trial.

Patients with diabetes mellitus have less favourable outcomes after percutaneous coronary intervention (PCI) than non-diabetics. We performed a subgroup analysis of the multicentre RAVEL trial to examine the impact of the sirolimus-eluting stent (SES) on outcomes in diabetic patients. The RAVEL study randomized 238 patients to treatment with either sirolimus-eluting or bare metal stents. Forty-four patients were diabetic; 19 received sirolimus-eluting stents and 25 were treated with bare metal stents. The differences in outcomes between diabetic and non-diabetic patients treated with SES (n=101) were also assessed. Follow-up angiography was performed at 6 months. Major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), or target lesion revascularization (TLR) were analysed at 12-month follow-up. Six-month in-stent late lumen loss was significantly lower for the diabetic SES than the bare stent group (0.07+/-0.2 vs 0.82+/-0.5mm; P<0.001) and similar to that in non-diabetics treated with SES (-0.03+/-0.27mm). There was zero restenosis in the SES groups (diabetic and non-diabetic) compared to a 42% rate in the diabetic population assigned to bare metal stents (P=0.001). After 12 months, there was one non-Q-wave MI and one non-cardiac death in the diabetic SES group, while 12 patients in the bare metal stent group had MACE (one death, two MI, nine TLR) (P=0.01)-an event-free survival rate of 90% vs 52%, respectively (P<0.01). There were no TLRs in both SES groups compared to 36% rate in the diabetic bare metal stent group (P=0.007).Conclusion Diabetics treated with SES were associated with a virtual abolition of neointimal proliferation and low event rates at long-term follow-up.     

Cardiovascular risk-factors predict progression of urinary albumin-excretion in a general, non-diabetic population: a gender-specific follow-up study

Increased urinary albumin-excretion (UAE) predicts cardiovascular events and clusters with the metabolic syndrome. The aim of this population-based, prospective study was to assess the relationship between baseline and longitudinal changes in cardiovascular risk-factors and 7 years' increase in UAE. Three thousand and four hundred non-diabetic participants (1838 men, 1562 women) of the Troms? studies in 1994/1995 and 2001/2002 were included. In each survey, first-void spot-urine-samples were collected, and albumin-creatinine ratio (ACR) was calculated. Change in ACR (DeltaACR) was dichotomized into upper vs. the three lower quartiles. Median UAE in the population did not increase during follow-up. Baseline predictors for DeltaACR in the upper quartile were: age (OR 1.32 per 5 years, 95% CI 1.22-1.43), HbA1c (OR 1.43 per %, 95% CI 1.08-1.91) and waist circumference (OR 1.11 per 5 cm, 95% CI 1.04-1.19) in men, and age (OR 1.14 per 5 years, 95% CI 1.04-1.25) and current smoking (OR 1.71, 95% CI 1.27-2.30) in women. Systolic blood pressure and estimated glomerular filtration rate were predictors without gender-specificity. Clustering of three or more metabolic traits did not predict ACR increase independently. Protective factors against ACR increase were initiation of antihypertensive treatment in women (OR 0.59, 95% CI 0.39-0.87) and hard physical activity in men (OR 0.70, 95% CI 0.51-0.96). In summary, cardiovascular risk-factors at baseline predicted ACR increase, but initiation of antihypertensive therapy (women) and physical activity (men) seemed to protect from ACR increase during follow-up. Endpoint-data are needed to explore the clinical significance of low-grade UAE increase.     

Beat-to-beat QT dynamics in paroxysmal atrial fibrillation

BACKGROUND: QT dynamics parameters are used only in sinus rhythm. However, because many patients with paroxysmal atrial fibrillation undergo antiarrhythmic treatment that changes QT, developing methods for measuring QT dynamics during atrial fibrillation is important. OBJECTIVES: The purpose of this study was to evaluate whether QT dynamics in atrial fibrillation can be measured more reliably if additional RR intervals are included in the QT calculation. METHODS: QT and RR intervals were measured in 15 patients with atrial fibrillation and sinus rhythm on the same 24-hour Holter recording. Full QT adaptation is not instantaneous but lags behind over several beats. To correct for this lag, we adapted a weighted average method using five successive RR intervals. Linear regression was performed on (QT, RR) and (QT, RR(modified)) pairs. Variability ratio (standard deviation of all QT intervals/standard deviation of all RR intervals) and modified variability ratio (standard deviation of all QT intervals/modified standard deviation of all RR intervals) were calculated. RESULTS: QT-RR slope was reduced in atrial fibrillation compared with sinus rhythm (0.076 +/- 0.009 vs 0.113 +/- 0.0013, P = .0005). When correcting for lag, using the QT-RR(modified) slope, the slope in atrial fibrillation became similar to the slope in sinus rhythm (0.126 +/- 0.013 vs 0.126 +/- 0.013, P = .9547). The variability ratio was reduced in atrial fibrillation compared with sinus rhythm (0.175 +/- 0.017 vs 0.240 +/- 0.031, P = .009), but when correcting for the lag, the modified variability ratio was similar in atrial fibrillation and sinus rhythm (0.262 +/- 0.029 vs 0.267 +/- 0.038, P = .80). CONCLUSION: The results of this study demonstrate that QT dynamics can be measured reliably in atrial fibrillation using 24-hour Holter recordings.     

How do we best detect toxic effects of drugs taken during pregnancy? A EuroMap paper.

It is a major clinical and public health problem that there is no clear strategy as to how we best make use of information obtained when pregnant women take drugs. For this reason, some pregnant women are not treated as they should be and some are given drugs they should not use. We suggest a monitoring system that combines some of the available datasets in Europe. Using these sources as a starting point, one can develop a system that has sufficient power to detect even rare diseases like congenital malformations and sufficient diversity to detect several possible outcomes from spontaneous abortions to childhood disorders. We also suggest that case-crossover designs should be used in case-control monitoring systems that carry a high risk of recall bias. These considerations are based upon our results from a European Union-funded concerted action called EuroMaP (Medicine and Pregnancy).     

Unexplained chest/epigastric pain in patients with normal endoscopy as a predictor for ischemic heart disease and mortality: A Danish 10-year cohort study

Background  

Normal upper endoscopy may be a marker of ischemic heart disease in patients with unexplained chest/epigastric pain.