'Palm reading' as a diagnostic aid

In four patients, a man aged 53, a woman aged 63 and two men aged 67 and 53 years, respectively, inspection of the hand led to the final diagnosis. In the first patient who presented with clubbing of the fingers and pulmonary hypertension, a small atrial septal defect was detected. The second patient had thick curved yellow nails and recurrent pleural effusions as part of this yellow nail syndrome. The third patient presented with clubbing and hypertrophic osteoarthropathy, a secondary complaint to adenocarcinoma of the lung. The fourth patient had increasing pulmonary hypertension as a secondary complaint to recurrent multiple pulmonary embolism from deep venous malformations of his right hand, arm and shoulder as a part of the Klippel-Trenaunay syndrome. These cases show that inspection of the hand may give a clue to the diagnosis.     

Nutrition and health--carbohydrates, the risks to health from the postprandial glycaemic response and the possibilities for its manipulation

Carbohydrates are the most important source of food-derived energy. The metabolic effects of different types of carbohydrate can vary considerably, partially due to differences in glucose and insulin response. Several studies indicate that postprandial hyperglycaemia is associated with an increased risk of cardiovascular disease in patients with diabetes mellitus. For these patients, and possibly also for individuals with impaired glucose tolerance as well as for the healthy population at large, it may be of benefit to prevent postprandial hyperglycaemia. In order to manipulate the postprandial glycaemic response, an understanding of the underlying mechanisms of this response is crucial. The postprandial blood glucose level is influenced by a number of factors, such as the amount and type of ingested carbohydrates, gastric emptying rate and digestion and secretion of gastrointestinal and other hormones. Different approaches can be chosen to prevent postprandial hyperglycaemia, including changes in the diet and the use of drugs that delay gastric emptying or digestion of carbohydrates. The administration of gastrointestinal hormones or manipulation of the secretion of these hormones, are also possibilities. Investigating the regulation of the postprandial blood-glucose concentration and its possible manipulation could result in new approaches to preventing postprandial hyperglycaemia.     

Doppler sonography of uterine arteries at 20-23 weeks: risk assessment of adverse pregnancy outcome by quantification of impedance and notch

OBJECTIVE: To assess the diagnostic value of Doppler sonography of the uterine arteries (DSUA) at 20-23 gestational weeks as screening procedure in a low risk population. PATIENTS AND METHODS: The study group consisted of 7508 singleton low-risk pregnancies. Doppler sonography of both uterine arteries was performed as routine part of anomaly scan. Impedance of both uterine arteries was registered using the mean PI of the two uterine arteries. In case of notch, "Notch-Index" was defined as (C-D)/C with D = post-systolic nadir and C = following zenith of the waveform. Outcome variables were placental abruption, pre-eclampsia, intrauterine growth retardation, intrauterine/neonatal death and preterm delivery before 32 completed gestational weeks. To discriminate normal and pathological waveform, incidence of adverse pregnancy outcome was related to four different definitions of pathological waveform. To describe the severity of impairment of perfusion, the frequency of adverse pregnancy outcome was related to different classes of impedance. RESULTS: To find a simple discrimination between normal and pathological uterine perfusion, best diagnostic performance was reached by a definition using a combination of high impedance and notch (no notch and mean PI > P'95 or unilateral notch and mean PI > P'90 or bilateral notch and mean PI > P'50). The prevalence of notch in nulliparae (8.5%) was higher than in parae (4.7%) and decreased with increasing gestational age (20 weeks: 8.6%-23 weeks: 5.4%). We found a clear relation between elevation of impedance, depth of notch and frequency of adverse pregnancy outcome with a frequency of complications varying from 3.2% (mean PI < or = 0.8, mean NI = 0.1) to 38.4% (mean PI > 2.0, mean NI > 0.1). CONCLUSION: Doppler sonography of the uterine arteries at 20-23 weeks has the capacity to predict at least a part of severe forms of adverse pregnancy outcome and to assess the probability of complications by quantification of the impairment of the uterine blood flow.     

Carbon Dioxide in the Aortic Arch: Coronary Effects and Implications in a Swine Study

Purpose: CO₂ angiography is considered dangerous in the aortic arch where bubbles may cause critical cerebral and cardiac ischemia. We investigated CO₂ distribution, physiologic effects in the heart, methods of detection and treatments. Methods: Eight pigs had CO₂ and iodinated contrast arch angiograms in supine and both lateral decubitus positions. An electrocardiogram, physiologic data and cardiac ultrasound were obtained. Therapies included precordial thumps and rolls to lateral decubitus positions. Results: Supine high descending aorta CO₂ injections floated retrograde up the arch during diastole and preferentially filled the right coronary artery (RCA): mean score 3.5 (of 4), innominate artery 2.4, left coronary artery 1.2; n = 17; p = 0.0001. Aortic root injections preferentially filled the RCA when the animal was supine, left coronary in the right decubitus position, and showed a diffuse pattern in the left decubitus position. Right decubitus rolls filled both coronaries causing several lethal arrhythmias. Precordial thumps successfully cleared CO₂. Ultrasound is a sensitive detector of myocardial CO₂. Conclusion: Arch distribution of CO₂ primarily involves the RCA. Diagnostic ultrasound detects cardiac CO₂ well. Precordial thumps are an effective treatment.     

Endotoxin impairs endothelium-dependent vasodilation more in the coronary and renal arteries than in other arteries of the rat

Endotoxemia may result in endothelial dysfunction, and some vascular beds may be affected more than others. To test this hypothesis, we studied, in vitro, the reactivity of isolated rat coronary, renal, superior mesenteric, and hepatic arteries exposed to endotoxin (E. coli, 50 microg. mL(-1)) or saline for 2 h at 37 degrees C. Vascular smooth muscle function was tested using 125 mM KCl, the vasoconstrictors norepinephrine (NE), and the thromboxane analog U46619 (coronary artery). Endothelium-dependent vasorelaxation was tested with acetylcholine (ACh) in preconstricted vessels. Although differing between vessel types, the smooth muscle contractile responses were not affected by endotoxin, either in the presence or absence of L-arginine. Endotoxin impaired the response to ACh in rat coronary arteries (92.7 +/- 4.6% vasodilation in control and 41.3 +/- 11.6% in endotoxin-exposed segments) and in renal arteries (66.7 +/- 5.2% vasodilation in control and 43.2 +/- 4.9% in endotoxin-exposed segments), so that there was a mean 55% decrease vs controls in coronary and a mean 35% decrease in renal arteries. Endotoxin did not affect superior mesenteric and hepatic arteries. Brief endotoxin exposure of isolated rat arteries may thus inactivate endothelial NO synthase, independent of iNOS. The increase in heterogeneity among endothelium-dependent vasodilation after endotoxin may help to explain early blood flow maldistribution in endotoxin shock.     

Dynamic contrast-enhanced MR imaging in monitoring response to isolated limb perfusion in high-grade soft tissue sarcoma: initial results

The objective of this study was to evaluate whether dynamic contrast-enhanced MR imaging can determine tumor response and localize residual viable tumor after isolated limb perfusion (ILP) chemotherapy in soft tissue tumors. Twelve consecutive patients, with histologically proven high-grade soft tissue sarcoma, prospectively underwent non-enhanced MR and dynamic contrast-enhanced MR imaging before and after ILP. Tumor volume was measured on non-enhanced MR images. The temporal change of signal intensity in a region of interest on dynamic contrast-enhanced MR images was plotted against time. Start, pattern, and progression of enhancement were recorded. Histopathologic response was defined as complete response if no residual viable tumor was present, partial remission if <50% viable tumor was present, and no change if ≥50% viable tumor was present in the resection specimen. Resected specimens for correlation with histopathology were available for 10 patients; 5 patients had partial remission and 5 had no change. Volume measurements correctly predicted tumor response in 6 of 10 patients. Dynamic contrast-enhanced MR correctly predicted tumor response in 8 of 10 patients. Early rapidly progressive enhancement correlated histologically with residual viable tumor. Late and gradual, or absence of enhancement, was associated with necrosis, predominantly centrally located, or granulation tissue. These preliminary results show that dynamic contrast-enhanced MR imaging offers potential for non-invasive monitoring of response to isolated limb perfusion in soft tissue sarcomas due to identification of residual areas of viable tumor and subsequently may provide clinically useful information with regards to timing and planning of additional surgery. Further prospective studies in a larger patient population is warranted.     

Prevalence of mutations in AGPAT2 among human lipodystrophies

Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous genetic disease characterized by near absence of adipose tissue and severe insulin resistance. We have previously identified mutations in the seipin gene in a subset of our patients' cohort. Recently, disease-causing mutations in AGPAT2 have been reported in BSCL patients. In this study, we have performed mutation screening in AGPAT2 and the related AGPAT1 in patients with BSCL or other forms of lipodystrophy who have no detectable mutation in the seipin gene. We found 38 BSCL patients from 30 families with mutations in AGPAT2. Three of the known mutations were frequently found in our families. Of the eight new alterations, six are null mutations and two are missense mutations (Glu172Lys and Ala238Gly). All the patients harboring AGPAT2 mutations presented with typical features of BSCL. We did not find mutations in patients with other forms of lipodystrophies, including the syndromes of Lawrence, Dunnigan, and Barraquer-Simons, or with type A insulin resistance. In conclusion, mutations in the seipin gene and AGPAT2 are confined to the BSCL phenotype. Because we found mutations in 92 of the 94 BSCL patients studied, the seipin gene and AGPAT2 are the two major genes involved in the etiology of BSCL.     

Electrical impedance tomography to measure pulmonary perfusion: is the reproducibility high enough for clinical practice?

A possible clinical application of electrical impedance tomography (EIT) might be to monitor changes in the pulmonary circulation, provided the reproducibility of the EIT measurement is adequate. The purpose of this study was threefold: the intra- and inter-investigator variability of repeated measurements was investigated. Three different regions of interest (ROI) were analysed to assess the optimal ROI. Twenty-four healthy subjects and six patients were included. The Sheffield applied potential tomograph (DAS-01P, IBEES, Sheffield, UK) was used. Electrodes were attached by investigator A, and duplicate EIT measurements were performed. After detachment and 45 min of rest, the protocol was repeated by another investigator B, and afterwards by the initial investigator A. Three ROIs were analysed: whole circle, 'inner half circle' and contour. The mean difference in impedance changes between observers is presented in arbitrary units (AU) +/- SD. Finally, the influence of age, body composition and sex on the EIT result was examined. For the contour ROI, the mean difference for the intra-investigator situation was -1.44 x 10(-2) +/- 18.45 x 10(-2) AU (-0.7 +/- 9.0%), and was 5.46 x 10(-2) +/- 21.66 x 10(-2) AU (2.7 +/- 10.8%) for the inter-investigator situation. The coefficient of reproducibility of the intra- and inter-investigator reproducibility varied between 0.89 and 0.97 for all ROIs (P < 0.0001). There is a relation between impedance change and age (correlation coefficient r = -0.63, P < 0.01 for contour ROI), and between impedance change and body mass index (BMI) (r = -0.53, P < 0.05). We found a significant difference in mean impedance change between groups of males and females. In conclusion, EIT results are highly reproducible when performed by the same investigator as well as by two different investigators.     

Electrical impedance tomography in the assessment of extravascular lung water in noncardiogenic acute respiratory failure

STUDY OBJECTIVES: To establish the value of electrical impedance tomography (EIT) in assessing pulmonary edema in noncardiogenic acute respiratory failure (ARF), as compared to the thermal dye double indicator dilution technique (TDD). DESIGN: Prospective clinical study. SETTING: ICU of a general hospital. PATIENTS: Fourteen ARF patients. INTERVENTIONS: In order to use the TDD to determine the amount of extravascular lung water (EVLW), a fiberoptic catheter was placed in the femoral artery. Measurements and main results: Fourteen consecutive ARF patients receiving mechanical ventilation were measured by EIT and TDD. EIT visualizes the impedance changes caused by the ventilation in two-dimensional image planes. An impedance ratio (IR) of the ventilation-induced impedance changes of a posterior and an anterior part of the lungs was used to indicate the amount of EVLW. For the 29 measurements in 14 patients, a significant correlation between EIT and TDD (r = 0. 85; p < 0.001) was found. The EIT reproducibility was good. The diagnostic value of the method was tested by receiver operator characteristic analysis, with 10 mL/kg of EVLW considered as the upper limit of normal. At a cutoff level of the IR of 0.64, the IR had a sensitivity of 93%, a specificity of 87%, and a positive predictive value of 87% for a supranormal amount of EVLW. Follow-up measurements were performed in 11 patients. A significant correlation was found between the changes in EVLW measured with EIT and TDD (r = 0.85; p < 0.005). CONCLUSION: We conclude that EIT is a noninvasive technique for reasonably estimating the amount of EVLW in noncardiogenic ARF.