Effects of candesartan cilexetil “add-on” treatment in congestive heart failure outpatients in daily practice

Aims  In the present study, we investigated the efficacy and safety of candesartan cilexetil (candesartan) as “add-on” treatment in congestive heart failure (CHF) in daily practice. Methods and results  In this open-label, multicenter study 414 CHF outpatients (NYHA II/III) with left ventricular ejection fraction (LVEF) ≤ 40% and plasma brain natriuretic peptide (BNP) levels > 200 pg/ml at baseline were enrolled. Patients were treated with standard therapy including at least one angiotensin converting enzyme inhibitor in addition to another CHF drug; 91% of the patients received beta-blockers. Candesartan was uptitrated to 32 mg/day (target dose if tolerated) during 6 weeks followed by constant dosing over 16 weeks. The primary endpoint plasma BNP was significantly reduced by 25% at week 22 (from 394 to 295 pg/ml, P < 0.0001 vs. baseline). Candesartan produced early and sustained improvements of plasma BNP/NT-pro-BNP, LVEF, and quality of life (SF-36) compared to baseline. Of patients on beta-blockers, 37% improved towards NYHA II/I at week 22 (P < 0.0001) and 53.5% of the patients in NYHA III at baseline improved into NYHA II/I at week 22 (n = 232, P < 0.0001). Candesartan was well tolerated; no unexpected findings were reported besides known adverse reactions including hypotension, hyperkalemia, and serum creatinine elevations. Conclusion  Candesartan “add-on” treatment provides a good benefit/risk ratio in CHF outpatients in daily practice, although high-risk patients should be managed with frequent monitoring of BP, serum potassium, and renal function.     

Developmental aspects of nociception

Research has documented the existence of multiple, endogenous systems that modulate nociception. Based on the effects of opioid antagonists and endocrine lesions, endogenous analgesia systems have been organized into four classes: neural-opioid, neural-nonopioid; hormonal-opioid; hormonal-nonopioid. Developmental research on the ontogeny of endogenous analgesic function has revealed differential rates of maturation. Front-paw shock, a stimulus that activates a neural-opioid analgesic response, has been shown to be functionally mature by 28 days of age in the rat. Similarly, hind-paw shock, a stimulus that elicits a neural-nonopioid analgesic response, reaches maturity after two months of age. However, the hormonal-opioid analgesic system activated by cold-water immersion reaches adult levels by 10 days of age. Food deprivation produces a hormonal-opioid analgesic response in adult rats, and food deprivation/isolation of rat pups has been found to elicit an analgesic response in 6-day-old rats. From these data it seems that the rate of development of the different endogenous analgesic systems is related to the activation of neural or hormonal components. Whether the differential rates of development and the neural-hormonal distinction are related to the ecological validity of the activating stimulus remains to be determined.     

Gadoxetic acid enhanced MRI for differentiation of FNH and HCA: a single centre experience

Objectives

Evaluation of enhancement characteristics of histopathologically confirmed focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HCAs) with gadoxetic acid-enhanced MRI.

Methods

Sixty-eight patients with 115 histopathologically proven lesions (FNHs, n?=?44; HCAs, n?=?71) examined with gadoxetic acid-enhanced MRI were retrospectively enrolled (standard of reference: surgical resection, n?=?53 patients (lesions: FNHs, n?=?37; HCAs, n?=?53); biopsy, n?=?15 (lesions: FNHs, n?=?7; HCAs, n?=?18)). Two radiologists evaluated all MR images regarding morphological features as well as the vascular and hepatocyte-specific enhancement in consensus.

Results

For the hepatobiliary phase, relative enhancement of the lesions and lesion to liver enhancement were significantly lower for HCAs (mean, 48.7 (±48.4) % and 49.4 (±33.9) %) compared to FNHs (159.3 (±92.5) %; and 151.7 (±79) %; accuracy of 89 % and 90 %, respectively; P?<?0.001). Visual strong uptake of FNHs vs. hypointensity of HCAs in the hepatobiliary phase resulted in an accuracy of 92 %. This parameter was superior to all other morphological and dynamic vascular criteria alone and in combination (accuracy, 54–85 %).

Conclusions

For differentiation of FNHs and HCAs by means of MRI, gadoxetic acid uptake in the hepatobiliary phase was found to be superior to all other criteria alone and in combination.

Key Points

? EOB-MRI is well suited to differentiate FNHs and hepatocellular adenomas. ? For this purpose hepatobiliary phase is superior to unenhanced and dynamic imaging. ? Hepatobiliary phase (peripheral) hyper- or isointensity is typical for FNH. ? Hepatobiliary phase hypointensity is typical for hepatocellular adenomas. ? EOB-MRI helps to avoid misinterpretations of benign hepatocellular lesions.     

Postnatal confirmation of prenatally diagnosed trisomy 20 mosaicism in a patient with linear and whorled nevoid hypermelanosis

Linear and whorled nevoid hypermelanosis (LWNH) is characterized by hyperpigmented reticulate macules in a Blaschko linear arrangement without atrophy or preceding inflammation. Underlying chromosomal mosaicism was often assumed, but has been verified in only a few published cases. We report a 7-year-old boy with LWNH associated with congenital ventricular septal defect and psychomotor retardation. Prenatal chromosomal analysis of amniocytes revealed trisomy 20 mosaicism, which was not confirmed in peripheral blood lymphocytes after birth. Histologic sections of skin biopsy specimens taken at age 6 years showed hyperpigmentation of the basal epidermal layer with prominent melanocytes and isolated melanophages in the upper dermis. Cytogenetic analysis of cultured skin fibroblasts revealed an extra chromosome 20 in 5 of the 30 metaphases studied (17%). Mosaic trisomy 20 is one of the most common autosomal mosaicisms identified in amniocytes and is, as a rule, compatible with normal pregnancy outcome. In postnatal analysis of peripheral blood lymphocytes, an extra chromosome 20 could never be detected. However, when confirmed in skin fibroblasts, trisomy 20 mosaicism may be associated with systemic anomalies. The present case shows for the first time an association of LWNH with trisomy 20 mosaicism and emphasizes the importance of analyzing skin fibroblasts in cases of prenatally diagnosed trisomy 20.     

Varicella exposure in a neonatal intensive care unit: case report and control measures

Forty-six infants in a neonatal intensive care unit and 138 health care workers were exposed to a pediatric medical resident during the prodromal period and the early days of unrecognized varicella. An attempt was made to prevent an outbreak of additional cases by the institution of emergency control measures. These measures included rapid identification of varicella antibody status in exposed neonates, varicella antibody testing of health care workers with unknown or uncertain history of varicella, prompt administration of varicella zoster immune globulin to potentially susceptible persons, and cohorting neonates on the basis of exposure and antibody status. Passive maternal antibody was detected in 44 of the neonates. Of 27 health care workers who reported either a negative or an uncertain history of varicella, 26 had detectable antibody. No overt cases of varicella occurred in exposed patients or personnel.     

The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen

The differentiation of the urinogenital system and the appendicular skeleton in vertebrates is under the control of Hox genes. The common control of digit and gonad differentiation raises the possibility that patterns of digit formation may relate to spermatogenesis and hormonal concentrations. This work was concerned with the ratio between the length of the 2nd and 4th digit (2D:4D) in humans. We showed that (i) 2D:4D in right and left hands has a sexually dimorphic pattern; in males mean 2D:4D = 0.98, i.e. the 4th digit tended to be longer than the 2nd and in females mean 2D:4D = 1.00, i.e. the 2nd and 4th digits tended to be of equal length. The dimorphism is present from at least age 2 years and 2D:4D is probably established in utero; (ii) high 2D:4D ratio in right hands was associated with germ cell failure in men (P = 0.04); (iii) sperm number was negatively related to 2D:4D in the right hand (P = 0.004); (iv) in men testosterone concentrations were negatively related to right hand 2D:4D and in women and men LH (right hand), oestrogen (right and left hands) and prolactin (right hand) concentrations were positively correlated with 2D:4D ratio and (v) 2D:4D ratio in right hands remained positively related to luteinizing hormone and oestrogen after controlling for sex, age, height and weight.