Acute testicular torsion in children: the role of sonography in the diagnostic workup

Acute testicular torsion in children is an emergency and has to be diagnosed urgently. Doppler sonography is increasingly used in imaging the acute scrotum. Nevertheless, in uncertain cases, surgical exploration is required. In this study, we attempted to define the role of Doppler sonography in the diagnostic workup of the acutely painful scrotum. All patients admitted between 1999 and 2005 with acute scrotal pain were included. After clinical assessment, patients were imaged by Doppler sonography with a ''high-end'' instrument. In cases of absent arterial perfusion of the testis in Doppler sonography, surgical exploration was carried out. Patients with unaffected perfusion were followed clinically by ultrasound for up to 2 years. Sixty-one infants and children aged 1 day to 17 years (median: 7.9 years) were included. In 14 cases, sonography demonstrated absent central perfusion, with abnormal parenchymal echogenicity in six. Absence of venous blood flow together with reduction of central arterial perfusion was found in one infant. In these 15 patients, surgical exploration confirmed testicular torsion. Among the other 46 patients, we found four cases with increased testicular perfusion and 27 with increased perfusion of the epididymis. In one infant, a testicular tumour was found sonographically, and orchiectomy confirmed diagnosis of a teratoma. Follow-up examinations of the conservatively treated patients showed good clinical outcome with physiologic central perfusion as well as normal echogenic pattern of both testes. No case of testicular torsion was missed. By means of Doppler sonography, an unequivocal statement regarding testicular perfusion was possible in all cases. The initial Doppler diagnosis was confirmed by operative evaluation and follow-up ultrasound. Testicular torsion can therefore be excluded by correctly performed ultrasound with modern equipment.

The role of macrophages in the clearance of inhaled ultrafine titanium dioxide particles

The role of macrophages in the clearance of particles with diameters less than 100 nm (ultrafine or nanoparticles) is not well established, although these particles deposit highly efficiently in peripheral lungs, where particle phagocytosis by macrophages is the primary clearance mechanism. To investigate the uptake of nanoparticles by lung phagocytes, we analyzed the distribution of titanium dioxide particles of 20 nm count median diameter in macrophages obtained by bronchoalveolar lavage at 1 hour and 24 hours after a 1-hour aerosol inhalation. Differential cell counts revealing greater than 96% macrophages and less than 1% neutrophils and lymphocytes excluded inflammatory cell responses. Employing energy-filtering transmission electron microscopy (EFTEM) for elemental microanalysis, we examined 1,594 macrophage profiles in the 1-hour group (n = 6) and 1,609 in the 24-hour group (n = 6). We found 4 particles in 3 macrophage profiles at 1 hour and 47 particles in 27 macrophage profiles at 24 hours. Model-based data analysis revealed an uptake of 0.06 to 0.12% ultrafine titanium-dioxide particles by lung-surface macrophages within 24 hours. Mean (SD) particle diameters were 31 (8) nm at 1 hour and 34 (10) nm at 24 hours. Particles were localized adjacent (within 13-83 nm) to the membrane in vesicles with mean (SD) diameters of 592 (375) nm at 1 hour and 414 (309) nm at 24 hours, containing other material like surfactant. Additional screening of macrophage profiles by conventional TEM revealed no evidence for agglomerated nanoparticles. These results give evidence for a sporadic and rather unspecific uptake of TiO(2)-nanoparticles by lung-surface macrophages within 24 hours after their deposition, and hence for an insufficient role of the key clearance mechanism in peripheral lungs.

The role of epistasis in the manifestation of heterosis: a systems-oriented approach

Heterosis is widely used in breeding, but the genetic basis of this biological phenomenon has not been elucidated. We postulate that additive and dominance genetic effects as well as two-locus interactions estimated in classical QTL analyses are not sufficient for quantifying the contributions of QTL to heterosis. A general theoretical framework for determining the contributions of different types of genetic effects to heterosis was developed. Additive x additive epistatic interactions of individual loci with the entire genetic background were identified as a major component of midparent heterosis. On the basis of these findings we defined a new type of heterotic effect denoted as augmented dominance effect di* that comprises the dominance effect at each QTL minus half the sum of additive x additive interactions with all other QTL. We demonstrate that genotypic expectations of QTL effects obtained from analyses with the design III using testcrosses of recombinant inbred lines and composite-interval mapping precisely equal genotypic expectations of midparent heterosis, thus identifying genomic regions relevant for expression of heterosis. The theory for QTL mapping of multiple traits is extended to the simultaneous mapping of newly defined genetic effects to improve the power of QTL detection and distinguish between dominance and overdominance.

Do males matter? The role of males in population dynamics

Models of population dynamics generally neglect the presence of males. While this assumption holds under many circumstances, behavioural ecology increasingly tells us that the presence (or absence) of males may have an impact on female fitness, and hence population sizes. Here we ask the question of whether males matter to population dynamics, operationally defined as a dependency of population growth on the relative density of males. We provide simple models, and evaluate the current empirical evidence for them, that illustrate various mechanisms of such male influence: mate searching behavior, male resource use (including effects of sexual dimorphism), sexual harassment and sexual segregation. In each case, theory predicts that males can have an effect on population densities, and in some extreme cases a positive feedback between an increasingly male-biased sex ratio and the effects on female harassment may theoretically even bring about population extinction. The results of this study, and the literature reviewed, show that the males can have a substantial effect on population dynamics, particularly so when human influences result in biased sex ratios.

[The role of thoracoscopy in paediatric spontaneous pneumothorax]

Spontaneous pneumothorax in children is an emergency. A rapid and structured treatment is necessary. Indicating clinical signs are dyspnoea with unilateral reduced breath sounds and hypersonic percussion note. Chest x-ray confirms diagnosis. CT scan shows detailed information's of pathological changes in lung tissue and offers important considerations for the therapy. Today video assisted thoracoscopic surgery (VATS) takes a central role in the treatment of spontaneous pneumothorax. Thoracoscopy completes diagnosis detecting the pathologies, which were missed in imaging procedures. Definitive surgical treatment is performed simultaneously in the same anaesthesia.

The role of TRPV6 in breast carcinogenesis

TRPV6 is an endothelial calcium entry channel that is strongly expressed in breast adenocarcinoma tissue. In this study, we further confirmed this observation by analysis of breast cancer tissues, which indicated that TRPV6 mRNA expression was up-regulated between 2-fold and 15-fold compared with the average in normal breast tissue. Whereas TRPV6 is expressed in the cancer tissue, its role as a calcium channel in breast carcinogenesis is poorly understood. Therefore, we investigated how TRPV6 affects the viability, apoptosis, and calcium transport in the breast cancer cell line T47D. Hormones can also affect the tumor development; hence, we determined the effects of estradiol, progesterone, and 1,25-vitamin D on TRPV6 transcription. Interestingly, the estrogen receptor antagonist tamoxifen reduced expression of TRPV6 and is able to inhibit its calcium transport activity (IC(50), 7.5 micromol/L). The in vitro model showed that TRPV6 can be regulated by estrogen, progesterone, tamoxifen, and 1,25-vitamin D and has a large influence on breast cancer cell proliferation. Moreover, the effect of tamoxifen on cell viability was enhanced when TRPV6 expression was silenced with small interfering RNA. TRPV6 may be a novel target for the development of calcium channel inhibitors to treat breast adenocarcinoma expressing TRPV6.

The role of lymphadenectomy in high risk prostate cancer

Historically, patients with high risk prostate cancer were considered poor candidates for radical prostatectomy (RP) due to the likelihood of positive pelvic lymph nodes and decreased long term survival. Although there is still no consensus on the optimal therapy for this group of patients, there is increasing evidence that surgery could play a role. Cancer specific survival (CSS) rates after RP for locally advanced disease at 10 year follow up range from 29 to 72%, depending on tumor differentiation. The role of pelvic lymph node dissection (PLND) in prostate cancer remains a controversial topic. Nonetheless, in conjunction with RRP extended PLND (ePLND) should be performed as extended lymph node dissection in lieu of standard PLND may increase staging accuracy, influence decision making with respect to adjuvant therapy and possibly impact outcome. High risk patients with organ confined prostate cancer and low volume (micro)metastatic disease may be the ones to profit most from this approach.

Role of nutrition in liver transplantation for end-stage chronic liver disease

Patients with end-stage liver disease often reveal significant protein-energy malnutrition, which may deteriorate after listing for transplantation. Since malnutrition affects post-transplant survival, precise assessment must be an integral part of pre- and post-surgical management. While there is wide agreement that aggressive treatment of nutritional deficiencies is required, strong scientific evidence supporting nutritional therapy is sparse. In practice, oral nutritional supplements are preferred over parenteral nutrition, but enteral tube feeding may be necessary to maintain adequate calorie intake. Protein restriction should be avoided and administration of branched-chain amino acids may help yield a sufficient protein supply. Specific problems such as micronutrient deficiency, fluid balance, cholestasis, encephalopathy, and comorbid conditions need attention in order to optimize patient outcome.

Acetaldehyde as an underestimated risk factor for cancer development: role of genetics in ethanol metabolism

Chronic ethanol consumption is a strong risk factor for the development of certain types of cancer including those of the upper aerodigestive tract, the liver, the large intestine and the female breast. Multiple mechanisms are involved in alcohol-mediated carcinogenesis. Among those the action of acetaldehyde (AA), the first metabolite of ethanol oxidation is of particular interest. AA is toxic, mutagenic and carcinogenic in animal experiments. AA binds to DNA and forms carcinogenic adducts. Direct evidence of the role of AA in alcohol-associated carcinogenesis derived from genetic linkage studies in alcoholics. Polymorphisms or mutations of genes coding for AA generation or detoxifying enzymes resulting in elevated AA concentrations are associated with increased cancer risk. Approximately 40% of Japanese, Koreans or Chinese carry the AA dehydrogenase 2*2 (ALDH2*2) allele in its heterozygous form. This allele codes for an ALDH2 enzyme with little activity leading to high AA concentrations after the consumption of even small amounts of alcohol. When individuals with this allele consume ethanol chronically, a significant increased risk for upper alimentary tract and colorectal cancer is noted. In Caucasians, alcohol dehydrogenase 1C*1 (ADH1C*1) allele encodes for an ADH isoenzyme which produces 2.5 times more AA than the corresponding allele ADH1C*2. In studies with moderate to high alcohol intake, ADH1C*1 allele frequency and rate of homozygosity was found to be significantly associated with an increased risk for cancer of the upper aerodigestive tract, the liver, the colon and the female breast. These studies underline the important role of acetaldehyde in ethanol-mediated carcinogenesis.

Role of CYP27A1 in progesterone metabolism in vitro and in vivo

In the kidney, progesterone is inactivated to 20alpha-dihydro-progesterone (20alpha-DH-progesterone) to protect the mineralocorticoid receptor from progesterone excess. In an attempt to clone the enzyme with 20alpha-hydroxysteroid activity using expression cloning in CHOP cells and a human kidney expression library, serendipitously cDNA encoding CYP27A1 was isolated. Overexpression of CYP27A1 in CHOP cells decreased progesterone conversion to 20alpha-DH-progesterone in a dose-dependent manner, an effect enhanced by cotransfection with adrenodoxin and adrenodoxin reductase. Incubation of CHOP cells with 27-hydroxycholesterol, a product of CYP27A1, increased the ratio of progesterone/20alpha-DH-progesterone in a concentration-dependent manner, indicating that the effect of CYP27A1 overexpression was mediated by 27-hydroxycholesterol. In order to analyze whether these observations are relevant in vivo, progesterone and 20alpha-DH-progesterone were measured by GC-MS in 24-h urine of CYP27A1 gene knock out (ko) mice and their control wild type (wt) and heterozygote (hz) littermates. In CYP27A1 ko mice, urinary progesterone concentrations were decreased, 20alpha-DH-progesterone increased and the progesterone/20alpha-DH-progesterone ratio decreased threefold (p<0.001). Thus, CYP27A1 modulates progesterone concentrations. The underlying mechanism is inhibition of 20alpha-hydroxysteroid dehydrogenase by 27-hydroxycholesterol. Key words: Progesterone, sterol 27-hydroxylase, 27-hydroxycholesterol, 20a-steroid dehydrogenase, 20a-DH-progesterone.