TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Decreased risk of graft failure with maternal liver transplantation in patients with biliary atresia.

The presence of maternal cells in offspring may promote tolerance to noninherited maternal antigens (NIMAs). Children with biliary atresia (BA) have increased maternal cells in their livers, which may impact tolerance. We hypothesized that patients with BA would have improved outcomes when receiving a maternal liver. We reviewed all pediatric liver transplants recorded in the SRTR database from 1996 to 2010 and compared BA and non-BA recipients of maternal livers with recipients of paternal livers for the incidences of graft failure and retransplantation. Rejection episodes after parental liver transplantation were examined for patients transplanted at our institution. BA patients receiving a maternal graft had lower rates of graft failure compared to those receiving a paternal graft (3.7% vs. 10.5%, p = 0.02) and, consequently, fewer episodes of retransplantation (2.7% vs. 7.5%, p = 0.04). These differences were not seen among non-BA patients or among BA patients who received female deceased donor grafts. In patients transplanted at our institution, paternal liver transplantation was associated with an increased incidence of refractory rejection compared to maternal liver transplantation only in BA. Our data support the concept that maternal cells in BA recipients promote tolerance to NIMAs and may be important in counseling BA patients who require liver transplantation.

Effects of resistance training on cytokines.

It is speculated that exercise training decreases resting levels of tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP); reduces body mass and leptin (LP); and increases adiponectin (AD) and insulin sensitivity. This systematic review analyzed the effectiveness of resistance training (RT) longitudinal clinical studies on AD, LP, CRP and TNF-alpha. Seventeen studies were included and the majority of randomized controlled trials support that RT produces increases in AD, and decreases in both LP and CRP. Greater responses in AD and LP were evident in overweight and obese individuals; while RT appeared to be effective in reducing CRP in obese individuals, and older adults. Additionally, women may be more responsive to RT effects on AD, LP and CRP. Training duration and intensity may affect the response of AD and CRP with greater responses shown with 16 weeks or more of training and/or with intensities greater than 80% of one repetition maximum. No response to RT of TNF-alpha levels was apparent. Although based on a limited number of studies, some of which are uncontrolled non-randomized in design, our review suggests some positive effects of RT programs on cytokine levels, but specifics of the responses in different populations need further elucidation.

Effects of a supervised exercise program on the physical fitness and immunological function of HIV-infected patients.

AIM: Exercise effects in subjects with HIV/AIDS are not entirely understood. The study aimed to investigate the effects of a supervised exercise program on the physical fitness and immunological function of HIV-infected subjects. METHODS: Twenty-seven highly active antiretroviral therapy treated HIV-infected patients (age: 45±2 years; CD4-T: 21.3±2.2%) were assigned to a control (CG, n=8) or experimental (EG, n=19) group. The EG participated in a 12-week exercise program, consisting of aerobic training, strength, and flexibility exercises (3 times/wk; aerobic-30min: PWC 150; strength-50min: 3 sets of 12 reps of 5 exercises at 60-80% 12 RM; flexibility-10min: 2 sets of 30 s at maximal range of motion of 8 exercises). RESULTS: Prior to training there was no significant difference in any variable between the EG and the CG. Flexibility (23%, P<0.05), 12 repetition maximum in the leg press and seated bilateral row exercises (54% and 65% respectively, P<0.05) increased, while the heart rate at a given cycle ergometer workload declined (19% for slope and 12% for intercept, P<0.05) in the EG, but not in the CG. No significant differences were found for the relative and absolute CD4 T-cell counts between groups prior to or after training, but there was a slight enhancement trend in the EG (16%, P=0.19). CONCLUSION: Overall training can improve the muscle and aerobic fitness of HIV-infected patients with no negative effect on their immunological function.

A validated LC-MS/MS method for the determination of homocysteic acid in biological samples.

The role of homocysteic acid (HCA) in severe diseases like Alzheimer's disease is under discussion and some recent studies correlate elevated HCA concentrations with the diagnosis of Alzheimer's. However, non-selective and insufficiently sensitive methods have been used to quantitate HCA and results of different studies show large differences in the determined HCA concentration in samples from patients and controls, and therefore non-comparable results. An accurate and precise quantitation method for the determination of HCA in human serum, urine and CSF has been developed by using a combination of protein precipitation and solid phase extraction for sample preparation followed by an LC-MS/MS analysis using a combination of a HILIC separation and tandem mass spectrometry. The developed method has been fully validated in accordance with the guidelines provided by the US Food and Drug administration FDA and the European Medicines Agency EMA. Furthermore, the method has demonstrated its ability to determine the endogenous HCA concentration in serum and urine samples from healthy volunteers.

Determination of endocannabinoids and endocannabinoid-like substances in human K3EDTA plasma - LC-MS/MS method validation and pre-analytical characteristics.

The determination of endocannabinoids and endocannabinoid-like substances in biological human samples is a vibrant field of research with great significance due to postulated relevance of these substances in diseases such as Alzheimer's disease, multiple sclerosis, cancer and cardiovascular diseases. For a possible use as biomarker in early prediction or diagnosis of a disease as well as examination of a successful treatment, the valid determination of the analytes in common accessible human samples, such as plasma or serum, is of great importance. A method for the determination of arachidonoyl ethanolamide, oleoyl ethanolamide, palmitoyl ethanolamide, 1-arachidonoyl glycerol and 2-arachidonoyl glycerol in human K3EDTA plasma using liquid-liquid-extraction in combination with liquid chromatography-tandem-mass spectrometry has been developed and validated for the quantification of the aforementioned analytes. Particular emphasis was placed on the chromatographic separation of the isomers 1-arachidonoyl glycerol and 2-arachidonoyl glycerol, arachidonoyl ethanolamide and O-arachidonoyl ethanolamine (virodhamine) as well as oleoyl ethanolamide and vaccenic acid ethanolamide. During the validation process, increasing concentrations of 1-arachidonoyl glycerol and 2-arachidonoyl glycerol while storing plasma samples were observed. In-depth investigation of pre-analytical sample handling revealed rising concentrations for both analytes in plasma and for arachidonoyl ethanolamide, oleoyl ethanolamide and palmitoyl ethanolamide in whole blood, dependent on the period and temperature of storage. Prevention of the increase in concentration was not possible, raising the question whether human K3EDTA plasma is suitable for the determination of endocannabinoids and endocannabinoid-like substances. Especially the common practice to calculate the concentration of 2-arachidonoyl glycerol as sum of 1-arachidonoyl glycerol and 2-arachidonoyl glycerol is highly questionable because the concentrations of both analytes increase unequally while storing the plasma samples in the fridge.

Exercise capacity in a 78 year old patient with McArdle's disease: it is never too late to start exercising.

The case is reported of a 78 year old man with McArdle's disease and a history of treated coronary heart disease. Despite the pre-exercise administration of sucrose allowing the patient to exercise with normal physiological responses, and without typical McArdle's symptoms or biochemical evidence of muscle damage, his exercise capacity was very low (V(O2)peak = 10.7 ml/min/kg), probably attributable to his lifetime of sedentary living. The data suggest that, with pre-exercise sucrose administration, such patients may be candidates for systematic reconditioning, which may improve functional capacity and quality of life.

Management of Intracranial Incidental Findings on Brain MRI.

The wider use of MRI for imaging of the head in both research and clinical practice has led to an increasing number of intracranial incidental findings. Most of these findings have no immediate medical consequences. Nevertheless, knowledge of common intracranial incidental findings and their clinical relevance is necessary to adequately discuss the findings with the patient. Based on the author´s experiences from a large population-based study, the most common incidental MR findings in the brain will be presented, discussing their clinical relevance and giving recommendations for management according to the current literature and guidelines. Key points: • Intracranial incidental findings are common.• The majority of these findings have no immediate medical consequences.• Knowledge of common incidental findings is necessary for appropriate management. Citation Format: • Langner S, Buelow R, Fleck S et al. Management of Intracranial Incidental Findings on Brain MRI. Fortschr Röntgenstr 2016; 188: 1123 - 1133.

A general systems approach to severe family pathology.

The author proposes a general systems approach to the examination and understanding of family functioning. Scrutinizing the family as an open system with 1) evolutionary goals and tangible tasks, 2) a need for "semipermeable" boundaries, 3) cultural and subcultural communication modes, 4) leadership effectiveness, and 5) the nature and age-appropriateness of the affective bonds will enable clinical judgements about family functioning that indicate general system competencies and defects. Such a framework may also lead to a typology of family process because the major functions of the family as a system (creation, nurturance, enculturation, and guidance of the young into adulthood) can be evaluated regardless of symptoms or diagnoses.

Possible roles of Ca2+ and cGMP as mediators of the exflagellation of Plasmodium berghei and Plasmodium falciparum.

The roles of Ca2+ and cyclic nucleotides as secondary, intracellular messengers for exflagellation of Plasmodium berghei and Plasmodium falciparum were investigated. Treatment with Ca2+ antagonists such as TMB-8 (an inhibitor of intracellular Ca2+ release) or W-7 (a calmodulin inhibitor) strongly inhibited exflagellation induced by alkaline medium at pH 8.0 whereas EGTA (a Ca2+ chelator) or nicardipine and nifedipine (Ca2+ channel inhibitors) had no effect. These results may indicate that mobilization of parasites' internal resources of Ca2+ is a prerequisite for exflagellation. Agents which increase cAMP levels did not induce exflagellation at the non-permissive pH of 7.3, and had no significant inhibitory effect at the permissive pH of 8.0. IBMX (cAMP/cGMP-phosphodiesterase inhibitor), however, enhanced exflagellation at pH 7.3, indicating the possibility that cGMP, but not cAMP, may be involved in the induction of exflagellation. Furthermore, cGMP or agents which increase cGMP levels such as nitroprusside (a potent activator of guanylate cyclase), enhanced exflagellation at pH 7.3, whereas N-methyl-hydroxylamine (guanylate cyclase inhibitor) inhibited the exflagellation at pH 8.0. From these results, it may be concluded that the induction of exflagellation requires both Ca2+ mobilization and an increase in cGMP levels.

Antigenic and sequence diversity at the C-terminus of the merozoite surface protein-1 from rodent malaria isolates, and the binding of protective monoclonal antibodies.

Merozoite surface protein-1 (MSP-1) is a major candidate in the development of a vaccine against malaria. Immunisation with a recombinant fusion protein containing the two Plasmodium yoelii MSP-1 C-terminal epidermal growth factor-like domains (MSP-1(19)) can protect mice against homologous but not heterologous challenge, and therefore, antigenic differences resulting from sequence diversity in MSP-1(19) may be crucial in determining the potential of this protein as a vaccine. Representative sequence variants from a number of distinct P. yoelii isolates were expressed in Escherichia coli and the resulting recombinant proteins were screened for binding to a panel of monoclonal antibodies (Mabs) capable of suppressing a P. yoelii YM challenge infection in passive immunisation experiments. The sequence polymorphisms affected the binding of the antibodies to the recombinant proteins. None of the Mabs recognised MSP-1(19) of P. yoelii yoelii 2CL or 33X or P. yoelii nigeriensis N67. The epitopes recognised by the Mabs were further distinguished by their reactivity with the other fusion proteins. The extent of sequence variation in MSP-1(19) among the isolates was extensive, with differences detected at 35 out of the 96 positions compared. Using the 3-dimensional structure of the Plasmodium falciparum MSP-1(19) as a model, the locations of the amino acid substitutions that may affect Mab binding were identified. The DNA sequence of MSP-1(19) from two Plasmodium vinckei isolates was also cloned and the deduced amino acid sequence compared with that in other species.

Near fatal anticholinergic intoxication after routine fundoscopy.

We describe a case of severe anticholinergic intoxication following the topical instillation of tropicamide-containing eyedrops. Tropicamide is a short-acting atropine-like derivative and has been regarded as an effective and safe mydriatic. Half an hour after routine fundoscopy, a 62-year-old man experienced two generalized seizures with respiratory arrest and required intubation and mechanical ventilation. The patient was treated with physostigmine and made a full recovery.

Resistance-training experience and the pressor response during resistance exercise.

The purpose of this study was to examine the effects previous resistance-training experience has on the cardiovascular responses to resistance-training exercises. To investigate this, the intra-arterial blood pressure response of four body builders (BB), six novice weight-trained individuals (NT), and six sedentary controls (SC) were monitored during performance of one-arm overhead presses and one-leg knee extensions. One repetition at the maximal weight possible (1 RM) and sets to voluntary fatigue at 90, 80, 70, and 50% of 1 RM were performed. Across groups, the BB demonstrated a significantly (P less than 0.05) lower peak and a lesser magnitude of response (changes from rest to peak) for systolic and diastolic blood pressures than the the NT and SC groups during both exercises. The BB also demonstrated significantly lower values across groups for peak heart rate and magnitude of heart rate response during arm presses. During knee extensions across groups, peak heart rate but not magnitude of the heart rate response was significantly lower in the BB. The results indicate that previous weight-training experience reduces the pressor response to dynamic resistance exercises.

Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training.

Twelve male subjects with recreational resistance training backgrounds completed 12 wk of intensified resistance training (3 sessions/wk; 8 exercises/session; 3 sets/exercise; 10 repetitions maximum/set). All major muscle groups were trained, with four exercises emphasizing the forearm flexors. After training, strength (1-repetition maximum preacher curl) increased by 25% (P < 0.05). Magnetic resonance imaging scans revealed an increase in the biceps brachii muscle cross-sectional area (CSA) (from 11.8 +/- 2.7 to 13.3 +/- 2.6 cm2; n = 8; P < 0.05). Muscle biopsies of the biceps brachii revealed increases (P < 0.05) in fiber areas for type I (from 4,196 +/- 859 to 4,617 +/- 1,116 microns2; n = 11) and II fibers (from 6,378 +/- 1,552 to 7,474 +/- 2,017 microns2; n = 11). Fiber number estimated from the above measurements did not change after training (293.2 +/- 61.5 x 10(3) pretraining; 297.5 +/- 69.5 x 10(3) posttraining; n = 8). However, the magnitude of muscle fiber hypertrophy may influence this response because those subjects with less relative muscle fiber hypertrophy, but similar increases in muscle CSA, showed evidence of an increase in fiber number. Capillaries per fiber increased significantly (P < 0.05) for both type I (from 4.9 +/- 0.6 to 5.5 +/- 0.7; n = 10) and II fibers (from 5.1 +/- 0.8 to 6.2 +/- 0.7; n = 10). No changes occurred in capillaries per fiber area or muscle area. In conclusion, resistance training resulted in hypertrophy of the total muscle CSA and fiber areas with no change in estimated fiber number, whereas capillary changes were proportional to muscle fiber growth.

Catecholamine responses to short-term high-intensity resistance exercise overtraining.

Seventeen weight-trained males were divided into an overtraining group [OT; n = 11; age = 22.0 +/- 0.9 (SE) yr] that weight trained their legs daily for 2 wk with 100% 1 repetition maximum relative intensity on a squat machine and a control group (n = 6; age = 23.7 +/- 2.4 yr) that exercised 1 day/wk with low relative intensity (50% 1 repetition maximum). Test batteries including strength assessments and resting and exercise-induced concentrations of epinephrine and norepinephrine were conducted at the beginning, middle, and end (tests 1-3, respectively) of the study. Strength capabilities decreased by test 3 for the OT group (P < 0.05). Resting catecholamine concentrations did not change for either group during the study, whereas exercise-induced concentrations of both epinephrine (test 1 = 3,407.9 +/- 666.6 pmol/l, test 2 = 7,563.7 +/- 1,210.6 pmol/l, test 3 = 6,931.6 +/- 919.3 pmol/l) and norepinephrine (test 1 = 42.9 +/- 7.4 nmol/l, test 2 = 70.0 +/- 8.8 nmol/l, test 3 = 85.2 +/- 14.5 nmol/l) significantly increased by tests 2 and 3 for only the OT group. Correlation coefficients suggested decreased responsitivity of skeletal muscle to sympathetic nervous system activity. It appears that altered exercise-induced sympathetic nervous system activity accompanies high relative intensity resistance exercise overtraining and may be among the initial responses to the onset of the previously theoretical sympathetic overtraining syndrome.

Hormonal and growth factor responses to heavy resistance exercise protocols.

To examine endogenous anabolic hormone and growth factor responses to various heavy resistance exercise protocols (HREPs), nine male subjects performed each of six randomly assigned HREPs, which consisted of identically ordered exercises carefully designed to control for load [5 vs. 10 repetitions maximum (RM)], rest period length (1 vs. 3 min), and total work effects. Serum human growth hormone (hGH), testosterone (T), somatomedin-C (SM-C), glucose, and whole blood lactate (HLa) concentrations were determined preexercise, midexercise (i.e., after 4 of 8 exercises), and at 0, 5, 15, 30, 60, 90, and 120 min postexercise. All HREPs produced significant (P less than 0.05) temporal increases in serum T concentrations, although the magnitude and time point of occurrence above resting values varied across HREPs. No differences were observed for T when integrated areas under the curve (AUCs) were compared. Although not all HREPs produced increases in serum hGH, the highest responses were observed consequent to the H10/1 exercise protocol (high total work, 1 min rest, 10-RM load) for both temporal and time integrated (AUC) responses. The pattern of SM-C increases varied among HREPs and did not consistently follow hGH changes. Whereas temporal changes were observed, no integrated time (AUC) differences between exercise protocols occurred. These data indicate that the release patterns (temporal or time integrated) observed are complex functions of the type of HREPs utilized and the physiological mechanisms involved with determining peripheral circulatory concentrations (e.g., clearance rates, transport, receptor binding). All HREPs may not affect muscle and connective tissue growth in the same manner because of possible differences in hormonal and growth factor release.

Effects of different heavy-resistance exercise protocols on plasma beta-endorphin concentrations.

To examine the changes of plasma beta-endorphin (beta-EP) concentrations in response to various heavy-resistance exercise protocols, eight healthy male subjects randomly performed each of six heavy-resistance exercise protocols, which consisted of identically ordered exercises carefully designed to control for the repetition maximum (RM) resistance (5 vs. 10 RM), rest period length (1 vs. 3 min), and total work (joules). Plasma beta-EP, ammonia, whole blood lactate and serum cortisol, creatine kinase, urea, and creatinine were determined preexercise, midexercise, immediately postexercise, and at various time points after the exercise session (5 min-48 h), depending on the specific blood variable examined. Only the high total work-exercise protocol [1 min rest, 10 RM load (H10/1)] demonstrated significant increases in plasma beta-EP and serum cortisol at midexercise and 0, 5, and 15 min postexercise. Increases in lactate were observed after all protocols, but the largest increases were observed after the H10/1 protocol. Within the H10/1 protocol, lactate concentrations were correlated (r = 0.82, P < 0.05) with plasma beta-EP concentrations. Cortisol increases were significantly correlated (r = 0.84) with 24-h peak creatine kinase values. The primary finding of this investigation was that beta-EP responds differently to various heavy-resistance exercise protocols. In heavy-resistance exercise, it appears that the duration of the force production and the length of the rest periods between sets are key exercise variables that influence increases in plasma beta-EP and serum cortisol concentrations. Furthermore the H10/1 protocol's significant challenge to the acid-base status of the blood, due to marked increases in whole blood lactate, may be associated with mechanisms modulating peripheral blood concentrations of beta-EP and cortisol.

Changes in hormonal concentrations after different heavy-resistance exercise protocols in women.

Nine eumenorrheic women (age 24.11 +/- 4.28 yr) performed each of six randomly assigned heavy-resistance protocols (HREPs) on separate days during the early follicular phase of the menstrual cycle. The HREPs consisted of two series [series 1 (strength, S) and series 2 (hypertrophy, H)] of three protocols, each using identically ordered exercises controlled for load [5 vs. 10 repetitions maximum (RM)], rest period length (1 vs. 3 min), and total work (J) within each three-protocol series. Blood measures were determined pre-, mid- (after 4 of 8 exercises), and postexercise (0, 5, 15, 30, 60, 90, 120 min and 24 and 48 h). In series 1, a significant (P < 0.05) reduction in growth hormone (GH) was observed at 90 min postexercise for all three protocols. In series 2, the 10-RM protocol with 1-min rest periods (H10/1) produced significant increases above rest in GH concentrations at 0, 5, and 15 min postexercise, and the H10/1 and H5/1 protocols demonstrated significant reductions at 90 and 120 min postexercise. Cortisol demonstrated significant increases in response to the S10/3 protocol at 0 min, to the H10/1 protocol at midexercise and at 0 and 5 min postexercise, and to the H5/1 protocol at 5 and 15 min postexercise. No significant changes were observed in total insulin-like growth factor I, total testosterone, urea, or creatinine for any of the HREPs. Significant elevations in whole blood lactate and ammonia along with significant reductions in blood glucose were observed. Hormonal and metabolic blood variables measured in the early follicular phase of the menstrual cycle varied in response to different HREPs. The most dramatic increases above resting concentrations were observed with the H10/1 protocol, indicating that the more glycolytic HREPs may stimulate greater GH and cortisol increases.