Fat intakes of children with PKU on low phenylalanine diets.

BACKGROUND: As part of a study on the effects of a fat-supplemented phenylalanine (phe)-free protein substitute on the fatty acid status of children with phenylketonuria (PKU), the adequacy of the diets of children aged 1-10 years for fat and essential fatty acids (EFA) was assessed. METHODS: Subjects randomized in a 1 : 1 ratio to a phe-free protein substitute supplemented with EFA (test-treatment group) or a phe-free, fat-free protein substitute (control group) for 20 weeks. 3-day semi-weighed records of food intakes collected at the end of the study period. RESULTS: Total fat and alpha-linolenic acid (alpha-LA) intakes were found to be poor in the control group (n = 19). Those in the test-treatment group (n = 24) had higher fat and EFA intakes (P < 0.05), bringing intakes closer to population norms. The youngest children (<5 years of age) in the control group appeared to be especially vulnerable to poor fat intakes because of the restricted diversity of their diets and, regardless of age, alpha-LA intakes by this group were poor compared with the non-PKU population. CONCLUSIONS: The quantity and quality of fat in the diets of children with PKU, in particular young children, should be given careful consideration in trying to optimize the ratio of linoleic acid: alpha-LA in their diets and in satisfying the requirements of this group for fat and alpha-LA.

Spectral integration in primary auditory cortex: laminar processing of afferent input, in vivo and in vitro.

Auditory cortex neurons integrate information over a broad range of sound frequencies, yet it is not known how such integration is accomplished at the cellular or systems levels. Whereas information about frequencies near a neuron's characteristic frequency is likely to be relayed to the neuron by lemniscal thalamocortical inputs from the ventral division of the medial geniculate nucleus, we recently proposed that information about frequencies spectrally distant from characteristic frequency is mainly relayed to the neuron via "horizontal" intracortical projections from neurons with spectrally-distant characteristic frequencies [J Neurophysiol 91 (2004) 2551]. Here we test this hypothesis by using current source density analysis to determine if characteristic frequency and spectrally-distant non-characteristic frequency stimuli preferentially activate thalamocortical and horizontal pathways, respectively, in rat auditory cortex. Characteristic frequency stimuli produced current source density profiles with prominent initial current sinks in layers 3 and 4--the termination zone of lemniscal inputs from medial geniculate nucleus. In contrast, stimuli three octaves below characteristic frequency produced initial current sinks mainly in the infragranular layers. Differences between current source density profiles were only apparent for initial current sinks; profiles for longer-latency current sinks evoked by characteristic frequency and non-characteristic frequency stimuli overlapped to a greater degree, likely due to shared mechanisms of intracortical processing or to longer-latency thalamocortical contributions (lemniscal and nonlemniscal). To identify current source density profiles produced by activation of lemniscal thalamocortical inputs alone, we utilized the mouse auditory thalamocortical slice preparation. Electrical stimulation of the medial geniculate nucleus in vitro produced major current sinks in cortical layers 3/4, and excitation spread horizontally from this point throughout primary auditory cortex to produce current sinks in multiple cortical layers. These data support the hypothesis that relay of thalamocortical information throughout auditory cortex via horizontal intracortical projections may be the basis of broad spectral integration in vivo.

Chlamydophila pneumoniae respiratory tract infection aggravates therapy refractory bronchitis or pneumonia in childhood.

BACKGROUND: Chlamydophila pneumoniae was frequently found in bronchial secretions of children with therapy-refractory bronchitis or pneumonia. It was studied, how the agent modifies the course of disease and what findings are associated with the infection. PATIENTS AND METHODS: Bronchial secretions obtained at bronchoscopy of 428 children were studied for C. pneumoniae infection using polymerase chain reaction with enzyme immunoassay detection. Children tested negative and positive were compared for their clinical findings. RESULTS: C. pneumoniae was found in 143 children (33 %). A C. pneumoniae infection has been found to be associated with a purulent bronchial inflammation (90/143 vs. 144/285, p = 0.02), a Streptococcus pneumoniae co-infection (13/143 vs. 6/285, p = 0.002) and a restrictive disturbance (11/51 vs. 8/93, p = 0.04). Purulent inflammation (Odds ratio 7.9; 95 % confidence interval [CI] 1.6-39.3), 2 co-infections (Odds ratio 14.3; 95 % CI 1.4-144.4) and co-infection with M. pneumoniae (4/4 versus 9/26, p = 0.03; Mantel Haentzel 3.0; 95 % CI 1.1-8.0) were identified as factors more often associated with a restrictive disturbance in children with bronchial C. pneumoniae infection. An adequate antibiotic therapy improved pulmonary function. No association was found for wheezing, eosinophil inflammation of the nasal mucosa, alpha-1 antitrypsin or immunoglobulin deficiency in serum, level of secretory IgA in bronchial mucus, pathological lung scintigram, gastro-esophageal reflux disease, sweat test and other co-infections. CONCLUSIONS: In children with therapy-refractory bronchitis or pneumonia bronchial C. pneumoniae infection was associated with a more severe disease in case of several, mostly bacterial co-infections. Adequate antibiotic therapy for C. pneumoniae infection has been demonstrated to improve pulmonary function.

Sympathetic reinnervation of rat kidney grafts.

BACKGROUND: Reinnervation occurs in many transplanted tissues and organs. Sympathetic reinnervation in rat kidney grafts was investigated. METHODS: Rats were syngeneically transplanted with a kidney and bilaterally nephrectomized. Reinnervation was assessed by immunohistochemical staining for neuron-specific protein gene product 9.5 (PGP 9.5) and by tissue norepinephrine measurements in grafts removed 1.5 (n=6), 3 (n=7), 6 (n=8), and 9 (n=7) months after transplantation. RESULTS: PGP 9.5-positive neural structures were significantly reduced in grafts removed 1.5 and 3 months after transplantation compared with native kidneys with slightly increased numbers at 6 and 9 months after transplantation. Median transplant norepinephrine concentrations remained at approximately 3% compared with native kidneys until 9 months after transplantation. CONCLUSIONS: In transplanted rat kidneys, some reinnervation occurs in the hilum within 9 months after transplantation. This is not accompanied by a significant recovery of norepinephrine concentration in renal tissue indicating persistent sympathetic denervation.

Thalamic stimulation largely elicits orthodromic, rather than antidromic, cortical activation in an auditory thalamocortical slice.

Stimulation of the medial geniculate body in an auditory thalamocortical slice elicits a short-latency current sink in the middle cortical layers, as would be expected following activation of thalamocortical relay neurons. However, corticothalamic neurons can have axon collaterals that project to the middle layers, thus, a middle-layer current sink could also result from antidromic activation of corticothalamic neurons and their axon collaterals. The likelihood of thalamic stimulation activating corticothalamic neurons would be reduced substantially if the corticothalamic pathway was not well preserved in the slice, and/or if the threshold for antidromic activation was significantly higher than for orthodromic activation. To determine the prevalence and threshold of antidromic activation, we recorded intracellularly from day 14-17 mouse brain slices containing infragranular cortical neurons while stimulating the medial geniculate or thalamocortical pathway. Antidromic spikes were confirmed by spike collision and characterized according to spike latency "jitter" and the ability to follow a high-frequency (100 Hz) stimulus train. The ability to follow a 100-Hz tetanus was a reliable indicator of antidromic activation, but both antidromic and orthodromic spikes could have low jitter. Thalamic stimulation produced antidromic activation in two of 69 infragranular cortical neurons (<3%), indicating the presence of antidromic activity, but implying a limited corticothalamic connection in the slice. Antidromic spikes in 13 additional neurons were obtained by stimulating axons in the thalamocortical pathway. The antidromic threshold averaged 214+/-40.6 microA (range 6-475 microA), over seven times the orthodromic threshold for medial geniculate-evoked responses in layer IV extracellular (28+/-5.4 microA) or intracellular (27+/-5.6 microA) recordings. We conclude that medial geniculate stimulation activates relatively few corticothalamic neurons. Conversely, low-intensity thalamic stimulation strongly activates thalamocortical neurons. Thus, at low-stimulus intensities, the auditory thalamocortical slice can be used to probe mechanisms of thalamocortical function with limited antidromic activation of corticothalamic neurons.

Neurotrophic factor S100 beta in major depression.

Disturbances in the serotonergic system are considered to be implicated in the pathophysiology of depressive disorders. The possible role of the neurotrophic factor S100 beta, which is suspected to regulate regeneration of serotonergic synapses, has not been investigated in depressive disorders. The S100 beta concentration in the cerebrospinal fluid was measured in 11 patients with the current diagnosis of mild or moderate depressive episodes (DSM-IV) and in 11 matched control patients. Using the t test for paired samples, the presence of a depressive episode was significantly associated with an elevation of the cerebrospinal fluid concentration of S100 beta (t = 2.6, d.f. = 10, p = 0.024). Replications of this finding in severely depressed patients are necessary to confirm the association between neurotrophic factor S100 beta and depressive disorders.

Chronic cold stress reduces the spontaneous activity of ventral tegmental dopamine neurons.

The dopamine (DA) neurons in the ventral tegmental area and medial substantia nigra (VTA/mSN) projecting to the limbic forebrain and prefrontal cortex have long been postulated to play a major role in cognitive and behavioral effects of stress. In this study, the effects of a chronic stressor (prolonged exposure to cold) on the spontaneous activity of DA neurons in the VTA/mSN were examined. Extracellular single-unit recordings of DA neurons were performed in rats following a 17-day continuous exposure to a cold (4 degrees C) environment. Compared to controls, cold-exposed rats displayed 64% fewer spontaneously active DA neurons. The average spike activity (average firing rate, average spikes fired in bursts) of the DA cells that remained active in the cold-exposed rats did not differ significantly from controls. However, a significantly larger proportion of those cells showed excessive burst activity, compared to the DA cell population in controls. These results show that chronic stress can lead to the cessation of spontaneous activity in a subpopulation of VTA/mSN DA cells. These changes may indicate that unlike acute stress, which can potently activate the mesolimbic/mesocortical DA systems, chronic stress leads to an adaptive reduction in the number of active DA cells, perhaps altering the response of these systems to subsequent stressors.

Association between glycated hemoglobin and diet and other lifestyle factors in a nondiabetic population: cross-sectional evaluation of data from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition Study.

BACKGROUND: Glycation reactions of proteins and other compounds, depending on blood glucose concentrations, have a detrimental effect on health. OBJECTIVE: The association of diet and other lifestyle factors with glycated hemoglobin (Hb A(1c)) values was examined in a nondiabetic population. DESIGN: This was a cross-sectional study of 1773 middle-aged men and women. Mean Hb A(1c) values were calculated for categories of diet and lifestyle factors, and odds ratios (ORs) for the highest versus lowest tertiles of Hb A(1c) were determined and compared. RESULTS: The OR of being in the highest Hb A(1c) tertile compared with the lowest increased with greater age [age 40-44 y compared with >60 y: men (OR: 2.86; 95% CI: 1.60, 5.20) and women: (6.11; 3.15, 12.30)] and greater obesity [body mass index (in kg/m(2)) >25 and waist-hip ratio >1.0 in men and >0.8 in women): men (2.80; 1.48, 5.45) and women (1.73; 1.15, 2.61)]. High energy and energy-adjusted saturated fat intakes were associated with increased risk of being in the highest tertile of Hb A(1c) [highest compared with lowest quintile: (1.53; 1.04, 2.26; P for trend = 0.013) and (1. 98; 1.33, 2.95; P for trend = 0.003), respectively]. No significant associations were observed for intakes of carbohydrates, protein, dietary fiber, or beta-carotene; however, some of the associations were nearly significant. Alcohol, vitamin C, and vitamin E intakes were inversely related to risk [highest compared with lowest quintile: (0.56; 0.38, 0.83; P for trend = 0.001), (0.50; 0.33, 0. 74; P for trend = 0.003), and (0.65; 0.43, 0.96; P for trend = 0. 036), respectively]. CONCLUSION: Hb A(1c) values might be modifiable by diet and other lifestyle factors.

The development of post-transplantation hypertension in recipients of an SHR kidney is independent of reinnervation of the graft.

The role of sympathetic reinnervation of kidney grafts for the development of renal post-transplantation hypertension was investigated. F1-hybrids (F1H) obtained from crossing spontaneously hypertensive (SHR) and Wistar-Kyoto rats were transplanted with an SHR kidney and bilaterally nephrectomized. Seven (n = 7) and 42 days after transplantation (n = 9), transplanted kidneys were removed and renal norepinephrine concentrations were determined. In addition, mean arterial pressure (MAP) was measured in conscious bilaterally nephrectomized recipients of an SHR (n = 9) or F1H kidney (n = 8) 6 weeks after transplantation. Renal norepinephrine concentrations (ng/g wet kidney weight) decreased dramatically from 348.3 +/- 31.7 ng/g before (n = 7) to 9.9 +/- 2.5 ng/g at 7 days and 6.5 +/- 1.1 ng/g at 42 days after transplantation, indicating that there was no substantial sympathetic reinnervation of the grafts throughout the observation period. Despite the lack of reinnervation of the grafts, recipients of an SHR kidney but not recipients of an F1H kidney developed post-transplantation hypertension (MAP 172 +/- 4 mmHg versus 124 +/- 3 mmHg P < 0.001) within 6 weeks after transplantation. We conclude that post-transplantation hypertension in recipients of an SHR kidney does not depend on sympathetic reinnervation of the graft.

Presence of factor-VII and -XIII activity in ultrafiltrate during hemofiltration.

UNLABELLED: Bleeding complications during renal replacement therapies can be attributed to coagulation system and platelet function alterations in uremia, and the application of heparin in extracorporeal circulation. Small protein losses during hemofiltration are always described, however the high molecular weight of coagulation factors should significantly prevent their removal during hemofiltration. To exclude degradation of coagulation factors under conditions of spontaneous ultrafiltration, the hemofiltrate of 40 patients with acute renal failure (treated with continuous veno-venous hemofiltration, CVVH) was sampled from the filtrate line after 1 h from the beginning of treatment and in 5 patients also after 12 and 24 h. Samples were investigated with human factor deficient plasma (VII, X, XI, XII) from donors with a congenital deficiency and with human plasma depleted of factor V, VIII, IX, and protein S and C. Factor XIII was detected photometrically. Subsequently the presence of factor- XIII and -VII activity was investigated in plasma and hemofiltrate from 16 patients treated with intermittent hemofiltration before (plasma) and after (plasma, hemofiltrate) therapy. These patients also suffered from acute renal failure and needed renal replacement therapies. Quality control was carried out with a buffer solution (<1% activity in the assays according to recommended protocols). RESULTS: Factor-V, -VIII, -IX, -X, -XI, and -XII activity, and protein C and S could not be detected in the hemofiltrate from continuous hemofiltration. Factor-VII and -XIII activity was present in the hemofiltrate (mean activity in CVVH: 1.93% for factor VII and 6.9% for factor XIII, mean activity in intermittent hemofiltration: <1% for factor-VII and 7.3% for factor-XIII). Three were no significant differences (Student's t-test) in plasma activity before and after intermittent hemofiltration of factor VII (44 vs. 47%, p = 0.39) and factor XIII (44 vs. 52%, p = 0.24). The presence of factor-VII and -XIII activity in the hemofiltrate cannot influence plasma activities in intermittent hemofiltration. Rapid new synthesis and short half-life should neutralize these effects. Elimination of coagulation factor-XIII activity should be excluded by the next generation of highly permeable membranes and on-line hemodiafiltration.

Disruption of male sex hormones with regard to pesticides: pathophysiological and regulatory aspects.

Several pesticides used as herbicides, insecticides and fungicides are known to be endocrine disrupting chemicals (EDCs). In three pair-matched studies we found changes in sex hormone concentrations and T-lymphocytes in relation to acute and chronic pesticide exposure. After acute exposure, 1 day later the concentrations of testosterone and especially estradiol decreased. T4- and T8-lymphocytes slightly increased. Effects of chronic occupational pesticide exposure were expressed by a higher level of testosterone and a larger ratio of T4-/T8-lymphocytes in comparison to control persons. Concentrations of LH in exposed men were higher after exposure than before. We assume an inhibition of the aromatase system by testosterone metabolites. The studies show two effects with regard to the duration of exposure: a hormonal and immune suppression after acute exposure and an activation of both systems following chronic exposure.

Which amino-acids do serum and hemofiltrate of critically ill patients with acute renal failure contain?

The removal of amino acids during continuous renal replacement therapies induces clinical problems. Previous studies on animals have shown nephroprotective (glycine, alanine) or negative effects (lysine) on renal function in occurrence of acute renal failure. Disturbed metabolism in acute renal failure needs adequate parenteral nutrition. On the other hand, experience with continuous renal replacement therapies of metabolic crises in inborn errors of metabolism indicate a good control of disturbed amino acid metabolism. The aim of our study was to find amino acids, that might play an important role in the pathogenesis, prognosis and detection of acute renal failure and severe illness, so far only estimated by lactic acid. Thirty-three probes (serum and hemofiltrate) were taken from patients, suffering with acute renal failure caused by septic shock, severe pancreatitis and hepatorenal syndrome, one hour after the beginning of extracorporal circulation, the conditions of treatment were standardized. The material was deproteinized and studied by the amino acid analyzer LBK 4251 Apha Plus (Pharmacia, Stockholm, Sweden), while the lactic acid concentration was determined in a standard laboratory. Proline, glycine, alanine, methionine and histidine showed a close relationship to the lactic acid levels, but these amino acids were an essential part of parenteral nutrition. A statistical relationship was also established in (amino acids with amide groups) asparagine, glutamine, citrulline, cystathionine and phosphoethanolamine. The mean values of most of the amino acids were higher than normal, but standard deviations were increased. The presence of these amino acids in hemofiltrate and the good sieving coefficients could mean that the better prognosis of critically ill patients in continuous renal replacement therapies may also be due to continuous control of amino acid levels (especially with amide groups).

[Bone alkaline phosphatase as an activity parameter of acromegaly]. / Alkalische Knochenphosphatase als Aktivitätsparameter der Akromegalie.

Serum levels of growth hormone (GH: arithmetic mean of three measurements eight hours apart), somatomedin C (SmC), alkaline phosphatase activity and the bone isoenzyme of alkaline phosphatase (as the liver/bone isoenzyme ratio) were measured in 26 patients with acromegaly (11 men and 15 women; mean age 45.5 [24-66] years), 18 in the active and eight in the nonactive phase of the disease. Activity was characterized by a raised (660 [330-1149] ng/ml), inactivity by a normal (186 [40-300] ng/ml) SmC concentration. All 18 patients with active acromegaly had an abnormally low liver/bone isoenzyme ratio (mean of 0.66 [0.01-1.28]). In seven of the eight patients with inactive acromegaly it was within normal limits. Thus measurement of bone alkaline phosphatase, which is significantly cheaper than that of SmC, is suitable for assessing activity.

[Insulin and glucagon secretion of the preserved dog pancreas]. / Die Insulin- und Glukagonsekretion des konservierten Hundepankreas.

Well defined results can be obtained quickly by in vitro test concerning the preservation effect of the preserved dog's pancreas. Clinical and chemical parameters were received during the hypothermic perfusion respectively during the refrigerant storage. The in vitro function tests were carried out after the preservation by insulin and glucagon stimulation. The results showed that the A and B cells of the dog's pancreas are completely able to function after a preservation of 24 hours. Thereby a strong formation of edemas by releasing high enzyme activities is caused during the mechanical perfusion of the organs. The simple refrigerant storage of the pancreata therefore, is the more suitable preservation form for organ transplantations.

[Erythrocyte-associated plasma proteins, a further aspect of erythrocyte function?]. / Erythrozytenassoziierte Plasmaproteine, ein weiterer Aspekt zur Erythrozytenfunktion?

The amount of plasma proteins associated to erythrocytes was determined or calculated by using three different techniques. Thus, there are 3.48 X 10(12) g of protein in a single erythrocyte or 94.12 g of protein respectively in the total of all erythrocytes in a healthy man with a body weight of 70 kg. The mass of plasma protein associated to erythrocytes will decrease in case of immunocomplex aggregates or otherwise denatured plasma proteins being fixed to the erythrocyte surface so that from a purely calculating point of view protein amounts on a scale of up to 46% of all plasma proteins may enter the free blood plasma under extreme conditions. In this, an immediately efficient possibility of compensation is seen by the authors in case of an acute consumption of blood proteins.

Use of amantadine in influenza: a second report.

Clinical influenza attacked 304 out of 576 boys at a west country boarding school. Influenza A/ENG/333/80 (H(1)N(1)), a drift from A/USSR/92/77, was isolated from 14 out of 40 throat swabs. Pre-epidemic sera from 64 new boys showed that 54 already had antibodies to H(1)N(1) and 40 of them had antibodies to this novel variant. Nevertheless, when their serum was re-examined post-epidemically, 36 showed a rise in antibody, indicating that infection had occurred.One hundred and twenty-six junior boys were given amantadine and, of these, 22 (17.4 per cent) developed influenza, whereas 218 (57 per cent) of 382 boys who did not take amantadine had influenza. The immune status was known for 64 boys, 43 of whom were given amantadine. Only five (11.6 per cent) became clinically ill while taking the drug, whereas 10 (47.6 per cent) of the remaining 21 boys became ill. When their serum was re-examined, it was found that 20/43 of those taking amantadine and 5/21 of those not taking the drug had subclinical infection. The two groups were comparable in their pre-epidemic antibody status and all lived within the same environment during the outbreak.It is concluded that amantadine secured a reduction in clinical influenza without protecting significantly against subclinical infection, thus allowing subtype specific immunity to develop.

[Demonstration of immune complexes on erythrocytes by scanning electron microscopy]. / Darstellung von Immunkomplexen an Erythrozyten im Rasterelektronenmikroskopbild (REMB).

If anti-sera are combined with native whole blood by an in-vitro technique, immunocomplexes are formed. They are fixed to erythrocytes and can be made visible by a scanning electron microscope on blood smears especially pretreated.

[Alkaline phosphatase isoenzymes and hyperthyroidism]. / Isoenzyme der alkalischen Phosphatase und Hyperthyreose.

We determined the serum total alkaline phosphatase as well as the alkaline phosphatase isoenzyme pattern in untreated and treated hyperthyreoses in the condition of euthyreosis and compared them with those of a healthy control group. The isoenzyme patterns, expressed as L/K quotient, ranged between 1.3 and 2.5 in the normal group and between 0.3 and 1.3 in the group with hyperthyreosis. The increase of the total alkaline phosphatase in hyperthyreosis was nearly exclusively conditioned by the increase of the activity of the osseous isoenzyme. The latter was increased already also then, when the total alkaline phosphatase had not transgressed the upper border of the normal. Depending on the functional condition of the thyroid gland the liver isoenzyme did not show any significant changes. In the course up to one year under thyrostatic therapy the increased activity of the osseous alkaline phosphatase decreased into the normal region as an expression of the very slowly repairing hyperthyreosis-conditioned disturbances of the osseous metabolism. An increase of the activity of the total alkaline phosphatase or of the osseous isoenzyme in the initial phase of a thyreostatic therapy of the sequel of an increase of the reactive activity of osteoblasts and must not lead to diagnostic and therapeutic uncertainties. By reason of the high sensitivity of the L/K quotient in hyperthyreoses (L/K at 95.5 % below 1.3) with a simultaneously high specifity of 89.5% the alkaline osseous phosphatase is to be discussed by all means as a helpful parameter of the peripheral function of the thyroid gland.