Spatiotemporal modeling of cerebral evoked magnetic fields to median nerve stimulation.

We measured somatosensory evoked magnetic fields during median nerve stimulation in 6 normal subjects. We applied multiple dipole models to study the spatiotemporal structure of early somatosensory evoked magnetic fields (SEFs), as well as the number, 3-dimensional location and time activity of their underlying neuronal sources. Two dipole sources were necessary to model the first 40 msec of SEFs explaining 85% of the data variance. Source 1 was located deeper than source 2, showed primarily a tangential orientation, and accounted for a larger part of the variance; source 2 showed no consistent orientation across subjects. Both sources showed biphasic time activities corresponding to the previously described N20-P30 and P25-N35 components. Spatiotemporal modeling could identify sources which could not be modeled consistently above noise by single moving dipoles (P25 component), revealed small latency differences of the two sources in some subjects suggesting parallel activation of these sources, and allowed separation of sources overlapping considerably both in space and time. We conclude that spatiotemporal modeling of SEFs may be useful to study functional anatomy of human sensorimotor cortex non-invasively.     

Infradian biorhythms of enzymuria in man?

The temporal courses of dipeptidyl peptidase IV gamma-glutamyltransferase and alanine aminopeptidase were followed over 70 days in the morning urine of 15 healthy persons. Subsequent to basic statistical analysis a two-step procedure was performed, including spectral analysis and the fit of a cosine function by non-linear regression. The excretion of the 3 enzymes followed an infradian biorhythm with a mean period length of 10.04 for dipeptidyl peptidase IV, 13.34 for gamma-glutamyltransferase and 10.17 for alanine aminopeptidase. In addition to the basic rhythmic process described by the fitted cosine functions, in most of the enzyme patterns steap peaks of very high excretory activity appeared which was verified in repeated measurements. These infradian biorhythms with changes in the range of 100% and more, as well as their interindividual variations, have to be considered in assessing the excretion of enzymes.     

Ileal release of glucagon-like peptide-1 (GLP-1)

There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II,N=6), and during endogenous stimulation by intraduodenal essential amino acid perfusion,N=6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P<0.01), and endogenously stimulated output by 68%, respectively (P<0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80–100% (allP<0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein, Decreased acid output is associated with release of GLP-1, but not PYY. These findings support the hypothesis that the distal small intestine may participate in the late postprandial inhibitory regulation of gastric secretory function in humans and that GLP-1 may be an intermediary factor.     

Percutaneous nephrostomy drainage in the management of neonatal anuria secondary to renal candidiasis

We report a case of anuria in a premature neonate secondary to bilateral ureteropelvic junction obstructions related to Candida bezoars. Percutaneous decompression and drainage of both kidneys contributed significantly to the successful management of renal candidiasis in this patient. A review of the literature is presented.     

Klinische Wertigkeit einer dermatoskopischen Klassifikation von Clark‐Nävi

Background and objectives: The aim of this study was to evaluate the practical value of the dermatoscopic classification of Clark nevi Patients and methods: Dermatoscopic images of 268 lesions clinically and dermatoscopically diagnosed as Clark nevi were presented to 2 dermatologists without knowledge of the histological diagnosis. The dermatologists evaluated the lesions according to a simplified version of the classification scheme for Clark nevi proposed by Hofmann‐Wellenhof and differentiated between 12 different types of Clark nevi. Results: The most common type of Clark nevus was the reticular‐homogenous type (n = 64, 23,9 %), followed by the globular‐homogeneous type (n = 32, 12 %) and by the homogenous type (n = 30, 11,2 %). The overall inter‐rater agreement between the examiners was moderate to good (kappa = 0,58). The highest level of agreement was found for the peripheral hyperpigmented type (kappa = 0,83). Histologically, 17 lesions (6,3 %) were diagnosed as melanomas. The frequency of melanoma was highest among the peripheral‐hyperpigmented type for one observer and among the homogenous type for the other observer. No melanoma was found among the globular, reticular‐globular, and the central‐hyperpigmented types. Conclusions: A dermatoscopic classification of Clark nevi is practically feasible and allows – to some extent – a risk stratification of Clark nevi, which could be useful for clinical management.     

Corticosteroids and Inhaled Salbutamol in Patients with Reversible Airway Obstruction Markedly Decrease the Incidence of Bronchospasm after Tracheal Intubation

Background: In patients with bronchial hyperreactivity, airway instrumentation can evoke life-threatening bronchospasm. However, the best strategy for the prevention of bronchospasm has not been defined. Therefore, in a randomized, prospective, placebo-controlled study, the authors tested whether prophylaxis with either combined salbutamol-methylprednisolone or salbutamol alone (1) improves lung function and (2) prevents wheezing after intubation.

Methods: Thirty-one patients with partially reversible airway obstruction (airway resistance > 180%, forced expiratory volume in 1 s [FEV1] < 70% of predicted value, and FEV1 increase > 10% after two puffs of salbutamol), who were naive to anti-obstructive treatment, were randomized to receive daily for 5 days either 3 x 2 puffs (0.2 mg) of salbutamol alone (n = 16) or salbutamol combined with methylprednisolone (40 mg/day orally) (n = 15). Lung function was evaluated daily. Another 10 patients received two puffs of salbutamol 10 min before anesthesia. In all patients, wheezing was assessed before and 5 min after tracheal intubation.

Results: Within 1 day, both salbutamol and salbutamol-methylprednisolone treatment significantly improved airway resistance (salbutamol, 4.3 +/- 2.0 [SD] to 2.9 +/- 1.3 mmHg [middle dot] s [middle dot] l-1; salbutamol-methylprednisolone, 5.5 +/- 2.9 to 3.4 +/- 1.7 mmHg [middle dot] s [middle dot] l-1) and FEV1 (salbutamol, 1.79 +/- 0.49 to 2.12 +/- 0.61 l; salbutamol-methylprednisolone, 1.58 +/- 0.66 to 2.04 +/- 1.05 l) to a steady state, with no difference between groups. However, regardless of whether single-dose salbutamol preinduction or prolonged salbutamol treatment was used, most patients (8 of 10 and 7 of 9) experienced wheezing after intubation. In contrast, only one patient receiving additional methylprednisolone experienced wheezing (P = 0.0058).     

Functional parameters before and after parathyroidectomy: a prospective, randomized long-term trial on different rat strains.

For clinical controls before and after parathyroidectomy and for evaluation of the function of transplants of parathyroid tissue, it is necessary to establish standard values of relevant laboratory parameters for donor and recipient animals as well as for different types of nutrition. Since no such data are yet available, it was the purpose to define such standards. In a prospective randomized trial on 400 rats of the Dark Agouti (DA) and Lewis strain, different functional laboratory parameters such as total calcium, intact parathyroid hormone, phosphate, 1.25-dihydroxyvitamin D, and alkaline phosphatase were measured under a standard and low calcium diet over a period of 40 weeks. Two hundred of these animals underwent a parathyroidectomy four weeks after the beginning of the study and specimens were evaluated histologically. For all eight different study groups normal values could be defined within tight limits for parameters which describe the function of the parathyroid gland or elements of calcium metabolism under different conditions. The optimal conditions for a transplantation model of parathyroid glands were established. Lewis-rats were identified as the ideal donor and DA rats as the better recipient animals. These data can serve as reference values for future studies on transplantation of the parathyroid without immunosuppression.     

Safety and efficacy of pimecrolimus cream 1% in the daily practice: Results of a patient self‐observation study in patients with atopic dermatitis

Background: Pimecrolimus cream 1% has proven to be well‐tolerated and effective in controlled clinical studies in patients with atopic dermatitis (AD). In a 15‐week patient self‐observation study, safety and efficacy was investigated in the daily practice. Patients and methods: 3502 patients with AD (mean age 26.2 ± 18 years, 62% female) received pimecrolimus cream 1% from 810 physicians in the German Federal Republic.The severity of the disease was assessed at baseline, two times during the 15‐week observation period and at the end of treatment.Patients recorded daily the degree of erythema and pruritus. At the end of treatment, safety and efficacy were assessed by the physician based on patient's daily records and by the patient. Results: The percentage of patients with severe or massive AD decreased from 25% to 7%, whereas the percentage of patients without or with mild symptoms increased from 9% to 55%.The efficacy of treatment was rated by physicians as good or very good in 83.5% of cases and by 79% of patients.At baseline 35% of the patients were free of flares as compared to 75% at the end of therapy. Disease control was better in patients who followed the recommended treatment algorithm for pimecrolimus cream.Tolerability was mostly rated as good or very good. Conclusion: Treatment with pimecrolimus cream 1% for patients with AD is well‐tolerated and effective in daily practice.     

Ethyl-EPA in Huntington disease—Potentially relevant mechanism of action

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.