Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer''s disease: an autoradiographic study

We have used quantitative light microscopic autoradiographic techniques to analyze changes in muscarinic cholinergic receptors in the hippocampus in Alzheimer type dementia (ATD). The density and distribution of muscarinic cholinergic receptors has been correlated with the density of neurons, neuritic plaques and neurofibrillary tangles in the CA1 subfield of the hippocampus of control and ATD patients. The number of pyramidal cells per mm² in the CA1 sector was significantly decreased in ATD cases as compared to controls, although there were large variations among cases. The most marked reductions in cell counts were observed in patients with a history of profound dementia. The densities of muscarinic receptors, as well as the proportions of M₁ and M₂ subtypes, in the CA1 sector and dentate gyrus were not significantly different between ATD and old non-demented patients. Neuritic plaques, even in high numbers, did not affect the density of muscarinic receptors; moreover, the densities of receptors over the neuritic plaques did not differ from the surrounding neuropil. However, in some ATD cases there was a marked decrease in the concentration of these receptors in the CA1 sector and subiculum, with no change in the proportions of muscarinic receptor subtypes. These patients exhibited frequent extracellular remnants of neurofibrillary tangles (ghost tangles), but scarce neuritic plaques, and were those showing severe losses of pyramidal cells. There was a significant positive correlation between the total concentration of muscarinic receptors in the CA1 and the density of pyramidal cells, suggesting that decreases in receptor concentration result from a severe neuronal loss. We observed that the ratio of muscarinic receptors per pyramidal cell was significantly increased in ATD patients. This might indicate a possible upregulatory mechanism for muscarinic receptors in the population of remaining neurons in ATD. However, decreases of receptor numbers following severe neuronal fall out suggest that compensatory mechanisms are no longer possible in such cases. The question is raised whether these differences between cases reflect different diseases or different stages of the same disease.     

Chemical aspects of self-etching enamel-dentin adhesives: a systematic review.

OBJECTIVES: The paper gives an overview on the components and the polymer chemical aspects of currently used self-etching enamel-dentin primers/adhesives. In addition, the contribution of new adhesives monomers and cross-linkers exhibiting enhanced hydrolytic stability than methacrylates to improve the performance of single-bottle adhesives is discussed. SOURCES: Information from original scientific papers or reviews about enamel-dentin adhesives, the patent literature concerning dental adhesives and manufacturer information of commercial self-etching adhesives were included in this review. DATA: The most efficient self-etching enamel-dentin adhesives are based on strongly acidic adhesive monomers, containing dihydrogenphosphate, phosphonic acids or carboxylic acid groups. Serious problems of single-bottle water-based, strongly acidic self-etching enamel-dentin adhesives arise both from the hydrolytic instability of the methacrylate monomers used and the side reaction of the applied initiator components. CONCLUSIONS: The stability of the self-etching enamel-dentin adhesives can be improved by using new acrylic ether phosphonic acids or mono- or difunctional acrylamides, while more stable and compatible components have to be developed in the future.     

Current practice patterns in pancreatic surgery: Results of a multi-institutional analysis of seven large surgical departments in germany with 1454 pancreatic head resections, 1999 to 2004 (german advanced surgical treatment study group)

Despite decreasing mortality rates, morbidity is still high after pancreatic head resection. Comparative data in the United States and Europe show a relationship between hospital volume and mortality. Treatment strategies vary frequently, partially because of the lack of evidence-based data. We performed a multi-institutional analysis in Germany evaluating current numbers, indications, techniques, and complication rates of pancreatic head resection. Questionnaires were completed by seven high-volume surgical departments regarding quantitative and qualitative aspects of pancreatic head resections in the period from 1999 to 2004 (five prospective and two retrospective institutional databases). A total of 1454 pancreatic head resections (944 for malignancy) were reported. Mean annual hospital volume ranged from 14 to 52 (10 to 43 in malignancy). Mortality was between 1.1% and 4.8%, morbidity was between 24% and 46%, and pancreatic leakage was between 9% and 20%. In malignant disease, all centers perform standard lymphadenectomy and regard arterial infiltration as a contraindication for resection. However, the rate of portal vein resection varied from 0% to 28%. No consensus is seen on the type of surgery for malignancy and chronic pancreatitis. After resection for pancreatic cancer less than one fourth of the patients receive adjuvant therapy. The results of our analysis in Germany confirm that pancreatic head resection can be performed with low mortality in specialized units. Variations in indications, operative technique, and perioperative care may demonstrate the lack of evidence-based data and/or personal and institutional experience. The low number of patients receiving adjuvant therapy after resection of pancreatic cancer suggests that more efforts must be made to establish novel adjuvant therapies under randomized study conditions. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

The costs of atopy and asthma in children: Assessment of direct costs and their determinants in a birth cohort

The aim of this study was to estimate costs accrued by the health care of children with asthma in comparison to children with atopic eczema and seasonal rhinitis and to investigate cost determinants. From the multicenter cohort study (MAS-90), we selected children with an asthma, atopic eczema and/or seasonal rhinitis diagnosis during the first 8 years of life, and overall 8-year health care utilization was estimated retrospectively by reviewing medical records. Asthma treatment (n = 76) incurs an average cost of US$ 627 per year, 44% due to hospital stays. Atopic eczema treatment (n = 91) cost on average US$ 219 and seasonal rhinitis (n = 69) US$ 57 per year. In asthma and atopic eczema, costs increase significantly with disease severity. Allergy diagnostics use accounts for only 1% of total costs. Costs for asthma and atopic eczema treatment are highest in those years when topical steroids are used for the first time, but decrease with every further year of steroid use. A remarkable 25% of asthmatic children with severe symptoms were not treated according to national guidelines, so that most steroid treatment was initiated during the first hospital stay. In the case of asthma, total direct costs increased until the 3rd year of the disease, and then decreased with further years of diagnosis, while steroid use continued to increase. These results indicate a 'learning effect' in the treatment of asthma and atopic eczema for each patient as well as considerable cost-saving potential by preventing severe asthma. Moreover, the importance of considering cost-driving factors and using cohort or longitudinal designs in cost-of-illness approaches is emphasized.     

Mechanism of action of the epileptogenic drug pentylenetetrazol on a cloned neuronal potassium channel

The action of the epileptogenic agent pentylenetetrazol (PTZ) on a cloned potassium channel of the rat brain was studied. The Kv1.1 channel was expressed in oocytes ofXenopus laevis and potassium currents were investigated in outside-out and inside-out membrane patches. The results show that PTZ increased the multi-channel potassium currents at strongly negative potentials and decreased them at potentials positive to −35 mV both in outside-out and inside-out membrane patches. The extent and manner of PTZ action, the concentration dependence as well as the onset and time course of the PTZ effect were the same both in outside-out and inside-out membrane patches. The single-channel potassium currents showed an increase in open probability and frequency of opening and a decrease in close time at −50 mV and vice versa at 0 mV with application of PTZ. The amplitude of single-channel current, the open time and the latency to the first channel opening remained almost unchanged under PTZ. The results indicate that PTZ acts via the cell membrane and influences the membrane-associated part of the potassium channel. Thereby, PTZ accelerates the transition from the inactivated to the open state of the channel at strongly negative potentials and reduces it at slightly negative and positive potentials. This mechanism may be the basis for a gate function which is in favour of the development of epileptic discharges.     

Immunohistochemical detection of 6-oxo-PGF1 alpha and PGE2 in radicular cysts

Prostaglandin synthesis in the wall of radicular cysts was determined by immunohistochemistry and radiothinlayer chromatography. PGE2 is predominantly produced by plasma cells and histiocytic elements, whereas much less is synthesized by fibroblasts and endothelial cells as estimated using immunohistochemistry. 6-oxo-PGF1 alpha, however, was primarily found to be generated by endothelial cells and fibroblasts; only small amounts seem to be derived from histiocytic elements and plasma cells. The response of the cystic epithelium to anti-PGE2 and anti-6-oxo-PGF1 alpha antibodies was negative or showed only minimal staining. It can thus be concluded that the granulation tissue and its cellular components modulating the inflammatory process are the main source of prostaglandin synthesis in the wall of radicular cysts and may therefore be responsible for the resultant osteolytic activity.     

Safety of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III)

In a prospective clinical trial the risk of infection after application of virus inactivated antithrombin III concentrate ANTITHROMBIN III IMMUNO (AT III) was investigated in patients undergoing cardiovascular surgery. The study was conducted according to the recommendations of the International Committee on Thrombosis and Hemostasis (ICTH), with the exception that most patients required additional blood products as well as AT III.

Twenty-seven patients were eligible to test for the risk of acquiring hepatitis B. Twenty-six patients could be evaluated in terms of hepatitis NANB transmission considering ALT-levels whereas 20 patients could be tested for anti-HCV one year after surgery. Samples from 78 patients could be monitored for anti-HIV-1. None of these patients showed any signs of infection. AT III IMMUNO seems to be an antithrombin III concentrate with low or absent infectivity.     

Thoracoscopic wedge resection

Summary Thoracoscopic surgery is decidedly expanded by the ability to perform pulmonary wedge resections of the lung by using the Endo-GIA-stapler. In addition to thoracoscopic biopsies, since July 1991 we have carried out wedge resections in 12 patients suffering from spontaneous pneumothorax (nine) or peripheral bronchial carcinoma (three). Postoperatively one air fistula persisted over 9 days. The chest tube was removed within 48 h in all other patients. There was no other major complication. The postoperative hospitalization period lasted 4.6 days (1–9 days). Operating time was 44 min (30–70 min). The benefit for the patient consists in the little-impaired breathing mechanics, the short hospital stay, and the favorable cosmetic result.     

Vigilance--a state of order or a force that produces order?

The variety of meanings nowadays attached to the notion of "vigilance" essentially mask H. Head's original intentions when he introduced the term more than half a century ago. In an attempt to overcome the obviously existing disturbance in scientific communication, we contrast the new meanings, both with each other and with Head's original conception. We also discuss the importance of "vigilance" as a precursor of a current change of paradigms. We conclude that the original intention of "vigilance" is in line with recently elaborated proposals stressing the self-referential character of living systems. This revised notion of "vigilance" might serve as a conceptual base for empirical research taking self-reference into consideration, and hence for biological research in the true sense of the word.     

Decrease of elastic tissue fibres in stem villus blood vessels of the human placenta during IUGR and IUGR with concomitant pre-eclampsia

In a recent study we described an increase of elastic tissue fibres in blood vessel walls of placental stem villi during pre-eclampsia when compared to uncomplicated pregnancies. Furthermore, the thickness of these blood vessel walls was enhanced in pre-eclampsia. Since it is known that elastic tissue fibres increase in systemic hypertension, it may be assumed that the enhancement of elastic tissue fibres in placental stem villi during pre-eclampsia may be induced by the hypertension. To get further insight into this assumption, we examined the amount of elastic tissue fibres in stem villus blood vessels of placentae of pregnancies complicated by intrauterine growth retardation (isolated IUGR, fourteen cases), a disease without hypertension of the mother and such with pre-eclampsia and concomitant IUGR (IUGR+PE, nine cases). Each study group was compared with uncomplicated pregnancies (twenty-six cases). Unfixed cryostat serial sections were processed for conventional orcein staining and for the demonstration of alpha-actin-immunoreactivity. The intensity of orcein staining of stem villus blood vessel walls was evaluated by a semiquantitative score method. Significant lower intensities of orcein staining were calculated for blood vessel walls of placentae of isolated IUGR (P=0.0007) and IUGR+PE (P=0.0039) when compared to uncomplicated pregnancies each. Additionally, the blood vessel wall thickness of stem villi of isolated IUGR (P=0.0081) and IUGR+PE (P=0.0007) was significantly reduced. In comparison to the above mentioned investigation, our results show that, in contrast to isolated pre-eclampsia, elastic tissue fibres are decreased during pregnancies complicated by IUGR, independently of the occurrence of concomitant pre-eclampsia when compared to uncomplicated pregnancies. From our studies it may be considered that the increase of elastic tissue fibres in placentae of patients with isolated pre-eclampsia may be induced by systemic hypertension. Furthermore, our study underline arguments that IUGR may be an independent disease of the fetus.