Alveolar capillary dysplasia with left heart obstruction - rare but lethal.

Alveolar capillary dysplasia (ACD) is a rare neonatal lung disease characterized anatomically by a defective and hypoplastic development of pulmonary alveoli leading to persistent pulmonary hypertension (PPHN) and finally lethal respiratory failure. It is often associated with congenital left heart obstruction. Given the fatal prognosis an early diagnosis is important. However, due to the fast onset of PPHN in neonates and lack of pathognomonic signs for its cause, safe and fast detection of ACD is challenging. Therefore, following the exclusion of cardiac and common pulmonary causes, lung biopsy becomes essential for diagnosis.We hereby report a case of ACD with atrial septal defect type one and hypoplastic aortic arch with an ante-mortem diagnosis and discuss the current state of medicine in relation to ACD.

Ischaemic pre-conditioning means an increased adenosine metabolism with decreased glycolytic flow in ischaemic pig myocardium.

BACKGROUND: Ischaemic pre-conditioning (IP) is a potent protective mechanism for limiting the myocardial damage due to ischaemia. It is not fully known as to how IP protects. The metabolism of adenosine may be an important mechanistic component. We study the role of adenosine turnover together with glycolytic flow in ischaemic myocardium subjected to IP. METHODS: An acute myocardial ischaemia pig model was used, with microdialysis sampling of some metabolites (lactate, adenosine, glucose, glycerol, taurine) of ischaemic myocardium. An IP group was compared with a control group before and during a prolonged ischaemia. ¹4C-labelled adenosine and glucose were infused through microdialysis probes, and lactate, ¹4C-labelled lactate, glucose, taurine and glycerol were analysed in the effluent. The glycogen content in myocardial biopsies was determined. RESULTS: The ¹4C-adenosine metabolism was higher as there was a higher production of ¹4C-lactate in IP animals compared with the controls. The glycolytic flow, measured as myocardial lactate formation, was retarded during prolonged ischaemia in IP animals. Myocardial free glucose and glycogen content decreased during the prolonged ischaemia in both groups, with higher free glucose in the IP group. We confirmed the protective effects of IP with lower myocardial concentrations of markers for cellular damage (glycerol). CONCLUSIONS: This association between increased adenosine turnover and decreased glycolytic flow during prolonged ischaemia in response to IP can possibly be explained by the competitive effect for the metabolites from both glucose and adenosine metabolism for entering glycolysis. We conclude that this study provides support for an energy-metabolic explanation for the protective mechanisms of IP.

Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidemia with dense LDL.

INTRODUCTION: The association of elevated plasma triglyceride concentrations, decreased HDL-cholesterol, and dense LDL (dLDL) is referred to as the atherogenic lipoprotein phenotype. dLDL particularly plays a role in the metabolic syndrome and type 2 diabetes and may be one of the factors responsible for the increased risk for coronary artery disease in these patients. The effect of fenofibrate and atorvastatin on the LDL subfraction profile in patients with combined hyperlipidemia and a preponderance of dLDL was studied in a sequential design. METHODS: Six male patients with combined hyperlipidemia and dLDL received 160 mg/die supra-bioavailable fenofibrate. After a washout phase of 8 weeks all patients received 10 mg/die atorvastatin for another 8 weeks. At baseline, after fenofibrate, and after atorvastatin treatment LDL subfractions were analyzed by equilibrium density gradient ultracentrifugation. RESULTS: Treatment with atorvastatin and fenofibrate reduced serum cholesterol by 30 % and 21 % (p = 0.046) (p-values for differences between treatment groups), triglycerides by 32 % and 45 %, LDL cholesterol by 28 % and 16 %, and increased HDL cholesterol by 3 % and 6 %, respectively. Atorvastatin and fenofibrate treatment resulted in the following changes of apoB and LDL subfractions: LDL-1 (1.019 - 1.031 kg/L) - 31 % and + 15 % (p = 0.028); LDL-2 (1.031 - 1.034 kg/L) - 14 % and + 57 % (p = 0.028); LDL-3 (1.034 - 1.037 kg/L) - 20 % and + 30 % (p = 0.028); LDL-4 (1.037 - 1.040 kg/L) - 25 % and - 6 %; LDL-5 (1.040 - 1.044 kg/L) - 29 % and - 38 %; and LDL-6 (1.044 - 1.063 kg/L) - 39 % and - 55 % (p = 0.028). As a consequence, fenofibrate reduced LDL density significantly (p = 0.028 versus atorvastatin). CONCLUSIONS: Atorvastatin decreased all LDL-subfractions to a similar extent (quantitative effect) whereas fenofibrate reduced predominantly dLDL and changed the LDL profile towards medium dense LDL-particles (qualitative effect). Since medium dense LDL have a higher affinity to the LDL-receptor fenofibrate may have a higher antiatherogenic potential than assessed by the reduction of total LDL-cholesterol and triglycerides alone.

Quantification of the major brown shrimp allergen Pen a 1 (tropomyosin) by a monoclonal antibody-based sandwich ELISA.

BACKGROUND: Among 13 allergens found in extracts of cooked brown shrimp (Penaeus aztecus) the 36 kd muscle protein tropomyosin has been identified as the only major shrimp allergen (Pen a 1). Cross-reacting molecules with similar molecular weights were detected in other crustacea species such as crab, lobster, and crawfish. Because Pen a 1 and Pen a 1-like allergens are important in crustacea allergy, the aim of this study was to develop a monoclonal antibody (mAb)-based sandwich ELISA to quantify Pen a 1 and to evaluate Pen a 1 levels in four commercial shrimp, crab, and lobster extracts. METHODS: Two Pen a 1-specific mAbs with different epitope specificities were selected. ELISA plates coated with captured mAb 3.2 were incubated with samples containing Pen a 1. Bound Pen a 1 was detected by a combination of biotinylated mAb 4.9.5 and alkaline phosphatase-labeled streptavidin. RESULTS: The optimized sandwich ELISA could detect Pen a 1 concentrations ranging from 4 to 125 ng/ml. Four commercial shrimp extracts demonstrated a 40-fold difference in Pen a 1 levels (24 to 920 microg/ml). Crab and lobster extracts contained detectable levels of Pen a 1-like proteins. No reactivity to cockroach, house dust mite, oyster, codfish, or peanut extracts was detected, which indicates that the developed assay is crustacea-specific. CONCLUSION: A sensitive sandwich assay was developed to quantify Pen a 1. This assay will be helpful to standardize shrimp extracts in regard to the content of the major allergen, Pen a 1, and to study cross-reactivities among and evaluate occupational exposure to different crustacea species.

Cockroach allergenic activity: analysis of commercial cockroach and dust extracts.

Previous investigations demonstrated that cockroach whole bodies and feces are important sources of allergens in the induction/exacerbation of bronchial asthma. The current study investigated different cockroach source materials, commercial extracts, and house dust extracts for cockroach allergenic activity. In general, extracts from four different sources of either American or German cockroaches contained similar amounts of allergenic activity by RAST inhibition. Three commercial American cockroach extracts compared by RAST inhibition had similar allergenic activity on an equal protein basis. Skin test results correlated house dust reactivity to both commercial and inhouse cockroach wholebody extracts and to fecal extracts. Six different samples of house dust obtained from vacuum cleaners in the New Orleans area and three commercially obtained house dust extracts contained varying quantities of cockroach allergenic activity by RAST inhibition. These studies demonstrate that commercial cockroach extracts vary in allergenic activity and that all house dust extracts tested contain cockroach allergens.

Comparison of fifteen production batches of house dust mite extract (Dermatophagoides pteronyssinus).

An important measurement of quality of allergenic extracts is the batch to batch uniformity. Using different methods of protein and immunobiochemical analysis, we could demonstrate, that 15 production batches of house dust mite Dermatophagoides pteronyssinus extract prepared during the course of 4 years from different lots of the source material, (purified whole mite bodies) showed reproducible data.

Molecular recognition by secondary metabolites.

Aspects of molecular recognition based on the interaction between the vancomycin group of antibiotics and bacterial cell wall precursor analogues are discussed. The energetically unfavourable folding-in of the residue 1 sidechain in vancomycin and ristocetin A is discussed in terms of the favourable entropy associated with simultaneous release of solvent molecules. The effect of the sugar amino substituent on the strength of an adjacent hydrophobic interaction in the vancomycin/acetyl-D-Ala-D-Ala complex is rationalised as an intramolecular "salting-out" of hydrocarbon entities. The slow on-rate for dimerisation of the ristocetin A/N,N-diacetyl-L-Lys-D-Ala-D-Ala complex is attributed to the need for the relatively rigid peptide backbone of the antibiotic to be extensively desolvated before dimerisation can occur. Some of these concepts are then applied to understanding the interactions between antibiotics and the minor groove of double-helical DNA, the receptor site with which they have probably evolved to interact. Two structural motifs (pi-polarised aromatic rings and deoxy sugars) are postulated to be important in this recognition process. The possible roles of these structural features are discussed.

Comparison of Alternaria tenuis extracts prepared from different raw materials.

Alternaria extracts, prepared from three different sources under the same conditions, were compared by several biochemical/immunochemical methods. Two raw materials (A,G) contained mostly mycelia. The third raw material (C) contained mycelia (35%) and spores (65%). Extracts A and G were different in total allergenic potency, antigen/allergen pattern, and in the Alt 1 content. Extract C was of similar total allergenic potency as extract A but showed a somewhat different antigen/allergen pattern and a different Alt 1 content. Although there were some compositional differences among the extracts, all extracts regardless of source materials (spores and mycelia) demonstrated strong RAST inhibition activity and parallelism of the inhibition curves.

Why are secondary metabolites (natural products) biosynthesized?

We adopt the definition of a natural product as a substance that has no known role in the internal economy of the producing organism. The literature abounds with conflicting views for the existence of such natural products. We propose that all such structures serve the producing organisms by improving their survival fitness. We argue that this conclusion is necessitated by the fact that natural products are normally complex structures, whose biosynthesis is programmed by many kilobases of DNA. If it were otherwise, the pressures of Darwinian natural selection would have precluded the expenditure of so much metabolic energy in their construction and the development of such complexity. We further conclude that a natural product improves the producer's survival fitness by acting at specific receptors in competing organisms. Current studies of natural products interacting with receptors support this view, in terms of both the sophistication of the molecule/molecule recognition and the mechanistic details of physiological action. By the application of Occam's razor and general weaknesses of other hypotheses, these other hypotheses are rejected. It is a consequence of our proposal that natural product/receptor interactions of sophistication comparable to enzyme/substrate interactions will be commonplace. Additionally, structures that are candidates to interact with known receptors (e.g., double helical DNA) can on occasion be suggested by inspection of the structures. A range of evidence to support the general conclusions is presented.

Comparison of in-house allergen extracts of Phleum pratense (timothy grass) pollen with the international standard and investigation of IgE specificities of a grass-pollen serum pool from West Germany and of the one recommended by the World Health Organization.

We compared our in-house reference extract (RE) and a production extract (PE) with the international reference preparation (IRP) of International Union of Immunological Societies of timothy-grass pollen, using various biochemical and immunochemical methods. Furthermore, we compared the IgE composition of our in-house grass-pollen serum pool (West Germany) with the serum pool recommended by the World Health Organization, using the RE for crossed radioimmunoelectrophoresis (CRIE). Our extracts (RE and PE) were nearly comparable with the IRP. Only by CRIE one more allergen could be detected in RE and PE than in IRP and in another extract purchased from an American company. This finding may depend on the region where the source materials were harvested and which source materials were used for the preparation of the extracts. Furthermore, by high-performance liquid chromatography in the low-molecular-weight range, two distinct peaks could be detected in the nondiafiltered IRP, which were detected in the diafiltered RE and PE as traces only. The IgE composition of our in-house grass-pollen serum pool was comparable with the serum pool recommended by the World Health Organization, as detected by CRIE using RE.

(Radio) rocket immunoelectrophoresis a useful screening method for house dust extracts.

House dust (HD) extracts prepared from HD collected in households from West Germany, USA, and Spain were investigated by (radio) rocket immunoelectrophoresis. By pouring agarose gels containing different antisera side by side in strips onto a glass plate, the antigen/allergen components of HD extracts could be detected simultaneously in one electrophoretic separation. In addition to mite and animal dander, antigens/allergens of pollens, mold and food (ovalbumin and cow serum) could be detected in most of the extracts.

Allergenic activity of short ragweed pollen (Ambrosia elatior) from different years and/or suppliers: criteria for the selection of an in-house allergen reference preparation.

We have investigated dialyzed extracts (A-F) of short ragweed pollens (Ambrosia elatior) from six consecutive production years and four different companies by protein nitrogen units, high performance liquid chromatography, isoelectric focusing, SDS-PAGE, RAST inhibition, crossed radioimmunoelectrophoresis, and antigen E contents. Extract A showed lowest yields in all quantitative assays. Isoelectric focusing, SDS-PAGE, crossed immunoelectrophoresis, and crossed radioimmunoelectrophoresis showed comparable patterns for all extracts except for extract A. Apparently, the activity of short ragweed pollens depends on the year of production and/or the skill of the producer. These findings are in contrast to similar examinations of other pollen species.

[Catamnestic examinations in a crisis intervention ward of a general hospital (author's transl)]. / Katamnestische Untersuchung in einer Kriseninterventionsstation am Allgemeinkrankenhaus.

The article reports on a catamnestic examination of patients of a crisis intervention center at a general hospital, conducted during the period from 1.5.1977 to 31.5.1978. A total of 560 admissions was recorded comprising 492 patients. Examination was carried out via an open questionnaire, plus data taken from the hospital's care index file. In 59% of the patients, the state of crisis was relieved in the course of an average hospitalisation period of 4.2 days; in 1.23% (= 6 patients), suicide occurred after hospitalisation. 2.4% only of the treated patients were re-admitted to inpatients treatment because of mental difficulties during the period of this study. Improvement of treatment is represented by the institution of facilities of transitional treatment which make it easier to transfer the patient from the crisis-intervention ward, motivating him to participate in long-term outpatient therapy.

[Experimental investigations on arter injury due to bone cement (author's transl)]. / Experimentelle Untersuchung zur Frage der Gefässschädigung durch Knochenzement (Palacos).

The observation of eight patients with lesions of great arteries after total hip replacement led to experimental investigations to determine whether Palacos might cause such vessel lesions. Palacos was applied to the adventitia of the abdominal aorta and both iliac arteries in rabbits. Angiographic examinations 14 days after implantation indicated no lesion at the intima of aorta and iliac arteries in the regio of Palacos. Histological investigations showed only necrosis of fat tissue and a slight distention of the muscle fibers of the artery wall. Lesions of aorta or great arteries are not caused by implantation of Palacos.