Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Hemoglobin oxygen affinity in patients suffering from arterial occlusive disease of the legs

Summary Parameters characterizing the hemoglobin oxygen affinity were determined in blood of 12 male patients suffering from arterial occlusive disease (AOD) of the legs and compared with data obtained earlier from healthy human subjects (controls). Due to a COHb content of 4.8%±2.2% in the cigarette-smoking AOD patients, the standard oxygen dissociation curve (ODC) was left-shifted, the half-saturation pressure (P₅₀) amounted to 24.8±1.7 mmHg (3.30±0.23 kPa), although the 2,3-diphosphoglycerate concentration was increased to 15.3±1.7 µmol/g Hb. Correcting the effects of elevated COHb shifts the P₅₀ to 26.3 mmHg (3.5 kPa) and increases the steepness of the ODC (Hill's n) from 2.79±0.27 to about 2.99, which is significantly different from controls. The Bohr coefficients after acidification of blood with lactic acid (BC_Lac) show high values at low oxygen saturations of hemoglobin (–0.50±0.04 in AOD patients, –0.32±0.04 in controls;P<0.05 at 10% S_O2). The cause of the alterations in hemoglobin oxygen affinity may be a reduced mean erythrocyte age, but also the influence of unknown factors generated, e.g., from anaerobic muscle metabolism in AOD.Abbreviations AOD Arterial occlusive disease of the legs - BC Bohr coefficient - BC_CO2 Bohr coefficient after acidification of blood with CO₂ - BC_Lac Bohr coefficient after acidification of blood with lactic acid - DPG 2,3-Diphosphoglycerate - ODC Oxygen dissociation curve - P₅₀ Oxygen pressure when hemoglobin is half-saturated     

Decision support in psychiatry – a comparison between the diagnostic outcomes using a computerized decision support system versus manual diagnosis

Background  

Correct diagnosis in psychiatry may be improved by novel diagnostic procedures. Computerized Decision Support Systems (CDSS) are suggested to be able to improve diagnostic procedures, but some studies indicate possible problems. Therefore, it could be important to investigate CDSS systems with regard to their feasibility to improve diagnostic procedures as well as to save time.     

Symptoms of hypoglycemia — A comparison between porcine and human insulin

Summary For more than 2 years now it has been controversially debated whether awareness of hypoglycemia is reduced when type I diabetic patients are switched from porcine to human insulin. In order to address this question, we studied nine C-peptide negative diabetics (age 27.6 years, Broca index 106%, duration of diabetes 5.7 years, HbA₁, 8.8%) in comparison with eight healthy volunteers (age 22.4 years, Broca index 104%). Following euglycemic monitoring overnight, a controlled hypoglycemia was induced by altering the algorithms of the Biostator. This was done in a double-blind, cross-over fashion using porcine or human insulin on 2 nonconsecutive days. There were no differences between the results obtained with respect to the time course of the study, blood glucose, amount of insulin infused, and concentration of venous free insulin achieved. Of the nine diabetics, eight were aware of hypoglycemia at a higher blood glucose level under porcine insulin. The first symptom of hypoglycemia was percieved at a mean blood glucose level of 61.1±5.4 mg/dl under porcine insulin and of 44.4 ± 5.3 mg/dl under human insulin (P0.05). Thirty symptoms were noted under porcine insulin exclusively or preferentially as opposed to only eight which were observed exclusively or preferentially under human insulin. The healthy volunteers evidenced fewer symptoms at lower blood glucose concentrations than the diabetics. The clear difference between human and porcine insulin could not unequivocally be reproduced in this group. We conclude that type I diabetic patients, who are maintained on a treatment regimen with human insulin, perceive symptoms of hypoglycemia at higher blood glucose concentrations when hypoglycemia is induced by porcine insulin as compared with human insulin. As every single patient and healthy volunteer was aware of at least one symptom of hypoglycemia under both insulins, it is possible to react appropriately to counteract this situation. Nevertheless, diabetic patients should be informed about this phenomenon.Abbreviations P porcine insulin - H human insulin - IU international units Supported by Nordisk Deutschland     

Immunohistochemical and ultrastructural analysis of a mammary cystic hypersecretory carcinoma

Cystic hypersecretory carcinoma (CHC) is a rare variant of intraductal carcinoma. A CHC in a 50-year-old woman was excised and processed for light and electron microscopy and immunohistochemistry. The tumor had a marked cystic appearance. The walls of the cysts consisted of epithelial and myoepithelial cells and a well-developed basement membrane. The epithelial cells contained well-developed rough-surfaced endoplasmatic reticulum and Golgi apparatus. Secretory granules were not detected, with the exception of a few mucus-producing cells. The secretion was predominantly homogenous, reminiscent of thyroid colloid, and demonstrated distinct PAS positivity. The cells displayed a strong labeling with epithelial membrane antigen (EMA) and EMA-positive structures were observed within the intraluminal secretion, too. Some of these were stained by alcian blue. In addition, the colloid-like material was admixed with mucus showing a filamentous internal structure and lipid droplets resulting in some heterogenity of the secretion. Intraductal micropapillary proliferation in some of the cysts and adjacent nondistended ducts was a further defining feature of the tumor. Steroid hormone receptor and Ki-67 proliferation marker immuno his Tochemistry showed scattered positivity among the tumor cells. These results are in agreement with previous observations and further clarify the nature of this low-grade in situ cancer.     

The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM

BACKGROUND: The insertion-deletion (I/D) polymorphism of the angiotensin converting enzyme gene is a diallelic polymorphism that constitutes a genetic influence on the progression of renal diseases such as IgA nephropathy. Patients with the DD genotype have an accelerated progression towards end stage renal failure in these diseases. The role of the I/D polymorphism in the pathogenesis of diabetic nephropathy in IDDM is unresolved. PATIENTS AND METHODS: We therefore set out to study the contribution of the I/D polymorphism in 79 patients (age 39.5 +/- 7.6 years (mean +/- SD) with end stage renal failure due to diabetic nephropathy, who were recipients of a combined kidney-pancreas transplantation (n = 60), or who were on the waiting list for such a procedure (n = 19). The control series consisted of 82 patients (age 39.5 +/- 9.6 years) without microalbuminuria after fifteen years of IDDM. RESULTS: The ACE genotype distribution in patients was not in accordance with the Hardy-Weinberg equilibrium due to a significant overrepresentation of the DD genotype (X2 = 8.9, p = 0.01). This resulted in a significant increase of the D-allele frequency in the cases compared to controls (X2 = 4.9, p = 0.03). The presence of one D-allele did not increase the risk of end stage renal failure (odds ratio ID/II = 1.0, 95% CI 0.4-2.2). The presence of the DD genotype increased the risk of end stage renal failure twofold compared to the other genotypes (odds ratio 2.1, 95% CI 1.1-4.0). The risk estimate seemed slightly higher in patients with good metabolic control (odds ratio 2.6, 95% CI 1.0-7.1), than in patients with poor control (odds ratio 1.6, 95% CI 0.59-4.3). CONCLUSION: It is concluded that the risk of end-stage renal failure in patients with IDDM is twofold increased in patients with the DD genotype as compared to patients with other genotypes.