Thermodynamics of the hydration equilibrium derived from the luminescence spectra of the solid state for the case of the Eu-EDTA system.

The luminescence properties of two compounds, [C(NH2)3][Eu(EDTA)(H2O)3] (I) and [C(NH2)3]2[Yb0.97Eu0.03(EDTA)(H2O)2]ClO4·6H2O (II), were determined. The weighted sum of luminescence spectra of I and II was used to reproduce the spectra of the Eu-EDTA system in aqueous solution in the temperature range 276-363 K. By implementing this method it was possible to determine the thermodynamic functions (ΔH = 18113 ± 506 J mole(-1) and ΔS = 62.5 ± 4.9 J mole(-1) K(-1)) of the reaction [Eu(EDTA)(H2O)3](-)⇆ [Eu(EDTA)(H2O)2](-) + H2O, which is difficult using other methods.

Z-velocity in screening for intrauterine growth restriction.

OBJECTIVES: Ultrasound scans provide the basis for detection of intrauterine growth restriction (IUGR) but often fail to distinguish IUGR from small-for-gestational age (SGA) fetuses. This study introduces the concept of Z-velocity, calculated as changes in Z-scores over time, as an additional criterion in the diagnosis of IUGR. METHODS: A computer program simulated 50 000 fetal abdominal circumference (FAC) scans based on published growth formulae. False-positive rates were calculated to determine optimal scan time and scan intervals. Using an independent simulation of 32 500 FAC scans, the two methods were compared using receiver-operating characteristics (ROC) curve analysis. RESULTS: ROC showed areas under the curve of > 0.74 over the complete range of scan intervals. The positive predictive value of growth arrest as the only diagnostic criterion was, however, too low to recommend it as an exclusive or the first diagnostic criterion. CONCLUSIONS: Z-velocity can be used to decide whether further investigations for growth abnormality are required in fetuses that fall below the 10(th) percentile. The gain of combined diagnostic approaches should be calculated from large databases that include the neonatal ponderal index as the gold standard.

Enhanced quality and quantity of retrieval of Critically Appraised Topics using the CAT Crawler.

As healthcare moves towards the implementation of Evidence-Based Medicine (EBM), Critically Appraised Topics (CATs) become useful in helping physicians to make clinical decisions. A number of academic and healthcare organizations have set up web-based CAT libraries. The primary objective of the presented work is to provide a one-stop search and download site that allows access to multiple CAT libraries. A web-based application, namely the CAT Crawler, was developed to serve physicians with an adequate access to available appraised topics on the Internet. Important information is extracted automatically and regularly from CAT websites, and consolidated by checking the uniqueness and availability. The principle of meta-search is incorporated into the implementation of the search engine, which finds relevant topics following keyword input. The retrieved result directs the physician to the original resource page. A full-text article of a particular topic can be converted into a proper format for downloading to Personal Digital Assistant (PDA) devices. In summary, the application provides physicians with a common interface to retrieve relevant CATs on particular clinical topics from multiple resources, and thus speeds up the decision making process.

Operative treatment of renal autonomous hyperparathyroidism: cause of persistent or recurrent disease in 304 patients.

BACKGROUND: Subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX and AT) are standard procedures in the treatment of renal autonomous hyperparathyroidism. In contrast to primary hyperparathyroidism, the persistence/recurrence rate is reported of up to 12.0%. PATIENTS AND METHODS: Between 1986 and 2000 we operated on 304 patients with renal autonomous hyperparathyroidism including 14 patients who were admitted after a primary operation in an outside hospital. Mean observation period was 51.4+/-38.9 months. RESULTS: The overall persistence/recurrence rate in our patients was 9.0% (26/290). After SPTX, excluding patients with an incomplete operation, it was 3.7%, and after TPTX and AT it was 6.0%. Reasons for developing recurrent or persistent disease in these patients were removal of less than 3.5 glands ( n=12), hyperplastic autograft ( n=5), and supernumerary gland ( n=4). After the first reoperation 7 patients (26.9%) had persistent or recurrent disease. CONCLUSIONS: An incomplete primary operation caused by missed cervical glands was the major reason for persistent ( n=8) or recurrent ( n=4) disease after different operative strategies in renal autonomous hyperparathyroidism.

Quantitative heel ultrasound in assessment of bone structure in renal transplant recipients.

Many patients with advanced renal disease have osteopenia or even osteoporosis by the definition of the World Health Organization based on bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA), the standard method to assess BMD, is not always available. Quantitative heel ultrasound (QUS) is an inexpensive, mobile, and radiation-free diagnostic alternative, yet few data address this method's usefulness in patients with renal disease. The present study assessed the value of QUS in detecting changes in bone structure in renal transplant recipients compared with DXA. In a cross-sectional analysis, 50 patients (29 women) with a mean age of 50 +/- 13 years, mean time since transplantation of 60 months (range, 1 to 205 months), and stable renal allograft function were studied. BMD was quantified by DXA of the hip and spine. QUS of the left heel measured broadband ultrasound attenuation (BUA) and speed of sound (SOS). Stiffness index (SI) was calculated as SI = (0.67 * BUA + 0.28 * SOS) - 420. DXA measurements established the diagnoses of osteopenia and osteoporosis in 49% and 22% of the patients, respectively. Femoral neck BMD and QUS parameters showed good correlation (r = 0.638; P < 0.001). Sensitivities of BUA, SOS, and SI for diagnosing osteoporosis were 100%, and specificities were 73%, 76%, and 78%, respectively. Positive predictive values were 50%, 53%, and 56%, and negative predictive values were 100%. QUS can be recommended for screening patients who do not have osteoporosis. Those suspected of osteopenic bone structure should be examined by additional DXA measurement for quantification before initiation of therapy.

[Therapy options in systemic AL-amyloidosis with renal involvement]. / Therapieoptionen bei systemischer AL-Amyloidose mit Nierenbeteiligung.

BACKGROUND AND OBJECTIVE: Despite significant efficacy of melphalan and prednisone in the therapy of systemic AL(light chain amyloid)amyloidosis the prognosis of the disease is poor. In patients with severe renal manifestation the reported results of low-dose melphalan therapy are inconclusive with respect to relief of clinical symptoms and overall prognosis. PATIENTS AND METHODS: We report our results of therapy in a group of 22 patients (8 women, 14 men, mean age 60 years) with renal involvement as the main manifestation of systemic AL-amyloidosis without overt myeloma. RESULTS: Ten patients were treated with low doses of melphalan and prednisone. No significant clinical improvement was observed in any case: the patients died an average of 12 months after diagnosis of the disease. Three patients were treated with high doses of melphalan followed by autologous stem cell transplantation. One patient died due to septicaemia after high-dose chemotherapy. Two of the patients experienced significant remission and live virtually free of clinical symptoms 12 and 18 months after therapy. Nine patients were treated only symptomatically: four of them were alive an average of 30 months after diagnosis of systemic AL-amyloidosis. CONCLUSIONS: Only high-dose melphalan therapy offered a realistic chance of amelioration of clinical symptoms in our group of patients, although therapy-associated risks seem to be high. In patients with severe renal amyloidosis, who are not considered for high-dose therapy, particularly careful consideration of potential benefits and possible risks of conventional melphalan therapy is necessary, because the results of this approach are in doubt.

AL-amyloidosis of the kidney initially presenting as minimal change glomerulonephritis.

Small amounts of amyloid in kidney biopsy specimens may be missed on routine examination unless specifically targeted. Occasionally, this oversight results in a diagnosis of minimal change glomerulonephritis (MCGN). This misdiagnosis may be facilitated by the fact that typical "minimal changes" with flattening and effacement of the epithelial foot processes can be found in capillary loops directly affected by amyloid deposition as well as in capillary loops of glomeruli with only mild amyloid deposition in the mesangium. Repeatedly, the diagnosis of MCGN had to be corrected to renal amyloidosis when re-examination by special techniques succeeded in detecting even small amounts of amyloid fibrils. We present the case of a previously healthy 49-year-old man who suddenly developed nephrotic syndrome. A first renal biopsy showed MCGN. Proteinuria remained refractory to immunosuppressive treatments, and creatinine clearance deteriorated rapidly. Two years later, a repeat renal biopsy showed AL-amyloidosis. In this case, re-examination of the first biopsy in the light of the final diagnosis again did not show any deposition of amyloid fibrils. We suspect that proteinuria and epithelial podocyte changes in amyloidosis are caused by factors other than deposition of amyloid fibrils itself. Possibly a cytokine release during the early fibril formation leads to abnormalities even before the typical structural changes of renal amyloidosis can be detected. This is analogous to the hypothesis of a circulating factor that leads to proteinuria in focal segmental glomerulosclerosis or the speculation of altered lymphokine expression associated with the development of MCGN in Hodgkin's disease.

Ischemic preconditioning in cardiac surgery: a word of caution.

OBJECTIVE: Ischemic preconditioning is now established as an effective means of reducing infarct size. However, it remains uncertain whether preconditioning can improve the myocardial protection afforded by cardioplegia. The present study was designed to address this issue. METHODS: After the institution of cardiopulmonary bypass, 10 patients were preconditioned with 3 minutes of aortic crossclamping followed by 2 minutes of reperfusion before the onset of retrograde continuous warm cardioplegic arrest. Ten case-matched patients served as controls. Three blood samples were drawn simultaneously from the radial artery and the coronary sinus before bypass, at the end of the 5-minute preconditioning protocol or after 5 minutes of bypass in control patients, and at the end of cardioplegic arrest. These samples were assayed for creatine kinase MB isoenzyme and lactate. Right atrial biopsy specimens taken at the same time points were processed by Northern blotting for the expression of messenger ribonucleic acid of both c-fos and heat shock protein 70. RESULTS: At the end of arrest, the release of creatine kinase MB from the myocardium was markedly greater in preconditioned patients than in the controls. The transmyocardial lactate gradient was shifted toward production in the preconditioned group (+0.22 +/- 0.13 mmol/L) and toward extraction in the control group (-0.06 +/- 0.21 mmol/L). Molecular biology data did not suggest a protective effect of preconditioning. There were no clinical adverse events related to preconditioning. CONCLUSIONS: Preconditioning does not enhance cardioplegic protection and might even be deleterious. These results do not dismiss its use in cardiac operations. They rather emphasize the need for identifying pharmacologic mediators that could safely and effectively duplicate the cardioprotective effects of ischemic preconditioning.

Decrease in beta 1-adrenergic and M2-muscarinic receptor mRNA levels and unchanged accumulation of mRNAs coding for G alpha i-2 and G alpha s proteins in rat cardiac hypertrophy.

During compensatory cardiac hypertrophy in the rat, hemodynamic overload induces a parallel decrease in the densities of both beta 1-adrenergic (beta 1-AR) and M2-muscarinic (M2-MR) receptors in the left ventricle, but the total number of receptors remains unchanged. It is not known whether this reduction is transcriptionally or translationally regulated, or if the functionally closely linked alpha-subunits of G protein (G alpha s and G alpha i-2) partake in this regulation. In order to resolve these questions, the absolute concentrations of mRNAs for both receptors and for G alpha s and G alpha i-2 were quantified by slot blot analysis of the left ventricles of adult rats 5 weeks after aortic banding. The results showed a significant decrease of both receptor mRNA levels in hypertrophied left ventricle (beta 1-AR: -48%; M2-MR: -42%) that paralleled the reduction in receptor protein densities and was negatively correlated with the left ventricular weight/body weight ratio (LVW/BW). By contrast, the relative levels of G alpha s and G alpha i-2 mRNAs remained unchanged, and both accumulated proportionally to the increase in LVW/BW. These results show that the beta 1-AR and the M2-MR were pretranslationally regulated. This suggests the hypothesis that the corresponding genes do not follow the general increase in transcriptional activity. By contrast, the genes coding for G alpha s and G alpha i-2 may follow the general pattern of activation during hypertrophy. Receptors and coupling proteins belong to two different groups of genes that are controlled by distinct mechanisms of regulation.

Biological adaptation of the myocardium to chronic mechanical overload. Molecular determinants of the autonomic nervous system.

Cardiac hypertrophy due to chronic mechanical overload is the physiological reaction of the heart to a disease, but is not a disease itself. The hypertrophied heart is both quantitatively and qualitatively modified, and these changes allow the heart to produce normal active tension at a low cost in terms of heat production. The biological cascade which finally leads to hypertrophy includes a trigger which is likely to be mechanical stretch, the phosphoinisitol pathway and a target at the level of DNA. Most of the physiological alterations observed during cardiac overload include changes in systolic and diastolic function and arrhythmias. The components of the autonomous nervous system are also greatly modified and their regulation is a rather complex issue. Future research to elucidate these mechanisms centres on the regulation process and the possibilities offered by gene transfer.