Area under the viraemia curve versus absolute viral load: utility for predicting symptomatic cytomegalovirus infections in kidney transplant patients

A novel approach to predicting symptomatic cytomegalovirus (CMV) infections combines the level and the duration of viraemia in a single parameter. Sixty-four kidney transplant recipients were monitored by quantitative shell vial culture, pp65 antigenaemia, and polymerase chain reaction (PCR) of leucocytes. The area under the curve (AUC) of each parameter was determined from the onset of viraemia to the beginning of antiviral treatment. The AUC values were significantly higher in symptomatic than in asymptomatic patients. For antigenaemia and PCR, optimal AUC thresholds for predicting symptomatic CMV infections were determined. They were superior to standard cutoff levels of absolute viral load in sensitivity, specificity, and positive and negative predictive value. In 8 of the 23 patients who became symptomatic, impending clinical features were indicated earlier by the AUC thresholds than by standard viral load. In conclusion, the concept of the AUC should facilitate identification of patients at risk of symptomatic CMV infection.     

Age-dependent alterations of microtubule-associated enzyme activities from bovine brain (protein kinase, adenosine triphosphatase, guanosine triphosphatase)

Microtubules have been isolated from immature (3-4 weeks' old) and old (11-13 years' old) bovine brains. Quantitative studies revealed that the concentration of extractable microtubule protein per gram of wet brain decreased from 0.47 mg (immature animals) to 0.34 mg (old animals). The major components of microtubule protein (tubulin and high-molecular-weight microtubule-associated proteins) do not undergo an age-correlated change. Determination of the endogenous protein kinase activity revealed that the activity associated with "immature" calf brain microtubules was six times higher than the activity present in "old" preparations. In contrast, the stimulatory effect of cyclic AMP on protein phosphorylation in microtubules from old bovine brains exceeds nine-fold the value obtained from immature animals. After addition of casein (exogenous acceptor), the basal activities increased in both preparations without altering the age-correlated difference in the specific activity. By comparing the radioactivity pattern of sodium dodecyl sulfate polyacrylamide gels after autophosphorylation of microtubule protein with [gamma-32P]ATP, 1.5 moles of phosphate per mole of high-molecular-weight microtubule-associated protein were estimated to be incorporated in preparations from immature animals and 0.9 mole of phosphate per mole of associated protein in the experiments with "old" microtubule protein. Adenosine triphosphatase activity, associated with the high-molecular-weight microtubule-associated protein 1, was determined to be 15% reduced in preparations from old animals, compared to the activity in "young" preparations. In contrast, the guanosine triphosphatase activity increased five-fold during ageing; the higher activity of this enzyme was observed both during the initial and the steady-state phases of microtubule formation.     

Pulmonary tuberculosis due to bacille Calmette-Guérin

Summary Immunotherapy using bacille Calmette-Guérin (BCG) has gained increasing acceptance in the management of superficial bladder cancer. Systemic reactions after intravesical instillation of BCG are rare. However, when the therapy is complicated, the lung often becomes involved. Since the pathogenesis of lung infiltrates after immunotherapy is unknown, we report on a patient who developed a lung infiltrate after receiving BCG immunotherapy for bladder cancer. The infectious etiology was established by culture confirmation of a BCG strain in the broncheoalveolar lavage fluid.Abbreviation BCG bacille Calmette-Guérin     

Über die prednisolonähnliche Wirkung von Corticosteronderivaten

Zusammenfassung Es wird über die Prüfung zweier Derivate des Corticosterons an 67 bzw. 34 Patienten eines dermatologischen Krankengutes berichtet. Die klinische Wirksamkeit des einen Pr?parates war deutlich geringer als die von Prednisolon, w?hrend die des anderen dem therapeutischen Effekt von Prednisolon entsprach.

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Summary The results of a clinical trial with two derivatives of corticosterone in 67 resp. 34 dermatological cases are described. The efficiency of the first substance was significantly less than that of prednisolone, while the other one was equally efficient as prednisolone.

     

Charcot-Marie-Tooth neuropathy type 2 and P0 point mutations: two novel amino acid substitutions (Asp61Gly; Tyr119Cys) and a possible "hotspot" on Thr124Met

Mutations in the gene for the major protein component of peripheral nerve myelin, myelin protein zero (MPZ, P0), cause hereditary disorders of Schwann cell myelin such as Charcot-Marie-Tooth neuropathy type 1B (CMT1B), Dejerine-Sottas syndrome (DSS), and congenital hypomyelinating neuropathy (CHN). More recently, P0 mutations were identified in the axonal type of CMT neuropathy, CMT2, which is different from the demyelinating variants with respect to electroneurography and nerve pathology. We screened 49 patients with a clinical and histopathological diagnosis of CMT2 for mutations in the P0 gene. Three heterozygous single nucleotide changes were detected: two novel missense mutations, Asp61Gly and Tyr119Cys, and the known Thr124Met substitution, that has already been reported in several CMT patients from different European countries. Haplotype analysis for the P0 locus proved that our patients with the 124Met allele were not related to a cohort of patients with the same mutation, all of Belgian descent and all found to share a common ancestor. Our data suggest that P0 mutations account for a detectable proportion of CMT2 cases with virtually every patient harbouring a different mutation but recurrence of the Thr124Met amino acid substitution. The high frequency of this peculiar genotype in the European CMT population is presumably not only due to a founder effect but Thr124Met might constitute a mutation hotspot in the P0 gene as well.     

Vorschlag für eine Konsensus-Klassifikation der periprothetischen Membran gelockerter Hüft- und Knieendoprothesen

After 10 years, loosening of total joint endoprostheses occurs in about 3 to 10 percent of all patients, requiring elaborate revision surgery. A periprosthetic membrane is routinely found between bone and loosened prosthesis. Further histomorphological examination allows determination of the etiology of the loosening process. Aim of this study is the introduction of clearly defined histopathological criteria for a standardized evaluation of the periprosthetic membrane. Based on histomorphological criteria and polarized light microscopy, four types of the periprosthetic membrane were defined: periprosthetic membrane of wear particle type (type I), periprosthetic membrane of infectious type (type II), periprosthetic membrane of combined type (type III), periprosthetic membrane of indifferent type (type IV). Periprosthetic membranes of 268 patients were analyzed according to the defined criteria. The correlation between histopathological and microbiological diagnosis was high (89%, p<0,001), the inter-observer reproducibility was sufficient (95%). This classification system enables a standardized diagnostic procedure and therefore is a basis for further studies concerning the etiology of and pathogenesis of prosthesis loosening.     

False-positive results of plasma PCR for cytomegalovirus DNA due to delayed sample preparation

Positive results by cytomegalovirus (CMV) PCR of plasma are considered predictive of active CMV infection in kidney allograft recipients. To assess whether contamination with leukocyte-derived CMV DNA can distort the results, aliquots of whole-blood samples from 60 CMV immunoglobulin G-positive patients with leukocyte CMV DNAemia were stored for up to 24 h at room temperature (RT) and at 4 degrees C before plasma preparation. Native and ultrafiltered plasma samples were tested by CMV and beta-globin PCRs. Among 30 latently infected patients (negative for CMV pp65 antigens), low baseline rates (10%) and levels (median number of copies, 10 [per 10 microl]) of CMV plasma DNAemia in native plasma samples increased significantly over time (after 4 h at RT, 37% [P < 0.001]; median number of copies, 45 [P < 0.001]). Similar effects were found during storage at 4 degrees C. Ultrafiltration reduced the levels of CMV plasma DNAemia, but by 6 h of storage the levels were significantly elevated as well. CMV and beta-globin DNA kinetics in plasma were parallel. In contrast, 30 actively infected patients (pp65 positive) had high baseline rates (87% in native samples) and levels (median number of copies, 75) of CMV plasma DNAemia. No significant effects of storage or ultrafiltration and no concordance with beta-globin DNA kinetics were seen. In conclusion, delayed preparation of plasma samples bears a significant risk of false-positive CMV PCR results, probably due to leukocyte lysis. This has important implications in the clinical setting and for PCR standardization.     

Clinical Significance of Epithelial Peptide Antibiotics

Although the epithelium of macro-organisms is constantly exposed to microbial threats, infections are rather rare. Antimicrobial substances produced by epithelial cells may explain the high natural resistance of the exposed epithelia. Gene-encoded antimicrobial peptides that are believed to kill micro-organisms via pore formation have been found in the surface cells and secretions of plants and insects, and in the skin of frogs. The tongues and lungs of cattle are usually free of infection, and the first mammal-derived epithelial antimicrobial peptides, which belong to the so-called beta-defensin family, were discovered in bovine trachea and tongue. These beta-defensins are induced by infections and inflammatory agents, and are upregulated in specific anatomical sites of the epithelia, where infections occur. Recent studies have revealed that human epithelia also express beta-defensins: the tissues of the urogenital tract constitutively express human beta-defensin-1 (HBD-1), and a second human beta-defensin, HBD-2, is produced in skin and lung upon stimulation of epithelial cells with infectious or inflammatory agents. This brief review summarises our current knowledge about epithelial antimicrobial peptides, and discusses their possible role and relevance in the clinic. This includes the possibility of defective production in patients with recurrent infections, the therapeutic use of synthetic antimicrobial peptides, and the induction of their synthesis as an alternative strategy to prevent infections.