Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity.

The nephrotoxicity and ototoxicity associated with once-daily versus twice-daily administration of aminoglycosides was assessed in patients with suspected or proven gram-negative bacterial infections in a randomized, double-blind clinical trial. Patients who received therapy for >/=72 h were evaluated for toxicity. Patients also received concomitant antibiotics as deemed necessary for treatment of their infection. Plasma aminoglycoside concentrations, prospective aminoglycoside dosage adjustment, and serial audiologic and renal status evaluations were performed. The probability of occurrence of a nephrotoxic event and its relationship to doses and daily aminoglycoside exposure served as the main outcome measurement. One hundred twenty-three patients were enrolled in the study, with 83 patients receiving therapy for at least 72 h. For 74 patients plasma aminoglycoside concentrations were available for analysis, and the patients formed the group evaluable for toxicity. The primary infectious diagnosis for the patients who were enrolled in the study were bacteremia or sepsis, respiratory infections, skin and soft tissue infections, or urosepsis or pyelonephritis. Of the 74 patients evaluable for toxicity, 39 received doses twice daily and 35 received doses once daily and a placebo 12 h later. Nephrotoxicity occurred in 6 of 39 (15.4%) patients who received aminoglycosides twice daily and 0 of 35 patients who received aminoglycosides once daily. The schedule of aminoglycoside administration, concomitant use of vancomycin, and daily area under the plasma concentration-time curve (AUC) for the aminoglycosides were found to be significant predictors of nephrotoxicity by multivariate logistic regression analysis (P

[Electronic data processing in a surgical and medical intensive care unit]. / EDV-Dokumentation auf einer chirurgischen und einer medizinischen Intensivstation.

A prospective documentation of patients data on an internal and a surgical intensive care unit (ICU) has been transacted. The physician and nursing staff used an online electronic documentation program, which has been developed in Frankfurt. Main emphasis has been placed on the epidemiological data, clinical diagnoses as well as diagnostically and therapy costs. The medical ICU of university hospital of Frankfurt has been analysed since 1992 and the surgical ICU of Städtisches Krankenhaus of Lüneburg since 1994. Up to now data from 2001 patients from Frankfurt are available. Period spent on the ICU was 4.7 +/- 0.16 days (average +/- SEM), mortality was 15%. 47% of the whole group suffered from cardiac disease, of which 211 had an acute myocardial infarction (10.6%), 156 patients a serious ventricular arrhythmia (7.8%) as well as 88 patients an unstable angina (4.4%). Long-term observation revealed a rise of the duration spent on the ICU (from 4.1 +/- 0.17 to 5.5 +/- 0.38 days, P < 0.0002), an increasing number of technical examinations (for example: chest x-ray from 2.25 +/- 0.13 to 4.52 +/- 0.4/patient, P < 0.0001) and a steady mortality between 1992 and 1994. Detailed analysis of patients with acute myocardial infarction showed an impressive reduction of total mortality within the 3 years observed. In Lüneburg data of 1004 patients have been recorded so far. The average time spent on the ICU was 6.4 +/- 0.33 days. 4.1% patients passed away. Neoplasia of gastric intestinal tract (143; 14.2%), femoral neck fracture (64; 6.4%) and ilei (54; 5.4%) have been the most frequent diagnoses. Patients underwent 2.2 +/- 0.12 chest x-rays and 1.4 +/- 0.1 ultrasound investigations. The study shows that an online data processing is practicable and can be integrated in the daily work flow. Furthermore, it can be seen that the collected data play an important role to secure the increasing administrative requisition to the modern medicine in view of costs and quality management.

Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif.

Using site-directed mutagenesis, we tested whether a potential integrin-binding site, (composed of the amino acids RGD) which is predicted in the adeno-associated virus 2 (AAV-2) capsid open reading frame (ORF), plays a role in the infectivity of AAV-2. Nucleotide sequencing of wild-type and mutant capsid protein-coding sequences, however, revealed discrepancies with the published sequence data at several positions, including a frameshift in the carboxy terminus which cancels the RGD motif and extends the capsid ORF by 27 amino acids. This sequence was confirmed by protein sequencing of proteolytic fragments of VP3. Thus, the virus mutant (pTAV-p), in which the intention was to exchange D of the putative RGD motif for E, resulted in replacing I480 by S in the newly established ORF. A second virus mutant (pTAV-d), in which the intention was to delete the RGD peptide, in fact gave a shift into the ORF of the originally published sequence. The pTAV-p mutant showed a strongly reduced infectivity compared to wild-type AAV-2, whereas pTAV-d was not infectious at all. Neither mutant accumulated viral ssDNA as detected by Hirt extraction. Analysis of virus particle formation and subcellular localization of the capsid proteins revealed a defect of the mutant capsid proteins in capsid assembly. This shows that the newly established C-terminal sequence of the AAV capsid proteins plays an important role in viral assembly.

Prospective evaluation of red man syndrome in patients receiving vancomycin.

The incidence of red man syndrome (RMS) and its relationship to histamine were investigated in patients receiving vancomycin or an aminoglycoside (control). During the 60-min infusions, patients were observed for signs or symptoms consistent with RMS, including pruritus, erythema, angioedema, and cardiovascular depression. Four blood samples were obtained at 30-min intervals for determination of histamine concentrations. One (3.4%) of 29 vancomycin- and none of 8 aminoglycoside-treated patients had documented RMS. The mean maximum changes in blood pressure and heart rate were not significant and were similar between groups. Increases in histamine concentrations to > 1 ng/mL occurred only in 25% (2/8) of the aminoglycoside patients. Vancomycin induced minimal changes in histamine concentrations despite the occurrence of RMS. From these observations, it appears that RMS is not closely associated with histamine release, and elevated histamine concentrations do not predict RMS. Further investigation is needed to elucidate other mediators of RMS.

Assembly of viruslike particles by recombinant structural proteins of adeno-associated virus type 2 in insect cells.

The three capsid proteins VP1, VP2, and VP3 of the adeno-associated virus type 2 (AAV-2) are encoded by overlapping sequences of the same open reading frame. Separate expression of these proteins by recombinant baculoviruses in insect cells was achieved by mutation of the internal translation initiation codons. Coexpression of VP1 and VP2, VP2 and VP3, and all three capsid proteins and the expression of VP2 alone in Sf9 cells resulted in the production of viruslike particles resembling empty capsids generated during infection of HeLa cells with AAV-2 and adenovirus. These results suggest a requirement for VP2 in the formation of empty capsids. Individual expression of the AAV capsid proteins in HeLa cells showed that VP1 and VP2 accumulate in the cell nucleus and VP3 is distributed between nucleus and cytoplasm. Coexpression of VP3 with the other structural proteins also led to nuclear localization of VP3, indicating that the formation of a complex with VP1 or VP2 is required for accumulation of VP3 in the nucleus.

Community health nursing in an urban day care center.

This paper has endeavored to depict some of the student achievements during community health nursing practice in a less traditional clinical setting, a day care center for infants and toddlers. There appear to have been a number of advantages to such a clinical placement. For one thing, students had the opportunity to devise a package of preventive/maintenance health services for a specific group of healthy children. This they were able to implement in collaboration with the day care center staff and the children's families. In the course of delivering the health services, they learned firsthand the strategies inherent in planning and negotiating among one another. In recognition of the integrity of child health as a component of family health care, they accounted regularly to the parents in both individualized and group fashion. Through the experiences over the course of the quarter, there seemed to be a heightened awareness of the potential for innovative nursing practice in urban communities.