Activities of different classes of acyclic nucleoside phosphonates against BK virus in primary human renal cells.

BK virus (BKV), a virus belonging to the polyomavirus family, is a circular double-stranded DNA virus that causes nephropathies in immunocompromised patients after kidney or bone marrow transplantation. The occurrence of polyomavirus-associated nephropathy in kidney transplant patients may trigger graft loss, and guidelines for the management of BKV infection have not yet been clearly established. Treatment of BKV nephropathy with cidofovir (CDV) {(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC)}, an acyclic phosphonate analogue of dCMP with a broad antiviral activity against DNA virus infections, has been proposed. The benefit of this small-molecule-based treatment has been evaluated only with a limited number of cases. In this study, we report the evaluation of three different classes of acyclic nucleoside phosphonates for their activities against BKV replication in two different primary renal cells: renal proximal tubular epithelial cells (RPTECs) and human renal cortical epithelial (HRCE) cells. The data indicate that besides HPMPC and its cyclic form, (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (HPMP-5-azaC), cyclic HPMP (cHPMP)-5-azaC, hexadecyloxyethyl (HDE)-cHPMP-5-azaC, and 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) are the most selective inhibitors of BKV replication. On the contrary, leflunomide, which has also been proposed for the management of BKV-associated diseases, is not able to inhibit BKV replication at nontoxic concentrations.

Inhibitory potency of 5-benzyluracil, 5-phenylcytosine and 5-phenylpyrimidin-2-one nucleosides against uridine phosphorylase from mouse leukemic L1210 cells.

The inhibitory activity of a series of novel sugar-modified nucleosides derived from 5-benzyluracil, 5-phenylcytosine and 5-phenylpyrimidin-2-one against uridine phosphorylase purified from mouse leukemic L-1210 cells was investigated. Significant activity was encountered with O2,2'-anhydro-5-benzylcytidine hydrochloride, 2',3'-dideoxy-5-benzyluridine, 2',3'-dideoxy-4-thiouridine and alpha- and beta-anomers of 5-benzyl-1-(2-deoxy-D-arabino-hexopyranosyl)uracil.

Selected polyhalogenated hydrocarbons in breast milk.

Breast milk samples were collected and analysed within a comprehensive programme co-ordinated by WHO EURO to evaluate the possible health risk for breast-fed infants in chosen localities of European countries ('exposed' and 'control' ones). The samples of breast milk were collected, stored transported and analysed by a standardised study protocol to assure the comparability of the results from different areas (of 19 European countries). The study included three categories of chemicals: polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs), dioxine like polychlorinated biphenyls (PCBs) and other PCBs. The results obtained confirmed the correct choice of 'exposed' and 'control' regions in the Czech Republic as a suitable tool used to identify certain geographical areas with relatively high exposure levels for further risk management actions and possible follow-up epidemiological studies. The results obtained have shown high levels of PCBs in exposed region but not in the dioxine-like fraction, that ranged within a lower rank of a relevant European data. PCDs/PCDFs levels ranged in the same lower rank of values in comparison with e.g. Benelux countries. The data of this study does not confirm ideas about wide spread excessive exposure of central European population to polyhalogenated hydrocarbons via excessive contamination of a local food basket.

Solid-phase synthesis of oligo(2'-deoxyxylonucleotides) and PCR amplification of base-modified DNA fragments.

1-(2'-Deoxy-beta-D-threo-pentofuranosyl)thymine (xTd) and -adenine (xAd) were converted into their appropriately protected 3'-phosphonates 1a, 2a as well as their 2-cyanoethyl phosphoramidites 1b, 2b. These compounds were used for solid-phase syntheses of the oligo(2'-deoxy-beta-D-xylonucleotides) 5-8. Structural properties and behavior against nucleases is described. Apart from oligo(2'-deoxyxylonucleotides) the PCR-amplification of a pUC18 DNA fragment with Taq polymerase was studied in the presence of the 7-deazapurine derivatives of dGTP, dATP, and dITP. The incorporation efficiency of the modified compounds was compared with those of the parent nucleotides. 7-Deaza-2'-deoxyguanosine protected the DNA-fragment from hydrolysis by the restriction endodeoxyribonuclease Eco RI, Pst I, Bam HI, and Sma I if the nucleoside was located within the recognition site.

Prevalence of nosocomial infections in general surgery, orthopedic surgery and urological departments in the Czech Republic.

Two prevalence studies of Nosocomial Infections carried out in 1987 (based on 4479 patients in 64 general surgery departments and 1603 patients in 29 orthopedic surgery departments) and in 1988 (based on 1263 patients in 32 urological departments) are summarized. The prevalence rate of nosocomial infections (NI) in general surgery departments was 14.0%, in orthopedic surgery departments 8.0% and in urological departments 20.9%. The highest degree of risk of acquiring NI was run by patients above 60 years of age in urological and general surgery departments. Surgical wound infections in departments of general surgery accounted for 60%, in orthopedic surgery departments for 47% and in urological departments for 37% of all NI. The prevalence of wound infections amongst general surgical patients was 8.4%, amongst orthopedic surgical patients 3.8% and in urological patients 7.7%. The prevalence of urinary tract infections in general surgery departments was 14.4%, in orthopedic surgery departments 18.6% and in urological departments 51.6%. The problems discussed include the role of intrinsic and in-hospital risk factors and the involvement of pathogens responsible for the onset of NI.

[Prevalence of nosocomial infections in surgery and orthopedic departments in the Czech Republic]. / Prevalence nozokomiálních nákaz na chirurgických a ortopedických oddeleních v CSR.

The paper deals with the results of a prevalence study of nosocomial infections which was conducted in October 1987 in 64 surgical and 29 orthopaedic departments in the CSR selected at random. Epidemiological analysis of 559 nosocomial infections (NI) detected in 4,479 patients of surgical departments (prevalence 12.5%) and analysis of 122 NI in 1603 orthopaedic patients (prevalence 7.6%) was done by age, sex, site of the affected systems, predisposing factors and the etiological agent. Analysis of early infections (from the total number of NI early infections in surgical departments accounted for 67% and in orthopaedic departments for 50%) as tract (surgery) and in traumatological wounds (orthopaedic department). Analysis of the most important predisposing factors (9 of 32) as regards their prevalence in patients with NI revealed that the majority of factors (with the exception of bed sores and multiple injuries in surgical departments) occurs in more than 75% in combinations. Roughly one third of the patients with NI had none of the nine mentioned factors. An overall analysis of the results of the prevalence study of NI in surgical and orthopaedic departments revealed a more favourable position in orthopaedic departments.

[The occurrence of early infections in surgical and orthopedic departments in Czechoslovakia]. / Výskyt ranných nákaz na chirurgických a ortopedických oddeleních v CSR.

The authors made an epidemiological analysis of early infections (EI) based on a prevalence study conducted in October 1987 in 64 surgical and 29 orthopaedic departments in the CSR, selected at random. A total of 4479 patients were examined in surgical departments, the prevalence of EI in 2415 operated patients was 15.6. In orthopaedic departments 1603 patients were examined, the prevalence of EI in 846 operated patients was 7.2. Early infections were analyzed with regard to the type of surgical wound, geographical distribution, type of operation and its duration, degree of inflammatory affection and time during the postoperative period when it developed. The analysis confirmed a more favourable position as regards EI in orthopaedic departments and indicated the main trends of the fight for their reduction.

National prevalence survey of hospital-acquired infections in Czechoslovakia.

A nationwide 1-day prevalence survey of a total of 12,260 patients in 23 hospitals across Czechoslovakia yielded 751 cases of hospital-acquired infection (HAI), a prevalence of 6.1%. Analysis of the data revealed that the prevalence of HAI amongst surgical patients was almost twice that amongst medical patients (8.2% vs. 4.4%). Persons aged over 60 on the urological and surgical wards were at highest risk of acquiring infection. The most frequent site of HAI was the urinary tract (25%), followed by surgical wounds (15%) and the upper respiratory tract (13%). Fifty per cent of infection in gynaecological patients occurred within 6 days of admission compared with 15% in urological patients, and a wide variation was seen in other specialties.

Frequency of nosocomial infections as revealed by a prevalence survey.

In 1984, a prevalence survey based on the methodology, definitions and criteria meeting the WHO requirements was carried out in the Czech Socialist Republic. This prevalence study on a total of 12,260 hospital patients revealed 751 active cases of nosocomial infection (NI). The conclusions emerging from an epidemiological analysis of the collected NI patient records were as follows: 60% of all infections were acquired on the surgical services, predominantly on the surgery service; 60% of those who developed NI were persons over 50 years of age; hospital-associated infections afflicted 366 males and 385 females; the ratio of infections acquired prior to hospital presentation to those originating while in hospital care was about 4:1, with a tendency to vary depending on type of hospital service; the urinary tract was the most frequent site of infection (25%), followed by surgical wounds (15%) and upper respiratory tract (13%); 17% of NI patients contracted the infection in spite of preventive doses of antimicrobials, 28% of NI patients received no antimicrobial prophylaxis; among the 78% (589 out of 751) of patients examined bacteriologically, 46% of infections were caused by Gram-negative rods, 19% by staphylococci, 7% by streptococci and 6% by Pseudomonas aeruginosa; 22% of NI patients were not examined for the pathogen. The prevalence survey methodology turned out to be useful as a tool for detecting the immediate magnitude of the NI problem, but can also be used as a control method.

Epidemiological analysis of the incidence of yersiniosis by the monthly notified isolations of Yersinia enterocolitica 03 in the microbiological laboratories of the regional and district hygiene centres in Czechoslovakia.

The incidence of bacteriologically confirmed Yersinia enterocolitica 03 infections was recorded in absolute and relative numbers as well as in maps. There were more cases in children, especially of the youngest age group, than in adults, an in males than in females. Some differences in seasonal and regional incidence were found: a considerable rise during the winter months in Slovakia, whereas in Bohemia relatively high incidence was observed over several seasons of the year.