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R Bax

Publications and source records attributed to R Bax.

At least 19 recordsLinked to original sources
PubMed2005

Congenital cataract, muscular hypotonia, developmental delay and sensorineural hearing loss associated with a defect in copper metabolism.

Deficiencies of different proteins involved in copper metabolism have been reported to cause human diseases. Well-known syndromes, for example, are Menkes and Wilson diseases. Here we report a patient presenting with congenital cataract, severe muscular hypotonia, developmental delay, sensorineural hearing loss and cytochrome-c oxidase deficiency with repeatedly low copper and ceruloplasmin levels. These findings were suggestive of a copper metabolism disorder. In support of this, the patient's fibroblasts showed an increased copper uptake with normal retention. Detailed follow-up examinations were performed. Immunoblotting for several proteins including ATP7A (MNK or Menkes protein), ATP7B (Wilson protein) and SOD1 showed normal results, implying a copper metabolism defect other than Wilson or Menkes disease. Sequence analysis of ATOX1 and genes coding for proteins that are known to play a role in the mitochondrial copper metabolism (COI-III, SCO1, SCO2, COX11, COX17, COX19) revealed no mutations. Additional disease genes that have been associated with cytochrome-c oxidase deficiency were negative for mutations as well. As beneficial effects of copper histidinate supplementation have been reported in selected disorders of copper metabolism presenting with low serum copper and ceruloplasmin levels, we initiated a copper histidinate supplementation. Remarkable improvement of clinical symptoms was observed, with complete restoration of cytochrome-c oxidase activity in skeletal muscle.

Adenosine Triphosphatases↗
PubMed2002

Microbicides--evaluating multiple formulations of C31G.

Despite a significant worldwide need for effective microbicides to reduce sexually transmitted diseases (STD) and HIV transmission, none is currently available. C31G, a surface active anti-infective agent that is active in vitro against bacterial and viral STD pathogens, was evaluated in a 3-day, once-daily dosing clinical trial designed to assess multiple formulations for safety and acceptance. The trial used a scoring algorithm that was based on relevant subject reported symptoms and signs observed at follow-up. Differences in tolerance and acceptability between the formulations were demonstrated, as was consistency with the results from a previous 7-day trial that involved two of the formulations (1.2% HEC gel, 2.0% N-9). The 1.0% C31G co-polymer gel was the best tolerated, most acceptable formulation, and will be advanced to longer, more comprehensive trials. Thus, formulation differences are relevant to microbicide tolerance and acceptability, and the 3-day trial design validated in this study can be used to assess formulations.

Administration, Intravaginal↗
PubMed2001

Surveillance of antimicrobial resistance--what, how and whither?

OBJECTIVE: To express the views of a working party held to consider antibiotic resistance surveillance systems, their strengths and weaknesses, and their current and future applications. METHODS: The participants, all of whom were experienced in this field, discussed the development of surveillance systems in relation to the increasing prevalence of resistance to antibacterial agents and the current interest in surveillance systems shown by many official bodies, in both the human and veterinary fields. The problems inherent in surveillance systems were considered together with the applications of different systems. RESULTS: The properties of good antibiotic resistance surveillance systems were defined. Surveillance systems vary widely from those with a narrow base, focusing on few organisms in one disease area, to those covering many diseases, many organisms (including normal flora) and many compounds. Whatever their design, they should be able to detect significant differences and shifts in susceptibility to various antibacterial agents, and the information derived from them should reach as many interested parties as possible in a timely manner. In using this information to decide strategies, criteria for action need to be determined by pragmatic consensus. Funding remains a major problem, with few large studies being supported by official bodies in spite of their professed enthusiasm for surveillance. In consequence, many current systems are funded by the pharmaceutical industry and are of necessity restricted in their focus. CONCLUSIONS: Antibiotic resistance surveillance studies should and can be well planned and well executed. Many current systems suffer from well-recognized but uncorrected biases. Consortium funding will be necessary for large schemes to be successful. There is no "ideal" surveillance system.

Animals↗
PubMed2000

The millennium bugs--the need for and development of new antibacterials.

Global antibacterial resistance is becoming an increasing public health problem. Bacteria resistant to almost all of the available antibacterials have been identified. The pharmaceutical industry and fledgling biotechnology companies are responding to the threat of antibiotic resistance with renewed efforts to discover novel antibacterials in attempts to overcome bacterial resistance. Both short term and long term strategies are being vigorously pursued. Short-term efforts are focused on developing novel antibacterial agents with a narrow spectrum of action to combat the problem of gram-positive resistant bacteria. Long-term approaches include the use of microbial genomic sequencing techniques to discover novel agents active against potentially new bacterial targets. Better use of existing agents using pharmacodynamic data to optimise antibiotic regimens is increasingly being addressed and the hope is that such measures will prevail until the newer agents are available.

Anti-Bacterial Agents↗
PubMed1998

Molecular approaches to diagnosis of pulmonary diseases due to Mycoplasma pneumoniae.

In this prospective study, the use of a culture-enhanced PCR assay for the detection of Mycoplasma pneumoniae, followed by hybridization with a specific probe (MP-HPCR) or without hybridization (MP-PCR), and the use of a nested PCR (MP-NPCR) were evaluated. Clinical samples (190 specimens) from 190 patients with respiratory complaints were incubated in culture broth overnight and then subjected to PCR. The results of the PCR were compared to those obtained by culture, the direct antigen test, and serologic testing by microparticle agglutination and by immunoblotting in unclear cases. The sensitivities were 19 CFU for MP-PCR, 1.9 CFU for MP-HPCR, and 0.019 CFU for MP-NPCR. PCR amplification of the beta-globin gene was possible in 98% of cases: after dilution of the beta-globin-negative samples, all samples were reactive. Correlation between negative MP-NPCR results and negative serology results was found in 89% of cases; a positive correlation was found with 10% of the patients. Samples from three immunocompromised patients were MP-NPCR positive but serologically negative. High respiratory colonization by M. pneumoniae (>10(5) CFU/ml) in patients with acute respiratory disease could be detected by culture, MP-PCR, and MP-NPCR. These results indicate that MP-PCR and MP-NPCR are reliable methods for the detection of M. pneumoniae in respiratory tract samples of patients with respiratory complaints.

Adult↗
PubMed1997

Molecular discrimination between Campylobacter jejuni, Campylobacter coli, Campylobacter lari and Campylobacter upsaliensis by polymerase chain reaction based on a novel putative GTPase gene.

Polymerase chain reaction (PCR) mediated DNA fingerprinting has resulted in the identification of a novel Campylobacter jejuni gene, encoding a GTPase protein. The gene, consisting of 383 amino acids contained semi-conserved GTP-binding sites (designated G-1 to G-4), that are characteristic for members of the GTPase protein superfamily. Remarkably, this gene from C. Jejuni appears to encode a member of a novel family of GTP-binding proteins, containing two separate putative GTP-binding domains, each comprising a series of semi-conserved GTP-binding motifs. Spacing between these motifs is highly conserved. Based on this novel gene, a general PCR strategy for the identification of C. jejuni, C. coli, C. lari and C. upsaliensis was developed. PCR primers were deduced from GTP-binding motifs G-1 and G-3 of the first GTP-binding domain. These GTP-binding sites flank a variable region of precisely 117 bp in the four Campylobacter spp. that allowed the development of species-specific probes. This PCR-hybridization assay offers a novel tool for rapid molecular detection and specific identification of the thermophilic Campylobacter spp.

Amino Acid Sequence↗
PubMed1995

Multicenter evaluation of arbitrarily primed PCR for typing of Staphylococcus aureus strains.

Fifty-nine isolates of Staphylococcus aureus and a single strain of Staphylococcus intermedius were typed by arbitrarily primed PCR (AP-PCR). To study reproducibility and discriminatory abilities, AP-PCR was carried out in seven laboratories with a standardized amplification protocol, template DNA isolated in a single institution, and a common set of three primers with different resolving powers. The 60 strains could be divided into 16 to 30 different genetic types, depending on the laboratory. This difference in resolution was due to differences in technical procedures (as shown by the deliberate introduction of experimental variables) and/or the interpretation of the DNA fingerprints. However, this did not hamper the epidemiologically correct clustering of related strains. The average number of different genotypes identified exceeded those of the more traditional typing strategies (F. C. Tenover, R. Arbeit, G. Archer, J. Biddle, S. Byrne, R. Goering, G. Hancock, G. A. Hebert, B. Hill, R. Hollis, W. R. Jarvis, B. Kreiswirth, W. Eisner, J. Maslow, L. K. McDougal, J. M. Miller, M. Mulligan, and M. A. Pfaller, J. Clin. Microbiol. 32:407-415, 1994). Comparison of AP-PCR with pulsed-field gel electrophoresis (PFGE) indicated the existence of strains with constant PFGE types but variable AP-PCR types. The reverse (constant AP-PCR and variable PFGE patterns) was also observed. This indicates additional resolution for combined analyses. It is concluded that AP-PCR is well suited for genetic analysis and monitoring of nosocomial spreading of staphylococci. The interlaboratory reproducibility of DNA-banding patterns and the intralaboratory standardization need improvement.

Bacterial Typing Techniques↗
PubMed1994

Comparison of four genotyping assays for epidemiological study of methicillin-resistant Staphylococcus aureus.

Twenty-six methicillin-resistant Staphylococcus aureus strains were genetically differentiated by interrepeat PCR and the results compared with those of ribotyping, pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA analysis obtained in a previous study for the same strains. The comparison showed that the PCR-mediated assays were as discriminatory as PFGE, whereas ribotyping was the least powerful genotyping method. Due to the ease of performance, PCR fingerprinting may become the method of choice for establishing clonal relationship among Staphylococcus aureus isolates.

Genetic Techniques↗
PubMed1993

[Typing of methicillin-resistant Staphylococcus aureus strains for epidemiological studies using the polymerase chain reaction].

OBJECTIVE: To determine whether polymerase chain reaction (PCR) fingerprinting can be used to gain insight into the epidemiology of methicillin resistant Staphylococcus aureus (MRSA). DESIGN: Retrospective DNA analysis of MRSA strains. BACTERIAL STRAINS: MRSA strains were collected in two Dutch and one Belgian hospital (Reinier de Graaf Gasthuis, Delft; St. Antonius Ziekenhuis, Nieuwegein; St. Jan Ziekenhuis, Brugge). METHODOLOGY: MRSA DNA was isolated by standard procedures. Differences in genomic organisation were detected with the aid of exponential enzymatic synthesis of intrinsically variable DNA domains. This so-called PCR fingerprinting, a relatively new technique, was performed in direct comparison with phage typing. The latter is the current golden standard for S. aureus typing. RESULTS: The results of both PCR fingerprinting and phage typing appeared to be useful for strain identification. All results were consistent with other epidemiological data. CONCLUSION: Genotyping MRSA with PCR fingerprinting is complementary to phage typing. In some instances PCR fingerprinting is even to be preferred to the other technique. PCR fingerprinting is well suited for the analysis of MRSA spreading.

Aged↗
PubMed1993

Comparison of phage typing and DNA fingerprinting by polymerase chain reaction for discrimination of methicillin-resistant Staphylococcus aureus strains.

A typing procedure for methicillin-resistant Staphylococcus aureus (MRSA) based on the polymerase chain reaction (PCR) amplification of both mecA sequences and variable DNA sequences as present in the prokaryotic genome has been developed. Two primers based on the sequences of DNA repeats as discovered in gram-negative members of the family Enterobacteriaceae allow detection of variable regions in the genome of a gram-positive bacterium such as S. aureus, as does a newly described arbitrary primer. This procedure, enabling the detection of 23 different genotypes in a collection of 48 MRSA isolates, was validated by comparisons with phage typing studies. It appeared that within the same group of isolates only 13 different phagovars could be identified. Combination of the results from both phage typing and genotyping allowed the discrimination of 34 of 48 isolates. However, depending on the primer-variable complexity of the PCR fingerprints, which could also be modulated by combination of PCR primers, clear homologies between the groups defined by either phage typing or fingerprinting were observed. An analysis of an MRSA outbreak in a geriatric institution showed a collection of genetically homogeneous isolates. In agreement with phage typing, PCR fingerprinting revealed the identical natures of the MRSA strains isolated from all patients.

Aged↗
PubMed1993

Concordant clonal delineation of methicillin-resistant Staphylococcus aureus by macrorestriction analysis and polymerase chain reaction genome fingerprinting.

Pulsed-field gel electrophoresis of DNA macrorestriction fragments (macrorestriction analysis) allows epidemiologic typing and delineation of genetic relatedness of methicillin-resistant Staphylococcus aureus (MRSA) by indexing variations in the global chromosome architecture. Polymerase chain reaction (PCR)-mediated genome fingerprinting can also discriminate MRSA strains by detecting locally variable DNA motifs. To assess the correlation between these methods, 48 epidemic MRSA strains collected from 20 hospitals over a 10-year period were tested in a blind comparison by (i) macrorestriction analysis with SstII or SmaI endonuclease and (ii) PCR fingerprinting with four primer sets aimed at the mecA gene, enterobacterial repetitive intergenic consensus sequences, and arbitrary sequences. Isolates were discriminated into 22 macrorestriction patterns and 15 PCR fingerprints. MRSA strains belonging to 12 distinct clones by macrorestriction analysis showed 11 distinct PCR genotypes distinguished by multiple band differences. In contrast, 34 of 37 MRSA strains found to be clonally related by macrorestriction analysis clustered in two highly related PCR genotypes that differed by a single DNA fragment (P < 0.0001). These data demonstrate concordant clonal delineation of epidemic MRSA by macrorestriction analysis and PCR fingerprinting and thereby indicate that the rapid PCR assay may be an efficient epidemiologic typing system.

Base Sequence↗
PubMed1991

Cowdria ruminantium is recognized by a monoclonal antibody directed against the major outer membrane protein of Chlamydia trachomatis.

The relationship between Cowdria ruminantium and Chlamydia trachomatis was studied by immunofluorescence. A monoclonal antibody directed against the major outer membrane protein of C. trachomatis recognized rickettsial colonies of C. ruminantium in infected goat brain. No specific fluorescence was observed in non-infected brain. Two commercial Chlamydia-specific monoclonal antibodies as well as polyvalent anti-Chlamydia rabbit serum recognized C. trachomatis, but did not recognize Cowdria. Moreover, polyvalent Cowdria antiserum failed to recognize C. trachomatis cultivated in HeLa cells. It is concluded that Cowdria and Chlamydia are to a certain extent related, confirming similarities in ultrastructure and developmental cycle.

Animals↗
PubMed1988

The development of hypoprothrombinaemia following antibiotic therapy in malnourished patients with low serum vitamin K1 levels.

A group of nine well-nourished patients, with normal serum vitamin K1 levels (mean 546, range 310-1350 pg/ml), maintained normal prothrombin times (PTs) and factor VII clotting activities throughout a 7 d course of i.v. cefotetan disodium, an N-methyl-thiotetrazole (NMTT) containing cephalosporin antibiotic. However, 11 of 20 patients, with acute intra-abdominal sepsis and initially normal PTs who underwent emergency surgery, developed prolonged PTs (INR 1.4-3.1) associated with reduction in factor VII activities (0.74-0.38 u/ml) after 3-7 d of antibiotic therapy. Nine of these 11 patients had clinical evidence of malnutrition and nine had subnormal serum vitamin K1 levels (mean 119, range 43-354 pg/ml) on admission. Seven received cefotetan but four were treated with a non-NMTT-containing cephalosporin or antibiotics belonging to other groups. The nine patients who maintained normal PTs all had normal nutritional status and normal serum vitamin K1 levels (mean 279, range 103-915 pg/ml) at presentation. The PT is a relatively insensitive indicator of vitamin K stores, and malnourished patients with low serum vitamin K1 levels are at risk of developing hypoprothrombinaemia following intravenous antibiotic therapy.

Adult↗
PubMed1987

The effects of cefotetan disodium on haemostasis.

A 7-day course of intravenous cefotetan disodium was given to nine patients. No significant changes were observed in haematological or biochemical parameters and serum vitamin K1 levels, prothrombin times, factor VII levels, thrombin times and activated partial thromboplastin times remained within the normal ranges throughout the treatment period in all patients. There was no evidence of clinical bleeding in any patient although in two the bleeding time was prolonged up to 13.0 min after 7 days' therapy. Notably, adenosine-5-diphosphate (ADP)-induced platelet aggregation responses were significantly increased (P less than 0.05) at the end of the treatment period. These data indicate that cefotetan disodium at a dose of up to 4 g daily can be used without risk of a bleeding diathesis. In situations associated with vitamin K1 deficiency, potential prolongation of the prothrombin time should be avoided by prophylactic vitamin K1 administration.

Adult↗