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Biomedical subjects

R J Meyer

Publications and source records attributed to R J Meyer.

At least 19 recordsLinked to original sources
PubMed2001

Hemodialysis followed by continuous hemofiltration for treatment of lithium intoxication in children.

Hemodialysis is the usual recommended treatment for severe lithium intoxication; however, rebound of lithium levels may require repeated hemodialysis treatments. We proposed that the addition of continuous hemofiltration after hemodialysis would prevent rebound by providing ongoing clearance of lithium. We report two pediatric patients with lithium intoxication treated by hemodialysis followed by continuous venovenous hemofiltration with dialysis (CVVHD). Both patients were symptomatic at presentation and had initial lithium levels more than three times the usual therapeutic range. Hemodialysis followed by CVVHD resulted in rapid resolution of symptoms, followed by continuous clearance of lithium without requiring repeated hemodialysis sessions. Both patients had return of normal mental status during CVVHD treatment, and neither patient experienced complications of hemodialysis or CVVHD. Total duration of treatment with hemodialysis followed by CVVHD was 34.5 hours for the first patient and 26 hours for the second patient. We conclude that hemodialysis followed by CVVHD is a safe and effective approach to the management of lithium intoxication in children.

Adolescent↗
PubMed2000

Recognition of oriT for DNA processing at termination of a round of conjugal transfer.

Conjugal transfer of plasmid DNA is terminated when the transferred strand, linearized at the 38 base-pair origin of transfer (oriT), is recircularized. For the plasmid R1162, it is the protein MobA, covalently linked to the linear strand, that rejoins the ends by a reversible transesterification reaction. We have identified from those oligonucleotides with a partially degenerate oriT base sequence, subpopulations bound by MobA that undergo transesterification, and support efficient termination of conjugal transfer. Two domains of oriT, a ten base-pair inverted repeat and an adjacent TAA, are required for tight binding by the protein, whereas the location of the dinucleotide YG determines the site of strand cleavage. The results indicate that capture of MobA by oriT, and subsequent processing of the DNA for termination, are determined by different sequence motifs within this locus.

Bacterial Proteins↗
PubMed2000

Methanol poisoning.

AIMS: This study examines clinical experience with methanol poisoning during a one-year period. METHODS: All admissions with the diagnosis of suspected methanol toxicity were analysed and the current guidelines for the management of this problem were reviewed. RESULTS: Twenty-four subjects were identified. Most had a history of chronic use of methylated spirits. Four died before admission to hospital and the other 20 patients had 26 admissions to hospital and form the basis for this report. Four patients died in the Intensive Care Unit. In total 11 patients were admitted to the Intensive Care Unit. Seven patients received haemodialysis. There was no correlation between the methanol level and the outcome. The strongest predictor of death or a poor outcome was a blood pH < 7.0. Some patients, in spite of potentially lethal methanol levels of up to 160 mmol/L, did not develop signs of toxicity. CONCLUSIONS: The overall mortality was high and ethanol was given to most of the patients for up to several days. Some patients did not show any toxicity and some of those were not given ethanol. It is recommended that chronic meths drinkers, who are not acidaemic and are generally well, do not require ethanol treatment. Only the complete removal of methanol from methylated spirits will reduce the morbidity of this condition.

Adult↗
PubMed2000

Cymbal array: a broad band sound projector.

A prototype 3 x 3 planar cymbal transducer array was built and tested. The array has a radiating area of 5.5 cm x 5.5 cm and a thickness of less than 8 mm. The measured transmitting voltage response was above 134 dB re 1 microPa/V @ 1 m and flat over the frequency range of 16 and 100 kHz. Array interaction was analyzed using an equivalent circuit model. The array interaction leads to variations in radiation resistance and velocity of the transducers in the array according to their surroundings in the array. The effect is enhanced overall efficiency and a flat response.

Equipment Design↗
PubMed2000

Nonpulmonary organ failure and outcome in children treated with high-frequency oscillatory ventilation.

PURPOSE: The purpose of this study was to quantitate the contribution of nonpulmonary organ failure to mortality of patients treated with high-frequency oscillatory ventilation (HFOV) and to determine which gas-exchange differences are associated with improvement on HFOV. MATERIALS AND METHODS: Charts of all patients treated with HFOV in our pediatric intensive care unit from January 1992 until January 1997 were retrospectively reviewed. RESULTS: Sixty-six patients were treated and 21 patients improved during HFOV (group 1); 45 patients did not improve (group 2). Seventeen patients (26%) had isolated respiratory failure and their mortality was 12%. Percentages of patients with 2, and 3 or more organ failure were 45%, 29%, and their mortality was significantly higher, 67% and 95%, respectively. Patients with primary respiratory failure demonstrated a significantly greater risk of improvement on HFOV (RR ratio of 2.5, 95% CI 1.5 to 4.2). There was a significantly greater proportion of patients with primary cardiac failure who did not improve on HFOV compared with all other patients. Oxygenation index significantly improved over the first 72 hours for both groups, but then significantly worsened over the next 48 hours in group 2 but not in group 1. CONCLUSION: Patients with nonpulmonary organ failure were significantly less likely to improve on HFOV and had a significantly higher mortality than patients with isolated respiratory failure. Children who do not improve on HFOV appear to reach a plateau in oxygenation indices after 3 days of HFOV.

Adolescent↗
PubMed1999

A United States regulator's perspective on the ongoing chlorofluorocarbon transition.

The Food and Drug Administration (FDA) put in place a general ban on the use of chlorofluorocarbons for the products it regulates (medical devices, drugs, and foods) in 1978, exempting those products where chlorofluorocarbon use was determined to be essential for the public health. In the intervening years, as the international commitment to a full transition away from all chlorofluorocarbon use took shape under the Montreal Protocol, the FDA has worked with industry to facilitate the development and testing of alternative technologies and products for inhalation drug products. As these alternative products begin to move from testing through the approval process and into marketing, the FDA is working collaboratively with the Environmental Protection Agency, other governmental agencies, and nongovernmental stakeholders to develop a transition policy for the United States. The transition policy for metered dose inhalers must be one that achieves the dual aims of first protecting the patients who rely on these vital medical products, while also achieving the public health need of protecting the ozone layer. As a part of developing such a transition strategy, the FDA published an advance notice of proposed rulemaking (ANPRM) in March 1997. The ANPRM proposed mechanisms by which the FDA could determine when chlorofluorocarbon use in a drug product could no longer be considered essential. The ANPRM resulted in a large amount of valuable public debate and input. The FDA is now working to incorporate the knowledge gained from these public comments as it continues the rule-making process.

Chlorofluorocarbons↗
PubMed1999

Stabilization of the relaxosome and stimulation of conjugal transfer are genetically distinct functions of the R1162 protein MobB.

MobB is a small protein encoded by the broad-host-range plasmid R1162 and required for efficient mobilization of its DNA during conjugation. The protein was shown previously to stabilize the relaxosome, the complex of plasmid DNA and mobilization proteins at the origin of transfer (oriT). We have generated in-frame mobB deletions that specifically inactivate the stabilizing effect of MobB while still allowing a high rate of transfer. Thus, MobB has two genetically distinct functions in transfer. The effect of another deletion, extending into mobA, indicates that both functions require a specific region of MobA protein that is distinct from the nicking-ligating domain. The mobB mutations that specifically affected stability also resulted in poor growth of cells, due to increased transcription from the promoters adjacent to oriT. The effects of the mutations could be suppressed not only by full-length MobB provided in trans, as expected, but also by additional copies of oriT, cloned in pBR322. In addition, in the presence of MobA both the full-length and truncated forms of MobB stimulated recombination between oriT-containing plasmids. We propose a model in which MobB regulates expression of plasmid genes by altering the stability of the relaxosome, in a manner that involves the coupling of plasmid molecules.

Bacterial Proteins↗
PubMed1997

An audit of the assessment and management of adults admitted to Christchurch Hospital with community acquired pneumonia.

AIMS: To audit the management of adult patients admitted with community acquired pneumonia including the standards of clinical assessment, use of modified British Thoracic Society prognostic criteria and antibiotic therapy. METHODS: A prospective, 16 week, study of consecutive patients admitted to Christchurch Hospital with community acquired pneumonia. RESULTS: Ninety-six patients met the inclusion criteria. The median age was 70 years. A pathogen was identified in 28 (26%) patients. Forty two patients fulfilled the modified British Thoracic Society criteria for severe disease and all 9 deaths occurred in that subgroup. The management guidelines were followed without exception in only 15% of cases. Documentation of the prognostic criteria was often incomplete and therefore only 33% of those patients with severe disease were correctly identified. Seventy one percent of those with severe disease were treated with only one antibiotic and there was significant delay in administering the first dose in 44% of cases. A follow up chest radiograph was performed in 43 (51%) of those discharged. CONCLUSIONS: There was poor compliance with the management guidelines. There was a lack of awareness of the severity criteria leading to inadequate treatment in many cases. Further educational initiatives are indicated.

Adult↗
PubMed1997

Acquisition of resistance genes by the IncQ plasmid R1162 is limited by its high copy number and lack of a partitioning mechanism.

R1162 is a representative member of the broad-host-range IncQ group of multicopy plasmids. Lower-copy-number derivatives of R1162 were constructed in vitro and shown to be unstable, indicating that partitioning of plasmid copies at cell division is due to random distribution and not to an active partitioning mechanism. However, the normal copy number of R1162 reduces cell fitness during growth in broth and favors the emergence of unstable, lower-copy-number variants. As a result, plasmid-borne antibiotic resistance genes active at a low copy number eventually result in plasmid loss during periods of no selection. We argue that the maintenance of R1162 in a population requires a gene that is selected only at high levels. This reduces the potential for acquiring genes from other R factors and could explain the limited variety of antibiotic resistance genes contained by naturally occurring IncQ plasmids.

DNA Replication↗
PubMed1996

Replication of a plasmid lacking the normal site for initiation of one strand.

The origin of replication of the plasmid R1162 contains an initiation site for the synthesis of each DNA strand. When one of these sites (oriL) is deleted, synthesis on the corresponding strand is no longer initiated efficiently in vitro by the R1162-encoded replication proteins, and the plasmid is no longer stably maintained in the cell. However, in vivo the two strands of the plasmid duplex molecule are active at a similar level as templates for DNA synthesis, and newly synthesized copies of each strand are incorporated into daughter molecules at a similar rate. No secondary, strong initiation sites on the delta oriL strand were detected in the region of the origin. The delta oriL plasmid induces the SOS response, and this is important for plasmid maintenance even in a recombination-proficient strain. Our results indicate that an SOS-induced host system can maintain an R1162 derivative lacking one of its initiation sites.

Base Sequence↗
PubMed1996

The primase of broad-host-range plasmid R1162 is active in conjugal transfer.

The broad-host-range plasmid R1162 is conjugally mobilized at high frequency by the IncP-1 plasmid R751 but is poorly mobilized by pOX38, a derivative of the F factor. In both cases, the origin of transfer (oriT) and the Mob proteins of R1162 are required, indicating that these plasmids are mobilized by similar mechanisms. R1162 encodes a primase, essential for vegetative replication of the plasmid, that is made both as a separate protein and as the carboxy-terminal domain of MobA, one of the R1162 mobilization proteins (P. Scholz, V. Haring, B. Wittman-Liebold, K. Ashman, M. Bagdasarian, and E. Scherzinger, Gene 75:271-288, 1989). When R751 is the mobilizing vector, the primase is not required for mobilization of plasmids containing cloned mob-oriT R1162 DNA. However, detectable mobilization of such plasmids by pOX38 requires both the primase and its cognate initiation site, oriented for synthesis of the complement to the transferred strand. The long form of the primase is required for optimal transfer: R1162 replicons lacking this form also are not transferred detectably by pOX38 and are less well mobilized by R751. The distance between oriT and the primase initiation site affects the frequency of mobilization, and this effect is polar in the direction of transfer. Our results indicate that the R1162 primase is active in mobilization of R1162 and suggest that the MobA-linked form is an adaptation increasing its effectiveness during transfer.

Conjugation, Genetic↗
PubMed1996

Acupuncture and postoperative vomiting in day-stay paediatric patients.

The stimulation of the acupuncture point P6 has been used to prevent nausea and vomiting in the adult population. It has, however, been subject to limited comparative evaluation in children. We proposed that stimulation of P6 and the analgesic point Li4 would reduce the incidence of postoperative vomiting. Eighty-four unpremedicated paediatric patients having day-stay surgery (circumcision or herniotomy/orchidopexy) were included in a randomized, double-blind, placebo-controlled study of transcutaneous stimulation of P6 and Li4, or no stimulation. The incidence of vomiting was recorded for 24 hours postoperatively. There was no statistically significant difference in total postoperative vomiting in those patients who were stimulated, compared with the control group (P = 0.909), or between any group for postoperative vomiting in the recovery ward, day-stay ward or at home. For all groups, vomiting was more common within the first four hours and more likely to occur in the day-stay ward.

Acupuncture Points↗
PubMed1995

Localized denaturation of oriT DNA within relaxosomes of the broad-host-range plasmid R1162.

The broad-host-range, multicopy plasmid R1162 is efficiently mobilized during conjugation by the self-transmissible plasmid R751. The relaxosome, a complex of plasmid DNA and R1162-encoded proteins, forms at the origin of transfer (oriT) and is required for mobilization. Transfer is initiated by strand- and site-specific nicking of the DNA within this structure. We show by probing with potassium permanganate that oriT DNA is locally melted within the relaxosome, in the region from the inverted repeat to the site that is nicked. Mutations in this region of oriT, and in genes encoding the protein components of the relaxosome, affect both nicking and melting of the DNA. The nicking protein in the relaxosome is MobA, which also ligates the transferred linear, single strand at the termination of a round of transfer. We propose that there is an underlying similarity in the substrates for these two MobA-dependent, DNA-processing reactions. We also show that MobA has an additional role in transfer, beyond the nicking and resealing of oriT DNA.

Bacterial Proteins↗
PubMed1994

Nitrofurantoin-induced pulmonary hemorrhage in a renal transplant recipient receiving immunosuppressive therapy: case report and review of the literature.

A 33-year-old woman received a cadaveric renal transplant for focal segmental glomerulosclerosis. Nitrofurantoin urinary prophylaxis was started on postoperative day 13 but coughing and mild hemoptysis began 2 days later. Diffuse infiltrates and worsening hemoptysis led to intubation and open lung biopsy. Clinical course, culture results and pathological evaluation excluded infectious etiologies and were consistent with a drug reaction. The case is described, and the literature on the nitrofurantoin pulmonary toxicity syndromes and pathophysiology is reviewed.

Adult↗