Consensus statement on injury definitions and data collection procedures for studies of injuries in rugby union.

Wide variations in the definitions and methodologies used for studies of injuries in rugby union have created inconsistencies in reported data and made interstudy comparisons of results difficult. The International Rugby Board established a Rugby Injury Consensus Group (RICG) to agree on appropriate definitions and methodologies to standardize the recording of injuries and reporting of studies in rugby union. The RICG reviewed the consensus definitions and methodologies previously published for football (soccer) at a meeting in Dublin to assess their suitability for and application to rugby union. Following this meeting, iterative draft statements were prepared and circulated to members of the RICG for comment; a follow-up meeting was arranged in Dublin at which time all definitions and procedures were finalized. At this stage, all authors confirmed their agreement with the consensus statement. The agreed-on document was presented to and approved by the International Rugby Board Council. Agreement was reached on definitions for injury, recurrent injury, nonfatal catastrophic injury, and training and match exposures together with criteria for classifying injuries in terms of severity, location, type, diagnosis, and causation. The definitions and methodology presented in this consensus statement for rugby union are similar to those proposed for football. Adoption of the proposals presented in this consensus statement should ensure that more consistent and comparable results will be obtained from studies of injuries within rugby union.

Defining the roles of individual residues in the single-stranded DNA binding site of PcrA helicase.

Crystal structures and biochemical analyses of PcrA helicase provide evidence for a model for processive DNA unwinding that involves coupling of single-stranded DNA (ssDNA) tracking to a duplex destabilization activity. The DNA tracking model invokes ATP-dependent flipping of bases between several pockets on the enzyme formed by conserved aromatic amino acid residues. We have used site-directed mutagenesis to confirm the requirement of all of these residues for helicase activity. We also demonstrate that the duplex unwinding defects correlate with an inability of certain mutant proteins to translocate effectively on ssDNA. Moreover, the results define an essential triad of residues within the ssDNA binding site that comprise the ATP-driven DNA motor itself.

Making a successful transition to cash balance. Using employee choice and financial education.

As employee work patterns change, the need for flexible plan design has increased. Hybrid plans such as cash balance plans offer a plan design variation that incorporates elements of the traditional defined benefit plan as well as those of defined contribution plans. This article examines plan design trends and discusses both negative and positive reactions to those trends. Finally, the solution of offering choice to plan participants is suggested, and the issues that must be considered are discussed.

Uncoupling DNA translocation and helicase activity in PcrA: direct evidence for an active mechanism.

DNA footprinting and nuclease protection studies of PcrA helicase complexed with a 3'-tailed DNA duplex reveal a contact region that covers a significant region of the substrate both in the presence and absence of a non-hydrolysable analogue of ATP, ADPNP. However, details of the interactions of the enzyme with the duplex region are altered upon binding of nucleotide. By combining this information with that obtained from crystal structures of PcrA complexed with a similar DNA substrate, we have designed mutant proteins that are defective in helicase activity but that leave the ATPase and single-stranded DNA translocation activities intact. These mutants are all located in domains 1B and 2B, which interact with the duplex portion of the DNA substrate. Taken together with the crystal structures, these data support an 'active' mechanism for PcrA that involves two distinct ATP-dependent processes: destabilization of the duplex DNA ahead of the enzyme that is coupled to DNA translocation along the single strand product.

Type 2 cytokine serum levels in healthy sickle cell disease patients.

Sickle cell disease (SCD) is characterized by significant morbidity and early mortality. Children with this hemoglobinopathy exhibit many of the manifestations associated with immunodeficiency disorders. Serum was obtained from 56 healthy SCD subjects and 45 normal healthy controls. Type 2 cytokines interleukin (IL)-4, IL-6, and IL-10 serum levels were measured. Concentrations were determined by reference to a standard curve, and results were expressed in pg/mL. Results revealed significant levels of IL-4 in 6 (13%) of 45 SCD patients compared with 1 (2%) of 45 controls. Increased levels of IL-6 were present in 35 (78%) of 45 SCD patients and 12 (41%) of 29 controls. Elevated levels of IL-10 were detectable in 13 (41%) of 42 SCD patients and 1 (4%) of 25 controls. High circulating levels of type 2 cytokines may suppress both humoral and cell-mediated immune functions in SCD, with resultant increased morbidity.

Development of a user-defined surgical database using a personal computer network.

Advances in personal computer technology have made powerful methods for the collection and analysis of patient information available to clinical users. This report details the development of a multi-user database distributed across a network of personal computers that facilitates operative scheduling, and collection and analysis of operative data. Clinicians from each surgical service in our medical center developed customized data entry programs that contribute information centrally through a telephone-line network to prepare the daily operative schedule. Subsequently, information from the operating rooms is added to the preoperative database to form an operative log, which is distributed to client services for further analysis and modification. This system has improved the efficiency and accuracy of operative scheduling and information management and shifted the burden of data collection away from the physician. Widespread availability of these data has contributed to the development of an effective quality improvement program and facilitated effective management of personnel and resources.

Secondary Emergency Visits: Patients seeking care for problems recently managed elsewhere.

This study surveyed patients seeking emergency care at three Calgary hospitals during a 7-day period in February 1989. Twenty-one percent had seen another physician for the same medical problem within 72 hours. The study suggests that secondary visits at emergency departments affect health care costs. Further study is needed to investigate the extent and appropriateness of such visits.

Structural relationships between senfolomycins and paulomycins.

Senfolomycins A and B (Antimicrob. Agents Chemother.-1965: 828-831, 1966) are two antibacterial agents with physico-chemical and biological properties similar to those of paulomycin. Recent studies indicate that senfolomycin A (C29H36N2O16S, MW 700) has molecular composition and fast atom bombardment MS fragmentation pattern identical to those of paulomycin E. Extensive NMR work indicates that the two antibiotics, which have been separated by HPLC and TLC, differ only in the stereochemistry of the OCH3 group present in their respective sugar moieties. Indirect evident suggests that senfolomycin B is dihydrosenfolomycin A (C29H38N2O16S, MW 702) and in this respect it is related to paulomycin F. The proposed structures for senfolomycins A and B are discussed.

Chemical modification of steffimycin B.

Fifteen 3-substituted analogues of steffimycin B (1) have been synthesized and their activity against P388 murine leukemia has been determined. Three of these were substantially more active than the parent compound.

Paulomycin-related antibiotics: paldimycins and antibiotics 273a2. Isolation and characterization.

The isolation of paulomycins A and B from fermentations of Streptomyces paulus has been reported earlier [J. Antibiotics 35: 285-294, 1982]. Further work on the antibiotics produced by S. paulus revealed the production of two paulomycin-related compounds, antibiotics 273a1 and 273a2 which were isolated by procedures involving extractions and chromatography over buffered silica gel. Antibiotic 273a1 which has been named paldimycin, was found to be a mixture of two materials, paldimycins A and B (antibiotics 273a1 alpha, and 273a1 beta). Similarly, antibiotic 273a2 was found to consist of antibiotic 273a2 alpha and antibiotic 273a2 beta. Paldimycin and antibiotic 273a2, which are produced by addition of two or one molecules of N-acetyl-L-cysteine, respectively, to paulomycins A and B, are active vs. Gram-positive bacteria.

Enzymatic phosphorylation of macrolide antibiotics.

Five macrolide antibiotics (erythromycin A, 1; oleandomycin, 3a; tylosin, 4a; spiramycins, 5a; leucomycin A3, 6a) have been phosphorylated enzymatically using cell-free extracts derived from Streptomyces coelicolor UC 5240. The necessary cofactors and the rates of the conversion have been determined.

Structure--activity relationships of nogalamycin analogues.

Nogalamycin (1) has been modified by changes at C-10 and C-7 and in the dimethylamino group to prepare an extensive series of analogues. The chemistry involved in the modifications and structure--activity relationships among these nogalamycin analogues are discussed, as well as comparisons with previously reported compounds 1, 7-con-O-methylnogarol (2), and disnogamycin (11).

Primary amoebic meningoencephalitis.

The third case in the UK of primary amoebic meningoencephalitis is reported; it affected an 11-year-old girl. Six days before admission the girl had swum in a pool fed by hot spring water in which the causative agent Naegleria fowleri was found. Early treatment with amphotericin B would seem to offer the only hope of recovery in this almost uniformly fatal infection.

Microbial conversion of steffimycin and steffimycin B to 10-dihydrosteffimycin and 10-dihydrosteffimycin B.

It has been shown that steffimycin (1) and steffmycin B (2) are reduced at the C-10 carbonyl by Actinoplanes utahensis, UC-5885 and Chaetomium sp., UC-4634, respectively. Using cell-free extracts of the latter organism, the optimum conversion time, pH, and enzyme concentration have been determined for the conversion of 2 to 4. The biochemical conversion of 2 has been found to be TPNH linked.

Improved antitumor activity by modification of nogalamycin.

Nogalamycin, an antitumor antibiotic, has been converted to a series of analogs by removal of the carbomethoxy group at C-10 and replacement of the neutral sugar at C-7 by other groups. Removal of the carbomethoxy group to give disnogamycin (6) followed by acidic alcoholysis gave pairs of isomeric 7-alkoxy compounds differing in configuration at C-7. Treatment of 6 with trifluoroacetic acid followed by nucleophiles gave a series of analogs having substituents at C-7 with a configuration at C-7 opposite to that of nogalamycin. Among the analogs prepared, 7-con-O-methylnogarol (7) is a highly active antitumor agent.

Mammalian and microbial cell-free conversion of anthracycline antibiotics and analogs.

Cell-free preparations of Streptomyces nogalater and rat liver catalyze reduced pyridine nucleotide dependent conversion of nogalamycin to 7-deoxynogalarol and nogalose (Scheme 1). The mammalian process requires TPNH and has a specific activity of 85 nmoles of 7-deoxynogalarol formed per hour per mg of protein while the bacterial process prefers DPNH and has a specific activity of 5. The oxygen-sensitive conversions have pH optima of 7.5 (rat) and 9 (S. nogalater). Other anthracycline substrates converted to their 7-deoxyaglycones by both systems include nogamycin, 7(R)-O-methylnogarol, 7(R)-O-methylnogalarol, doxorubicin (Adriamycin), steffimycin, and steffimycin B.