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Biomedical subjects

D R Martin

Publications and source records attributed to D R Martin.

At least 55 records · Page 3Linked to original sources

Pneumococci causing invasive disease in New Zealand, 1987-94: serogroup and serotype coverage and antibiotic resistances.

AIMS: Development of polysaccharide-conjugated pneumococcal vaccines, prompted by the ineffectiveness of the current 23-valent vaccine for young children, requires an understanding of the pneumococci causing invasive disease worldwide. We have reviewed the capsular serogroups and serotypes, and the antibiotic resistances of pneumococci identified from invasive disease in New Zealand, for the period 1987-94. METHODS: Pneumococci referred from invasive disease were serogrouped and serotyped using the Neufeld test and allocated a capsular type according to the Danish system of nomenclature. Antibiotic susceptibility testing was performed by an agar dilution method following National Committee for Clinical Laboratory Standards (NCCLS) guidelines. RESULTS: A total of 1506 pneumococci were examined of which, 584 (39.8%) were sourced from children less than 15 years and 573 (39%) were from adults 60 years or greater. The majority (88.3%) were from blood cultures. In descending order of frequency serogroups or serotypes 14, 19, 6, 9, 23, 7, 4 and 1 were common to all age-groups but serogroups 6 and 18 were significantly (p < 0.001) associated with children under 15 years and serotype 3 with adult patients. Penicillin resistance was demonstrated by 22 (1.4%) isolates, five of which showed high level resistance (MIC > or = 2 mg/L) and multidrug resistance. Fourteen percent of all isolates were resistant to at least one antibiotic and serogroups 23, 6, 18, 19 and serotype 14 accounted for 82.6% of these resistant isolates. CONCLUSIONS: The serogroups and serotypes found most frequently associated with pneumococcal disease, and antibiotic resistance, were consistent with those described overseas. Continuing surveillance of antibiotic resistances and serotypes of pneumococci causing invasive disease is recommended.

Adolescent↗

Insulin-like growth factor-I attenuates delayed graft function in a canine renal autotransplantation model.

BACKGROUND: Insulin-like growth factor-I (IGF-I) has been shown to accelerate recovery in animal models of ischemic or toxic acute renal injury. Ischemic renal injury is frequently encountered after cadaveric transplantation manifested as delayed graft function. This study was performed to determine whether perfusion of kidneys with preservation solution supplemented with IGF-I would improve the course of renal injury in a canine autotransplantation model of delayed graft function. METHODS: Dogs underwent unilateral nephrectomy with kidneys perfused and stored in Euro-Collins solution supplemented with vehicle (n = 11) or IGF-I (n = 8). After 24 hours of kidney preservation, a contralateral nephrectomy was performed and the stored kidney was autotransplanted. Renal function was examined for 5 days after the transplantation, and an inulin clearance was obtained at the time of death. RESULTS: Compared with dogs that received kidneys preserved in the vehicle, dogs receiving the IGF-I preserved kidneys had significantly lower daily serum creatinine and blood urea nitrogen levels during the course of 5 days after transplantation. Inulin clearance at death was nearly double in the IGF-I treated animals compared with the vehicle-treated controls (1.37 +/- 0.16 ml/min/kg versus 0.77 +/- 0.13 ml/min/kg; p < 0.05). CONCLUSIONS: Perfusion and storage of kidneys with preservation solution supplemented with IGF-I can attenuate the course of delayed graft function in a canine renal autotransplantation model. IGF-I may have potential for use in cadaveric human renal transplantation.

Animals↗

Emergency medicine journal clubs.

OBJECTIVE: To ascertain the status of journal club within emergency medicine (EM) residency programs and to describe 3 currently used formats. METHODS: The directors of U.S. Residency Review Committee for Emergency Medicine (RRC-EM)-approved residency programs were surveyed to determine the features of their programs' journal clubs. Responses to 3 questions assessing the degree of satisfaction (5-item scales from very good to very poor) with the "current format," "resident participation," and "faculty participation" from the survey were grouped according to the program director's impressions of resident and faculty "enjoyment" (2 3-item scales) and whether the journal club is a "success" (3-item scale) to develop an overall satisfaction index. Three journal club formats currently in use at EM residencies are described in detail. RESULTS: Of the 101 directors surveyed, 91 (90%) responded. The respondents' overall satisfaction index was highest when the journal club was held in the evening (p < 0.008) or at a faculty member's home (p < 0.0004). The format of the journal club (e.g., by topic, with a statistical focus, with a research design, focus, or as a clinical practice update) was not associated with the overall satisfaction index. CONCLUSION: Journal clubs associated with EM residencies vary in format and perceived success. The 3 representative journal clubs illustrate different format options.

Cross-Sectional Studies↗

Increased transforming growth factor-beta 1 expression in regenerating rat renal tubules following ischemic injury.

To gain insight into the role that transforming growth factor-beta 1 (TGF-beta 1) plays in the regeneration of kidneys following acute renal failure, we characterized the expression of TGF-beta 1 mRNA and the expression of active and latent TGF-beta peptide at various times during recovery from acute ischemic injury in rat. Levels of whole kidney TGF-beta 1 mRNA were elevated significantly at 12 h postinjury (1.5-fold vs. sham-operated controls), and by 24 h postinjury were elevated by 3.6-fold. Levels remained elevated for 14 days following ischemia, but were no longer elevated at 28 days postinjury. In situ hybridization demonstrated that the elevated expression of TGF-beta 1 was localized predominantly to cells in the regenerating tubules in the outer medulla. When examined at 14 days postischemia, levels of TGF-beta 1 mRNA were elevated in the outer medulla only in tubules that appeared incompletely regenerated. Immunohistochemical staining localized active TGF-beta to the lumen of proximal tubules in control animals and in desquamated and regenerating tubular epithelial cells following ischemia. TGF-beta 1 latency-associated peptide was present intracellularly in proximal tubules of sham-operated rats and reduced following ischemia. We hypothesize that endogenous renal TGF-beta serves to promote tissue regeneration following acute injury via an autocrine or paracrine mechanism.

Animals↗

Insulin-like growth factor I-enhanced renal expression of osteopontin after acute ischemic injury in rats.

Pretreatment of rats with insulin-like growth factor I (IGF-I) ameliorates the course of acute ischemic renal injury. Differential display PCR was used to identify genes that are expressed in kidney after induction of acute ischemic renal injury in rats pretreated with vehicle or IGF-I. One amplification product that showed enhanced expression in kidneys of rats rendered ischemic compared to kidneys of sham-operated rats was identified as osteopontin. Sequence analysis of full-length complementary DNAs revealed a single species. Renal tissue was obtained for study 12 h and 1, 2, 3, 5, 7, 14, and 28 days postinjury. Levels of whole kidney osteopontin messenger RNA (mRNA) in rats rendered ischemic 1 day previously were elevated approximately 18-fold compared to levels measured in sham-operated controls, as determined by Northern analysis. No differences were noted 12 h postinjury. Levels of osteopontin mRNA remained elevated for 14 days after ischemia, but were no longer elevated at 28 days. IGF-I pretreatment resulted in enhanced levels of osteopontin mRNA 12 h, 1 day, and 5 days postinjury. In situ hybridization demonstrated that the elevated expression of osteopontin 1 day postinjury was localized predominantly to cells in the distal tubule and medullary thick ascending limb of Henle's loop. Immunostaining showed an identical localization for elevated protein expression. Five days postinjury, osteopontin peptide and mRNA were clearly detected in regenerating proximal tubules in addition to distal tubule and medullary thick ascending limb. We propose that endogenous osteopontin serves to promote tissue regeneration and tissue remodeling within 1 day after acute ischemic injury of kidney. IGF-I enhanced expression of osteopontin at an earlier time postischemia may ameliorate the course of injury.

Animals↗

A single emm gene-specific oligonucleotide probe does not recognise all members of the Streptococcus pyogenes M type 1.

Serological typing of the streptococcal M protein has recently been challenged by a number of unique molecular methodologies based on oligonucleotide recognition of allelic variations within the M protein (emm) gene. In these methods, stringent hybridization of an oligonucleotide probe to a polymerase chain reaction amplified emm gene is used as confirmation of specific M type identity. A sample of 17 isolates from 7 previously defined distinct genotypes were tested using a single M1 oligonucleotide probe. Isolates from only three of the genotypes hybridized with the probe. The results demonstrate that a single emm-specific oligonucleotide probe can not identify all members of M type 1, as defined by conventional serotyping using polyclonal antisera.

Amino Acid Sequence↗

Genetic diversity and relationships among Streptococcus pyogenes strains expressing serotype M1 protein: recent intercontinental spread of a subclone causing episodes of invasive disease.

Chromosomal diversity and relationships among 126 Streptococcus pyogenes strains expressing M1 protein from 13 countries on five continents were analyzed by multilocus enzyme electrophoresis and restriction fragment profiling by pulsed-field gel electrophoresis. All isolates were studied for the presence of the gene encoding streptococcal pyrogenic exotoxin A by PCR. Strain subsets were also examined by automated DNA sequencing for allelic polymorphism in genes encoding M protein (emm), streptococcal pyrogenic exotoxin A (speA), streptokinase (ska), pyrogenic exotoxin B (interleukin-1 beta convertase) (speB), and C5a peptidase (scp). Seven distinct emm1 alleles that encode M proteins differing at one or more amino acids in the N-terminal variable region were identified. Although substantial levels of genetic diversity exist among M1-expressing organisms, most invasive disease episodes are caused by two subclones marked by distinctive multilocus enzyme electrophoretic profiles and pulsed-field gel electrophoresis restriction fragment length polymorphism (RFLP) types. One of these subclones (ET 1/RFLP pattern 1a) has the speA gene and was recovered worldwide. Identity of speA, emm1, speB, and ska alleles in virtually all isolates of ET 1/RFLP type 1a means that these organisms share a common ancestor and that global dispersion of this M1-expressing subclone has occurred very recently. The occurrence of the same emm and ska alleles in strains that are well differentiated in overall chromosomal character demonstrates that horizontal transfer and recombination play a fundamental role in diversifying natural populations of S. pyogenes.

Amino Acid Sequence↗

Antigenic diversity within a family of M proteins from group A streptococci: evidence for the role of frameshift and compensatory mutations.

The genes (emm) encoding M proteins, from isolates of group-A streptococci (GAS) serotyped as M52, M53, M80 and M nontypeable (MNT; serologically related to M53 and M80), were examined. Characterization of emm from these GAS revealed some discrepancies with serotyping, illustrating the difficulty in serotype determination when cross-reactions occur. DNA sequences corresponding to the N-terminal region of M proteins from the isolates showed considerable similarity both in the hypervariable region and the repeat regions. We propose that these serotypes form a family of closely related M types. Frameshift mutations in the hypervariable region followed by a corrective (compensatory) frameshift were observed. This may be an effective mechanism for generating antigenic diversity in the M protein.

Amino Acid Sequence↗

Protective immunity to the group A Streptococcus may be only strain specific.

M protein enables Group A streptococci to resist phagocytosis. Protective immunity is considered to be mediated by opsonic antibodies directed against this M protein. In recent studies we have shown that genetically distinct populations exist within an M-type. The question asked in this study was whether human and rabbit type specific M1 antibody was opsonic for all strains of M-type 1, irrespective of their restriction fragment length polymorphism type. When locating a blood donor from among our staff for use in the indirect bactericidal test, selective variation in opsonic ability was demonstrated by one person. Subsequent testing of 44 randomly selected human sera revealed that 11 (25%) had opsonic antibody. Of these 11, 6 opsonised all seven strains and 5 demonstrated selective opsonisation. We conclude that opsonic antibody is not necessarily type specific but may be strain specific.

Adult↗

Outcome of insulin-treated diabetics receiving epinephrine during cardiac arrest.

The purpose of this study was to determine the effects of epinephrine in insulin-treated diabetics (DM) compared with nondiabetic (ND) controls during cardiopulmonary resuscitation (CPR). A retrospective analysis from a multicenter study of out-of-hospital cardiac arrest included 62 DM and 1,151 ND. Outcome parameters included return of spontaneous circulation (ROSC), blood pressure (BP), emergency department admissions (EDA), hospital admissions (HA), and hospital discharge (DC). In DM treated with standard-dose epinephrine (SDE), there were trends toward improved ROSC, BP, EDA, and HA compared with ND. DC was not different. With high-dose epinephrine (HDE) these outcomes were not different. Comparison of the outcomes of DM given SDE versus those given HDE were not different. However, none of the DM given HDE (n = 24) were discharged from the hospital. These results suggest that DM may have improved resuscitation rates with SDE and may be adversely affected with HDE. Larger prospective studies are needed to confirm these findings.

Aged↗

Equivalence classes for the double-digest problem with coincident cut sites.

When restriction sites are modeled by a random process, the number of solutions to the double-digest problem (DDP) increases exponentially with the length of the DNA molecule. Cassette transformations define equivalence classes on the set of solutions to the DDP for the case of no coincident cut sites. Pevzner (1994) completely characterized the solutions to the DDP in the case of no coincident cut sites by associating solutions to DDP with alternating Eulerian paths in an edge-bicolored graph. In this paper we extend the definition of cassettes and their transformations to the general case allowing coincident cut sites. Solutions to the DDP in the general case are again characterized by associating solutions to the DDP with alternating Eulerian cycles in an extended graph.

Mathematics↗

Acute rheumatic fever in Auckland, New Zealand: spectrum of associated group A streptococci different from expected.

Annual specific rates for acute rheumatic fever (ARF) in Auckland children less than 15 years were 22/100,000 for the years 1980 to 1984. From 1984 to 1992 the rates remained relatively constant with an average of 45 (range, 30 to 70) children annually admitted with ARF to the Auckland Children's Hospital. This study examined retrospectively Group A streptococci identified from hospitalized pediatric patients during these 9 years. The total of 2410 isolates included 32 isolates from well-documented cases of ARF and an additional 6 from siblings of cases. Results of M typing indicated that streptococci associated with ARF are generally different from those described overseas and involved types which cause more skin than throat infections in the community.

Adolescent↗

Determination of the role for CD21 during Epstein-Barr virus infection of B-lymphoblastoid cells.

Epstein-Barr virus (EBV), a herpesvirus with oncogenic potential, is camouflaged with glycoprotein 350/220, which mimics the human ligand C3dg and thereby binds to and exploits complement receptor type 2 (CR2; CD21), the EBV receptor. It has not been possible to determine the role of CR2 during postbinding events of viral infection because all B lymphocytes express endogenous CR2, precluding an informative study of receptor mutants. We have overcome this obstacle through creation of a novel experimental system based on molecular dissection of the ligand-binding domains of human CR2 and murine CR2. Our results demonstrate first, that two discontinuous amino acid substitutions within the ligand-binding domain of murine CR2 render it capable of mediating EBV infection of human B-lymphoblastoid cells, and second, that the specific role of CR2 during EBV infection is to capture virions at the cell surface, after which cofactors not associated with CR2 mediate postbinding events. These are the first studies to be described in which a cell that is normally susceptible to viral infection can be manipulated so as to direct entry of virions via recombinant or endogenous receptors.

Amino Acid Sequence↗

Hepatocyte growth factor accelerates recovery from acute ischemic renal injury in rats.

Effects of hepatocyte growth factor (HGF) administration were examined in a model of acute ischemic renal injury induced by bilateral renal artery occlusion in rats. Compared with rats administered vehicle, rats administered 20 micrograms HGF subcutaneously 30 min postischemia had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion, enhanced insulin clearances measured on day 2 postocclusion, reduced mortality, and much less injury evident by examination of kidney histologies 7 days postinjury. The tubular regeneration that occurred postischemic injury was reflected by increased incorporation of 5-bromo-2'-deoxyuridine (BrdU) in cortical tubular epithelium compared with incorporation in kidneys from noninjured rats. HGF enhanced BrdU incorporation compared with vehicle, indicating enhanced mitogenesis. The weight loss that occurs postischemic injury was not ameliorated by the dose of HGF we employed. We conclude that administration of HGF postischemic injury to rats stimulates the recovery of normal kidney function and the regeneration of proximal tubular epithelium.

Animals↗

Rat models for clinical use of insulin-like growth factor I in acute renal failure.

Insulin-like growth factor I (IGF-I) improves kidney function and histopathology, when given within a short time (0.5 or 5 h) after an ischemic renal insult in rats. To examine the effects of IGF-I at times that would be more applicable if it were to be used as a therapeutic agent for acute renal failure in humans, we administered IGF-I to rats 24 h after ischemic injury or prior to the induction of injury (pretreatment). In rats that received IGF-I 24 h postischemia, serum creatinine and blood urea nitrogen (BUN) values were significantly lower during the subsequent 6 days than in vehicle-treated rats, and incorporation of 5-bromo-2'-deoxyuridine into tubular cells of the regenerating cortex, measured 48 h postischemia, was enhanced. When examined 7 days postinjury, kidneys from rats that received IGF-I 24 h postischemia were improved in histopathological appearance compared with kidneys from vehicle-treated animals. Whereas creatinine and BUN values were elevated above baseline in both vehicle and IGF-I-pretreated groups, recovery of normal renal function was accelerated by pretreatment with IGF-I. In addition, although we could detect no differences in histopathology at 24 h postinjury, IGF-I pretreatment resulted in more normal renal histology at 7 days postischemic injury and reduced weight loss after injury. Our data show that IGF-I hastens recovery and accelerates regeneration or repair of damaged epithelia following acute renal failure in rats when administered either 24 h postinjury or prior to induction of acute renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗