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Biomedical subjects

D R Martin

Publications and source records attributed to D R Martin.

At least 73 records · Page 4Linked to original sources

An analysis of gainsharing in a health care setting.

This study examines the effect a gainsharing plan has had on the productivity of two hospitals. Previously, the hospitals had been using a set of ratios to determine changes in productivity. However, we use a nonparametric productivity measure because it simultaneously considers the relationship between the hospitals' inputs and outputs. Our results show that the gainsharing program had no significant effect on productivity in one hospital and a negative effect on productivity in the other hospital. These results raise questions as to whether gainsharing will help health care providers improve productivity.

Data Interpretation, Statistical↗

Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes.

The CD21/CD19/TAPA-1 complex of B lymphocytes amplifies signal transduction through membrane immunoglobulin (mIg), recruits phosphatidylinositol 3-kinase (PI3-kinase), and induces homotypic cellular aggregation. The complex is unique among known membrane protein complexes of the immune system because its components represent different protein families, and can be expressed individually. By constructing chimeric molecules replacing the extracellular, transmembrane, and cytoplasmic regions of CD19 and CD21 with those of HLA-A2 and CD4, we have determined that CD19 and TAPA-1 interact through their extracellular domains, CD19 and CD21 through their extracellular and transmembrane domains, and, in a separate complex, CD21 and CD35 through their extracellular domains. A chimeric form of CD19 that does not interact with CD21 or TAPA-1 was expressed in Daudi B lymphoblastoid cells and was shown to replicate two functions of wild-type CD19 contained within the complex: synergistic interaction with mIgM to increase intracellular free calcium and tyrosine phosphorylation and association with the p85 subunit of PI3-kinase after ligation of mIgM. The chimeric CD19 lacked the capacity of the wild-type CD19 to induce homotypic cellular aggregation, a function of the complex that can be ascribed to the TAPA-1 component. The CD21/CD19/TAPA-1 complex brings together independently functioning subunits to enable the B cell to respond to low concentrations of antigen.

Antigens, CD↗

Initial countershock in the treatment of asystole.

BACKGROUND: Routine provision of defibrillatory countershock (CS) in the initial management of asystolic cardiac arrest has been advocated because certain cases of ventricular fibrillation (VF) may present as asystole (AS). OBJECTIVE: To determine the value of initial CS versus endotracheal intubation and pharmacologic therapy alone in the treatment of asystolic cardiac arrest. DESIGN/PARTICIPANTS: A retrospective analysis of data collected prospectively during a multicenter study of out-of-hospital cardiac arrest. The study subjects were all patients whose initial cardiac arrest rhythm was AS and were treated with standard advanced cardiac life support (ACLS). SETTING: Six urban emergency medical services (EMS) systems. INTERVENTION: Patients in AS were treated initially with CS followed by ACLS therapy (CS Group), and were compared to those patients receiving endotracheal intubation and pharmacologic therapy alone (No CS Group). OUTCOME MEASURES: Those receiving initial CS were compared to those not receiving CS using both Chi-square and logistic regression analysis. Outcome parameters included: rates of return of spontaneous circulation (ROSC), emergency department admission, hospital admission and hospital discharge. RESULTS: Of the 194 patients presenting with AS, 77 received CS as their initial therapy. Of these, 13 (16.9%) had ROSC compared to 27 of the 117 (23.1%) from the No CS Group (P = 0.30). Emergency department and hospital admission rates were not significantly different; 13.0% versus 18.0% (P = 0.36), and 13.0% versus 11.1% (P = 0.69) for CS versus No CS, respectively. None of the patients in the CS Group were discharged alive versus two (1.7%) from No CS (P = 0.52). Of 42 patients with bystander-witnessed cardiac arrests, 13.3% in the CS Group had ROSC compared to 40.7% in the No CS Group (P = 0.07). Emergency department admission rates were 6.7% for the CS Group and 33.3% for the No CS Group (P = 0.07); while hospital admission rates were 6.7% and 22.2%, respectively (P = 0.39). When these comparisons were adjusted for bystander-initiated CPR, CPR interval, and paramedic response interval, the P-values became 0.10, 0.05 and 0.17, respectively. CONCLUSIONS: Although, statistically, the results for both groups were not distinguishable, outcomes for asystolic patients had a tendency to be better when the initial therapy did not involve CS. Larger study populations are recommended to confirm these preliminary observations.

Aged↗

Effect of first-responder automated defibrillation on time to therapeutic interventions during out-of-hospital cardiac arrest. The Multicenter High Dose Epinephrine Study Group.

STUDY OBJECTIVES: The effect of automated defibrillation provided by basic emergency medical technician (EMT) first-responder units on the time intervals to other critical interventions in the management of out-of-hospital cardiac arrests is unknown. The purpose of this study was to define and compare elapsed time intervals to basic CPR, paramedic arrival, initial countershock, endotracheal intubation, IV access, and initial adrenergic drug therapy in first-responder automated defibrillation/paramedic versus basic EMT/paramedic emergency medical services systems. DESIGN: Prospectively collected data from a 15-month multicenter study of out-of-hospital, nontraumatic cardiac arrests were analyzed. The mean time intervals to critical therapeutic interventions between first-responder automated defibrillation/paramedic and basic EMT/paramedic groups were compared using the Student's t-test with Bonferroni correction. SETTING: Three first-responder automated defibrillation/paramedic and three basic EMT/paramedic urban emergency medical services systems. PARTICIPANTS: 1,578 patients with out-of-hospital cardiac arrest. INTERVENTIONS: The first-responder automated defibrillation/paramedic group received initial ECG analysis and/or automated countershock by first-responder/EMTs; the basic EMT/paramedic group received initial ECG analysis and/or manual countershock by paramedics. RESULTS: Elapsed time intervals in minutes +/- SD for first-responder automated defibrillation/paramedic versus basic EMT/paramedic groups, respectively, were as follows: Collapse to CPR, 4.3 +/- 3.9 versus 5.4 +/- 5.2 (P = .017); collapse to countershock, 10.7 +/- 5.9 versus 13.0 +/- 6.0 (P = .017); collapse to paramedic arrival, 13.0 +/- 5.4 versus 10.3 +/- 6.1 (P = .0001); paramedic arrival to IV access, 5.1 +/- 3.9 versus 7.0 +/- 5.0 (P = .0001); paramedic arrival to endotracheal intubation, 4.8 +/- 4.0 versus 6.8 +/- 5.8 (P = .0001); paramedic arrival to initial adrenergic drug therapy, 7.4 +/- 4.5 versus 8.2 +/- 4.7 (P = .015); collapse to IV access, 17.7 +/- 6.1 versus 16.6 +/- 7.4 (P = .10); collapse to endotracheal intubation, 17.3 +/- 6.4 versus 16.6 +/- 7.8 (P = .32); collapse to initial adrenergic drug therapy, 20.4 +/- 6.7 versus 18.1 +/- 7.2 (P = .010). The time intervals from paramedic arrival to IV access, endotracheal intubation, and initial adrenergic drug therapy remained shorter in the first-responder automated defibrillation/paramedic systems despite stratification by presenting cardiac rhythm. CONCLUSION: First-responder automated defibrillation/paramedic systems provide not only shorter times to initial countershock, as compared with basic EMT/paramedic systems, but by having delegated initial countershock to first-responders, they also allow for significantly shorter times from paramedic arrival to IV access, endotracheal intubation, and initial adrenergic drug therapy interventions.

Electric Countershock↗

Physiologic measurement of the ventricular fibrillation ECG signal: estimating the duration of ventricular fibrillation.

Estimating the duration of ventricular fibrillation may help determine the best initial therapy and provide estimates of the most appropriate dose of epinephrine to administer during cardiac arrest and resuscitation. In addition, estimating this time can provide a more sound methodologic approach to stratifying patients in the analysis of cardiac arrest studies. In an initial series of studies in swine, we attempted to determine whether changes in the frequency or amplitude (power) of the ventricular fibrillation ECG signal during cardiac arrest could be used to estimate this time. These studies characterized the dynamics of both the total power and the frequency distribution of the power in the ECG over time during ventricular fibrillation in swine. Our purpose was to determine whether sufficient information existed in either parameter to estimate the duration of ventricular fibrillation. The median frequency of the power spectrum was used to track power distribution. Both parameters followed a dynamic and repeatable pattern. A mathematical model of median frequency was developed and used with data obtained from additional swine to estimate the duration of ventricular fibrillation. The model estimated the duration of ventricular fibrillation to within +/- 1.3 minutes of the actual duration from one to ten minutes after the onset of ventricular fibrillation. We recently characterized the time course of the median frequency during ventricular fibrillation in human beings. The median frequency was extracted from each four-second segment of the ventricular fibrillation ECG recordings and plotted versus time from the onset of cardiac arrest. The median frequency in human beings followed a repeatable time course during ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Arthroscopic treatment of triplane fractures of the ankle.

Failure to obtain and/or maintain adequate closed reduction of triplane ankle fractures is an indication for surgical reduction and internal fixation. Operative treatment requires anteromedial and/or anterolateral incisions for adequate visualization of fracture fragments. The added surgical trauma associated with operative treatment of these fractures can be minimized without loss of efficacy using minimally invasive techniques under arthroscopic control. Arthroscopic reduction and internal fixation (ARIF) of two-part triplane fractures provides the advantages of complete evacuation of fracture hemarthrosis, accurate and certain reduction of the articular surface, and secure fixation of fracture fragments. Two patients treated with ARIF demonstrated rapid and complete fracture healing without complication. Follow-up at 6-12 months showed no leg length discrepancy, angulation, swelling, persistent symptoms, or limitation of function. ARIF of triplane ankle fractures reduces surgical trauma, provides a method for accurate delineation of fracture fragment orientation, and ensures accurate reduction and joint congruity under direct visualization.

Adolescent↗

Molecular epidemiology of group A streptococcus M type 1 infections.

Data were reviewed about 665 streptococcus M type 1 isolates received by the Streptococcus Reference Laboratory of the New Zealand Communicable Disease Centre between 1980 and 1991. Isolates were voluntarily submitted by diagnostic laboratories throughout New Zealand as part of a surveillance system for streptococcal infections. Over the study period, distribution of M type 1 was uneven, and two waves of infections occurred, each with a distinctive disease pattern. Molecular typing using restriction fragment length polymorphism (RFLP) analysis was used to examine phylogenetic relationships among isolates randomly selected from different geographic locations for each of the years studied. Although six distinct RFLP patterns occurred, most isolates (74%), including those of both waves, belonged to type 1a. This type and one other were also identified among additional isolates originating from Australia and the United States. Typed isolates from cases of severe invasive disease occurring both in the United States and in New Zealand in the late 1980s belonged to RFLP type 1a.

Humans↗

How useful is the UMLS metathesaurus in developing a controlled vocabulary for an automated problem list?

We are developing a set of problem list phrases to be used in the automated problem list of a prototype clinical computing system. Because of the large number of terms in the Unified Medical Language System (UMLS) and the links between them, we are experimenting with the use of the UMLS as the foundation for our problem list phrase set. We have found the UMLS to be very useful for this project, but that it lacks many phases clinicians wish to include in the problem list. Internal linkages between phrases provided in the UMLS are not well suited to our needs. We plan to continue our use of the UMLS but to add problem list phrases and linkages between phrases to support browsing and decision support applications.

Ambulatory Care Information Systems↗

Insulin-like growth factor I accelerates recovery from ischemic acute tubular necrosis in the rat.

The effects of administering insulin-like growth factor I (IGF-I) were examined in a model of ischemic acute tubular necrosis in rats. Injury was induced by 75 min of bilateral renal artery occlusion. Compared to rats administered vehicle, rats administered IGF-I (100 micrograms/day via continuous subcutaneous infusion) had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion. Glomerular filtration rate as determined by inulin clearance was examined on day 2 postocclusion and was significantly increased in IGF-I-treated animals (0.16 +/- 0.02 ml per min per 100 g of body weight) compared to vehicle-treated controls (0.08 +/- 0.02 ml per min per 100 g of body weight). The weight loss that occurred during the course of acute tubular necrosis was ameliorated by IGF-I. Mortality was reduced from 36.7% in vehicle-treated rats to 7.1% in rats administered IGF-I. Histologically, there was much less renal injury evident at day 7 postocclusion in the IGF-I-treated rats compared to vehicle-treated controls. In contrast, growth hormone (200 micrograms administered subcutaneously for 4 days) did not affect recovery of renal function or reduce mortality postreperfusion. This report demonstrates a beneficial effect of IGF-I administration in the setting of acute tubular necrosis. Several properties of IGF-I render it a pharmacological agent with excellent potential for treatment of this condition in humans.

Animals↗

A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group.

BACKGROUND: Experimental and uncontrolled clinical evidence suggests that intravenous epinephrine in doses higher than currently recommended may improve outcome after cardiac arrest. We conducted a prospective, multicenter study comparing standard-dose epinephrine with high-dose epinephrine in the management of cardiac arrest outside the hospital. METHODS: Adult patients were enrolled in the study if they remained in ventricular fibrillation, or if they had asystole or electromechanical dissociation, at the time the first drug was to be administered to treat the cardiac arrest. Patients were randomly assigned to receive either 0.02 mg of epinephrine per kilogram of body weight (standard-dose group, 632 patients) or 0.2 mg per kilogram (high-dose group, 648 patients), both given intravenously. RESULTS: In the standard-dose group 190 patients (30 percent) had a return of spontaneous circulation, as compared with 217 patients (33 percent) in the high-dose group; 136 patients (22 percent) in the standard-dose group and 145 patients (22 percent) in the high-dose group survived to be admitted to the hospital. Twenty-six patients (4 percent) in the standard-dose group and 31 (5 percent) in the high-dose group survived to discharge from the hospital. Ninety-two percent of the patients discharged in the standard-dose group and 94 percent in the high-dose group were conscious at the time of hospital discharge. None of the differences in outcome between the groups were statistically significant. CONCLUSIONS: In this study, we were unable to demonstrate any difference in the overall rate of return of spontaneous circulation, survival to hospital admission, survival to hospital discharge, or neurologic outcome between patients treated with a standard dose of epinephrine and those treated with a high dose.

Aged↗

Peripheral deletion of mature CD8+ antigen-specific T cells after in vivo exposure to male antigen.

It has been well established that T cell tolerance to self Ag occurs primarily via clonal deletion of immature thymocytes in the thymus. Evidence also exists that there are additional mechanisms operative on mature T cells for establishing and maintaining tolerance in the periphery. To follow the fate of mature Ag-specific T cells in vivo, we used female transgenic mice, which contain a large population of male H-Y Ag-specific T cells that can be identified by immunostaining with mAb directed against CD8 and the transgenic TCR. H-Y Ag was introduced into these mice by injecting Ag-bearing male lymphocytes using conditions known to induce CTL precursor response reduction. The number of Ag-reactive CD8+ transgenic T cells in the periphery started to decrease after 2 days of in vivo exposure to male Ag. Decline was maximum (up to 80% of total) by 7 days, and stayed at this level for at least 6 wk. CD4+ cells and those CD8+ cells that did not carry the transgenic TCR were not affected. Most or all of the remaining Ag-reactive CD8+ cells in the periphery were fully responsive when stimulated by male Ag in vitro. Maturation of transgenic T cells in the thymus of injected mice remained the same as that of control animals. Our data provide direct evidence that mature Ag-reactive CD8+ cells are susceptible to clonal deletion in the periphery when exposed to the Ag in vivo. These findings suggest the presence of two types of APC in the periphery: stimulatory APC (e.g., macrophages and dendritic cells) required for initiating an active immune response; and functionally deleting APC (or veto cells) capable of deleting mature T lymphocytes that recognize Ag presented on their surface. Functionally deleting APC that present self Ag to peripheral T cells may provide a fail-safe mechanism against autoreactive cells that escaped deletion during differentiation in the thymus.

Animals↗

Haemophilus influenzae in New Zealand: subtyping of isolates from invasive disease using outer membrane protein profiling.

Invasive Haemophilus influenzae type b disease affects one in every 350 New Zealand children by the age of five, leaving some with severe handicap. As part of a national surveillance programme aimed at determining the epidemiology of H influenzae b disease in this country, the diversity of local isolates causing invasive disease was examined using outer membrane protein (OMP) profiling. Of 81 H influenzae b isolates examined, 70 (86%) had identical OMP profiles. Among the other 11 H influenzae b isolates, eight different OMP profiles were observed. Nontype b Haemophilus influenzae isolates (n = 13) showed a greater diversity of OMP patterns.

Bacterial Outer Membrane Proteins↗

Clonal differences within M-types of the group A Streptococcus revealed by pulsed field gel electrophoresis.

Digestion of chromosomal DNA with the rare cutting restriction enzyme SfiI in association with pulsed field gel electrophoresis was used to observe restriction fragment length polymorphisms (RFLP) among isolates of group A Streptococcus. Streptococci examined included isolates belonging to the same M-type (epidemiologically related and unrelated), and isolates from other M-types. RFLP patterns were quite distinct between all serotypes tested. More importantly, isolates from within a serotype could be differentiated by this technique.

DNA, Bacterial↗

Prehospital bicarbonate use in cardiac arrest: a 3-year experience.

The American Heart Association no longer recommends the routine use of sodium bicarbonate in cardiac arrests. Reasons cited include the lack of documented effect on clinical outcome and potential adverse effects of metabolic alkalosis and hypernatremia. We reviewed 36 months of experience with 619 nontrauma adult, prehospital cardiac arrest patients to identify 273 successful resuscitations who had emergency department blood gases and electrolytes performed. Determination of complications associated with prehospital intravenous sodium bicarbonate and its impact on survival in resuscitated patients was undertaken. Fifty-eight patients did not receive sodium bicarbonate (NO HCO3 group) and had short cardiopulmonary resuscitation (CPR) times (7.4 +/- 5.5 minutes). Two hundred fifteen patients did receive sodium bicarbonate (HCO3 group) and had significantly longer CPR times (23.3 +/- 13.5 minutes, P less than or equal to .001). Both groups demonstrated routine early chest compression and hyperventilation as evidenced by no significant difference in paramedic response time or rate of intubations. Initial emergency department blood gas results of both groups were not significantly different. No patients in the NO HCO3 group had hypernatremia (sodium [Na]+ greater than 150), whereas four patients (2%) in the HCO3 group were hypernatremic. Eight patients (14%) in the NO HCO3 group and 37 patients (17%) in the HCO3 group were alkalotic with pH values greater than 7.49 (P = NS). Six patients (10%) of the NO HCO3 group and 24 patients (11%) of the HCO3 group had a metabolic component to the alkalosis as defined by a positive base excess value (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗

Rapid and long-term changes to host cytotoxic T lymphocyte precursors reactive to donor antigens caused by intravenous injection of histoincompatible lymphocytes.

It has been shown previously that a single intravenous injection of mouse F1 LNC into either parent results in a rapid reduction in the ability of the recipient to generate CTL reactive against donor antigens in an in vitro MLR. The underlying mechanism appears to be the inactivation of host CTL precursors that can recognize donor lymphocytes that have entered the recirculating pool. The donor lymphocytes may be acting as functionally deleting APC, or veto cells. Here, we have injected C57BL/6 (B6) mice with (C57BL/6 x DBA/2) F1 (F1) LNC. The CTL response against donor LNC was maximally reduced by 2 days and stayed reduced for at least 6 weeks, but ultimately recovered to normal levels. The response reduction mechanism remained operative during the period when the response was reduced: Fresh FITC-labeled B6 LNC introduced into B6 recipients of an earlier injection of F1 LNC were as effectively deleted of F1-reactive CTLp as the original host B6 LNC population, the fresh FITC-labelled B6 LNC being separated from host B6 LNC by cell sorting before testing. When B6 mice injected with F1 LNC ultimately recovered their response against F1 donor antigens, reinjection of F1 LNC did not induce a new response reduction. Instead of entering the recirculating pool, the injected F1 cells were rapidly removed by a specific immune process.

Animals↗

Identification of sequence types among the M-nontypeable group A streptococci.

Streptococcal diseases, namely, acute glomerulonephritis and acute rheumatic fever, are common features in the aboriginal population of the Northern Territory of Australia. We examined the group A streptococcal M types identified during various surveys conducted since 1987. Streptococci were predominantly isolated from skin infections. A high proportion of the isolates could not be serotyped by conventional means and were designated M nontypeable (MNT). M-specific DNA sequences from the MNT isolates were examined, and sequence types were proposed for the classification of MNTs. This allowed a more precise estimate of the M types present in a population study.

Amino Acid Sequence↗

Determination of the structural basis for selective binding of Epstein-Barr virus to human complement receptor type 2.

Epstein-Barr virus (EBV) is an oncogenic herpesvirus that selectively infects and immortalizes human B lymphocytes. One determinant of this narrow tropism is human CR2, the only viral receptor within the superfamily of proteins that contain short consensus repeats (SCRs). Human CR2 serves as a receptor for both C3dg and the gp350/220 glycoprotein of EBV, and binds the monoclonal antibody (mAb) OKB7, which blocks binding of both ligands to the receptor. In contrast, although murine CR2 is capable of binding human C3dg and this interaction can be blocked with the mAb 7G6, it does not bind OKB7 or EBV. We have determined the structural basis for absolute specificity of EBV for human CR2 through characterization of a panel of 24 human-murine chimeric receptors, all of which bind human C3dg. The results indicate that preferential binding of EBV to human CR2 is not due to unique amino acids that are capable of binding the virus, but reflects a distinct receptor conformation that can be achieved in murine CR2 with single amino acid substitutions in two discontinuous regions of the primary structure: replacement of proline at position 15 with the corresponding serine from human CR2, and elimination of a potential N-linked glycosylation site between SCR-1 and SCR-2. Furthermore, species-specific binding of EBV, OKB7, and 7G6 can all be manipulated through substitutions among residues 8-15, suggesting that this octapeptide is part of a structural determinant that is critical for binding of both viral and natural ligands to CR2.

Amino Acid Sequence↗

Frequency analysis of the human and swine electrocardiogram during ventricular fibrillation.

Recent studies in swine have suggested that estimating the duration of ventricular fibrillation (VF) could have important implications regarding the selection of the best therapeutic intervention during cardiopulmonary resuscitation (CPR). Successful defibrillation resulting in a pulsatile rhythm is more likely with VF of short duration, whereas VF of longer duration may require interventions designed to augment myocardial blood flow prior to defibrillation. Duration of VF has been estimated in a swine model by modelling the median frequency (FM) of the VF ECG signal. The purpose of this study was to characterize the time course of the FM ECG signal in humans during VF and compare the characteristics of the human VF ECG signal to that previously described in swine. Seven two-channel human VF ECG recordings were analyzed via fast Fourier transformation. The FM was extracted from each four-second segment of the recordings and plotted versus time. The FM in humans followed a repeatable time course during VF. The human data revealed an FM which had two peaks with subsequent gradual decline. The data in swine revealed an FM during VF which decreased initially then increased to a peak followed by a gradual decline. Our preliminary results demonstrate that a characteristic median frequency exists in humans which could be used to estimate the duration of VF.

Animals↗