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J Murray

Publications and source records attributed to J Murray.

At least 163 records · Page 9Linked to original sources
PubMed1998

Cost-effectiveness of oral cholera vaccine in a stable refugee population at risk for epidemic cholera and in a population with endemic cholera.

Recent large epidemics of cholera with high incidence and associated mortality among refugees have raised the question of whether oral cholera vaccines should be considered as an additional preventive measure in high-risk populations. The potential impact of oral cholera vaccines on populations prone to seasonal endemic cholera has also been questioned. This article reviews the potential cost-effectiveness of B-subunit, killed whole-cell (BS-WC) oral cholera vaccine in a stable refugee population and in a population with endemic cholera. In the population at risk for endemic cholera, mass vaccination with BS-WC vaccine is the least cost-effective intervention compared with the provision of safe drinking-water and sanitation or with treatment of the disease. In a refugee population at risk for epidemic disease, the cost-effectiveness of vaccination is similar to that of providing safe drinking-water and sanitation alone, though less cost-effective than treatment alone or treatment combined with the provision of water and sanitation. The implications of these data for public health decision-makers and programme managers are discussed. There is a need for better information on the feasibility and costs of administering oral cholera vaccine in refugee populations and populations with endemic cholera.

Administration, Oral↗
PubMed1997

Regulation of neutrophil apoptosis by tumor necrosis factor-alpha: requirement for TNFR55 and TNFR75 for induction of apoptosis in vitro.

Granulocyte apoptosis is an important mechanism underlying the removal of redundant neutrophils from an inflammatory focus. The ability of many proinflammatory agents to impede this event suggests that such agents act not only in a priming or secretagogue capacity but also increase neutrophil longevity by delaying apoptosis. We have examined whether this hypothesis holds true for all neutrophil priming agents, in particular tumor necrosis factor-alpha (TNF-alpha), which has been variably reported to either induce, delay, or have no effect on neutrophil apoptosis. After 20 hours coincubation TNF-alpha inhibited neutrophil apoptosis; however, more detailed analysis demonstrated its ability to promote apoptosis in a subpopulation of cells at earlier (2 to 8 hours) times. Formyl-Met-Leu-Phe, platelet-activating factor, inositol hexakisphosphate, lipopolysaccharide, leukotriene B4, and granulocyte-macrophage colony-stimulating factor all inhibited apoptosis at 6 and 20 hours. The early proapoptotic effect of TNF-alpha was concentration-dependent (EC50 2.8 ng/mL), abolished by TNF-alpha neutralizing antibody, and was not associated with any change in cell viability or recovery. Of relevance to the inflamed site, the ability of TNF-alpha to accelerate apoptosis was lost if neutrophils were primed with 1 micromol/L PAF or aged for 6 hours before TNF-alpha addition. The TNFR55-selective TNF-alpha mutants (E146K, R32W-S86T) induced neutrophil apoptosis but with a potency 14-fold lower than wild-type TNF-alpha. Although the TNFR75-selective mutant (D143F) did not induce apoptosis, blocking antibodies to both receptor subtypes abolished TNF-alpha-stimulated apoptosis. Hence, TNF-alpha has the unique ability to induce apoptosis in human neutrophils via a mechanism where TNFR75 facilitates the dominant TNFR55 death effect. This may be an important mechanism controlling neutrophil longevity and clearance in vivo.

Antibodies, Monoclonal↗
PubMed1997

Analysis of colorectal cancer stage among HMO members targeted for screening.

BACKGROUND: This study is a retrospective analysis of data collected from patient medical records, a fecal occult blood test (FOBT) screening program, and computerized health maintenance organization (HMO) claims and encounters records. OBJECTIVE: To identify factors associated with a diagnosis of early (Dukes A and B) colorectal cancer among older adults targeted for annual FOBT screening. METHODS: Study subjects were insured by the former US Healthcare Inc (Blue Bell, Pa), an independent practice association-type HMO. The HMO was recently integrated into Aetna-US Healthcare. Before diagnosis, subjects were eligible for free annual FOBT screening through the HMO's colorectal cancer screening program. The study subjects included men and women (N = 222) who were aged 50 years or older and had a diagnosis of colorectal cancer between 1987 and 1990. Variables considered were patient age, gender, socioeconomic status, medical history, screening history, length of enrollment in the HMO, and stage of disease at diagnosis. RESULTS: Univariate analyses indicate that colorectal cancer diagnosis due to FOBT screening (P = .03), frequency of FOBT screening (P = .09), and length of HMO membership (P = .10) were positively related to being diagnosed as having early stage colorectal cancer. Multivariable analysis shows that having a screen-detected colorectal cancer was significantly and positively related (P = .03) to being diagnosed as having early stage disease. CONCLUSIONS: Findings support annual FOBT screening among older adults. Results illustrate the value of applying standard methods to the collection and analysis of patient data in a managed care context. The study also highlights a need for research on patient adherence to screening and physician follow-up of abnormal screening test results.

Aged↗
PubMed1997

Red cell membranes of ankyrin-deficient nb/nb mice lack band 3 tetramers but contain normal membrane skeletons.

The role of ankyrin in the formation and stabilization of the spectrin-based skeletal meshwork and of band 3 oligomers was studied by characterizing, in nb/nb mouse red cells, the effect of ankyrin deficiency on skeletal ultrastructure, band 3-skeleton associations, and band 3 oligomeric states. Despite severe ankyrin deficiency, nb/nb mouse red cell skeletal components formed a relatively uniform two-dimensional hexagonal array of junctional complexes cross-linked by spectrin tetramers. Treatment of nb/nb ghosts with the nonionic detergent C12E8 (octaethylene glycol n-dodecyl monoether) resulted in nearly complete extraction of band 3. The extracted band 3 was present exclusively as band 3 dimers. Fluorescence photobleaching recovery and polarized fluorescence depletion measurements showed increases in the laterally (33% vs 10%) and rotationally (90% vs 76%) mobile fractions of band 3 in intact nb/nb compared to control red cells. The rotational correlation time of the major fraction of band 3 molecules was 10-fold shorter in nb/nb compared to control red cells, indicating a significant relaxation of rotational constraints in nb/nb cells. These data suggest that, although ankyrin plays a major role in strengthening the attachment of the skeleton to the membrane bilayer, ankyrin is not required for the formation of a stable two-dimensional spectrin-based skeleton. The absence of band 3 tetramers in the membrane of ankyrin-deficient red cells suggests that ankyrin is required for the formation of stable band 3 tetramers.

Animals↗
PubMed1997

Characterization of the underlying molecular defect in hereditary spherocytosis associated with spectrin deficiency.

Several subsets of patients with hereditary spherocytosis (HS) have been defined based on the specific red blood cell membrane protein deficiencies involving spectrin, ankyrin, band 3, and protein 4.2. Mutations of the genes encoding these proteins are currently being uncovered. Regarding spectrin, only three isolated cases of beta-spectrin gene mutations were recently reported in association with HS and spectrin deficiency. We have screened the coding region of the beta-spectrin gene using the SSCP technique, in 40 families with HS associated with spectrin deficiency or combined spectrin and ankyrin deficiencies. In this report we describe six frameshift and nonsense mutations and four missense mutations of the beta-spectrin gene in 11 unrelated families. Taking advantage of modifications in the restriction enzyme recognition sequences introduced by the mutations, we show, in all cases of frameshift and nonsense mutations, the loss of heterozygosity at the cDNA level when compared to genomic DNA, reflecting the absence of the mutant mRNA transcripts. In one family with a large pedigree including six generations and 112 members, we firmly establish the autosomal dominant inheritance of one of the beta-spectrin null mutations. Most of the mutations described are responsible for a phenotype of mild to moderate autosomal dominant form of HS associated with a conspicuous spherocytosis with frequent spiculated cells (8% to 15% acanthocytes). One missense mutation appears to be associated with a recessive form of the disease. Five common restriction enzyme polymorphisms of the coding region of the beta-spectrin gene are also described. Overall, these findings underscore the importance of the beta-spectrin gene mutations in the pathogenesis of HS and reemphasizes the extreme heterogeneity of the underlying molecular basis of this condition.

DNA, Complementary↗
PubMed1997

Localized primary malignant lymphoma of bone.

PURPOSE: A single institution's experience with the treatment of localized primary malignant lymphoma of bone (PLB) was analyzed to identify major prognostic factors, toxicity, and optimal treatment for this rare malignancy. METHODS AND MATERIALS: A retrospective analysis of 45 previously untreated patients with Ann Arbor stage IE and IIE PLB from 1967 to 1992 was undertaken. All histopathologic material was reviewed. Irradiated patients received at least 40 Gy. Systemic chemotherapy was generally doxorubicin based. Overall survival (OS), progression free survival (PFS), and disease-specific survival (DSS) were calculated actuarially. RESULTS: Histologically, there were 41 diffuse large cell, 2 diffuse mixed cell, 1 lymphocytic, and 1 lymphoblastic lymphomas. International Index scores were assessed on 43 patients. Thirty-six patients were treated with chemotherapy and radiation (CMT), five patients were treated with radiation only, and four patients were treated with chemotherapy only. Univariate analysis revealed significantly improved 5-year OS for those patients who had International Index scores of 0 vs. scores of 1 or 2 (85 vs. 53%, respectively, p = 0.004). Analysis failed to demonstrate a difference in OS, PFS, or DSS when comparing radiotherapy alone versus CMT, stage IE vs. stage IIE, or axial skeleton involvement vs. extremities. CONCLUSION: The outcome of patients with PLB is relatively favorable in the era of CMT. Doses of radiation in the range of 46 Gy provide optimal local control with an acceptable rate of complications. The International Index is a valid prognostic tool for PLB.

Adolescent↗
PubMed1997

Patterns of injury in victims of urban free-falls.

The objective of this study was to identify the patterns of injury in urban free-fall victims so as to establish guidelines of management. This prospective study at an academic level I trauma center included 187 consecutive patients who presented to our trauma center during a 9-month period (September 1994 to June 1995) after a fall from a height of 5 to 70 feet. Only three falls were from heights of more than 40 feet. Of these patients, 116 (65.1%) suffered significant trauma. Fractures were the most common injuries, accounting for 76.2% of all injuries. Spinal fractures were detected in 37 patients and were associated with neurologic deficits in 7. Intraabdominal injuries occurred in 11 patients, requiring operative intervention in 9 of them. Solid organ lacerations prevailed, but small bowel perforation and bladder rupture were present in one case each. A significant retroperitoneal hematoma was detected in only one case and a thoracic aortic rupture in one more. The height of the fall correlated highly with the incidence of intoxication and severity of injury, the need for operation, the length of hospitalization, and mortality. Most urban free-falls occur from moderate heights. The spinal column is frequently injured and therefore should be thoroughly assessed clinically and radiographically in all fall victims. Intraabdominal organ injuries are much more common than retroperitoneal ones. Thus the abdominal cavity should be the primary target of aggressive workup in hemodynamically unstable patients. The height of the fall is a good predictor of injury severity and outcome prognosis.

Accidental Falls↗
PubMed1997

A unified approach to the surgical exposure of pancreatic and duodenal injuries.

One of the greatest challenges to any surgeon is the intraoperative detection and surgical management of duodenal and pancreatic injuries. A uniform approach to the surgical exposure of all suspected pancreatic and duodenal injuries will decrease their morbidity and mortality by identifying all injuries. Proper intraoperative assessment and grading will help with procedure selection from the broad surgical armamentarium available to manage these injuries.

Duodenum↗
PubMed1997

An intervention study with husband and wife carers of older people with a psychiatric illness.

BACKGROUND: Individual packages of care were devised for spouses of older people with psychiatric illness. METHOD: Randomised controlled trial with blind follow up. Intervention group members were offered multidisciplinary packages while controls received no extra help. Both groups were reassessed 12-14 weeks later. The initial control group then received intervention; both were reassessed at 24-28 weeks. RESULTS: Although no significant differences emerged in group mean scores for affective illness or social difficulties, carers who were mentally ill at outset improved significantly. CONCLUSION: Interventions targeted at caregiving spouses with affective disorder are acceptable and efficacious. LIMITATION: It was impossible to compare treatment with no treatment.

Aged↗
PubMed1997

Safety, feasibility, and early efficacy of subfascial endoscopic perforator surgery: a preliminary report from the North American registry.

PURPOSE: The North American Subfascial Endoscopic Perforator Surgery (NASEPS) Registry was established to evaluate the safety, feasibility, and efficacy of minimally invasive endoscopic Linton operations for treatment of chronic venous insufficiency. METHODS: Retrospective analysis was performed on the clinical data of 151 patients who underwent attempt at 158 SEPS in 17 medical centers in the United States and Canada between June 1993 and February 1996. RESULTS: SEPS was completed on 155 limbs of 148 patients, 81 male and 67 female (mean age, 56 years; range, 27 to 87 years). Three procedures were aborted. Seven patients had bilateral procedures (data from one limb were analyzed). One hundred four limbs (70%) had active ulcers, and 22 (15%) had healed ulcers. A single endoscopic port without insufflation was used in 66 procedures (45%) and laparoscopic instrumentation, with two or three ports, in 82 (55%), with CO2 insufflation in 78 (53%). A tourniquet was used on 112 patients (76%). Concomitant venous procedures were performed in 106 patients (72%; saphenous stripping in 71, high ligation in 17, varicosity avulsion in 85). No early deaths or thromboembolism occurred. Complications included wound infections (9), superficial thrombophlebitis (5), cellulitis (4), and saphenous neuralgia (10). Seven patients with wound infection had open ulcers; nine of 10 with neuralgia had concomitant procedures. A roll-on tourniquet caused skin necrosis in one patient. The clinical score improved from 9.4 to 2.9 after surgery (p < 0.0001). Mean follow-up was 5.4 months; 31 patients had > or = 6 months follow-up. Ulcers healed in 88% (75 of 85); recurrence or new ulcer was reported in 3% (4 of 120). CONCLUSIONS: The SEPS modified Linton operation appears safe, with no postoperative deaths or early thromboembolism. Wound infection after SEPS remains important. Early results indicate rapid ulcer healing. Prospective evaluation of long-term results is warranted.

Adult↗
PubMed1997

Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway.

Death receptor 4 (DR4) is a recently described receptor for the cytotoxic ligand TRAIL that reportedly uses a FADD-independent pathway to induce apoptosis and does not activate the NF-kappaB pathway. We have isolated a new member of the tumor necrosis factor receptor (TNFR) family, designated DR5, which bears a high degree of sequence homology to DR4. However, contrary to the previous reports, both DR4- and DR5-induced apoptosis can be blocked by dominant-negative FADD, and both receptors can activate NF-kappaB using a TRADD-dependent pathway. Finally, both receptors can interact with FADD, TRADD, and RIP. Thus, both DR5 and DR4 use FADD, TRADD, and RIP in their signal transduction pathways, and FADD is the common mediator of apoptosis by all known death domain-containing receptors.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Penetrating esophageal injuries: time interval of safety for preoperative evaluation--how long is safe?

OBJECTIVES: This study was performed to assess the experience with penetrating esophageal injuries of an urban Level I trauma center and to attempt to correlate the time to establish a diagnosis with outcome including death, surgical intensive care unit length of stay, and esophageal-related complications. METHODS: Retrospective study over a 72-month period at a single institution comparing age, admission blood pressure, Revised Trauma Score (RTS), Injury Severity Score (ISS), mechanism and anatomic location of injury, and time interval from admission to the operating room (OR) between nonsurvivors and survivors. Patients who survived to reach the operating room were divided into two groups: those who went immediately to the operating room (no preoperative evaluation) and those who underwent diagnostic studies to identify their injuries (preoperative evaluation). Data analysis was done of the same parameters plus average number of associated injuries, complications, and intensive care unit length of stay. Statistical methods used univariate analysis (Fisher's exact test and Student's t test). RESULTS: Forty-three patients were identified with penetrating esophageal injuries and had the following characteristics: 36 males (84%) and 7 females (16%); mean RTS, 9.39; mean ISS, 28.1; mean time interval to OR, 9.8 hours. Associated injuries occurred with 42 patients (98%). The overall complication rate was 14 of 32 (44%), and the overall mortality was 11 of 43 (26%). Corrected mortality was 22%. Differences were noted between nonsurvivors and survivors in the following parameters: admission blood pressure < 90, 11 of 11 versus 3 of 29 (p < 0.001); RTS, 2.364 versus 11.406 (p < 0.001); ISS, 45 versus 21 (p < 0.001); time interval from admission to OR, 18.3 minutes versus 9.8 hours (p < 0.05). Thirty-six patients survived to reach the operating room, 18 in the no preoperative evaluation group and 17 in the preoperative evaluation group. No statistically significant differences were noted between these two groups in the following parameters: age, RTS, ISS, admission blood pressure, anatomic location of injury, number of associated injuries, or intensive care unit length of stay. Average length of time to the operating room was 16.7 hours in the preoperative evaluation group and 1.4 hours in the no preoperative evaluation group (p < 0.001). Twelve complications (all esophageal-related) occurred among seven patients in the preoperative evaluation group, and seven complications (five esophageal-related) occurred among seven patients in the no preoperative evaluation group. Because of the small sample size, this failed to reach a statistical difference (p < 0.05). CONCLUSIONS: Esophageal injuries carry a high morbidity and mortality. Although no definite conclusion can be drawn because of the small sample size, there does appear to be an increased morbidity associated with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, the rapid diagnosis and definitive repair of esophageal injury should be made a high priority.

Adult↗
PubMed1997

Characterization of Alu repeats that are associated with trinucleotide and tetranucleotide repeat microsatellites.

The association of subclasses of Alu repetitive elements with various classes of trinucleotide and tetranucleotide microsatellites was characterized as a first step toward advancing our understanding of the evolution of microsatellite repeats. In addition, information regarding the association of specific classes of microsatellites with families of Alu elements was used to facilitate the development of genetic markers. Sequences containing Alu repeats were eliminated because unique primers could not be designed. Various classes of microsatellites are associated with different classes of Alu repeats. Very abundant and poly(A)-rich microsatellite classes (ATA, AATA) are frequently associated with an evolutionarily older subclass of Alu repeats, AluSx, whereas most of GATA and CA microsatellites are associated with a recent Alu subfamily, AluY. Our observations support all three possible mechanisms for the association of Alu repeats to microsatellites. Primers designed using a set of sequences from a particular microsatellite class showed higher homology with more sequences of that class than probes designed for other classes. We developed an efficient method of prescreening GGAA and ATA microsatellite clones for Alu repeats with probes designed in this study. We also showed that Alu probes labeled in a single reaction (multiplex labeling) could be used efficiently for prescreening of GGAA clones. Sequencing of these prescreened GGAA microsatellites revealed only 5% Alu repeats. Prescreening with primers designed for ATA microsatellite class resulted in the reduction of the loss of markers from approximately 50% to 10%. The new Alu probes that were designed have also proved to be useful in Alu-Alu fingerprinting.

Animals↗