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Biomedical subjects

M R Jackson

Publications and source records attributed to M R Jackson.

At least 19 recordsLinked to original sources
PubMed2004

Analyses of eutectoid phase transformations in Nb-silicide in situ composites.

Nb-silicide in situ composites have great potential for high-temperature turbine applications. Nb-silicide composites consist of a ductile Nb-based solid solution together with high-strength silicides, such as Nb5Si3 and Nb3Si. With the appropriate addition of alloying elements, such as Ti, Hf, Cr, and Al, it is possible to achieve a promising balance of room-temperature fracture toughness, high-temperature creep performance, and oxidation resistance. In Nb-silicide composites generated from metal-rich binary Nb-Si alloys, Nb3Si is unstable and experiences eutectoid decomposition to Nb and Nb5Si3. At high Ti concentrations, Nb3Si is stabilized to room temperature, and the eutectoid decomposition is suppressed. However, the effect of both Ti and Hf additions in quaternary alloys has not been investigated previously. The present article describes the discovery of a low-temperature eutectoid phase transformation during which (Nb)3Si decomposes into (Nb) and (Nb)5Si3, where the (Nb)5Si3 possesses the hP16 crystal structure, as opposed to the tI32 crystal structure observed in binary Nb5Si3. The Ti and Hf concentrations were adjusted over the ranges of 21 to 33 (at.%) and 7.5 to 33 (at.%) to understand the effect of bulk composition on the phases present and the eutectoid phase transformation.

Journal Article↗
PubMed2002

Accurate power approximations for chi2-tests in case-control association studies of complex disease genes.

A popular method for the analysis of case-control association studies is to compare the frequencies of the alleles between cases and controls by means of Pearson's chi2-statistic. Here, an approach for computing the power of this test is presented, which by computer simulation is shown to be more reliable than a previously published power approximation. Since the test based on Pearson's chi2- statistic can be anti-conservative if there is an excess of homozygotes for the susceptibility allele in the general population, it has been proposed to analyze case-control association studies by means of a trend test based on genotypes instead of alleles. We present an accurate power approximation for the trend test. The power approximations are implemented in an available computer program 'GenOdyPower', which in addition has an option to determine the empirical power of these tests by simulations.

Algorithms↗
PubMed2001

Global modulation of cellular transcription by human cytomegalovirus is initiated by viral glycoprotein B.

Human cytomegalovirus (HCMV) infection alters the expression of many cellular genes, including IFN-stimulated genes (ISGs) [Zhu, H., Cong, J.-P., Mamtora, G., Gingeras, T. & Shenk, T. (1998) Proc. Natl. Acad. Sci. USA 95, 14470-14475]. By using high-density cDNA microarrays, we show that the HCMV-regulated gene expression profile in fibroblasts does not differ substantially from the response generated by IFN. Furthermore, we identified the specific viral component triggering this response as the envelope glycoprotein B (gB). Cells treated with gB, but not other herpesviral glycoproteins, exhibited the same transcriptional profile as HCMV-infected cells. Thus, the interaction of gB with its as yet unidentified cellular receptor is the principal mechanism by which HCMV alters cellular gene expression early during infection. These findings highlight a pioneering paradigm for the consequences of virus-receptor interactions.

Cytomegalovirus↗
PubMed2001

Fibrin sealants in surgical practice: An overview.

The need to effectively manage hemostasis and tissue sealing during surgery has had a strong influence on the development of modern surgical techniques. A group of agents known as surgical tissue adhesives has been developed to promote hemostasis and tissue sealing during surgery, and these comprise both natural and synthetic agents. Fibrin sealants are the most effective tissue adhesives currently available, and they are biocompatible and biodegradable. The fibrin sealants are comprised of purified, virus-inactivated human fibrinogen, human thrombin, and sometimes added components, such as virus-inactivated human factor XIII and bovine aprotinin. These agents mimic the final steps of the physiological coagulation cascade to form a fibrin clot. The use of any plasma-derived product in the surgical setting carries a potential risk of viral transmission. In fact, it was the risk of viral transmission from fibrinogen and thrombin that halted development work on fibrin sealants in the United States. Since that time, new techniques for isolating and concentrating plasma fractions have been developed, and national and international guidelines have been introduced to ensure the safety of all plasma products. All plasma donors are carefully selected and their plasma units screened for viral contamination before processing. All plasma donations and bovine tissue used in the production of commercial fibrin sealants undergo rigorous viral reduction/elimination steps. As a result of this carefully controlled and monitored process, there have been no proven cases of viral transmission associated with the use of commercial fibrin sealant. Fibrin sealants are currently used in a number of surgical specialties, including cardiovascular surgery, thoracic surgery, neurosurgery, plastic and reconstructive surgery, and dental surgery. The use of fibrin sealants has a positive effect on surgical outcomes, such as improved time to hemostasis, reduced blood loss, and reduced complications. This review describes the development of fibrin sealants, the composition of currently available products, and their use in surgical practice.

Drug Approval↗
PubMed2001

New and potential uses of fibrin sealants as an adjunct to surgical hemostasis.

Commercially prepared fibrin sealants have been available in Europe and Japan for many years. However, current formulations are exclusively two-component, liquid fibrin sealants, and delivery devices are rather rudimentary. To date, this has had the effect of limiting the number of clinical applications that make use of fibrin sealants. The recent licensing of fibrin sealants by the Food and Drug Administration in the United States has the potential to expand the use of these products in established procedures. As surgeons gain experience with fibrin sealants, it is likely that new clinical applications will be developed in a wider range of surgical specialties. The aim of this article is to explore the potential future formulations and uses of fibrin sealants and highlight a range of surgical procedures that may benefit from these products.

Angioscopy↗
PubMed2001

The clinical course of new-onset atrial fibrillation after elective aortic operations.

BACKGROUND: The onset of atrial fibrillation (AFIB) in the postoperative setting has been associated with increased morbidity and mortality in patients undergoing major noncardiothoracic operations. The purpose of this study was to determine the incidence, associated complications, and outcomes of AFIB after open aortic operations. STUDY DESIGN: We studied 211 consecutive patients undergoing elective aortic operations at a single hospital during a recent 6-year period. Postoperatively all patients had continuous ECG monitoring in the ICU for a mean (+/- SD) of 6 +/- 8 days and routine cardiac enzyme determinations. RESULTS: AFIB developed in 22 of the 211 patients (10%), a mean (+/- SD) of 2 +/- 1 days after operation, and it lasted for a mean of 4 +/- 6 days after onset. Sixteen patients spontaneously reverted to normal sinus rhythm, 3 required cardioversion (2 chemical, 1 electrical), and 3 continued in AFIB at discharge. Four of the 22 patients suffered additional cardiac complications, including antecedent MI in 3 (14%) and sustained cardiogenic shock requiring electrical cardioversion in 1. By comparison, the incidence of MI in the other 189 patients was 4% (no significant difference [NSD]). There were no deaths in the AFIB patients. Cardiac emboli developed in none of the 22 patients, and all patients had normal sinus rhythm on ECG obtained a mean of 14 +/- 10 months after discharge. Comparing the 22 patients with AFIB with the 189 patients without AFIB, there were no differences in the mean duration of ICU stay (6 +/- 4 versus 6 +/- 8 days), total length of hospital stay (10 +/- 5 versus 11 +/- 10 days), or hospital mortality (0% versus 0.5%). AFIB patients were older (71 versus 66 years, p = 0.016), but there was no difference in gender or use of beta-blockers between the two groups. CONCLUSIONS: These data suggest that AFIB is not uncommon after aortic operations but is not associated with increased morbidity, mortality, or length of hospital stay. Although a minority of affected patients can have other cardiac complications such as MI, these complications are usually recognized before the onset of AFIB. AFIB does not affect the outcomes of aortic operations. Most patients will revert spontaneously to normal sinus rhythm and do not require longterm anticoagulation to prevent thromboembolic complications.

Aged↗
PubMed2001

The crystal structures of K(bm1) and K(bm8) reveal that subtle changes in the peptide environment impact thermostability and alloreactivity.

The K(bm1) and K(bm8) natural mutants of the murine MHC class I molecule H-2K(b) were originally identified by allograft rejection. They also bind viral peptides VSV8 and SEV9 with high affinity, but their peptide complexes have substantially decreased thermostability, and the K(bm1) complexes do not elicit alloreactive T cell responses. Crystal structures of the four mutant complexes at 1.7-1.9 A resolution are similar to the corresponding wild-type K(b) structures, except in the vicinity of the mutated residues, which alter the electrostatic potential, topology, hydrogen bonding, and local water structure of the peptide binding groove. Thus, these natural K(b) mutations define the minimal perturbations in the peptide environment that alter antigen presentation to T cells and abolish alloreactivity.

Animals↗
PubMed2000

Effect of early maternal iron stores on placental weight and structure.

BACKGROUND: Large placental size and low birthweight have been implicated as factors predicting high blood pressure in adulthood. Maternal anaemia has been suggested as a link. We investigated the interaction between maternal iron status and other factors known to influence birthweight and placental size. METHODS: In a prospective study of 1650 low-risk, singleton, caucasian pregnancies, we related placental size and birthweight to maternal iron status, socioeconomic status, and parity. Placental morphology was assessed in 17 randomly chosen primigravid pregnancies. FINDINGS: Parity was an important determinant of birthweight (mean standard deviation score -0.13 [SD 0.90] para 0; -0.24 [0.90] para 1; 0.32 [1.1] para 2; 0.21 [1.1] para > or = 3; p<0.0001) and placental weight (mean 655 g [SD 130]; 679 g [122]; 675 g [139]; 694 g [157], respectively; p=0.01). Cigarette smoking influenced birthweight only. Socioeconomic status had little effect after correction for parity. In addition to parity, the factors influencing placental weight were maternal height, weight, and serum ferritin concentration at booking, but not haemoglobin concentration. Serum ferritin concentrations were associated with folate intake and parity. In the placental morphology subset, serum ferritin concentration was inversely related to overall measures of peripheral villous capillarization. Haemoglobin concentration showed no such association. INTERPRETATION: These findings show a relation between maternal anaemia and placental size and birthweight across the normal range for these measures. Low ferritin concentrations in early pregnancy were associated with increased placental vascularisation at term. The association between ferritin concentration and folate supplementation emphasises the importance of preconceptional health, particularly in women at high risk of iron deficiency.

Adult↗
PubMed2000

T cells can use either T cell receptor or CD28 receptors to absorb and internalize cell surface molecules derived from antigen-presenting cells.

At the site of contact between T cells and antigen-presenting cells (APCs), T cell receptor (TCR)-peptide-major histocompatibility complex (MHC) interaction is intensified by interactions between other molecules, notably by CD28 and lymphocyte function-associated antigen 1 (LFA-1) on T cells interacting with B7 (B7-1 and B7-2), and intracellular adhesion molecule 1 (ICAM-1), respectively, on APCs. Here, we show that during T cell-APC interaction, T cells rapidly absorb various molecules from APCs onto the cell membrane and then internalize these molecules. This process is dictated by at least two receptors on T cells, namely CD28 and TCR molecules. The biological significance of T cell uptake of molecules from APCs is unclear. One possibility is that this process may allow activated T cells to move freely from one APC to another and eventually gain entry into the circulation.

Animals↗
PubMed2000

Acute pancreatitis after abdominal vascular surgery.

BACKGROUND: Retroperitoneal dissection and ischemia have been proposed as risk factors for postoperative pancreatitis. Although both are routine components of abdominal vascular operations, postoperative pancreatitis has not been adequately evaluated in vascular patients. The purpose of this study was to determine the incidence and outcomes of pancreatitis after abdominal vascular surgery. STUDY DESIGN: We collected pre-, intra-, and postoperative data on 21 patients who developed pancreatitis after abdominal vascular operations. For comparison, we studied 21 age- and gender-matched case controls undergoing identical operations during the same period. RESULTS: The incidence of pancreatitis among all patients undergoing abdominal vascular operations during the 6-year study period was 1.8%. Pancreatitis was diagnosed 9.8 +/- 8 days after operation and was associated with 3 or less Ranson signs in all 21 study subjects. The following outcomes data differed between the two groups: duration of npo (9 +/- 6 days for subjects versus 3.9 +/- 2 days for controls, p < 0.001) and need for parenteral nutrition (13 subjects versus no controls, p < 0.00 1). Although there was a trend towards longer hospitalization in the subjects (16 +/- 12 days versus 11 +/- 8 days, p = 0.08), there was no difference in complication rates between the two groups. Sixteen subjects (76%) had no complications. Three developed severe complications, two of whom died of causes unrelated to pancreatitis. One developed a pseudocyst that resolved spontaneously. Cholelithiasis was a causative factor in 2 subjects; no cause was established in the remaining 19. There was no difference in operative details between the two groups. CONCLUSIONS: These data indicate that pancreatitis is a rare and self-limited complication of abdominal vascular surgery. Our findings suggest that pancreatitis is costly and inconvenient but rarely serious after abdominal vascular operations.

Abdomen↗
PubMed2000

Incidental splenic injury during abdominal vascular surgery: a case-controlled analysis.

BACKGROUND: The small but finite risk of postsplenectomy sepsis is generally regarded as a firm indication for splenic preservation after iatrogenic injury, especially in the young. But splenectomy may be preferable in patients who sustain splenic injuries during vascular operations because of the potential for continued bleeding associated with anticoagulation. The purpose of this study was to determine the perioperative morbidity of incidental splenectomy among patients undergoing abdominal vascular operations. STUDY DESIGN: We studied 17 patients who underwent incidental splenectomy at the time of abdominal vascular operations. Complete data collected on each subject included preoperative and postoperative blood counts, operative indications and details, transfusion requirements, length of hospital stay, and outcomes. Using age- and gender-matched case controls undergoing identical vascular operations from the same period, we evaluated the complication rate and outcomes of patients who underwent splenectomy for iatrogenic injuries of the spleen, versus those who did not sustain splenic injuries. RESULTS: The estimated prevalence of iatrogenic splenic injury during the study period was 0.5%. Mean operative time, estimated blood loss, and duration of mechanical ventilation tended to be greater in the splenectomy patients, but the differences did not achieve statistical significance. Splenorrhaphy was attempted in seven patients, but continued bleeding mandated spleen removal in all cases. Splenectomy patients had a higher transfusion requirement (p = 0.03) and a longer mean length of stay (p = 0.03) than controls. Compared with controls, there was a higher prevalence of infectious complications in the splenectomy patients (p = 0.015), but there was no difference in the prevalence of thromboembolic complications between groups. Two of the splenectomy patients died in the postoperative period from multisystem organ failure, and one died of a missed splenic injury. CONCLUSIONS: These data suggest that incidental splenectomy during abdominal vascular operations is associated with increased postoperative infectious complications and prolonged hospitalization.

Aged↗
PubMed2000

Repair of a saccular aortic aneurysm with superficial femoral-popliteal vein in the presence of a pancreatic abscess.

When one is faced with impending rupture, repair of an aortic aneurysm cannot be delayed. In the presence of coexisting intra-abdominal sepsis, traditional therapy would call for aneurysm exclusion and axillofemoral bypass grafting. Consequences of this choice of treatment include limited long-term graft patency and recurrent prosthetic infection. Autogenous deep veins from the lower extremities have demonstrated exceptional patency and resilience to infection when used to replace infected aortic grafts. We now report a case of concomitant open drainage of a pancreatic abscess and repair of a saccular abdominal aortic aneurysm using the superficial femoral-popliteal vein as a conduit.

Abscess↗
PubMed2000

The consequences of a failed femoropopliteal bypass grafting: comparison of saphenous vein and PTFE grafts.

OBJECTIVES: Although there are numerous reports comparing saphenous vein (SV) and polytetrafluoroethylene (PTFE) with respect to the patency rates for femoropopliteal bypass grafts, the clinical consequences of failed grafts are not as well described. This study compares the outcomes of failed SV and PTFE grafts with a specific emphasis on the degree of acute limb ischemia caused by graft occlusion. METHODS: Over a 6-year period, 718 infrainguinal revascularization procedures were performed, of which 189 were femoropopliteal bypass grafts (SV, 108; PTFE, 81). Society for Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) standardized runoff scores were calculated from preoperative arteriograms. Clinical categories of acute limb ischemia resulting from graft occlusion were graded according to SVS/ISCVS standards (I, viable; II, threatened; III, irreversible). Primary graft patency and limb salvage rates at 48 months were calculated according to the Kaplan-Meier method. RESULTS: Patients were well matched for age, sex, and comorbidities. Chronic critical ischemia was the operative indication in most cases (SV, 82%; PTFE, 80%; P =.85). Runoff scores and preoperative ankle-brachial index measurements were similar for the two groups (SV, 6.0 +/- 2.5 [SD] and 0.51 +/- 0.29; PTFE, 5.3 +/- 2.8 and 0.45 +/- 0.20; P =.06 and P =.12). The distal anastomosis was made below the knee in 60% of SV grafts and 16% of PTFE grafts (P <.001). Grade II ischemia was more likely to occur after occlusion of PTFE grafts (78%) than after occlusion of SV grafts (21%; P =.001). Emergency revascularization after graft occlusion was required for 28% of PTFE failures but only 3% of SV graft failures (P <.001). Primary graft patency at 48 months was 58% for SV grafts and 32% for PTFE grafts (P =.008). Limb salvage was achieved in 81% of SV grafts but only 56% of PTFE grafts (P =.019). CONCLUSIONS: Patients undergoing femoropopliteal bypass grafting with PTFE are at greater risk of ischemic complications from graft occlusion and more frequently require emergency limb revascularization as a result of graft occlusion than patients receiving SV grafts. Graft patency and limb salvage are superior with SV in comparison with PTFE in patients undergoing femoropopliteal bypass grafting.

Aged↗
PubMed2000

Watchful waiting in cases of small abdominal aortic aneurysms- appropriate for all patients?

OBJECTIVE: The purpose of this study was to determine the effect of patient compliance on a program of watchful waiting in cases of small abdominal aortic aneurysms and to document the proportion of patients who become prohibitive operative risks during follow-up. STUDY DESIGN: A retrospective review was conducted at a regional military veterans medical center. The subjects were 101 male military veterans with abdominal aortic aneurysms measuring less than 5 cm who did not have medical contraindications to operative repair. The main outcome measures were (1) the proportion of patients who missed three scheduled radiologic tests in a row despite written notifications mailed to their homes and (2) the proportion of compliant patients who had medical illnesses and became prohibitive operative risks during follow-up. RESULTS: During a follow-up (mean +/- SEM) of 34 +/- 2 months, 69 patients (69%) were fully compliant with the watchful waiting program and underwent a mean of 4.5 +/- 0.3 radiologic tests. There were no abdominal aortic aneurysm ruptures in this subgroup. Twenty-five patients (36%) had indications for abdominal aortic aneurysm repair, and 28 (41%) have not met the criteria for repair. Sixteen (23%) of the 69 compliant patients developed prohibitive medical risks during follow-up; eight (50%) of these 16 patients died, all of the causes unrelated to their abdominal aortic aneurysms. Thirty-two (32%) of the 101 study subjects were noncompliant with the watchful waiting program. Twenty-seven (84%) of the noncompliant patients did not keep any scheduled appointments, and five (16%) were lost after one or two examinations. Three of the noncompliant patients experienced documented abdominal aortic aneurysm rupture, and it is suspected in a fourth. Direct contact was made with 28 (88%) of these patients or their families; all acknowledged having received written notifications regarding their watchful waiting program tests and had decided not to continue with surveillance for a variety of socioeconomic reasons. Between the 69 compliant patients and the 32 noncompliant patients, there were no differences with respect to mean age (70 +/- 1 years vs 73 +/- 2 years), distance from home of record to the hospital (62 +/- 14 miles vs 73 +/- 23 miles), or abdominal aortic aneurysm size at initial detection (3.75 +/- 0.5 cm vs 3.8 +/- 0.5 cm). CONCLUSIONS: Watchful waiting programs are imperfect and highly reliant on the motivation levels and means of the individual patients. Watchful waiting is reasonable among compliant patients with abdominal aortic aneurysms, inasmuch as fewer than half will meet the criteria for intervention within a mean of 3 years. Approximately one fourth of these patients will have medical contraindications to abdominal aortic aneurysm repair during follow-up, and many of these will die of causes other than abdominal aortic aneurysm rupture. In our experience, one third of candidates for watchful waiting programs are unable to participate and are at risk of rupture. These patients need special attention so that the reasons for their noncompliance can be determined, and they may be candidates for earlier intervention.

Aged↗
PubMed1999

Immune-associated nucleotide-1 (IAN-1) is a thymic selection marker and defines a novel gene family conserved in plants.

Positive selection of thymocytes is a complex and crucial event in T cell development that is characterized by cell death rescue, commitment toward the helper or cytotoxic lineage, and functional maturation of thymocytes bearing an appropriate TCR. To search for novel genes involved in this process, we compared gene expression patterns in positively selected thymocytes and their immediate progenitors in mice using the differential display technique. This approach lead to the identification of a novel gene, mIAN-1 (murine immune-associated nucleotide-1), that is switched on upon positive selection and predominantly expressed in the lymphoid system. We show that mIAN-1 encodes a 42-kDa protein sharing sequence homology with the pathogen-induced plant protein aig1 and that it defines a novel family of at least three putative GTP-binding proteins. Analysis of protein expression at various stages of thymocyte development links mIAN-1 to CD3-mediated selection events, suggesting that it represents a key player of thymocyte development and that it participates to peripheral specific immune responses. The evolutionary conservation of the IAN family provides a unique example of a plant pathogen response gene conserved in animals.

Amino Acid Sequence↗