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Biomedical subjects

M J George

Publications and source records attributed to M J George.

At least 19 recordsLinked to original sources

The site of action of epidurally administered opioids and its relevance to postoperative pain management.

The use of epidurally administered opioids to control postoperative pain is a well established and widely accepted technique. However, despite this longstanding use, there is still an ongoing debate concerning the site of action of the opioids used. Some argue that analgesia is mediated by a spinal mechanism and others that a supraspinal mechanism is responsible. On close inspection of the evidence it becomes apparent that epidural opioids act predominantly spinally when administered as a bolus, and predominantly supraspinally when administered as a continuous infusion. A concentration of 10 microg x ml(-1) appears to be the threshold at which epidurally administered fentanyl can elicit segmental analgesia, a value which may have significant clinical applications. The evidence supporting a synergistic relationship between epidural opioids and local anaesthetics is weak and unsupported by a plausible physiological mechanism. Thus the 'threshold concentration' of approximately 10 microg x ml(-1) is unlikely to be lowered by co-administering opioids with local anaesthetics.

Analgesia, Epidural↗

XAS-Collect: a computer program for X-ray absorption spectroscopic data acquisition.

A computer program for X-ray absorption spectroscopy (XAS) data acquisition, called XAS-Collect, is described. The software employs the X Windows system to provide a pull-down menu, dialog-box style of graphical user interface. The software provides state-of-the-art features while still being sufficiently simple for novice users.

Journal Article↗

Structure of the molybdenum site of Rhodobacter sphaeroides biotin sulfoxide reductase.

Conditions for heterologous expression of Rhodobacter sphaeroides biotin sulfoxide reductase in Escherichia coli were modified, resulting in a significant improvement in the yield of recombinant enzyme and enabling structural studies of the molybdenum center. Quantitation of the guanine and the molybdenum as compared to that found in R. sphaeroides DMSO reductase demonstrated the presence of the bis(MGD)molybdenum cofactor. UV-visible absorption spectra were obtained for the oxidized, NADPH-reduced, and dithionite-reduced enzyme. EPR spectra were obtained for the Mo(V) state of the enzyme. X-ray absorption spectroscopy at the molybdenum K-edge has been used to probe the molybdenum coordination of the enzyme. The molybdenum site of the oxidized protein possesses a Mo(VI) mono-oxo site (Mo=O at 1.70 A) with additional coordination by approximately four thiolate ligands at 2.41 A and probably one oxygen or nitrogen at 1.95 A. The NADPH- and dithionite-reduced Mo(IV) forms of the enzyme are des-oxo molybdenum sites with approximately four thiolates at 2.33 A and two different Mo-O/N ligands at 2.19 and 1.94 A.

Amino Acid Sequence↗

Reduction and coordination of arsenic in Indian mustard.

The bioaccumulation of arsenic by plants may provide a means of removing this element from contaminated soils and waters. However, to optimize this process it is important to understand the biological mechanisms involved. Using a combination of techniques, including x-ray absorption spectroscopy, we have established the biochemical fate of arsenic taken up by Indian mustard (Brassica juncea). After arsenate uptake by the roots, possibly via the phosphate transport mechanism, a small fraction is exported to the shoot via the xylem as the oxyanions arsenate and arsenite. Once in the shoot, the arsenic is stored as an As(III)-tris-thiolate complex. The majority of the arsenic remains in the roots as an As(III)-tris-thiolate complex, which is indistinguishable from that found in the shoots and from As(III)-tris-glutathione. The thiolate donors are thus probably either glutathione or phytochelatins. The addition of the dithiol arsenic chelator dimercaptosuccinate to the hydroponic culture medium caused a 5-fold-increased arsenic level in the leaves, although the total arsenic accumulation was only marginally increased. This suggests that the addition of dimercaptosuccinate to arsenic-contaminated soils may provide a way to promote arsenic bioaccumulation in plant shoots, a process that will be essential for the development of an efficient phytoremediation strategy for this element.

Arsenic↗

Identifying left lower lobe pneumonia at chest radiography: performance of family practice residents before and after a didactic session.

RATIONALE AND OBJECTIVES: The authors sought to determine whether the lateral chest radiograph is helpful in identifying left lower lobe pneumonia among inexperienced readers. MATERIALS AND METHODS: The authors selected all patients who presented to a family practice training program with radiologic and clinical evidence of left lower lobe pneumonia (n = 65). They then selected an equal number of patients in whom chest radiographs were taken to "rule out pneumonia" and were found to be normal. Eight 1st-year family practice residents were asked to read the radiographs before and after a didactic session that emphasized lateral chest radiograph interpretation. The radiographs were presented under two viewing conditions: posteroanterior (PA) only versus PA and lateral. Receiver operating characteristic (ROC) curve methods were used to compare the effect of both the didactic session and the viewing condition on diagnostic accuracy. RESULTS: There were no significant differences in performance before and after the didactic session and no differences between the two viewing conditions. After including only abnormal radiographs that demonstrated the "spine sign" (an apparent increased opacification of the lower vertebral bodies on the lateral view), the residents performed better when presented with both PA and lateral radiographs than when presented with the PA radiograph only (area under ROC curve, .8158 vs .7418, respectively; P = 0.24). CONCLUSION: In patients with left lower lobe pneumonia whose radiographs demonstrated the spine sign, diagnostic accuracy improved when the lateral chest radiograph was viewed.

Case-Control Studies↗

The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland.

PURPOSE: To assess impact of cytomegalovirus (CMV) donor-recipient serostatus, infection, or disease on development of invasive fungal infection in orthotopic liver transplant recipients. PATIENTS AND METHODS: An analysis of prospectively collected data in 146 liver transplant recipients (intention to treat cohort) from 4 tertiary care, university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). Patients were observed for 1 year after transplantation for the development of CMV infection, CMV disease, CMV pneumonia, as well as for the development of opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine and throat and every other week of buffy coat for CMV for 2 months, then monthly for 6 months, at 1 year, and at the time of any clinical illness. Pre- and posttransplant variables including CMV-serostatus of donor and recipient, fungal isolation from sterile body sites, fungemia, bacteremia, antibiotic use, immunosuppression, treatment for rejection, and volumes of blood products were measured. RESULTS: Survival analysis demonstrated that 36% of patients with CMV disease developed invasive fungal disease within the first year post-transplant compared with 8% of those without CMV disease (P < 0.0001). One-year mortality in patients with invasive fungal disease was 15 of 22 (68%) compared with 23 of 124 (19%) in those without invasive fungal disease (P < 0.001). A multivariable, time-dependent analysis demonstrated that being a CMV-seronegative recipient of a CMV-seropositive donor organ (P < 0.001), having bacteremia (P = 0.001), UNOS (United Network for Organ Sharing) status 4 (need for life support measures) at transplant (P = 0.002), and volume of platelets (P = 0.002) were independently associated with invasive fungal disease. Restriction of cases of invasive fungal disease to those that occurred more than 2 weeks after transplant demonstrated an association with CMV disease (P = 0.003), bacteremia (P = 0.003), need for life support (P = 0.03), and volume of blood products transfused (P = 0.02). CONCLUSION: CMV disease or being a CMV-seronegative recipient of a CMV-seropositive donor organ is an important predictor for invasive fungal disease following orthotopic liver transplantation.

Adolescent↗

Incidence and predictors of cytomegalovirus pneumonia in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG Study Group.

The incidence, predictors, and outcome of cytomegalovirus pneumonia in OLT recipients have not been well defined. We conducted an analysis of prospectively collected data from 141 OLT recipients who were included as part of a randomized, placebo-controlled trial of CMV immune globulin prophylaxis. Cytomegalovirus pneumonia was diagnosed in 13 of 141 (9.2%) OLT recipients during the first year posttransplant and was associated with a higher 1-year mortality compared with those recipients without CMV pneumonia (84.6 vs. 17.2%, P=0.0001). Univariate analysis demonstrated that CMV viremia (P=0.001), invasive fungal disease (P=0.0001), donor(+)/pretransplant recipient(-) CMV serologic status (P=0.013), abdominal operation (excluding retransplantation) after liver transplantation (P=0.0027), bacteremia (P=0.0105), and advanced United Network of Organ Sharing status (P=0.023) were associated with CMV pneumonia. Cytomegalovirus viremia was diagnosed in 11 of 13 patients with CMV pneumonia at a median of 11 days (range 1-66 days) before diagnosis of CMV pneumonia. In a multivariate analysis using a time-dependent, Cox proportional hazards model, CMV viremia (RR=8.6, 95% CI 1.8-39.7, P=0.0012), invasive fungal disease (RR=6.5, 95% CI 2.1-20.3, P=0.0001), and abdominal reoperation (RR=4.4, 95% CI 1.4-13.1, P=0.0043) were found to be independent predictors of CMV pneumonia. The attributable mortality associated with CMV pneumonia within the first year after liver transplantation for the patients with CMV pneumonia was 67.4%. Intensified measures for prevention of CMV should be considered for patients at high risk of developing CMV pneumonia.

Adult↗

Recurrent bacterial peritonitis caused by Neisseria cinerea in a chronic ambulatory peritoneal dialysis (CAPD) patient.

We present an unusual case of recurrent (chronic ambulatory peritoneal dialysis) CAPD-associated peritonitis caused by Neisseria cinerea. Using DNA restriction fragment length polymorphism (RFLP) analysis, we determined that the recurrent infection was caused by reinfection with a different N. cinerea strain rather than relapse with the index strain and that the probable origin of the reinfecting organism was the patient's upper respiratory tract.

Adult↗

Regulation of calcium-activated potassium channels by S-nitrosothiol compounds and cyclic guanosine monophosphate in rabbit coronary artery myocytes.

BACKGROUND: The patch-clamp technique was used to study a large conductance, calcium-activated potassium channel (IK(Ca) in coronary arterial smooth muscle cells from rabbits. The properties of this channel are similar to those of IK(Ca) found in many types of vascular tissue. A brief single channel characterization of IK(Ca) in this tissue type has been completed for this study. METHODS: The effects of S-nitrosothiol compounds on IK(Ca) were studied in cell-attached patches. RESULTS: The probability of opening for IK(Ca) increased from 0.008 +/- 0.004 to 0.780 +/- 0.07 following application of S-nitroso-L-cysteine. S-nitroso-N-acetylpenicillamine (SNAP) also increased the probability of opening for IK(Ca) from 0.022 +/- 0.01 to 0.601 +/- 0.05. The probability of opening for IK(Ca) also increased from 0.026 +/- 0.01 to 0.809 +/- 0.02 following application of membrane-permeable analogs of cyclic guanosine monophosphate (cGMP) to the bath of cell-attached patches, suggesting that IK(Ca) in coronary artery smooth muscle cells is regulated by a cGMP-dependent mechanism. Rp-8-pCPT-cGMP, a protein kinase G inhibitor, blocked the effect of SNAP, an S-nitrosothiol compound. CONCLUSIONS: These findings suggest that one of the effects of nitrosothiol compounds is the activation of IK(Ca) through a cGMP-dependent mechanism in coronary artery smooth muscle cells.

Animals↗

The present and future of hematopoietic cytokines in clinical practice.

Hematologic toxicities can be a major problem in the delivery of some chemotherapy regimens. The way clinicians manage myelosuppression has evolved from a symptomatic approach to the use of cytokines to ameliorate or prevent anemia and neutropenia. Soon, new cytokines will be commercially available to manage thrombocytopenia. Cytokines are transforming oncology by permitting dose intensification through delivery of chemotherapy at the full dose and on time, as well as permitting high-dose chemotherapy. Clinical trials are also exploring the benefits of cytokines for myeloablative chemotherapy with cellular support (bone marrow transplantation or peripheral blood progenitor cell transplantation). Future applications of cytokines include ex vivo expansion and gene transfer therapy. For cancer patients, the ability to receive intensive doses of chemotherapy might mean improved survival rates.

Antineoplastic Agents↗

Clinical evaluation and temperature monitoring in predicting viability in replantations.

Experiences with temperature and clinical monitoring in a series of 111 patients with 188 revascularized digits were reviewed. Criteria for abnormal temperature monitoring were defined. Monitoring of only clinical parameters showed a sensitivity of 1.00 and specificity of .97, but this technique was time-consuming and required experienced interpretation of subtle clinical changes. Temperature monitoring gave a sensitivity of 1.00, while the specificity was only .61. Drops in temperature were frequently not associated with vascular problems. Review of digits with abnormal clinical or temperature monitoring showed five patterns of abnormality. The first three groups had either abnormal clinical or temperature monitoring, but all fingers survived without reexploration. The fourth and fifth groups showed abnormalities in both clinical and temperature monitoring; all but one finger were found to be nonviable. Combined clinical and temperature monitoring was highly effective in early prediction of vascular compromise, with a sensitivity of 1.00 and a specificity of .99. The authors recommend the use of temperature monitoring. If a temperature drop occurs, monitoring of the clinical parameters can then be done. If both temperature and clinical monitoring yield abnormal results after a specified time, intervention should be carried out.

Body Temperature↗

In vitro activity of orally administered antimicrobial agents against Haemophilus influenzae recovered from children monitored longitudinally in a group day-care center.

To determine whether the prevalence of resistance to commonly used oral antimicrobial agents varied over time, we compared the in vitro susceptibilities of 217 strains of Haemophilus influenzae recovered from nasopharyngeal secretions of children in a day-care center studied longitudinally between 1979 and 1987. The overall rate of beta-lactamase production in these strains was 18%, with rates of 57% in type b isolates (n = 21) and 14% in non-type b isolates (n = 196). The percentages of isolates for which MICs were less than or equal to 1.0 micrograms/ml for amoxicillin alone, amoxicillin in combination with clavulanic acid, and cefuroxime alone were 82, 92, and 93%, respectively. The percentage of strains for which cefaclor MICs were less than or equal to 1.0 micrograms/ml was only 0.5%. Isolates for which chloramphenicol MICs were greater than 2.0 micrograms/ml or for which trimethoprim-sulfamethoxazole MICs were greater than 0.5/9.5 micrograms/ml were uncommon: 1 and less than 1%, respectively. High concentrations of erythromycin alone and in combination with sulfisoxazole were required to inhibit the majority of test strains; there was no evidence of erythromycin-sulfisoxazole synergy. In vitro susceptibility to commonly used oral antimicrobial agents remained at a constant level when H. influenzae isolates collected from children in a day-care center during 1979 through 1983 were compared with strains collected during 1984 through 1987.

Anti-Bacterial Agents↗

Disruption of neocortical lamina V neuronal bursts by serotonin in urethane anaesthetized rats.

Time-shared high speed cyclic voltametry using carbon fibre multibarrelled microelectrodes was used to monitor the concentration of 5-Hydroxytryptamine administered by iontophoresis to locations in lamina V of Sm l neocortex and to record spontaneous neuronal spike activity. In the absence of 5-Hydroxytryptamine at any one recording location the firing of two or more individual units was seen to be synchronized so that the pattern of multi-unit activity consisted of synchronized clusters of spike activity interspersed with period of neuronal silence. The repetition rate of such clusters of neuronal activity was seen to be between 0.5 and 4Hz. Maximum concentrations of 2.7 x 10(-7) M 5-Hydroxytryptamine produced by iontophoresis disrupted synchronized neuronal cluster activity. 5-Hydroxytryptamine at a concentration of 6.2 x 10(-8) M resulted in a greater than 50% inhibition of activity for 47 single units but a change in firing pattern from cluster restricted high frequency activity to a continuous mode of firing for a separate population of 11 units. Intraperitoneal administration of P-Chloroamphetamine produced similar changes of neuronal firing and hence loss of synchrony.

Animals↗

Bilateral receptive fields of cells in rat Sm1 cortex.

Single cells in the primary somatosensory (Sm1) cortex were investigated for responses to bilateral hindpaw stimulation in Wistar rats anaesthetised by continuous intravenous administration of Althesin. Fifty-one percent of cells sampled (N = 134) responded to equivalent punctate mechanical stimuli delivered to both the contralateral and ipsilateral hindpaws under light anaesthesia. The distribution by cortical depth of cells with receptive fields (RFs) on both hindpaws was not significantly different from cells which had only contralateral RFs. No cell was found with a purely ipsilateral RF. For 86% of cells tested (N = 44) the ipsilateral RF was partly or completely homologous with areas within the contralateral RF. The sizes of ipsilateral RFs were smaller on 66% of occasions when tested against their contralateral RFs. Modal latencies to ipsilateral mechanical stimulation were longer than to contralateral stimulation (34.1 +/- 9.1 ms (S.D) cf. 26.4 +/- 7.2 ms, N = 44). Ipsilateral RFs were lost for 77% of cells tested following a 33% increase in anaesthetic infusion rate. Conditioning mechanical stimuli applied to the centre receptive field (CRF) on the ipsilateral hindpaw reduced or abolished a cell's responses to equivalent test stimuli applied to it's contralateral CRF with C-T intervals of 20-200 ms. Conditioning stimuli applied to the CRF contralateral to the cell reduced or abolished responses to test stimuli on the cell's ipsilateral CRF using C-T intervals of 0-900 ms. Responses in one cortex to stimulation of the ipsilateral hindpaw were unaffected by elimination of responses from the same hindpaw in the opposite contralateral Sm1 cortex, where responses had been suppressed by topical Lignocaine administration. Retrograde transport of horseradish peroxidase from hindpaw Sm1 cortex labelled many cells in homolateral thalamus, but failed to label cells in the entire forebrain contralateral to the injection site. It is concluded that direct crossed thalamo-cortical and callosal Sm1-Sm1 pathways do not contribute to the production of hindpaw ipsilateral receptive fields.

Animals↗