Search PubMed⌕ Search

Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 181 records · Page 10Linked to original sources
PubMed1997

Sequence-specific inhibition of the tumor necrosis factor-alpha receptor I gene by oligodeoxynucleotides containing N7 modified 2'-deoxyguanosine.

Tumor necrosis factor-alpha (TNF-alpha) is a highly pleiotropic cytokine produced mainly by activated macrophages. This cytokine has been found to mediate the growth of certain tumors, the replication of HIV-1, septic shock, cachexia, graft-versus-host disease, and autoimmune diseases. The binding of TNF-alpha to the p55 tumor necrosis factor receptor type I (TNFRI) is considered one of the initial steps responsible for the multiple physiologic effects mediated by TNF-alpha. The role of TNF-alpha as an inflammatory mediator through TNFRI makes both of these genes attractive targets for intervention in both acute and chronic inflammatory diseases. We have designed antisense oligodeoxynucleotides (ODNs) containing chemically modified purine and pyrimidine bases that specifically inhibit TNFRI expression and functions. These ODNs were designed to hybridize to the 3'-polyadenylation signal region of the TNFRI gene. In cell-based assays, gene-specific antisense inhibition occurred in a dose-dependent fashion at submicromolar concentrations in the presence of cellular uptake enhancing agents. Within ODN sets with a common pattern of stabilizing backbone substitution, the inhibition of the gene expression is found to be correlated with the affinity of the ODNs for their cognate mRNA target sites, providing direct evidence for an antisense mechanism of action. In addition, events triggered by the binding of TNF-alpha to TNFRI, such as the production of IL-6 and IL-8, were significantly reduced by treatment of cells with the anti-TNFRI ODN. Therefore, antisense ODNs can be used to control biologic processes mediated by TNF-alpha and may be useful as therapeutic agents to treat conditions resulting from overproduction of TNF-alpha.

Antigens, CD↗
PubMed1997

Improved oocyte quality is obtained with follicle stimulating hormone alone than with follicle stimulating hormone/human menopausal gonadotrophin combination.

The aim of this study was to compare the efficacy of pure follicle stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin (HMG) combination in downregulated cycles. A total of 357 patients was evaluated retrospectively. Sixty percent of patients in the FSH group and 55% in the FSH/HMG group were new; the others were repeat patients. Ovulation was suppressed with leuprolide acetate in all patients, followed by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in patients' age, infertility factors, number of ampoules used, length of stimulation, oestradiol levels on day of human chorionic gonadotrophin (HCG) administration, number of oocytes recovered or the number of embryos transferred. Also, nuclear maturity at aspiration and fertilization rates were not different between the two groups. FSH stimulation resulted in a significantly higher percentage of mature oocytes that showed the typical 'mature' morphological characteristics (P < 0.0001). The clinical pregnancy rates per transfer were 40 and 28% in patients stimulated with pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher number of immature oocytes matured in vitro in the FSH/HMG group (P = 0.001) suggests a possible effect on in-vitro maturation, due to luteinizing hormone present in HMG. The difference in mature oocyte quality may be an important determinant in the higher pregnancy rates for the FSH-stimulated patients.

Chorionic Gonadotropin↗
PubMed1997

Intrathecal sufentanil for labor analgesia does not cause a sympathectomy.

BACKGROUND: Intrathecal sufentanil (ITS) is frequently used to provide analgesia during labor. Decreases in blood pressure and sensory changes in this circumstance suggest that ITS may have a local anesthetic effect and thus cause a sympathectomy. To determine whether ITS given to laboring women causes a sympathectomy, the authors evaluated central and lower extremity temperature changes after ITS administration. These findings were compared with those in a control group of women having spinal anesthesia with bupivacaine for elective cesarean section in whom an extensive sympathectomy was expected. METHODS: Twenty parturients classified as American Society of Anesthesiologists' physical status 1 or 2 had temperatures measured centrally, at the calf, and at the great toe at frequent intervals after receiving 10 microg ITS for labor analgesia (sufentanil group, n = 10), or hyperbaric bupivacaine 12 mg in their spinal anesthetic for cesarean section (bupivacaine group, n = 10). Calf-to-toe temperature indices (C-T) were calculated by subtracting toe temperature from calf temperature. A decrease in this index means that the toe had warmed compared with the calf and is an indication of vasodilation and a sympathectomy. RESULTS: There was no significant change in the C-T indices or central temperature in the sufentanil group, but the C-T indices and central temperature decreased significantly in the bupivacaine group. CONCLUSIONS: The decreases in the C-T index and central temperature in the bupivacaine group indicate the presence of a sympathectomy. The lack of change in the C-T indices and central temperature in the sufentanil group indicates that no significant vasodilation occurred. Therefore, the decrease in blood pressure seen after ITS administration for labor analgesia is unlikely to be the result of a sympathectomy.

Adult↗
PubMed1997

Type B lactic acidosis following cardiopulmonary bypass.

OBJECTIVE: To describe, characterize, and identify the associations of postcardiac surgical lactic acidosis occurring in the absence of clinical evidence of tissue hypoperfusion. DESIGN: The preliminary study is a report of a series of observations in 12 patients. The prospective study is also observational, involving the structured collection of hemodynamic and metabolic variables in a prescribed series of patients. SETTING: Cardiac surgical intensive care unit of a university teaching hospital. PATIENTS: Twelve patients who developed an unexplained lactic acidosis after cardiac surgery are reported in the preliminary study. The prospective study involved observations in 112 consecutive patients undergoing cardiopulmonary bypass for cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preliminary study: Cardiac index was increased before, during and after recovery from lactic acidosis. Recovery from lactic acidosis was associated with a decrease in oxygen transport index and significant increases in oxygen consumption index and oxygen extraction ratio. PROSPECTIVE STUDY: Hemodynamic, oxygen transport, and oxygen consumption variables, together with arterial blood gas and lactate concentrations, were assessed every 6 hrs for 24 hrs after surgery. Sixteen patients developed lactic acidosis (peak lactate concentration > 5.0 mmol/L). Compared with the remainder of the patients, this subgroup had longer duration of cardiopulmonary bypass (116 +/- 31 vs. 76 +/- 31 mins, p < .01), greater intraoperative hypothermia (24.9 +/- 2.0 degrees vs. 26.6 +/- 2.3 degrees C, p < .01), more frequent requirement for vasopressor agents (14/16 vs. 35/96, p < .05) and a higher frequency of hyperglycemia (15/16 vs. 28/96, p < .01). Hemodynamic variables, including cardiac index, were remarkably similar in the acidotic and nonacidotic groups. All of the acidotic patients, in both parts of this study, recovered from their acidosis. Eleven of the patients in the preliminary study and all of the 16 acidotic patients in the prospective study were ultimately discharged from the hospital. CONCLUSIONS: This report documents the occurrence of lactic acidosis in a subgroup of patients undergoing cardiopulmonary bypass. The pathogenesis of this disorder is uncertain, but it appears to not relate to inadequate oxygen delivery. Systemic vasodilation and reduced oxygen extraction appear to be features of this disorder, which has an excellent prognosis.

Acidosis, Lactic↗
PubMed1997

Protein characterization of Australian spotted fever group rickettsiae and monoclonal antibody typing of Rickettsia honei.

Rickettsial proteins rOmp A and rOmp B exist in both Rickettsia australis and Rickettsia honei but differ in molecular weight and antigenicity; in addition, they produce distinct immunogenic responses and appear to be to conformationally dependent antigens. Species-specific monoclonal antibodies for other spotted fever group rickettsial species did not react with R. honei. A PCR product of the repeat region of the rOmp A gene from R. honei was amplified and calculated to contain 11 repeat units.

Antibodies, Bacterial↗
PubMed1997

Hypoglossal neuropraxia following endotracheal intubation.

A case of hypoglossal nerve neuropraxia following elective drainage of bilateral chronic subdural haematomas is described. We postulate that the cause of neuropraxia was inadvertent extubation of the trachea with the cuff inflated, leading to compression and stretch of the nerve against the greater horn of the hyoid bone. The literature on cranial nerve palsies following endotracheal intubation is reviewed.

Aged↗
PubMed1997

Effect of alteration of maternal plasma progesterone concentrations on fetal behavioural state during late gestation.

Placental progesterone synthesis exposes the fetus to high levels of progesterone and progesterone metabolites during late gestation which may influence fetal behaviour. To determine the role of maternal progesterone synthesis in the control of fetal arousal state and fetal breathing movements (FBM), the effect of raising and lowering maternal progesterone concentrations was examined in chronically catheterised fetal sheep. Fetal and maternal vascular catheters, fetal tracheal and amniotic fluid catheters as well as electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted between 118 and 122 days gestational age (GA). Progesterone, 100 mg, administered twice daily i.m. for 3 days (130-133 days GA) resulted in a marked elevation in maternal plasma progesterone concentrations (370 +/- 121%, n = 5, P < 0.05), but had no effect on fetal plasma concentrations. Fetal EOG episodes and the duration of fetal behavioural arousal were significantly suppressed throughout the progesterone treatment period (74.4-81.1% and 58-65% respectively, P < 0.05, n = 5). Four ewes received Trilostane (25 mg i.v.), a 3 beta-hydroxysteroid dehydrogenase inhibitor, between 136 and 140 days GA. Maternal and fetal progesterone concentrations were significantly lowered by 60 min after treatment (19.8 +/- 8.0% and 39.5 +/- 24.3% respectively, P < 0.05). The incidence of fetal EOG activity increased from a pretreatment level of 26.8 +/- 1.5 min/h to 30.3 +/- 2.8 min/h at 1-6 h and to 35.0 +/- 1.7 min/h (P < 0.05) during the 7-12 h after Trilostane treatment. The duration of FBM episodes was significantly higher at 1-6 h and 7-12 h after Trilostane treatment (19.5 +/- 3.0 and 23.6 +/- 5.5 min/h respectively, P < 0.05) compared with pretreatment levels (11.2 +/- 1.2 min/h). We conclude that increasing maternal progesterone levels suppresses fetal EOG activity and behavioural arousal, whereas reducing maternal progesterone synthesis leads to an elevation of EOG activity and FBM.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

Transferring electronic medical records.

This article outlines the variety of computing environments, application systems and data structures that are available to the general practitioner. The transfer of data from and to electronic medical records systems will become more important as their use increases. Transferability requires the ability to match the data elements between the conversing application systems, and carry out a series of communication steps. Ways to ensure data element matching are described. The communications steps are delineated, and methods of achieving these steps briefly explained. The transfer methods proposed by the medical software industry of Australia are dealt with in detail. They involve the creation of an industry standard 'meta-record' which acts as a standard interface or gateway to the real record. The communication steps are carried out by a medical record 'agent', which is created and maintained by an independent organisation.

Australia↗
PubMed1997

Evidence for fusion between multilamellar endosomes and autophagosomes in HeLa cells.

The organelles of the endocytic and autophagic pathways were studied in HeLa cells using immunoelectron microscopy and stereological techniques. In the absence of autophagic stimulation, characteristic particulate structures containing closely packed layers of membrane received the fluid-phase marker horseradish peroxidase after 25 min uptake. These multilamellar endosomes contained the majority of the cellular immunogold labeling obtained by using a monoclonal antibody (1B5) directed against a lysosomal glycoprotein. Lysosomes with homogeneous dense content were only poorly labeled. After stimulation of autophagy, two classes of autophagosome profile appeared. One had a double limiting membrane and content that resembled the surrounding cytoplasm. The other most abundant type possessed a single limiting membrane and contained multilamellar structures which were strikingly similar to multilamellar endosomes, not only in form, but also in volume and membrane packing density. Immunogold labeling showed that now the majority of 1B5 labeling was located in the class of autophagosomes which contained multilamellar structures. Stereological methods showed that, after autophagic stimulation, multilamellar endosomes had become depleted, while multilamellar structures had appeared within the autophagosomes. Taken together, these data provide evidence that autophagosomes of HeLa cells fuse with preexisting multilamellar endosomes.

Autophagy↗
PubMed1997

Case study. Outcomes management in orthopaedics.

Improving outcomes while maintaining quality and satisfaction in today's healthcare environment is a challenge. This article shares some of the foundation work and the results of an interdisciplinary team effort toward that goal. Changes in care practices and their impact on outcomes can promote the welfare of the patient, institution, and the nation's health.

Hospital Charges↗
PubMed1997

International collaborative study to evaluate a recombinant L ferritin preparation as an International Standard.

A recombinant L ferritin preparation, lyophilized in ampoules and designated 94/572, was evaluated by 18 laboratories in 9 countries for its suitability as an International Standard (IS). The preparation was assayed in a wide range of in-house and commercial immunoassays against the 2nd IS for ferritin (of spleen origin; 80/578). The immunological reactivity of the recombinant material was similar to that of the 2nd IS for ferritin in the majority of assays and demonstrated adequate stability in accelerated degradation studies. On the basis of the results presented here, the WHO Expert Committee on Biological Standardization established 94/572 as the 3rd IS for ferritin, recombinant.

Automation↗
PubMed1996

Endoscopic exploration and lymph node sampling of the axilla. Preliminary findings of a randomized pilot study comparing clinical and anatomo-pathologic results of endoscopic axillary lymph node sampling with traditional surgical treatment.

OBJECTIVE: To describe the technique of endoscopic exploration of the axilla. To compare this technique to open surgical treatment by comparing the following variables: operative time, peri-operative complications, duration of hospital stay, node's histology and morphologic aspects and esthetic results. MATERIALS: Standard instruments for traditional operative laparoscopy plus a lipo-aspirator (0.8 Bar). PATIENTS: Forty patients, 20 (group A) undergoing open surgery and 20 (group B) undergoing axilloscopy. All patients with early invasive breast cancer are eligible for conservative operative treatment. METHOD: Randomized study. The technique is described and preliminary results are presented. RESULTS: The operative time for axilloscopy is approximately double that for open surgery. A comparable number of lymph nodes is collected by axilloscopy and open surgery. The nodes collected by axilloscopy are more likely to be fractured. What is the clinical consequence? Two loco-regional relapses are observed in the endoscopic group. DISCUSSION: Axillary sampling by endoscopic procedure gives the same pathologic information than surgical axillary sampling. Anatomo-pathologic aspects of nodes and possibilities of relapses were two drawbacks of this procedure. CONCLUSION: Operative time is increased for axilloscopy compared with open surgery. The techniques yield comparable anatomo-pathologic results. It is still unknown whether this endoscopic technique is as effective as traditional surgery or if the frequency or severity of lymphedema is decreased by the endoscopic approach.

Adult↗
PubMed1996

Growth and differentiation of fast and slow muscles in fetal sheep, and the effects of hypophysectomy.

1. Isometric contractile characteristics of fast-twitch (flexor digitorum longus, FDL; medial gastrocnemius, MG) and slow-twitch (soleus) muscles were determined in pentobarbitone-anaesthetized fetal sheep between 90 and 140 days gestation. Five fetuses were hypophysectomized (HPX) at 90-95 days gestation and then studied at 138-140 days. 2. At 90-95 days gestation the time to peak of single twitch contractions for the soleus, MG and FDL were not significantly different from each other; the mean value (+/-S.E.M.) for all the muscles at this age was 77.6 +/- 9.0 ms. At 120-125 days gestation the MG and FDL contracted significantly faster (44.0 +/- 0.9 and 40.8 +/- 1.8 ms, respectively) than at 90-95 days, and did not change significantly thereafter. In contrast, the soleus muscle contracted more slowly (111.9 +/- 6.6 ms) at 138-140 days than at 90-95 days and 120-125 days gestation. 3. Soleus muscle consisted of type I fibres at all gestational ages. There was no significant change with gestational age in the relative numbers of type I and II fibres in the MG and FDL, but in the diaphragm the number of type I fibres increased and the number of type II fibres decreased between 125 and 138 days gestation. 4. HPX abolished the normal increase of soleus weight relative to body weight between 125 and 138 days but did not alter the change of twitch contraction time with age. HPX significantly prolonged twitch time to peak and time to half-relaxation of MG and time to half-relaxation of FDL at 138 days. 5. The maximum rate of rise of the isometric tetanic contraction was unchanged by HPX in all three hindlimb muscles, but fatigue of MG and FDL was increased. 6. The relative proportions of different fibre types in the hindlimb muscles and the diaphragm were unchanged by HPX, but there was a significant decrease in mean areas of type I and II fibres in the FDL and MG of the HPX fetuses.

Animals↗