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Biomedical subjects

E Martin

Publications and source records attributed to E Martin.

At least 253 records · Page 14Linked to original sources
PubMed1998

A decade of caring for drug users entirely within general practice.

BACKGROUND: The government encourages general practitioners (GPs) to become involved in caring for drug users. However, in some areas of the country, including Bedford, secondary care support is inadequate. GPs in these areas have to decide how to cope with such patients entirely within general practice. AIM: To assess the characteristics and quality of care given without secondary care support to drug users by one practice in Bedford over a decade. METHOD: A search was made of the practice computer for all patients with a problem title of 'addiction drug' between 1986 and 1995. The age, sex, social characteristics, and drug history were recorded. RESULTS: One hundred and ninety-two patients were found, of which 155 took part in the practice programme; i.e. they consulted more than three times. Forty-three patients (37%) who took part and were prescribed Methadone were prescribed this drug as ampoules. Sixty-three patients (40.6%) who took part in the programme stopped using drugs. Thirty-two (33.6%) of the Methadone users became abstinent. A higher proportion of women (13-48%) than men (19-27.7%) stopped using Methadone (P = 0.019). Among patients who had a stable lifestyle, a higher proportion had been prescribed ampoules than mixture (22 out of 28: 78.6%; P = 0.001). Similarly, of those who had a job, eight out of 11 (72%; P = 0.037) had been prescribed methadone ampoules. Two-thirds of all patients prescribed amphetamines stopped using drugs. CONCLUSION: Long-term care of drug users entirely within general practice is feasible. Among those prescribed methadone ampoules, a higher than average proportion had stable lifestyles and had a stable job.

Adolescent↗
PubMed1998

Relationship between hepatic cytochrome P450 3A content and activity and the disposition of midazolam administered orally.

It was recently shown by others that the clearance of midazolam/kg body weight after iv administration correlates with hepatic cytochrome P450 (CYP or P450) 3A content in liver transplant patients. However, after po administration midazolam undergoes significant first-pass metabolism, with significant intestinal extraction. The relationship between hepatic CYP3A and midazolam disposition after po administration had not previously been investigated. The aim of this study was to compare intraindividually hepatic CYP3A content and activity with the in vivo pharmacokinetics of midazolam (7.5 mg) administered po. For 15 patients scheduled for partial liver resection, the AUC values for the observed time period (AUC0-5hr) and to infinity (AUCinf) and the clearance were determined. In a macroscopically normal area of resected liver tissue, the microsomal CYP3A4 content (nanomoles per nanomole of total P450) was measured by immunoblot analysis and parameters (apparent Vmax, apparent KM, and intrinsic clearance) for the microsomal alpha-hydroxylation of midazolam were determined. Clearance/kg in vivo correlated with the apparent Vmax (r2 = 0.45, p < 0.01) and the CYP3A4 content (r2 = 0.29, p < 0.05). We conclude that interindividual variability in the pharmacokinetics of po administered midazolam is in part determined by interindividual variability in the hepatic microsomal Vmax for the alpha-hydroxylation of midazolam. However, the relationship between the disposition of midazolam administered po and hepatic CYP3A content is weaker than that reported after iv administration, indicating the importance of the contribution of intestinal CYP3A to the in vivo disposition of midazolam administered po.

Adult↗
PubMed1998

[Guidelines for the evaluation of internal quality control of smears for screening of uterine cancer in France in the structures of Pathologic Anatomy and Cytology. French Association for Quality Assurance in Pathologic Anatomy and Cytology (AFAQAP)--Commission for cervical smears].

A national organized mass-screening effective programme is the only way to reduce the risk of cervical cancer, if properly organized and correlated with a system of Quality Assurance. Since 1900, an Association for Quality Assurance was created by the French pathologists, named "AFAQAP". These pathologists thus demonstrated their interest in this kind of action that should be effective if women and clinicians are also implied. The pathologists have concluded the first part of their programme with these French guidelines for internal quality control of pap smears.

Female↗
PubMed1998

Lasting cytotoxic edema as an indicator of irreversible brain damage: a case of neonatal stroke.

We describe a case of neonatal stroke in the territory of the left middle cerebral artery. Although the ischemic lesion appeared rather homogeneously hyperintense on T2-weighted MR images, corresponding diffusion-weighted images clearly delineated two separate zones of different cellular swelling and, thus, different prognoses. Lasting cytotoxic edema heralded infarction. We believe that the different rates of disintegration of neurons and glial cells may have caused the change from intracellular to interstitial volume fraction during the evolution of edema.

Brain Damage, Chronic↗
PubMed1997

Role of NFkappaB in the mortality of sepsis.

Binding activity for nuclear factor kappa B (NFkappaB) consensus probes was studied in nuclear extracts from peripheral blood mononuclear cells of 15 septic patients (10 surviving and 5 not surviving). Nonsurvivors could be distinguished from survivors by an increase in NFkappaB binding activity during the observation period (P < 0.001). The increase in NFkappaB binding activity was comparable to the APACHE-II score as a predictor of outcome. Intravenous somatic gene transfer with an expression plasmid coding for IkappaBalpha was used to investigate the role of members of the NFkappaB family in a mouse model of endotoxemia. In this model, increased NFkappaB binding activity was present after injection of LPS. Intravenous somatic gene transfer with IkappaBalpha given before LPS attenuated renal NFkappaB binding activity and increased survival. Endothelial cells and monocytes/macrophages were the major target cells for somatic gene transfer, transfected with an average transfection efficiency of 20-35%. Tissue factor, a gene under regulatory control of NFkappaB, was induced by LPS. Somatic gene transfer with a reporter plasmid containing the functional tissue factor promoter demonstrated NFkappaB-dependent stimulation by LPS. Intravenous somatic gene transfer with IkappaBalpha reduced LPS-induced renal tissue factor expression, activation of the plasmatic coagulation system (decrease of thrombin-antithrombin III complexes) and renal fibrin/fibrinogen deposition. Somatic gene transfer with an expression plasmid with tissue factor cDNA in the antisense direction (in contrast to sense or vector alone) also increased survival. Furthermore, antisense tissue factor decreased renal tissue factor expression and the activation of the plasmatic coagulation system.

Adult↗
PubMed1997

Intestinal formation of hypoxanthine and uric acid during endotoxemia.

The objective of this study was to examine the intestinal metabolism of high-energy purine compounds as sensitive indicators of tissue ischemia during endotoxemia. Arterial (art) and portal venous (PV) concentrations as well as the intestinal net concentration changes of adenosine (ADO), hypoxanthine (Hypo), and uric acid (UA) were measured at baseline and after 60 and 120 min in rats that were subjected to a 1-hr continuous infusion of endotoxin (1.5 mg/kg; group E), and in control animals (group C). Furthermore, the arterial (SaO2) and portal venous oxygen saturation (S(PV)O2) was determined at the same time points. Animals in both groups remained normotensive throughout the study period and no differences in mean arterial blood pressure were observed. In both groups, adenosine concentrations remained constant throughout the study and no changes in the net concentration difference (NCD) of adenosine between arterial and portal venous blood were observed [ADO(NCD); baseline: group E, -23 +/- 46 nmole/L; group C, 17 +/- 84 nmole/L; 120 min: group E, 14 +/- 38 nmole/L; group C, 5 +/- 40 nmole/L]. In contrast to control animals, hypoxanthine and uric acid concentrations increased in arterial and portal venous blood in endotoxemic rats after 120 min. This was accompanied with an increase in the intestinal net concentration differences of both hypoxanthine and uric acid, indicating the gut as the predominant source of these two compounds during endotoxemia [Hypo(NCD); baseline: group E, -36 +/- 53 nmole/L; group C, -53 +/- 185 nmole/L; 120 min: group E, 538 +/- 211 nmole/L; group C, 99 +/- 100 nmole/L] [UA(NCD); baseline: group E, 2.04 +/- 1.62 micromole/L; group C, -0.04 +/- 1.11 micromole/L; 120 min: group E, 9.58 +/- 3.04 micromole/L; group C, 0.35 +/- 1.34 micromole/L]. Furthermore, in endotoxemic rats the portal venous oxygen saturation decreased despite unaltered arterial oxygen saturation [SaO2; baseline: group E, 95.2 +/- 0.9%; group C, 94.2 +/- 0.9%; 120 min: group E, 95.4 +/- 0.7%; group C, 96.4 +/- 0.9%] [S(PV)O2; baseline: group E, 86.2 +/- 3.1%; group C, 85.7 +/- 1.4%; 120 min: group E, 69.1 +/- 4.5%; group C, 82.3 +/- 1.9%]. These results indicate the presence of tissue ischemia in the intestinal tract during early, normotensive endotoxemia. Furthermore, because of the direct toxic damage mediated by oxygen radicals that are generated during the production of uric acid, intestinal mucosal injury observed during endotoxemia may be related to an enhancement of the ATP-degradation pathway.

Adenosine↗
PubMed1997

Sequence analysis of two genomic regions containing the KIT and the FMS receptor tyrosine kinase genes.

The KIT and FMS tyrosine kinase receptors, which are implicated in the control of cell growth and differentiation, stem through duplications from a common ancestor. We have conducted a detailed structural analysis of the two loci containing the KIT and FMS genes. The sequence of the approximately 90-kb KIT locus reveals the position and size of the 21 introns and of the 5' regulatory region of the KIT gene. The introns and the 3'-untranslated parts of KIT and FMS have been analyzed in parallel. Comparison of the two sequences shows that, while introns of both genes have extensively diverged in size and sequence, this divergence is, at least in part, due to intron expansion through internal duplications, as suggested by the discrete extant analogies. Repetitive elements as well as exon predictions obtained using the GRAIL and GENEFINDER programs are described in detail. These programs led us to identify a novel gene, designated SMF, immediately downstream of FMS, in the opposite orientation. This finding emphasizes the gene-rich characteristic of this genomic region.

Animals↗
PubMed1997

Lactobacillus species as emerging pathogens in neutropenic patients.

The intensive use of broad-spectrum antibiotics in the context of prolonged and severe neutropenia has contributed to the emergence of unusual pathogens. Four new cases of severe Lactobacillus infections-three of septicemia and one of pneumonia-are reported. They occurred in patients with acute leukemia who had chemotherapy-induced neutropenia. All patients were treated in the same intensive care unit and received the same antimicrobial prophylaxis which included a total bowel decontamination containing vancomycin. The four patients were treated with a combination of intravenous ceftazidime and vancomycin prior to the development of Lactobacillus infection. Improvement in the condition of all patients was obtained with a treatment including penicillin and concurrent recovery of granulopoiesis.

Adult↗
PubMed1997

[Economic aspects of modern inhalation anesthetics with sevoflurane as an example].

The economic impact of the new German health care laws requires an awareness of cost-effectiveness when using newer drugs. The main goal in patient care, i.e., effective treatment, must be achieved by the rational use of restricted resources at a maximum degree of effectiveness. Economic aspects of the new inhalational anaesthetics such as sevoflurane are discussed in this article. The cost of inhalational anaesthetic agents accounts for up to 5% of all the running expenses of an anaesthesia department. The consumption and cost of an inhalational agent depend on fresh gas flow, vapour setting, and duration of anaesthesia. Comparing the cost for 1 MAC-h of anaesthesia, desflurane is more expensive at current market prices than sevoflurane and isoflurane. However, at low or minimal fresh gas flows, the price for one MAC-h is almost the same for these volatile anaesthetics. Total intravenous anaesthesia using propofol is even more expensive, partly due to wastage, i.e., opened ampoules with a remainder of propofol that has to be discarded after each case. When choosing an anaesthetic agent, the price of 1 ml liquid anaesthetic is an important factor. However, the overall cost-effectiveness analysis must balance the cost of the agent with its pharmacodynamic advantages such as more rapid recovery from anaesthesia. Furthermore, the indirect costs of side effects have to be taken into account. For example, nausea and vomiting lead to a prolonged stay in the recovery room after anaesthesia for outpatient surgery, which in turn incurs additional costs for antiemetic drugs and the extra time for nursing care. Therefore, a lower incidence of nausea and vomiting and a more rapid recovery from anaesthesia leading to earlier discharge from the recovery room may compensate for the higher price. Volatile agents account for up to 1% of the total intraoperative costs. In analysing the costs of 1 h of anaesthesia, other products such as plasma substitutes and blood products account for a much higher proportion than anaesthetic agents, and reductions or increases in costs pertaining to these products have a bigger impact on overall costs than do volatile anaesthetics. We conclude that volatile anaesthetics account for only a minor portion of the anaesthesia department budget and the cost of anaesthesia delivery. The higher market price of the new agents may be compensated for by the economic impact of fewer side effects and a shorter post-anaesthesia stay in the hospital. In analysing data for sevoflurane, this agent may be cost-effective, for example, for outpatient anaesthesia.

Anesthesia Department, Hospital↗
PubMed1997

Effect of the 21-aminosteroid tirilazad mesylate on leukocyte adhesion and macromolecular leakage during endotoxemia.

BACKGROUND: Interstitial accumulation of leukocytes has been related to the development of multiple organ failure after sepsis. Oxygen radicals are involved in the process of leukocyte adherence to the microvascular wall. This study investigates the effects of the oxygen radical scavenger tirilazad mesylate on leukocyte-endothelial interactions, macromolecular leakage, and microhemodynamics in mesenteric venules during endotoxemia. METHODS: Male Wistar rats were randomly allocated to receive tirilazad mesylate (group A, n = 10), its vehicle (group B, n = 10), or saline 0.9% (group C, n = 10) before a 120-minute infusion of endotoxin (2 mg/kg/hr). Furthermore, a control group without receiving endotoxin (group D, n = 10) was investigated. Leukocyte adherence, emigration of leukocytes, and macromolecular leakage were determined in postcapillary venules of the mesentery by using intravital videomicroscopy. RESULTS: During the administration of endotoxin the number of adherent leukocytes per square millimeter of vessel surface progressively increased in group B (baseline, 431 +/- 35 cells/mm2; 120 minutes, 1121 +/- 71 cells/mm2) and group C (baseline, 398 +/- 44 cells/mm2; 120 minutes, 1290 +/- 116 cells/mm2). In group A no increase in leukocyte adherence was observed after 120 minutes (baseline, 415 +/- 81 cells/mm2; 120 minutes, 638 +/- 87 cells/mm2). In control animals the leukocyte adherence remained unchanged (baseline, 347 +/- 41 cells/mm2; 120 minutes, 507 +/- 75 cells/mm2). After 120 minutes, tirilazad mesylate prevented the increase in leukocyte emigration observed in group B and C. Increased macromolecular leakage during endotoxemia (groups B and C) was not influenced by pretreatment with tirilazad. Tirilazad did not affect the decrease in red cell velocity, volumetric blood flow, and venular shear rate observed during endotoxemia. CONCLUSIONS: This study demonstrates inhibitory effects of tirilazad on endotoxin-induced leukocyte adherence and emigration, suggesting a potential therapeutic role for this substance in the prevention of sepsis-induced multiple organ failure.

Animals↗
PubMed1997

Positive prostate-specific antigen circulating cells detected by reverse transcriptase-polymerase chain reaction does not imply the presence of prostatic micrometastases.

OBJECTIVES: Detection of circulating tumor cells may improve the preoperative local staging of prostate cancers. The aim of this study was to perform enhanced reverse transcriptase-polymerase chain reaction (RT-PCR) of prostate-specific antigen (PSA) mRNA to define the predictive value of PSA-positive circulating cells in a large series of patients. METHODS: The study included 46 patients with Stage T1 to T2 prostate cancer, 94 with benign prostatic hyperplasia (BPH), and 51 (including 9 women) with nonprostatic disease. PSA-positive cells from peripheral blood samples were detected by Southern blot analysis of the RT-PCR products. Original oligonucleotide primers were defined to exclusively detect the three PSA mRNA splices. RESULTS: Circulating PSA-positive cells were observed in 8 (8.5%) of 94 patients with BPH, 10 (22%) of 46 with Stage T1 to T2 prostate cancer, and 9 (17.6%) of 51 with nonprostatic disease. The detection rate of PSA-positive circulating cells was significantly increased in patients with prostate cancer versus patients with BPH (P = 0.03). Among clinically localized prostate cancers with a Gleason score less than 8, a correlation was observed between PSA-positive circulating cells and Stage pT3 cancer (P = 0.038), capsular penetration (P = 0.04), and a positive margin (P = 0.038). The specificity of the assay for Stage pT3 cancer detection was 84.6%, with a positive predictive value of 60%. CONCLUSIONS: Although RT-PCR assay may have a role in preoperative local staging, this study demonstrated the absence of tissue and tumor specificity of PSA-positive circulating cells, accounting for the weak positive predictive value of this technique.

Aged↗
PubMed1997

The cerebral 'no-reflow' phenomenon after cardiac arrest in rats--influence of low-flow reperfusion.

OBJECTIVE: Experimental data indicate that early microcirculatory reperfusion is disturbed after cardiac arrest. We investigated the influence of prolonged cardiac arrest and basic life support (BLS) procedures on the quality of cerebral microcirculatory reperfusion. MATERIALS AND METHODS: In mechanically ventilated male Wistar rats anesthetized with N2O and halothane, cardiac arrest was induced by electrical fibrillation. Ten animals (group I) were subjected to 17 min of cardiac arrest (no-flow). Nine additional animals (group II) underwent only 12 min of cardiac arrest (no-flow), which was followed by a 5-min phase of BLS (i.e. mechanical ventilation and external cardiac compressions). In both groups, advanced resuscitation procedures including mechanical ventilation, external cardiac massage, 0.2 mg kg-1 epinephrine, 0.5 mmol kg-1 NaHCO3, and defibrillation were started 17 min after induction of cardiac arrest. The perfusion of the cerebral microcirculation was visualized by injection of 0.3 g kg-1 15% fluorescein isothiocyanate (FITC)-albumin 5 min after restoration of spontaneous circulation (ROSC), and the animals were decapitated 2 min later. The left hemispheres were fixed in 4% formalin, and coronal sections of 200 microns thickness at three different standard levels of the rat brain were investigated using fluorescence microscopy. Areas without capillary filling (cerebral 'no-reflow') were identified and calculated. RESULTS: ROSC could be achieved in five of 10 animals (50%) of group I, and in six of nine animals (67%) of group II (P = n.s.). The severity of cerebral 'no-reflow' was higher in group II compared with group I (6.9 +/- 7.6 vs. 0.7 +/- 0.7% of total sectional areas; P < or = 0.05). Two sham-operated animals showed homogeneous reperfusion. CONCLUSIONS: Wistar rats did not develop a marked cerebral 'no-reflow' phenomenon after circulatory arrest. A relevant degree of cerebral 'no-reflow' occurred, however, in animals subjected to a phase of BLS before circulatory stabilization. Therefore, low-flow states following prolonged cardiocirculatory arrest may aggravate early cerebral microcirculatory reperfusion disorders.

Animals↗
PubMed1997

Changes in intrathoracic fluid volumes during weaning from mechanical ventilation in patients after coronary artery bypass grafting.

PURPOSE: Although it is known that weaning from mechanical ventilation is associated with alterations in intrathoracic pressure, lung volume, and venous return, changes in intrathoracic fluid volumes during weaning are not reported. Especially in patients with impaired cardiac function, the development of pulmonary edema during weaning has been described. Thus, we investigated changes in intrathoracic fluid volumes in patients after coronary artery bypass grafting after changing the ventilatory pattern from mechanical to spontaneous ventilation. MATERIALS AND METHODS: Intrathoracic blood volume index (ITBVI), pulmonary blood volume index (PBVI), and extravascular lung water (EVLW) were calculated during mechanical ventilation (T1), T-piece breathing (T2), and spontaneous breathing after extubation of the trachea (T3) in 72 consecutive patients after coronary artery bypass grafting using a combined dye-thermal dilution method. RESULTS: Changing from mechanical ventilation to T-piece breathing resulted in an increase in ITBVI from 880 +/- 22 mL/m2 to 970 +/- 22 mL/m2 (P < .01), and in PBVI from 162 +/- 6 mL/m2 to 173 +/- 6 mL/m2 (P < .01). After extubation of the trachea, both parameters decreased again (ITBVI, 879 +/- 20 mL/m2; PBVI, 160 +/- 7 mL/m2). EVLW remained unchanged after transition to T-piece breathing (T1, 5.8 +/- 0.3 mL/kg; T2, 6.0 +/- 0.3 mL/kg), but increased to 6.6 +/- 0.5 mL/kg (P < .01) after extubation of the trachea. However, pathological values of EVLW were not observed. CONCLUSIONS: In patients after coronary artery bypass grafting, changes in intrathoracic intravascular fluid volumes during weaning are restricted to the period of T-piece breathing and reflect an increased venous return. The maintenance of EVLW in the normal range during weaning indicates that cardiac function was matched to this elevated preload.

Blood Volume↗
PubMed1997

Dobutamine maintains intestinal villus blood flow during normotensive endotoxemia: an intravital microscopic study in the rat.

PURPOSE: The gut plays a pivotal role in sepsis. Intestinal hypoperfusion with subsequent ischemia leads to translocation of endotoxin. Dobutamine has been demonstrated to increase mesenteric blood flow during endotoxic shock; however, its effects on mucosal blood flow especially in intestinal villi is not known. Therefore, we investigated its influence on the blood flow and the arteriolar diameters in intestinal villi in a model of normotensive endotoxemia. MATERIALS AND METHODS: Twenty-one male Wistar rats were divided into three groups: (1) control, saline; (2) endotoxin, endotoxin 1.5 mg/kg during 60 minutes; and (3) dobutamine, endotoxin 1.5 mg/kg (60 minutes) and dobutamine 2.5 micrograms/kg/min during 120 minutes. Villus blood flow and arteriolar diameters were determined at 0 minutes, 60 minutes, and 120 minutes in each group using intravital microscopy. RESULTS: Villus blood flow was constant in the control group, significantly reduced at 120 minutes in the endotoxin group (120 minutes, 55.1 +/- 7.4%), and remained at baseline values in the dobutamine group. The arteriolar diameters remained constant in the control and the dobutamine groups, but they were significantly reduced in the endotoxin group at 120 minutes (7.8 +/- 0.2 to 6.5 +/- 0.7 micron). CONCLUSION: Our results indicate that in rats with normotensive endotoxemia, arteriolar diameters and blood flow in intestinal villi were reduced. Dobutamine prevented arteriolar constriction and maintained villus blood flow at preendotoxemic values.

Adrenergic beta-Agonists↗