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Biomedical subjects

E Martin

Publications and source records attributed to E Martin.

At least 379 records · Page 21Linked to original sources
PubMed1995

Dose-response, time-course of action and recovery of rocuronium bromide in children during halothane anaesthesia.

Two groups of children, aged 1-4 years (n = 28) and 5-10 years (n = 28), respectively, received at random one of four doses of rocuronium (0.12, 0.17, 0.22 or 0.27 mg kg-1). When maximum block was obtained, further rocuronium to a total dose of 0.5 mg kg-1 was given. At a spontaneous T1 recovery of 25% the block was reversed with atropine and neostigmine in half the patients. The remainder were allowed to recover spontaneously. There was no difference in potency in the two age groups. An ED50 of 0.2 mg kg-1 was estimated. The estimates of ED50 were model-dependent of approximately 0.32 mg kg-1. The maximum block was found significantly higher in the younger age group (99.0 +/- 1.5% (mean +/- SD)) as compared to the older group (97.5 +/- 2.3%), and the clinical duration was also longer (16.6 +/- 5.3 min vs. 13.3 +/- 3.8 min), respectively. There was no significant difference between the two age groups in duration90 (26.9 +/- 6.5 min, 22.5 +/- 6.7 min, respectively) and duration0.7 (27.6 +/- 6.0 min, 24.9 +/- 7.9 min, respectively). Recovery time25-75, recovery time25-90, but not recovery time25-0.7 were found significantly longer in the 1-4 year group as compared to the times in older children. Neostigmine administration reduced recovery time by approximately half to two-thirds. MAP was not influenced by rocuronium. Following the injection of rocuronium in the younger age group there was a 15% increase in heart rate compared to a 10% increase in the age group 5-10 years.

Androstanols↗
PubMed1994

Role of interferon regulatory factor 1 in induction of nitric oxide synthase.

Interferon gamma (IFN-gamma) interacts synergistically with bacterial lipopolysaccharide (LPS) to induce transcription of iNOS, the isoform of nitric oxide synthase whose activity is independent of elevated Ca2+ and exogenous calmodulin. To define a cis-acting element mediating IFN-gamma-dependent synergy, we made deletions in iNOS promoter constructs fused to reporter genes, transfected RAW 264.7 macrophages, and treated the cells with IFN-gamma and/or LPS. This analysis implicated the region from positions -951 to -911, a cluster of four enhancer elements known to bind IFN-gamma-responsive transcription factors, including an interferon regulatory factor binding site (IRF-E) at nucleotides -913 to -923. Site-specific substitution of two conserved nucleotides within IRF-E in the context of the full-length iNOS promoter ablated IFN-gamma's contribution to synergistic enhancement of transcription. Electromobility shift assays performed with a probe containing IRF-E revealed the existence of a complex in nuclei of RAW 264.7 macrophages that was present only after treatment with IFN-gamma, which reacted specifically with anti-IRF-1 immunoglobulin G and which included a species migrating at 40-45 kD, consistent with the apparent molecular weight of murine IRF-1. Thus, the synergistic contribution of IFN-gamma to transcription of iNOS in RAW 264.7 macrophages requires that IRF-1 bind to IRF-E in the iNOS promoter. In conjunction with the work of Kamijo et al. (Kamijo, R., H. Harada, T. Matsuyama, M. Bosland, J. Gerecitano, D. Shapiro, J. Le, K. S. Im, T. Kimura, S. Green et al. 1994. Science [Wash. DC]. 263:1612), these findings identify iNOS as the first gene that requires IRF-1 for IFN-gamma-dependent transcriptional regulation.

Amino Acid Oxidoreductases↗
PubMed1994

Perioperative morbidity of intracavitary gynecologic brachytherapy.

PURPOSE: To define the incidence and severity of perioperative morbidity and its subsequent management with standard tandem and ovoid insertions and to evaluate pretreatment and treatment factors associated with an increased risk of perioperative morbidity. METHODS AND MATERIALS: Ninety-five tandem and ovoid insertions were performed at the Fox Chase Cancer Center between 1985 and 1992 for cervical (n = 91) and endometrial (n = 4) cancer. Patients were placed on antibiotics in 19%, usually for a positive routine preoperative urine culture, but no patient was given prophylactic antibiotic therapy. Deep-vein thrombosis prophylaxis was practiced for 70% of implants and included subcutaneous heparin (40%), graduated compression elastic stockings (16%), and external pneumatic calf compression (14%). All patients were placed on prophylactic diphenoxylate hydrochloride, with doses ranging from three to eight tablets/day. RESULTS: Intraoperative complications were seen in 3% of implants and included two perforations and a vaginal laceration in two patients. Twenty-four percent of implants (16 patients) developed temperatures of > 100.5 (range 100.6 to 103), although only one patient required implant removal because of fever. Management of fever included antibiotics in 35% and acetaminophen only in 65%. Five implants (5%) were removed emergently secondary to presumed sepsis (n = 1), exacerbation of chronic obstructive pulmonary disease, hypotension, change in mental status (n = 3), and myocardial infarction/congestive heart failure (n = 1). No patient developed a deep-vein thrombosis, pulmonary embolism, gastrointestinal obstruction, or died of a postoperative complication. Univariate analysis of pretreatment and treatment factors revealed older age (p < 0.005) and spinal/epidural anesthesia (p < 0.02) to be associated with increased perioperative morbidity, and older age (p < 0.05) and higher ASA classification (p < 0.02) to be associated with severe complications requiring removal of implant. Multivariate analysis revealed only older age (p < 0.01) to be significantly related to perioperative morbidity. CONCLUSIONS: Fever of > 100.5 was seen in 24% of implants and can be managed successfully without removal of the implant in 96% of cases. Use of antibiotics preoperatively and intraoperatively did not reduce the risk of perioperative temperature elevation. Use of routine diphenoxylate hydrochloride prophylaxis was tolerated without ileus or gastrointestinal obstruction clinically. Although routine deep-vein thrombosis prophylaxis is reasonable, our data would support a low risk of deep-vein thrombosis for untreated patients. Severe perioperative morbidity necessitated premature implant removal in only 5% of cases and was related to older age in multivariate analysis.

Adult↗
PubMed1994

B cells from M167 mu kappa transgenic mice fail to proliferate after stimulation with soluble anti-Ig antibodies. A model for antigen-induced B cell anergy.

The transgenic (TG) mouse strain 207-4, carries mu a + kappa transgenes ligated to the anti-phosphocholine (PC) VH1 and V kappa 24 V region genes from the MOPC-167 myeloma. Although B cells from mice carrying these transgenes respond both in vivo and in vitro to thymus-dependent Ags, they failed to proliferate in response to soluble goat anti-mu Ab or other soluble anti-Ig reagents. On the other hand, B cells from the Sp6 mu kappa anti-trinitrophenyl TG mouse line proliferated normally after stimulation with soluble anti-mu. However, the 207-4 anti-PC transgene positive (TG+) splenic B cells proliferated when stimulated with anti-mu, anti-idiotype, anti-allotype, or PC-conjugated to Sepharose beads. TG+ B cells were also induced to proliferate when stimulated with anti-Lyb-2; thus, their defect may be restricted to signaling through sigM. The lack of response to soluble anti-mu could not be reversed by addition of IL-4, by removal of T cells, by addition of anti-FcR Ab, or by stimulation with F(ab')2 anti-mu. Thus, the failure to proliferate was not caused by active T cell suppression or FcR-mediated inhibition. In mixed cultures of TG+ and transgene negative (TG-) spleen cells, the TG- cells were able to proliferate normally to soluble anti-mu, indicating that suppressive factors were not involved in the unresponsiveness of the TG+ anti-PC-specific B cells. These studies suggest that B cells in the 207-4 anti-PC TG mice exhibit a defect in activation through their sIgM receptors, and this unresponsiveness may reflect a form of Ag-induced tolerance.

Animals↗
PubMed1994

GTPase activation of ATP sulfurylase: the mechanism.

ATP sulfurylase from Escherichia coli K12 catalyzes two, coupled reactions: the hydrolysis of GTP and the formation of activated sulfate (APS). At saturating levels of GTP, the initial rate of APS formation is stimulated 116-fold. The mechanism of this activation has been investigated using isotope trapping, mass spectrometry, and initial velocity kinetic techniques. In the presence of GTP, APS formation proceeds via nucleophilic attack of sulfate at the alpha-phosphoryl group of ATP. Isotope-trapping experiments demonstrate productive, random binding of ATP and GTP. ATP is hydrolyzed to yield AMP and PPi. AMP production requires GTP and is suppressible by sulfate, suggesting GTP-dependent formation of an E*AMP intermediate in the synthesis of APS. Studies using the hydrolysis-resistant nucleotide analogues AMPCPP and GMPPNP demonstrate that GTP hydrolysis precedes scision of the alpha-beta bond of ATP. Product inhibition studies indicate that PPi release occurs prior to the addition of sulfate and APS formation. These results are used to construct a proposed mechanism for the GTP-activated synthesis of APS.

Adenosine Triphosphate↗
PubMed1994

Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part I: Cerebrum, cerebellum, cerebral gray and white matter.

Absolute metabolite concentrations were determined in four different brain regions using phosphorus magnetic resonance spectroscopy (31P MRS) on 10 healthy adult volunteers. Localized spectra were collected simultaneously from the cerebellum and the cerebrum and, later, from deep white matter and cortical gray matter by means of a two-volume ISIS pulse sequence and a Helmholtz-type RF-coli. Each brain spectrum was quantified with a calibration spectrum from a head-shaped simulation phantom. A time-domain fitting routine was used to process the fully relaxed data. Several metabolite concentrations (mmol/liter) differed significantly between the cerebrum and the cerebellum (PME = 3.2 +/- 0.3 and 4.0 +/- 0.6, PCr = 2.9 +/- 0.3 and 3.9 +/- 0.4, NTP = 2.9 +/- 0.2 and 2.6 +/- 0.2, respectively) and between cortical gray matter and deep white matter (PME = 3.1 +/- 0.4 and 4.3 +/- 0.8, PDE = 10.1 +/- 2.5 and 14.2 +/- 2.6, respectively). The concentration of free magnesium ion was found to be similar in all four brain regions (0.53 +/- 0.21 mmol/liter) but the intracellular pH was significantly higher in the cerebellum (7.04 +/- 0.03) than in the cerebrum (6.99 +/- 0.02).

Adult↗
PubMed1994

Assessment of absolute metabolite concentrations in human tissue by 31P MRS in vivo. Part II: Muscle, liver, kidney.

Absolute metabolite concentrations were assessed in the muscle, the liver, and the kidney of healthy human volunteers by 31P MRS. Fully relaxed in vivo spectra were acquired with a surface coil and were localized with an adiabatic ISIS pulse sequence. The spectra were quantified with a subsequent measurement of a calibration phantom and were processed iteratively in the time domain. The following mean metabolite concentrations (mmol/liter) were measured in the resting male calf muscle (n = 9), in the fasting liver (n = 12), and in the orthotopic kidney (n = 5): [PME] = 2.0 +/- 0.6, 3.8 +/- 0.7, and 2.6 +/- 0.9, [Pi] = 2.9 +/- 0.3, 1.8 +/- 0.3, and 1.6 +/- 0.4, [PDE] = 3.8 +/- 0.8, 9.7 +/- 1.5, and 4.9 +/- 1.1, [PCr] = 22.0 +/- 1.2, 0, and 0, [NTP] = 5.7 +/- 0.4, 2.9 +/- 0.4, and 2.0 +/- 0.3, respectively. Several interesting findings are to be emphasized: The concentrations of Pi, PCr, and NTP were 20% lower in the muscle of women than of men. In addition, the pHi was significantly lower in female muscle (6.99 +/- 0.03) than in male muscle (7.05 +/- 0.03). The pHi in the liver (7.12 +/- 0.09) and in the kidney (7.09 +/- 0.08) were higher than in the muscle of both genders. The free magnesium concentration (mmol/liter) was higher in the liver (1.40 +/- 0.64) than in the kidney (0.79 +/- 0.39) and in the muscle (0.52 +/- 0.10).

Adult↗
PubMed1994

Comparison of calibration strategies for the in vivo determination of absolute metabolite concentrations in the human brain by 31P MRS.

Cerebral concentrations of phosphorus metabolites can be assessed non-invasively by 31P MRS provided the metabolite signals are calibrated with the signal of a standard of known concentration. The reliability of the concentration estimates depends mainly on the strategy of calibration. Three strategies were compared by assessing the concentrations both in a test dummy and in the brain of volunteers. The first strategy utilized tissue water as an internal heteronuclear concentration standard. The second and third strategies used as phosphorus solution as an external homonuclear standard; this solution was either put into a reference bottle placed on top of the head or into a simulation phantom measured instead of the head. Localization was always achieved with the ISIS pulse sequence. The two external homonuclear strategies achieved a higher accuracy (mean error approximately 5%) and reproducibility (mean SD approximately 8%) of the concentration estimates than the internal heteronuclear strategy (mean error approximately 11%; mean SD approximately 15%).

Brain↗
PubMed1994

Recovery of human fibroblasts from attack by the pore-forming alpha-toxin of Staphylococcus aureus.

When applied at low concentrations (< 10 micrograms/ml), staphylococcal alpha-toxin generates a small channel in keratinocyte and lymphocyte membranes that permits selective transmembrane flux of monovalent ions. Here we show that a moderate concentration (1-50 micrograms/ml) of alpha-toxin similarly produces a small pore in membranes of human fibroblasts. This process leads to rapid leakage of K+ and to a drop in cellular ATP to 10-20% of normal levels in 2 h. In the presence of medium supplemented with serum and at pH 7.4, the cells are able to recover from toxin attack, so that normal levels of K+ and ATP are reached after 6-8 h at 37 degrees C. The repair process is dependent on the presence of serum in the medium and is very sensitive towards pH. Decreases of pH in the medium to < or = 7.0 as well as increases to > or = 7.8 causes the repair mechanism to fail. The fate of cell-bound toxin molecules was investigated by using a radiolabelled tracer and by immunological detection of toxin exposed at the cell surface. The results indicated that 50-70% of the toxin was shed from cell membranes. However, there was no clear correlation between shedding and recovery, and shedding was also observed in cells that died at pH 7.8. Shedding was not decisive for repair, since cells that had recovered from toxin attack continued to carry 30-40% of initially bound toxin on their cell surface. Blockade of Na+/K(+)-ATPases with ouabain evoked similar kinetics of K(+)-depletion in control cells, compared with cells that had just recuperated from toxin attack and that still carried 30-40% alpha-toxin on their surface. We therefore tentatively concluded that repair of alpha-toxin lesions was due to closure of small pores, rather than from compensation of membrane leaks by up-regulation of Na+/K(+)-ATPase activity. We speculate that repair of small membrane lesions may extend to other agents that produce channels of similar nature in nucleated cells. Larger pores created by E. coli hemolysin or streptolysin O, both of which form larger functional transmembrane lesions, could not be repaired by fibroblasts.

Adenosine Triphosphate↗
PubMed1994

A new type of a lethal osteochondrodysplasia with angel-shaped brachyphalangy.

A hydropic stillborn female fetus of 22 weeks gestation with shortlimbed skeletal dysplasia and brachyphalangy is described. The markedly shortened phalanges of both hands had a most unusual angel-like configuration radiologically. Histological examination and comparison with a normal hand of the same gestational age revealed this appearance to be due to disturbed enchondral ossification with premature calcification of epiphyseal cartilage and thickening and outfolding of diaphyseal bone as wing-shaped appositions. Magnetic resonance imaging of the fetus demonstrated marked hyperplasia of cartilage, most impressive in the pelvis. This new type of lethal bone dysplasia may be placed in the group of metatropic dysplasias and similar disorders.

Adult↗
PubMed1994

Transient bifrontal solitary periventricular cysts in term neonates.

We describe three children born at term investigated for neonatal seizures or transient apnoea. Cranial ultrasound and MRI unexpectedly revealed symmetrical periventricular cysts adjacent to the anterior horns. We found no evidence of prenatal viral infection, intraventricular or subependymal haemorrhage or hypoxic-ischaemic lesions. The lesions were not seen on MRI at 3 months of age, but there was no compensatory dilatation of the anterior horns nor secondary loss of white matter. The appearance and location of these transient cysts were different from those of the cystic changes which typically follow germinal matrix haemorrhage or periventricular leukomalacia. Their pathogenesis and clinical significance remain to be determined.

Brain Diseases↗
PubMed1994

Hemodynamic and respiratory effects of pneumoperitoneum and PEEP during laparoscopic pelvic lymphadenectomy in dogs.

Extended laparoscopic operations are being performed increasingly in high-risk patients. To assess the effects of increased intraabdominal pressure (IAP) and positive end-expiratory pressure (PEEP) on the hemodynamic and respiratory system during extended procedures a carbon dioxide pneumoperitoneum was artificially induced in 10 dogs undergoing laparoscopic pelvic lymphadenectomy. An increase in IAP up to 15 mmHg had no negative effect on the cardiovascular system. However, the combination of an increased IAP (10-15 mmHg) with PEEP (8 cmH2O) markedly depressed the hemodynamic variables. Measurement of arterial carbon dioxide and fractional end-tidal carbon dioxide revealed significant CO2 retention. We conclude from the results that laparoscopic pelvic lymphadenectomy should be performed in high-risk patients only under general anesthesia with expanded cardiopulmonary monitoring.

Animals↗
PubMed1994

Bolus injection of thrombolytic agents during cardiopulmonary resuscitation for massive pulmonary embolism.

Thrombolytic therapy has proved to be efficacious in the treatment of massive and fulminant pulmonary embolism (PE), but thrombolysis has been considered as contraindicated during cardiopulmonary resuscitation (CPR). This review on the administration of thrombolytic agents in patients who have suffered massive PE necessitating CPR summarises 14 anecdotal reports and three case series involving 34 patients. The case series revealed an overall initial survival rate of 55-100% following bolus administration of thrombolytic agents. In general, bleeding complications were managed conservatively. The establishment of the diagnosis may be feasible using echocardiography or bedside angiography during CPR. However, therapeutic measures should be taken without delay; the patient's history and the clinical picture may thus be the only diagnostic criteria. Even where myocardial infarction is misinterpreted as PE during CPR, bolus injection of a thrombolytic agent can be an appropriate therapeutic option. An alternative may be mechanical catheter fragmentation of the thrombus with subsequent local thrombolysis. Surgery may be restricted to hospitals with ready access to extracorporeal circulation. We conclude that early administration of thrombolytic agents during PE necessitating CPR may help to reduce mortality. We favour the administration of urokinase (2- to 3,000,000-U bolus) or rt-PA.

Adult↗
PubMed1994

Evoked potential monitoring during repeatedly induced ventricular fibrillation for internal defibrillator implantation.

Repeated induction of ventricular fibrillation (VF) with circulatory compromise during implantable cardioverter defibrillator (ICD) testing may cause cerebral injury. To test this hypothesis, somatosensory evoked potentials (SEP), a more sensitive marker of injury, were recorded in patients (N = 10) undergoing ICD implantation. SEP were recorded before induction of anesthesia, after induction of anesthesia, before and at several times following induction of VF. Possible modifying factors of the SEP measurements such as anesthetic application, blood pressure, body temperature, and hematocrit remained constant throughout the operations. Central conduction time was unaffected by ICD defibrillation testing. Amplitude of SEP primary complexes was transiently reduced at 34.9% (P < 0.01) by defibrillation testing, but returned to control within 10 minutes after testing. It is concluded that while ICD defibrillation testing may produce transient changes in SEP, there is no evidence of residual cerebral injury.

Adult↗
PubMed1994

[In vitro study of the formation of NO2 in inhalation of nitrogen monoxide].

OBJECTIVE: Nitric oxide (NO), an endogenous endothelium-derived relaxing factor, produces profound relaxation of vascular smooth muscle. Thus, inhaled NO is a potent and selective pulmonary vasodilator that may be useful for treatment of pulmonary hypertension of different aetiologies. However, the main danger of NO inhalation is spontaneous formation of toxic nitrogen dioxide (NO2) if NO is added to an oxygen-containing gas mixture. This chemical reaction depends on the time available for the oxidation and the concentration of NO and oxygen. The aim of this study was to assess in vitro the spontaneous formation of NO2 during administration of various NO concentrations with a ventilator. A modified ventilator system is described which can deliver NO within clinically relevant concentrations avoiding excessive formation of toxic NO2. METHODS: The system was evaluated using an artificial lung. NO and NO2 concentrations were measured by chemiluminescence at the proximal and distal end of the inspiratory limb. In-vitro NO2 formation was assessed during administration of 10, 20, 40, 80 ppm NO while ventilating with an FiO2 of 0.25, 0.5 and 0.75, an inspiratory minute volume of 5, 7.5 and 10 l/min (IMV) and a respiratory rate of 12/min. RESULTS: NO2 concentration correlated with increasing FiO2 and NO concentration and was inversely correlated to IMV. While ventilating with 5-40 ppm NO, an FiO2 of 0.25-0.75 and an IMV of 10 l per minute, the NO2 formation was measured to be less than 0.2 ppm and thus not clinically relevant. During administration of 80 ppm NO the NO2 formation increased to 0.3-0.6 ppm. CONCLUSION: We conclude that for patients safety concentrations less than 80 ppm of inhaled NO should be used with this ventilator system. In addition, online monitoring of the NO2 concentration in the inspiratory limb should always be performed.

Artificial Organs↗