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Biomedical subjects

M Mueller

Publications and source records attributed to M Mueller.

At least 73 records · Page 4Linked to original sources
PubMed1997

L-arginine treatment alters the kinetics of nitric oxide and superoxide release and reduces ischemia/reperfusion injury in skeletal muscle.

BACKGROUND: Constitutive nitric oxide synthase (cNOS) may produce species involved in ischemia/reperfusion (I/R) injury: NO in the presence of sufficient L-arginine and superoxide at the diminished local L-arginine concentration accompanying I/R. METHODS AND RESULTS: During hindlimb I/R (2.5 hours/2 hours), in vivo NO was continuously monitored (porphyrinic sensor), and L-arginine (chromatography), superoxide (chemiluminescence), and I/R injury were measured intermittently. Normal rabbits were compared with those infused with L-arginine 4 mg x kg(-1) x min(-1) for 1 hour. In both groups, approximately 6 minutes into ischemia, a rapid increase of NO from its basal level of 50+/-17 to 115+/-7 nmol/L, P<.005 (microvessels), was observed. In animals not treated with L-arginine, NO dropped below basal to undetectable levels (<1 nmol/L) during reperfusion. In animals treated with L-arginine, the decrease of NO was slower, such that substantial amounts accumulated during reperfusion (25 nmol/L). Decreased NO during I/R was accompanied by increased superoxide, which during reperfusion reached 50 nmol/L without or 23 nmol/L with L-arginine treatment. Calcium-dependent cNOS was a major source of superoxide release (inhibited 70% by L-NMMA and 25% by L-NAME) during I/R. CONCLUSIONS: L-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77+/-0.95 versus 11.66+/-2.21 microm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P<.005).

Animals↗
PubMed1997

Effectiveness of gabapentin in controlling spasticity: a quantitative study.

The purpose of this investigation was to study the effectiveness of gabapentin in controlling spasticity in persons with spinal cord injury (SCI) using a surface EMG-based quantitative assessment technique called the brain motor control assessment (BMCA). Six men from a Veterans Affairs Medical Center with spasticity due to traumatic SCI were studied as part of a multi-center, placebo-controlled, cross-over, clinical trial of gabapentin. Spasticity was evaluated using multi-channel surface EMG recordings of muscles in the lower extremities, abdomen and low back before and during treatment with oral gabapentin or placebo. Gabapentin or placebo was given orally in doses 400 mg three times daily for 48 h. Following a 10 day wash-out period subjects were crossed-over to receive the medication not received the first time. This was followed by an elective open-label extension. Group results during the controlled trial did not reach statistical significance at the dosage used. One subject demonstrated a dramatic improvement in spasticity that was apparent both clinically and with the BMCA. Other subjects demonstrated modest improvements which were seen in the BMCA but not recognized clinically. During the open label extension, the four subjects who participated experienced important clinical improvements with higher doses (to 3600 mg/day). These improvements were often in components of spasticity in which the BMCA had detected subclinical changes during the cross-over trial. A seventh subject was studied using the BMCA at doses of 1200 mg T.I.D. gabapentin, off gabapentin and 800 mg T.I.D. gabapentin and demonstrated quantitatively a dose-related effect with higher doses of gabapentin which matched clinical observations. Gabapentin at doses of 400 mg T.I.D. may be effective in controlling some features of spasticity in persons with SCI. Higher doses provide greater control of spasticity, and controlled studies using higher doses are needed to evaluate gabapentin's efficacy.

Acetates↗
PubMed1997

Gabapentin for the treatment of spasticity in patients with spinal cord injury.

Our serendipitous observations suggested that some patients with spasticity appeared to have improved following the administration of the anticonvulsant drug gabapentin. As some patients with spasticity are either refractory to or intolerant of established medical treatments, we conducted this study to investigate the effect of gabapentin on spasticity in patients with spinal cord injury. Twenty-five patients with spinal cord injury and spasticity received oral gabapentin (2400 mg over 48 h) in a randomized, double blind, placebo-controlled crossover study. We assessed responses by measuring the Ashworth spasticity scale, muscle stretch reflexes, presence of clonus and reflex response to noxious stimuli. Patient ratings were obtained using a Likert Scale. Administration of gabapentin, but not placebo, was associated with an 11% reduction in spasticity as measured by the Ashworth Scale (P = 0.04) and by a 20% reduction in the Likert Scale (P = 0.0013). Significant changes were not obtained for the other measures. The data obtained suggest that gabapentin may be useful in the management of spasticity associated with spinal cord injury.

Acetates↗
PubMed1997

Delayed cyanide poisoning following acetonitrile ingestion.

Acetonitrile (methyl cyanide) is a common industrial organic solvent but is a rare cause of poisoning. We report the first recorded UK case. Acetonitrile is slowly converted to cyanide, resulting in delayed toxicity. We describe a case of deliberate self-poisoning by a 39-year-old woman resulting in cyanide poisoning 11 hours later which was successfully treated by repeated boluses of sodium nitrite and thiosulphate. The half-life of conversion of acetonitrile was 40 hours and harmful blood cyanide levels persisted for over 24 hours after ingestion. Departments treating or advising in cases of poisoning need to be aware of the delayed toxicity of acetonitrile. Monitoring in an intensive care unit of cases of acetonitrile poisoning should continue for 24-48 hours.

Acetonitriles↗
PubMed1996

Addition of anticholinergic solution prolongs bronchodilator effect of beta 2 agonists in patients with chronic obstructive pulmonary disease.

A randomized, double-blind placebo-controlled clinical trial was designed to assess the safety, efficacy, and duration of the bronchodilation resulting from the addition of 500 micrograms of ipratropium bromide (Atrovent; Boehringer Ingelheim, CT) inhalation solution to standard small volume nebulizer treatments with 2.5 mg albuterol inhalation solution. A total of 195 patients (63% men, average age 64 years) with > 10 pack-year smoking histories and stable, moderate-to- severe chronic obstructive pulmonary disease (COPD; forced expiratory volume in 1 second [FEV1] 1.02 liter, 38.8% predicted) from eight university-affiliated chest clinics in seven U.S. cities were enrolled into the study. Asthma, rhinitis, and eosinophilia were exclusions, as was daily use of > 10 mg of prednisone (or 20 mg on alternate days). There was a 2-week stabilization period during which the patients were instructed in the use of the small volume nebulizers, which they used three times daily with albuterol alone. They were asked to keep daily logs of peak flow rates, pulmonary symptoms, and additional medication usage. On their test day 1 the subjects came to the pulmonary function laboratory having been off theophylline for 24 hours and beta 2-agonists for 12 hours and performed a baseline spirometry. They then received their morning small volume nebulizer treatment of albuterol to which was added either 500 micrograms if ipratropium bromide or a saline placebo. Spirometry was repeated at 15, 30, and 60 minutes, and then hourly for 8 hours. Subjects then took home a 2-week supply of albuterol and test drug for thrice daily use in their small volume nebulizer. They were evaluated for pulmonary symptoms and adverse effects every 14 days. The 8-hour spirometry was repeated on test day 43 and finally on test day 85. Primary data evaluated were the peak increase in FEV1 and the area between the FEV1 baseline value and the 8-hour FEV1 curve. Similar calculations were made for forced vital capacity (FVC) and 25-75% forced expiratory flow (FEF25-75%). On test day 1 the peak increase in FEV1 for the ipratropium bromide + albuterol subjects was 26% greater than those on placebo + albuterol (p < 0.003). The area under the 8-hour FEV1 curve was 64% greater in those given ipratropium bromide on test day 1 (p < 0.0002). Similar increases were seen in FVC and FEF25-75%. The peak improvements in FEV1 and FVC with the addition of ipratropium bromide to albuterol were maintained on test days 43 and 85. Considering the safety and efficacy profiles of this combination, the data would suggest that ipratropium bromide inhalation solution should be considered first-line therapy for those patients with COPD requiring small volume nebulizer treatments.

Administration, Intranasal↗
PubMed1996

Three dihydroanthracenones from Gasteria bicolor.

The stem and leaves of Gasteria bicolor afforded three new dihydroanthracenones namely 3,4-dihydro-2,6,9-trihydroxy-8-methyl-1(2H)-anthracenone (gasteriacenone A), 3,4-dihydro-2,4,9-trihydroxy-6-methoxy-8-methyl-1(2H)-anthracenone (gasteriacenone B) and 3,4-dihydro-4,6,9-trihydroxy-7-carbomethoxy-8-methyl-1(2H)-anthraceno ne (gasteriacenone C). Their structures were determined by spectroscopic methods including 2D NMR techniques.

Animals↗
PubMed1996

Tracheobronchial ruptures in children.

Tracheobronchial ruptures in children after blunt trauma are rare, with an incidence at our clinic of 0.17% of juvenile thoracic injuries in the years 1985 to 1994. The symptoms are variable, and these injuries frequently occur in conjunction with other thoracic injuries, leading to delays in diagnosis. Diagnosis, conservative and operative treatment, and late complications are discussed by presenting four different cases of children with lesions of the tracheobronchial tree after blunt trauma.

Adolescent↗
PubMed1996

Influence of different volume therapy regimens on regulators of the circulation in the critically ill.

Various vasoactive substances are involved in the regulation of the macro- and microcirculation. We have investigated if these regulators change during long-term volume therapy with human albumin (HA) or hydroxyethylstarch solution (HES) in trauma and sepsis patients. To maintain pulmonary capillary wedge pressure (PCWP) at 10-15 mm Hg, either 20% HA (HA-trauma, n = 14; HA-sepsis, n = 14) or 10% low-molecular weight HES solution (HES-trauma, n = 14; HES-sepsis, n = 14) were infused for 5 days, otherwise patient management did not differ between the two groups (trauma/sepsis). Mean arterial pressure (MAP), heart rate (HR), PCWP and cardiac index (CI) were monitored in all patients. Liver function was assessed using the monoethylglycinexylidide (MEGX) test, and gastric intramucosal pH (pHi) was monitored by tonometry to assess splanchnic perfusion. Plasma concentrations of vasopressin, endothelin-1, adrenaline, noradrenaline, atrial natriuretic peptide and 6-keto-prostaglandin F1 alpha were measured from arterial blood samples. All measurements were carried out on the day of admission to the intensive care unit (trauma patients) or on diagnosis of sepsis, and daily over the next 5 days at 12:00. MAP, HR and PCWP did not differ between the corresponding subgroups (trauma/sepsis). Cl increased significantly more in the HES than in the HA groups. pHi and MEGX plasma concentrations did not differ in the trauma patients throughout the study. Both were lower than normal in the sepsis groups and increased more markedly in the HES than in the albumin-treated patients (P < 0.05). In the trauma patients, concentrations of all vasoactive regulators were very similar in both groups. In both sepsis groups, vasopressors (vasopressin, endothelin-1, noradrenaline and adrenaline) were significantly increased above normal at baseline and decreased more markedly in HES than in HA patients. Concentrations of atrial natriuretic peptide increased only in the HA patients (from 159 (SD 31) to 215 (38) pg ml-1 on day 2). Plasma concentrations of 6-keto-prostaglandin F1 alpha decreased significantly only in the HES sepsis patients (from 112 (25) to 47 (15) pg ml-1).

Adult↗
PubMed1996

Inhibition of the growth of glioblastomas by CGP 41251, an inhibitor of protein kinase C, and by a phorbol ester tumor promoter.

Protein kinase C (PKC) plays a central role in signal transduction pathways that mediate the action of certain growth factors, tumor promoters, and cellular oncogenes. To explore whether PKC might be an appropriate target for the chemotherapy of human brain tumors, cell lines were established from five glioblastomas, one mixed gliosarcoma and glioblastoma, two astrocytomas, and one choroid plexus carcinoma. The staurosporine derivative CGP 41251, an inhibitor of PKC, inhibited cell proliferation in all nine cell lines with an IC50 in the range of 0.4 micrometer. Drug withdrawal and clonogenicity assays showed that CGP 41251 induced an irreversible growth arrest. Three cell lines were examined in detail: two human glioblastoma cell lines, GB-1 and GB-2, and one gliosarcoma cell line, GS-1. All of these three cell lines were highly aneuploid and displayed morphologies and immunohistochemical markers characteristic of the glial lineage. The compound 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter and activator of PKC, also inhibited the growth of these cell lines. CGP 41251 in combination with TPA caused further growth inhibition. Cultures treated with CGP 41251 displayed an increase in the fraction of cells in G2-M, a decrease of cells in S phase, and no consistent effect on G0-G1. Immunohistochemical analyses demonstrated that growth inhibition by CGP 41251 was associated with the formation of giant nuclei with extensive fragmentation and apoptotic bodies. These effects of CGP 41251 were abrogated by withdrawal of serum from the medium or by exposure of these cells to aphidicolin, actinomycin D, cycloheximide, or TPA. In contrast to the effects seen with the glioblastoma cell lines, nontransformed astrocyte lines remained viable in the presence of 0.4 and 0.8 micrometer CGP 41251 and displayed only a slight increase in the fraction of giant nuclei with fragmentation. The antitumor activity of CGP 41251 was demonstrated in vivo against xenografts of the glioblastoma cell lines U87 MG and U373 MG. These findings suggest that CGP 41251 might be a useful agent for the treatment of glioblastomas.

Aged↗
PubMed1994

Solution structure of a POU-specific homeodomain: 3D-NMR studies of human B-cell transcription factor Oct-2.

The POU DNA-binding motif defines a conserved family of eukaryotic transcription factors involved in regulation of gene expression. This bipartite motif consists of an N-terminal POU-specific domain (POUs), a flexible linker, and a C-terminal POU-specific homeodomain (POUHD). Here we describe the solution structure of a POU-specific homeodomain. An NMR model is obtained from Oct-2, a human B-cell specific transcription factor which participates in the regulation of immunoglobulin genes. A fragment of Oct-2 containing POUHD and an adjoining linker was expressed in Escherichia coli and characterized by three-dimensional nuclear magnetic resonance (3D-NMR) spectroscopy. Complete 1H and 15N resonance assignment of the POUHD moiety is presented. The POUHD solution structure, as calculated by distance geometry and simulated annealing (DG/SA), is similar to that of canonical homeodomains. A salient difference between solution and crystal structures is observed in the C-terminal segment of alpha-helix 3 (the HTH recognition helix), which is not well ordered in solution. Because this segment presumably folds upon specific DNA binding, its flexibility in solution may reduce the intrinsic DNA affinity of POUHD in the absence of POUs.

Amino Acid Sequence↗
PubMed1994

CGP 48664, a new S-adenosylmethionine decarboxylase inhibitor with broad spectrum antiproliferative and antitumor activity.

Inhibitors of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (SAMDC), derived from methylglyoxal-bis(guanylhydrazone) (MGBG), have been shown to have significant antitumor activity in several human solid tumor systems (U. Regenass et al., Cancer Res., 52:4712-4718, 1992). From an ongoing effort to synthesize derivatives with increased enzyme specificity and potency and improved antitumor efficacy, we have now identified CGP 48664, a 4-amidinoindan-1-one 2'-amidinohydrazone (J. Stanek et al., J. Med. Chem., 36:2168-2171, 1993). The compound displays potent inhibition of SAMDC (50% inhibitory concentration, 5 nM), modest inhibition of diamine oxidase (50% inhibitory concentration, 4 microM), and no detectable inhibition of ornithine decarboxylase. CGP 48664 inhibits the growth of a panel of human and mouse tumor cell lines, including one which expresses the multidrug resistance phenotype, with 50% inhibitory concentrations ranging between 0.3 and 3 microM. CGP 48664 does not seem to utilize the polyamine transport carrier system since it competes poorly with spermidine for uptake into L1210 cells (Ki 161 microM) and inhibits the growth of polyamine transport-deficient Chinese hamster ovary cells. Relative to MGBG or previously described MGBG analogues, CGP 48664 accumulates to much lower intracellular concentrations. Treatment of the L1210 cell for 48 h with 3 microM CGP 48664 decreases SAMDC activity to < 10% of control and initiates a compensatory 3-fold rise in ornithine decarboxylase. Consistent with SAMDC inhibition, putrescine pools increase 10-fold, whereas spermidine and spermine pools fall to < 10% of control. In contrast to MGBG, CGP 48664 displays attenuated antimitochondrial activity as indicated by a lack of effect on pyruvate oxidation and mitochondrial DNA levels under treatment conditions which inhibit cell proliferation. Specificity of drug action was indicated further by prevention of L1210 cell growth inhibition by exogenous spermidine or spermine. More convincingly, Chinese hamster ovary cells made approximately 1000-fold resistant by chronic exposure to the analogue were found to selectively overexpress SAMDC mRNA due to gene amplification. The new SAMDC inhibitor showed potent antitumor activity against syngeneic tumors (B16 melanoma and Lewis lung carcinoma) and nude mouse human tumor xenografts (T-24 bladder carcinoma, SK MEL-24 melanoma, and MALME-3M melanoma). On the basis of its novel structure, its apparent specificity of action, and its potent antitumor activity, CGP 48664 is the candidate drug for further preclinical development.

Adenosylmethionine Decarboxylase↗
PubMed1994

Changes in arterial wall compliance after endovascular stenting.

PURPOSE: The response of arterial wall to endovascular stenting after angioplasty is not well understood. Additionally, changes in the elastic properties of stented vessels are unknown in situ. Vascular compliance was measured in normal canine iliac arteries (n = 11) before and after intravascular ultrasound-guided deployment of self-expandable metallic stents. METHODS: Nine animals were restudied and killed 1, 2, and 4 weeks after initial deployment, and two dogs were studied at deployment only. An absolute induction angiometer was used to make in situ measurements of vessel compliance via catheter-based delivery. The angiometer consists of a wire loop probe, which conforms to the diameter of the vessel in which it is placed. Systolic/diastolic changes in loop diameter are translated into measureable changes of induced voltage. RESULTS: Mean compliance of the artery before and immediately after stenting was 4.4 +/- 2.1 and 1.9 +/- 2.0 (x 10(-2) diameter %/mm Hg), respectively. As early as 1 week after deployment, stented arteries began to lose expansile properties, and some were noncompliant. At explantation diminished compliance was accompanied by a periadventitial fibrous reaction around stented vessels. A thin, unobstructing layer of neointimal hyperplasia covered the iliac stents at all intervals, and all vessels remained patent and free of thrombus. CONCLUSIONS: The potential advantages provided by a flexible, radially compliant stent are lost within a relatively short time after implantation in nonatherosclerotic canine arteries.

Animals↗
PubMed1994

Traumatic coronary sinocameral fistula from a penetrating cardiac injury: case report and review of the literature.

Clinically apparent penetrating cardiac wounds require emergent surgical therapy without the theoretical benefit of preoperative evaluation apart from the physical examination. Residual intracardiac injuries discovered following the successful resuscitation and repair of immediate life-threatening cardiac wounds should be sought in survivors of chest trauma who demonstrate new regurgitant murmurs or evidence of congestive heart failure. To our knowledge, we report here the second case of a traumatic left ventricle-to-coronary sinus fistula, along with recommendations for its management.

Adult↗
PubMed1994

Effect of filler content of restorative resins on retentive strength to acid-conditioned enamel.

In this in vitro study the retentive strength of enamel, either conventionally etched with a phosphoric acid gel or conditioned with an oxalic acid containing etching agent, was investigated. Five experimental restorative resins with filler contents between 0 and 78% by weight were polymerized on the etched enamel surfaces. In spite of the pronounced micromorphological differences of the patterns generated with the two etching agents, the bond strengths mediated were very similar. Application of an intermediate low-viscous or adhesive resin had no influence on bond strength. Exponential relationships were found between the filler content of the resins on the one hand and their flexural moduli and flexural strengths on the other. Significant exponential relations were also demonstrated between filler content and bond strength to the etched enamel surface. The linear relationship between mechanical properties of the resins and their bond strengths to etched enamel indicates that debonding occurred by cohesive failure in resin.

Acid Etching, Dental↗
PubMed1993

[Does laparoscopic lysis of adhesions make sense?].

Between May 1989 and December 1991 23 patients were operated on laparoscopically for symptomatic peritoneal adhesions. 19 were followed up by telephone using a standardized questionnaire an average of 18.3 months post-operatively (range 5-36 months). 12 patients were totally painfree, 3 complained of slight pain, 2 patients of fairly severe and 2 of severe pain. 15 patients considered the outcome of the operation to be good or fairly good and 18 said they would undergo the same operation in similar circumstances. We therefore recommend laparoscopic adhesiolysis in cases of acute or chronic abdominal pain, provided other causes of abdominal discomfort have been ruled out.

Abdominal Pain↗