Cancer-related diarrhea: a neglected cause of cancer-related symptom distress.
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Clinical Nursing Research↗
Biomedical subjects
J Neumann
Publications and source records attributed to J Neumann.
Octreotide in the management of diarrhea induced by graft versus host disease.
PURPOSE/OBJECTIVES: To evaluate the potential benefit of the somatostatin analogue, octreotide, for the management of diarrhea induced by graft versus host disease (GVHD). DATA SOURCE: Pilot clinical trial involving 21 patients undergoing allogeneic transplant with positive histologic or radiographic evidence of GVHD of the gastrointestinal tract who failed antidiarrheal therapy with loperamide. DATA SYNTHESIS: A complete response, defined as resolution of diarrhea, was seen in 71% of trial participants (15 of 21 patients). At the dose and scheduling used (500 mcg i.v. three times daily for a median of seven consecutive days), octreotide was extremely well tolerated in all patients. CONCLUSIONS: In this pilot study, octreotide treatment was effective in reducing the amount of diarrhea in patients with acute GVHD. The data suggest that patients receiving octreotide early in the course of the diarrhea experienced more benefit than patients with persistent diarrhea prior to receiving octreotide. The demonstrated safety and efficacy of octreotide in this patient population support further investigation of this therapeutic strategy for GVHD-induced diarrhea. A randomized, controlled, clinical trial of octreotide versus loperamide for the initial treatment of GVHD-induced diarrhea is warranted. IMPLICATIONS FOR NURSING PRACTICE: Octreotide should be administered early in the course of GVHD as soon as onset of diarrhea is noted and should be discontinued as soon as diarrhea resolves to avoid constipation and the potential development of an ileus. Because response to the drug usually occurs quickly, maintaining treatment for additional days or weeks is unnecessary. If a benefit is not seen in four to seven days, continuing octreotide therapy is neither cost-effective nor prudent.
Adult↗
Long-term beta adrenoceptor-mediated alteration in contractility and expression of phospholamban and sarcoplasmic reticulum Ca(++)-ATPase in mammalian ventricle.
We studied the influence of prolonged administration of the beta adrenoceptor agonist isoproterenol on contractile parameters and expression of sarcoplasmic reticulum (SR) Ca(++)-ATPase and phospholamban, genes important for Ca++ uptake into the SR. Isoproterenol (Iso), 0.9% NaCl (Ctr), propranolol (Prop) or Iso plus Prop were administered to rats by subcutaneous infusion with osmotic minipumps for 1, 2, 3, 4, 8, 13 and 26 days, respectively. The positive inotropic effect of Iso was impaired in rats pretreated with Iso in vivo. Iso pretreatment shortened time to peak tension (TPT) by 28%, time of relaxation (RT) by 27% and total contraction time (TCT) by 27% compared with the appropriate controls (day 2). The shortening of time-dependent contractile indices started after 1 day of Iso pretreatment, reached a maximum after 2 days and remained reduced for 4 days. Longer treatment by Iso failed to affect time parameters, whereas the positive inotropic effect of Iso added to the isolated muscles persisted. The shortened contractile time parameters were accompanied by diminished mRNA and protein expression of phospholamban (PLB) and SR-Ca(++)-ATPase (SERCA). The mRNA levels for PLB and SERCA were maximally reduced by 31 +/- 1.3% and 41 +/- 1.4% in the Isopretreated group (2 days) respectively. The reduced mRNA levels were accompanied by reduced levels of the corresponding proteins. It is concluded that altered levels of PLB and SERCA probably account for the noted changes in contractile time parameters in the mammalian heart.
Animals↗
[The effect of the primary operation on reoperations on the thyroid gland].
The authors analyze the possibility to reduce the number of reoperations of the thyroid gland, based on a group of thyroid operations performed at the Surgical Clinic of the Second Medical Faculty Charles University and Faculty Hospital Motol during the 22-year period from 1975-1997. 507 reoperations from a total number of 4501 thyroid operations amount to 11.3%. In the authors opinion correct indication of the operation is most important as well as the correct extent and technique of the primary operation. The achieved results are except for unilateral temporary lesions of the NLR comparable with primary operations.
Adolescent↗
[Esophageal cyst--a rare cause of backache].
Cysts of the esophagus are rare mediastinal tumors presenting a large variety of clinical symptoms. Even with modern methods of examination an exact diagnosis is difficult to obtain and often only possible after histological examination. Complications are perforation, or pulmonary, thoracic or esophageal haemorrhage. First choice of therapy is the exstirpation. We report on a 50 year old man with backache and the initial diagnosis of renal colic. Only the magnetic resonance image showed an isolated mediastinal esophageal cyst as the reason. The cyst was removed by thoracotomy. The operation and treatment were without complications. Symptomatology, diagnostical pitfalls and the therapy are described.
Back Pain↗
Somatotopic source arrangement of 600 Hz oscillatory magnetic fields at the human primary somatosensory hand cortex.
Based on low-noise superconducting quantum interference devices (SQUIDs) magnetoencephalography allows the non-invasive detection of low-amplitude high-frequency brain responses evoked about 20 ms after electric hand nerve stimulation. The main spectral energy of these brief oscillatory bursts (near 600 Hz) is in the range typical for rapidly repeated action potentials. Here, the magnetic fields of median and ulnar nerve evoked 600 Hz bursts are shown to exhibit a somatotopic arrangement at the primary somatosensory hand cortex closely resembling that of the concomitant postsynaptic primary cortical response (¿N20m'). Two possible burst generators are discussed: (1) repetitive spike volleys conducted along the terminal segments of somatotopically arranged thalamocortical axons, and (2) early intracortical spike activity in nerve-specific subterritories of the 3b hand area.
Brain Mapping↗
Quantification of the cAMP response element binding protein in ventricular nuclear protein from failing and nonfailing human hearts.
Alterations in the expression of myocardial regulatory proteins (e.g. beta-adrenoceptor, inhibitory G-proteins) in human heart failure are associated with excessive stimulation of the cAMP signalling pathway by endogenous catecholamines. The transcription factor cAMP response element binding protein (CREB) mediates cAMP-dependent transcriptional activation and is expressed in the human heart. Here, CREB protein was immunologically quantified in ventricular nuclear protein preparations from nonfailing donor hearts (n = 8) and from failing hearts transplanted due to dilative (n = 10) or ischemic cardiomyopathy (n = 6). CREB expression was unchanged in ventricular nuclei from failing hearts compared to the nonfailing controls suggesting that expressional alterations in human heart failure cannot be explained by altered expression of CREB.
Cyclic AMP Response Element-Binding Protein↗
Rescue of cardiac alpha-actin-deficient mice by enteric smooth muscle gamma-actin.
The muscle actins in higher vertebrates display highly conserved amino acid sequences, yet they show distinct expression patterns. Thus, cardiac alpha-actin, skeletal alpha-actin, vascular smooth muscle alpha-actin, and enteric smooth muscle gamma-actin comprise the major actins in their respective tissues. To assess the functional and developmental significance of cardiac alpha-actin, the murine (129/SvJ) cardiac alpha-actin gene was disrupted by homologous recombination. The majority ( approximately 56%) of the mice lacking cardiac alpha-actin do not survive to term, and the remainder generally die within 2 weeks of birth. Increased expression of vascular smooth muscle and skeletal alpha-actins is observed in the hearts of newborn homozygous mutants and also heterozygotes but apparently is insufficient to maintain myofibrillar integrity in the homozygous mutants. Mice lacking cardiac alpha-actin can be rescued to adulthood by the ectopic expression of enteric smooth muscle gamma-actin using the cardiac alpha-myosin heavy chain promoter. However, the hearts of such rescued cardiac alpha-actin-deficient mice are extremely hypodynamic, considerably enlarged, and hypertrophied. Furthermore, the transgenically expressed enteric smooth muscle gamma-actin reduces cardiac contractility in wild-type and heterozygous mice. These results demonstrate that alterations in actin composition in the fetal and adult heart are associated with severe structural and functional perturbations.
Actins↗
Increased expression of cardiac phosphatases in patients with end-stage heart failure.
Type 1 phosphatase activity was increased in membrane vesicles from failing human ventricles compared with non-failing controls. Likewise, expression of the mRNA encoding for type 1 phosphatase was enhanced by 37%. The present study provides evidence that alterations of phosphatase activity coincide with end-stage heart failure. Thus, enhanced activity of phosphatases may be causally related to heart failure and/or may aggravate the well known decreased cardiac responsiveness to positive inotropic agents in end-stage heart failure.
Adenylyl Cyclases↗
Interaction of otoacoustic emissions with additional tones: suppression or synchronization?
The influence of an external tone on transitory evoked otoacoustic emissions (TEOAE) is investigated. Three different averaging techniques were used with the same acoustic stimulus paradigm. These techniques permitted the separation of those parts of the otoacoustic emission (OAE) that contribute to the transitory evoked otoacoustic emission and those parts of the OAE that are synchronized to the continuous tone. The experiments show that the total energy of the OAE is not reduced in the presence of an additional tone. The 'suppression' of TEOAEs is an effect of synchronization and the subsequent elimination of the 'suppressed' emission in the averaging procedure.
Acoustic Stimulation↗
The effect of the protein phosphatases inhibitor cantharidin on beta-adrenoceptor-mediated vasorelaxation.
1. Cantharidin, an inhibitor of protein phosphatase types 1 (PP1) and 2A (PP2A), increased basal tone of bovine isolated coronary artery rings (CARs) with and without endothelium in a time- and concentration-dependent manner with pEC50 values of about 5.1 and 5.2, respectively, for both preparations. 2. Beta-Adrenoceptor stimulation with isoprenaline (Iso; 0.03-100 microM) or inhibition of phosphodiesterase activity by 3-isobutyl-1-methylxanthine (IBMX; 10-1000 microM), respectively, relaxed CARs precontracted with KCl (75 mM). CARs with and without endothelium showed no difference in the relaxing response to Iso and IBMX, respectively. 3. Cantharidin (3 microM) attenuated vasorelaxation induced by Iso (0.03-100 microM) in CARs with and without endothelium in a time-dependent manner, whereas vasorelaxation induced by IBMX (10-1000 microM) was not attenuated by 3 microM cantharidin. 4. Cantharidin (3 microM) did not affect cyclic AMP content in bovine cultured vascular cells, i.e. coronary artery smooth muscle cells (BCs), aortic endothelial cells (BAECs) and aortic smooth muscle cells (BASMCs), either under basal conditions, after beta-adrenoceptor stimulation (Iso) or inhibition of phosphodiesterase activity (IBMX), respectively. 5. Cantharidin inhibited protein phosphatase activity in homogenates from bovine coronary artery rings with a pIC50 of about 6.0. In homogenates of bovine cultured vascular cells pIC50 values of cantharidin amounted to about 6.5 for BCs, 6.7 for BAECs and 6.7 for BASMCs, respectively. 6. It was concluded that cantharidin differently affects vasorelaxation due to stimulation of beta-adrenoceptors (Iso) or inhibition of phosphodiesterase activity (IBMX), respectively. The attenuation of beta-adrenoceptor-mediated vasorelaxation by phosphatase inhibition is not due to diminished adenosine 3':5'-cyclic monophosphate (cyclic AMP) generation but could be evidence for different subcellular compartments of cyclic AMP.
1-Methyl-3-isobutylxanthine↗
Nosocomial respiratory syncytial virus infections: prevention and control in bone marrow transplant patients.
OBJECTIVE: To assess the effectiveness of a multifaceted infection control strategy in limiting the nosocomial transmission of respiratory syncytial virus (RSV) infection to patients in a bone marrow transplant (BMT) unit. DESIGN: Before/after trial. SETTING: University-affiliated tertiary cancer center. PATIENTS: Adult BMT recipients hospitalized during two consecutive wintertime community outbreaks of RSV infection. INTERVENTIONS: An infection control strategy against nosocomial RSV infection was implemented in the BMT unit in February 1993. The strategy involved prompt identification, isolation, and cohorting of RSV-infected patients; prompt therapy with aerosolized ribavirin; use of masks and gloves by anyone entering an infected BMT patient's room; screening visitors for respiratory symptoms; restricting visitation by all children under 12 years of age and all family members and other visitors with RSV symptoms; and restricting symptomatic hospital staff from working in the BMT unit. RESULTS: After implementation of the multifaceted infection-control strategy, there were four cases of nosocomial RSV infection in 3,870 patient days (incidence density, 1.0 case/1,000 patient days) compared with 14 cases of nosocomial RSV infection in 3,152 patient days (incidence density, 4.4 cases/1,000 patient days) during the 1992-1993 RSV season (rate ratio, 4.4; 95% confidence interval [CI95]. 1.4-17.9: P < .01). This decrease in incidence occurred despite a comparable prevalence of community-acquired RSV cases between the two seasons (2.2% vs 3.2% in 1992-1993 and 1993-1994, respectively; prevalence ratio, 0.7; CI95, 0.2-2.1; P = 0.5). CONCLUSION: Institution of a multifaceted infection control strategy significantly reduced the frequency of nosocomial RSV infection in a high-risk group of adult BMT recipients.
Adult↗
Quantitation of diltiazem in human cardiac tissue using high-performance liquid chromatography.
A new high-performance liquid chromatographic method has been developed for the determination of diltiazem in human cardiac tissue. Tissue samples are homogenized and digested with trypsin solution. Diltiazem and the internal standard are extracted with acetone. The extract is evaporated to dryness and reconstituted in potassium phosphate buffer. Samples are then cleaned up with solid-phase extraction columns. Diltiazem and the internal standard show recoveries of 59% +/- 16 and 52% +/- 13. The linearity range is 0.12-2.25 ng/mg wet weight. The limit of quantitation is 0.12 ng/mg (w/w). The percentage coefficient of variation of intra-assay varies between 3.57 and 11.2, and that of interassay varies between 5.42 and 11.7. As an application of the assay, a diltiazem cardiac tissue level in a patient on oral therapy for supraventricular tachycardia is reported.
Calcium Channel Blockers↗
Characterization of biochemical effects of CGS 21680C, an A2-adenosine receptor agonist, in the mammalian ventricle.
Effects of a putative A2-adenosine receptor agonist 2-[(p-2-carboxyethyl)-phenethylamino]-5'-N-ethyl-carboxamide-adeno sine (CGS 21680C) on force of contraction, protein phosphorylation, cyclic adenosine monophosphate (cAMP) content, and the activity of phosphodiesterase (PDE) isoenzymes in guinea pig ventricular (GPV) preparations were studied. CGS 21680C (1-100 microM) did not affect force of contraction in isolated electrically driven papillary muscles and was ineffective in increasing phosphorylation of phospholamban (PLB) and the inhibitory subunit of troponin (TnI) in [32P]-labeled GPV cardiomyocytes. However, under the same conditions, CGS 21680C (10 microM) increased cAMP content from 4.3 +/- 0.2 to 13.0 +/- 0.6 pmol/mg protein, and this effect was completely abolished by A2-adenosine receptor antagonist 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo-(1,5-c)quinazolin++ +-5-imine (CGS 15943A). CGS 21680C (10 microM) inhibited PDE isoenzymes I, II, III, IV by 7.0, 8.3, 4.7, and 23.2%, respectively. Similarly, rolipram (100 microM), a selective PDE IV inhibitor, increased cAMP content from 4.4 +/- 0.3 to 7.2 +/- 0.3 pmol/mg protein without affecting the phosphorylation state of PLB and TnI. We conclude that CGS 21680C increases cAMP content in GPV cardiomyocytes by activation of adenylyl cyclase or in part by inhibition of PDE IV activity. The increase in cAMP content by CGS 21680C or rolipram is ineffective in increasing phosphorylation of PLB and TnI. These results support the concept of compartments for cAMP or protein kinase A or both in cardiomyocytes that are not coupled to phosphorylation and contractility.
Adenosine↗
Interaction between sotalol and an antacid preparation.
AIMS: The aim of the study was to investigate the pharmacokinetic interaction between sotalol and antacids, and its pharmacodynamic relevance. METHODS: In a randomized cross-over design with three treatment groups, six healthy volunteers received orally either 160 mg of sotalol alone (phase 1), or 160 mg sotalol plus 20 ml of a suspension of an antacid (MAH; magnesium hydroxide (1200 mg) and aluminium oxide (1800 mg)) (phase 2) or 160 mg sotalol plus the antacid given 2 h after sotalol administration (phase 3). Heart rate and plasma sotalol concentrations were measured before and 1, 2, 3, 4, 6, 8, 12 and 24 h after sotalol administration. Urinary sotalol excretion was measured for 24 h after sotalol application. RESULTS: Cmax of sotalol decreased from 1.22 +/- 0.22 mgl-1 (phase 1) to 0.89 +/- 0.29 mgl-1 (phase 2) and increased again to 1.27 +/- 0.18 mgl-1 in phase 3. A similar significant change was noted in AUC (15.6 +/- 2.75 mgl-1, 12.3 +/- 3.04 mg h l-1 and 15.0 +/- 2.06 mgl-1) and in the amount of cumulative urinary excretion (79.2 +/- 11.1 mg, 72.1 +/- 11.2 mg and 80.6 +/- 7.9 mg), respectively. tmax and elimination half-life (t1/2,z) of sotalol remained unchanged in the presence of MAH. After combined administration with MAH, the area under the heart rate curve of sotalol was reduced between 0 and 4 h when compared across treatments. CONCLUSIONS: Combined administration of sotalol and MAH decreased the serum sotalol levels. The interaction can be avoided by a two hour interval between application of these drugs.
Adsorption↗
Relations between notched-noise suppressed TEOAE and the psychoacoustical critical bandwidth.
Narrow-band transitory evoked otoacoustic emissions (TEOAE) were recorded for nine normal hearing subjects in the presence of a broadband tone complex suppressor. Introducing a spectral notch at the frequency of the narrow-band stimulus causes the suppression effect to decrease, the more so the wider the notch. This decrease in suppression permits an estimate of the size of one critical band. One advantage of this approach is that no active participation of the subjects is required. The estimated critical bandwidth is then compared with independent estimates based on a simultaneous masking experiment, using the same stimuli. The two measures of the critical bandwidth coincide well for those six subjects with spontaneous otoacoustic emissions. However, the bandwidth estimate based on the OAE measurements is too large for the other three subjects without spontaneous emissions. Simulations of the suppression effect with a driven van der Pol oscillator with moderate undamping produce critical bandwidth estimates consistent with those observed in the psychoacoustical experiments. This allows an estimate of the "effective" amount of undamping on the basilar membrane that is required to produce the critical bandwidth observable in psychoacoustic experiments.
Acoustic Stimulation↗
Use of octreotide in the symptomatic management of diarrhea induced by graft-versus-host disease in patients with hematologic malignancies.
PURPOSE: Diarrhea associated with acute gastrointestinal (GI) graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) can result in severe morbidity and mortality. A pilot study was conducted to evaluate the efficacy and toxicity of octreotide in the management of diarrhea in patients with GVHD after allogeneic BMT. PATIENTS AND METHODS: Twenty-one patients entered the study. Patients received either peripheral-blood stem cells (n = 13) or bone marrow (n = 8). Seven patients had grade 4, 13 grade 3, and one grade 2 GVHD. Intravenous (I.V.) octreotide 500 microg every 8 hours for 7 days was administered. Octreotide treatment was discontinued if no response was observed after 7 days or for grade 4 toxicity. RESULTS: Fifteen (71%) of 21 treated patients had a complete response within 7 days of the initiation of octreotide; three (14%) had a partial response and three (14%) failed to respond to treatment. Toxicities were minimal; hyperglycemia was seen in four patients and one patient developed a partial ileus. Octreotide was discontinued and the ileus resolved within 48 hours. CONCLUSION: If initiated early in the course of GI GVHD, octreotide appears to be an effective, well-tolerated agent in reducing severe voluminous diarrhea. Octreotide should be discontinued within 24 hours after the resolution of diarrhea to avoid the development of ileus. Because no additional reduction in the volume of diarrhea occurred after 7 days of therapy, continuation of the drug beyond this time is not cost effective.
Adult↗
Full length cDNA of rat RT1.DMa and RT1.DMb and expression of RT1.DM genes in dendritic and Langerhans cells.
MHC encoded DM heterodimers and classical MHC class II complexes meet in an endosomal/lysosomal compartment where DM heterodimers support peptide loading of MHC class II. Studies on peptide loading of rat class II and on peptide persistence in cells of the dendritic lineage prompted us to establish full length cDNA clones coding for the subunits alpha and beta of rat DM molecules as well as a mAb directed against the luminal moiety of the beta subunit. Here we describe the establishment of the first full length cDNA clones of rat RT1.DMa and RT1.DMb. The mode of expression of RT1.DM at the transcript level in bone marrow culture-derived dendritic cells, in Langerhans cells and in a number of additional accessory cells is reported. The beta protein was identified in detergent lysates of RT1.DM expressing cells by Western blot analysis using a newly established monoclonal antibody directed against the luminal part of RT1.DMbeta.
Amino Acid Sequence↗