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Biomedical subjects

J Christiansen

Publications and source records attributed to J Christiansen.

At least 19 recordsLinked to original sources
PubMed2005

Sacral nerve stimulation for faecal incontinence in patients with previous partial spinal injury including disc prolapse.

BACKGROUND: This study examined the use of sacral nerve stimulation (SNS) to treat faecal incontinence in patients with partial spinal injury. METHODS: Patients selected for SNS had experienced more than one episode of faecal incontinence per week to liquid or solid stool for more than 1 year and had failed maximal conservative treatment. All patients had an intact external anal sphincter. RESULTS: Temporary SNS was performed in 13 patients (median age 58.5 (range 39-73) years). The spinal insults were disc prolapse (six), trauma (four), spinal stenosis (one) or occurred during neurosurgery (two). Twelve patients (eight women and four men) had successful temporary stimulation and proceeded to permanent implantation. The median follow-up time was 12 (range 6-24) months. The mean(s.d.) number of episodes of incontinence decreased from 9.33(7.64) per week at baseline to 2.39(3.69) at last follow-up (P = 0.012). The number of days per week with incontinence and staining decreased significantly (both P < 0.001). Ability to defer defaecation improved from a median of not being able to defer (range 0-1 min) to being able to defer for 5-15 (range 0 to over 15) min (P = 0.022). CONCLUSION: SNS can benefit patients with faecal incontinence following partial spinal injury.

Adult↗
PubMed2004

Development and standardization of multiplexed antibody microarrays for use in quantitative proteomics.

BACKGROUND: Quantitative proteomics is an emerging field that encompasses multiplexed measurement of many known proteins in groups of experimental samples in order to identify differences between groups. Antibody arrays are a novel technology that is increasingly being used for quantitative proteomics studies due to highly multiplexed content, scalability, matrix flexibility and economy of sample consumption. Key applications of antibody arrays in quantitative proteomics studies are identification of novel diagnostic assays, biomarker discovery in trials of new drugs, and validation of qualitative proteomics discoveries. These applications require performance benchmarking, standardization and specification. RESULTS: Six dual-antibody, sandwich immunoassay arrays that measure 170 serum or plasma proteins were developed and experimental procedures refined in more than thirty quantitative proteomics studies. This report provides detailed information and specification for manufacture, qualification, assay automation, performance, assay validation and data processing for antibody arrays in large scale quantitative proteomics studies. CONCLUSION: The present report describes development of first generation standards for antibody arrays in quantitative proteomics. Specifically, it describes the requirements of a comprehensive validation program to identify and minimize antibody cross reaction under highly multiplexed conditions; provides the rationale for the application of standardized statistical approaches to manage the data output of highly replicated assays; defines design requirements for controls to normalize sample replicate measurements; emphasizes the importance of stringent quality control testing of reagents and antibody microarrays; recommends the use of real-time monitors to evaluate sensitivity, dynamic range and platform precision; and presents survey procedures to reveal the significance of biomarker findings.

Journal Article↗
PubMed2004

Continuous popliteal sciatic nerve block for outpatient foot surgery--a randomized, controlled trial.

BACKGROUND: A major problem in outpatient foot surgery is severe postoperative pain that is not sufficiently treated by peroral analgesics. METHODS: Sixty-three patients underwent foot surgery under spinal anesthesia. Immediately on conclusion of the operation, sciatic and saphenous nerve blocks were performed. The sciatic nerve was blocked in the popliteal fossa with 30 ml of ropivacaine 5 mg ml(-1) and a perineural catheter was passed through the cannula. The patients were randomized to receive either ropivacaine 2 mg ml(-1) (n=30) or saline (n=30) in the catheter through a disposable elastomeric pump with a fixed infusion rate of 5 ml h(-1) for 55 h. RESULTS: Analgesia was excellent until 23 h 44 min (14 h 34 min) in the treatment group and 18 h 16 min (7 h) in the placebo group [mean (SD), P=0.07]. Thereafter, pain was significantly less in the treatment group on the first and second postoperative days (P=0.001). Sleep disturbances because of the pain in the foot were experienced by 25% of the treatment group on the first night at home and by 50% of the control group (P=0.29). There were no differences between the groups in their need for rescue opioid medication. None of the patients had any major problem with the catheter or pump, and none had any toxic effect referable to the technique. CONCLUSION: This randomized, double-blind study shows that continuous blockade of the sciatic nerve in the popliteal fossa reduces postoperative pain and has no untoward effects in a patient group known to experience severe pain after ambulatory surgery.

Ambulatory Surgical Procedures↗
PubMed2004

A review of sacral nerve stimulation for the treatment of faecal incontinence.

Sacral nerve stimulation is an emerging surgical technique that uses chronic low-level electrical stimulation, applied to the nerves of the sacral plexus, to produce a clinically beneficial physiological effect on the lower bowel, pelvic floor and anal canal. Faecal incontinence is common, maximal conservative therapy may improve some patients but many require surgery. Results are variable and often unsatisfactory and further options are limited, the traditional end-point being the formation of a colostomy. Sacral nerve stimulation appears to be an alternative treatment that is successful, has low morbidity, is maintained in the medium term and associated with an improved quality of life. The technique has the advantage of a minimally invasive test procedure with high predictive value and the surgery is minor. The underlying mechanism of action although predominately neurological in nature remains to be determined. Precise patient selection is currently unclear however, results are superior to other techniques.

Electric Stimulation Therapy↗
PubMed2004

Invasive pneumococcal disease in Greenland.

INTRODUCTION: The purpose of the present study was to evaluate the incidence and outcome of pneumococcal infections in Greenland with special reference to serotypes. STUDY DESIGN: Retrospective study of invasive pneumococcal infections in Greenland in the period 1996-2002. METHODS: Cases were defined as patients with positive cultures of Streptococcus pneumoniae from blood and/or CSF received at the microbiological laboratory of Dronning Ingrids Hospital in Nuuk. Cultures were sent to Statens Serum Institut in Copenhagen for serotyping. Medical charts were reviewed. RESULTS: Fifty-one cases were identified. Incidence among Inuit was 54 and among non-Inuit 17 per 100,000 per year. Twenty-one patients were in the age group 35-49 years and 20 in the age group 50-64 years. Twenty patients had meningitis (incidence 6 per 100,000). Seventeen patients died (33%). Most common serotypes were 1 (6 cases) and 12F (8 cases). Mortality rate was significantly higher among patients with 12F than among others (p<0.01). No patients wit serotype 1 died. CONCLUSION: Like in Canada and Alaska, the incidence of invasive pneumococcal disease, especially meningitis, is high among the Inuit in Greenland. Young and middle-aged adults were most frequently affected. Serotype seems to be an important determinant of the outcome of invasive pneumococcal disease.

Adolescent↗
PubMed2003

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients.

BACKGROUND: The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD). OBJECTIVES: To investigate the reactivity to Malassezia allergens, measured as specific serum IgE, positive skin prick test and positive atopy patch test (APT), in adult patients with AD. METHODS: In total, 132 adult patients with AD, 14 with seborrhoeic dermatitis (SD) and 33 healthy controls were investigated for their reactions to M. sympodialis extract and three recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6). RESULTS: Sixty-seven per cent of the AD patients, but only one of the SD patients and none of the healthy controls, showed a positive reaction to at least one of the Malassezia allergens (extract and/or recombinant allergens) in at least one of the tests. The levels of M. sympodialis-specific IgE in serum correlated with the total serum IgE levels. Elevated serum levels of M. sympodialis-specific IgE were found in 55% and positive APT reactions in 41% of the AD patients with head and neck dermatitis. A relatively high proportion of patients without head and neck dermatitis and patients with low total serum IgE levels had a positive APT for M. sympodialis, despite lower proportions of individuals with M. sympodialis-specific IgE among these groups of patients. CONCLUSIONS: These results support that Malassezia can play a role in eliciting and maintaining eczema in patients with AD. The addition of an APT to the test battery used in this study reveals a previously overlooked impact of Malassezia hypersensitivity in certain subgroups of AD patients.

Adolescent↗
PubMed2003

Anorectal function following low anterior resection.

INTRODUCTION: Rectal function following rectal resection for carcinoma was studied in 43 patients. METHODS: Sixteen women and 27 men with a median age of 66 years (range 41-79 years) were included. Twenty-three patients had a diverting ileostomy at the time of resection. Eight patients had a 6-cm colonic J-pouch. Ten patients had anastomotic leakage including two patients without diverting ileostomy. One patient had pre-operative radiation with 25 Gy. The patients were studied at a median 12 months (range 3-30) after rectal resection. Distance from anal verge to the anastomosis was a median 7 cm (range 3-12 cm). Clinical data, anal manometry and rectal compliance were analysed. RESULTS: Stool frequency was 3 per day (range 1-10). Twenty-two (51%) patients were continent, 11 (26%) were incontinent for flatus, and 10 (23%) were incontinent for faeces (three for liquid and seven for solid stool). Fourteen (33%) patients had constipation, two of whom also had incontinence for solid or liquid stool. The level of the anastomosis for patients with postoperative constipation was 5 cm (range 3-12 cm), while it was 7 cm (range 3-10 cm) for nonconstipated patients (NS). Anal manometry was normal. Rectal compliance was lower in patients with incontinence for liquid or solid faeces than in patients with flatus incontinence only (P < 0.01), and rectal volume tolerability was lower in incontinent patients compared with continent patients (P < 0.05). The rectoanal reflex was present in 31 (72%) patients. There was a negative correlation between maximal rectal volume and stool frequency and between level of the anastomosis and degree of incontinence. Age did not affect functional outcome. CONCLUSION: Many patients had a poor functional result following low anterior resection. One in four suffered from incontinence to liquid or solid faeces and one third of the patients experienced constipation. A low level of anastomosis tended to increase stool frequency and carried a higher risk of incontinence. Patients with faecal incontinence tended to have lower rectal compliance and volume tolerability than patients who were continent, while there was no difference in anal pressures.

Adult↗
PubMed2002

Atomic-scale structure of dislocations revealed by scanning tunneling microscopy and molecular dynamics.

The intersection between dislocations and a Ag(111) surface has been studied using an interplay of scanning tunneling microscopy (STM) and molecular dynamics. Whereas the STM provides atomically resolved information about the surface structure and Burgers vectors of the dislocations, the simulations can be used to determine dislocation structure and orientation in the near-surface region. In a similar way, the subsurface structure of other extended defects can be studied. The simulations show dislocations to reorient the partials in the surface region leading to an increased splitting width at the surface, in agreement with the STM observations. Implications for surface-induced cross slip are discussed.

Journal Article↗
PubMed2002

Quality of life after anterior resection versus abdominoperineal extirpation for rectal cancer.

BACKGROUND: Abdominoperineal extirpation has been assumed to put patients at higher risk of disruption to quality of life than sphincter-preserving surgery in rectal cancer surgery. The aim of this study was to investigate quality of life in patients after anterior resection versus abdominoperineal extirpation for rectal cancer and to evaluate the psychometrics of the Danish version of a symptom-specific Fecal Incontinence Quality of Life Scale. METHODS: Fourteen patients undergoing abdominoperineal extirpation and 26 undergoing anterior resection. The generic quality of life instrument SF-36 together with a new symptom-specific Fecal Incontinence Quality of Life Scale were used. Psychometric analysis of the symptom-specific scale was carried out. RESULTS: The only significant difference between the two groups was found in the total score of the symptom-specific scale in favour of anterior resection (P = 0.02). Psychometric evaluation of the symptom-specific fecal incontinence questionnaire proved it reliable and valid. CONCLUSIONS: The present study shows that a stoma influences quality of life only slightly, while a relatively high anterior resection does not. However, a few appropriate newer studies indicate that the cost of spinchter-preserving techniques in the form of incontinence disturbances may influence the quality of life seriously, which should be borne in mind when low anterior resection is intended. Further studies in this field are necessary and could benefit from use of the Fecal Incontinence Quality of Life Scale, including its total score.

Abdomen↗
PubMed2001

Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin.

BACKGROUND: Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging. METHODS AND RESULTS: Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P<0.05) with TNF-alpha treatment because of increased attachment to activated leukocytes. Extensive attachment of MB(p) directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-alpha-stimulated mice, resulting in 4-fold greater (P<0.01) retention of MB(p) than either MB(iso) or MB. Enhanced retention of MB(p) was completely abolished in TNF-alpha-stimulated P-selectin-deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (P<0.05) for MB(p) (12+/-2 U) than either MB(iso) (6+/-3 U) or MB (5+/-3 U). In P-selectin-deficient mice, the signal for MB(p) was equivalent to that from control microbubbles. CONCLUSIONS: Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.

Animals↗
PubMed2001

An object-oriented framework for dynamic ecosystem modeling: application for integrated risk assessment.

Ecological risk assessment requires the integration of a wide range of data on anthropogenic processes, ecological processes and on processes related to environmental fate and transport. It is a major challenge to assemble a simulation system that can successfully capture the dynamics of complex ecological systems and an even more serious challenge to be able to adapt such a simulation to shifting and expanding analytical requirements and contexts. The dynamic information architecture system (DIAS) is a flexible, extensible, object-based framework for developing and maintaining complex simulations. DIAS supports simulations in which the real-world entities that make up ecological systems are represented as software 'entity objects'. The object-oriented integrated dynamic landscape analysis and modeling system (OO-IDLAMS) provides a good example of how DIAS has been used to build a suite of models for the purpose of assessing the ecological impacts of military land use and land management practices. OO-IDLAMS is a prototype conservation modeling suite that provides military environmental managers and decision-makers with a strategic, integrated and adaptive approach to natural resources planning and ecosystem management. The OO-IDLAMS prototype used Fort Riley, Kansas as a case study to demonstrate DIAS' capabilities to offer flexibility, interprocess dynamics and cost-effective reuse of code for ecosystem modeling and simulation. DIAS can also readily lend itself to other applications in ecological risk assessment. It has great potential for the integration of ecological models (associated with biological uptake and effects) with environmental fate and transport models. A DIAS ecological risk assessment application could be used to predict the magnitude and extent of ecological risks and evaluate remedy effectiveness in a timely and cost-effective manner.

Animals↗
PubMed2001

Stereospecificity of acetylene reduction catalyzed by nitrogenase.

In addition to catalyzing the reduction of dinitrogen to ammonia, the metalloenzyme nitrogenase catalyzes the reduction of a number of alternative substrates, including acetylene (C(2)H(2)) to ethylene (C(2)H(4)) and, in certain cases, to ethane (C(2)H(6)). The stereochemistry of proton addition for C(2)D(2) reduction to C(2)D(2)H(2) catalyzed by the Mo-dependent nitrogenase has been used to probe substrate binding and proton addition mechanisms. In the present work, the C(2)D(2) reduction stereospecificity of altered MoFe proteins having amino acid substitutions within the active site FeMo-cofactor environment was examined by Fourier transform infrared (FTIR) spectroscopy. Altered MoFe proteins examined included those having the alpha-subunit 96(Arg) residue substituted by Gln, Leu, or Ala, the alpha-subunit 69(Gly) residue substituted by Ser, and the alpha-subunit 195(His) residue substituted by Asn. The stereochemistry of proton addition to C(2)D(2) does not correlate with the measured K(m) values for C(2)H(2) reduction, or with the ability of the enzyme to reduce C(2)H(2) by four electrons to yield C(2)H(6). Instead, the electron flux through nitrogenase was observed to significantly influence the ratio of cis- to trans-1,2-C(2)H(2)D(2) formed. Finally, the product distribution observed for reduction of C(2)H(2) in D(2)O is not consistent with an earlier proposed enzyme-bound intermediate. An alternative model that accounts for the stereochemistry of C(2)H(2) reduction by nitrogenase based on a branched reaction pathway and an enzyme-bound eta(2)-vinyl intermediate is proposed.

Acetylene↗
PubMed2001

Mechanistic features and structure of the nitrogenase alpha-Gln195 MoFe protein.

EPR signals observed under CO and C(2)H(2) during nitrogenase turnover were investigated for the alpha-Gln(195) MoFe protein, an altered form for which the alpha-His(195) residue has been substituted by glutamine. Under CO, samples show S = 1/2 hi- and lo-CO EPR signals identical to those recognized for the wild-type protein, whereas the S = 3/2 signals generated under high CO/high flux conditions differ. Previous work has revealed that the EPR spectrum generated under C(2)H(2) exhibits a signal (S(EPR1)) originating from the FeMo-cofactor having two or more bound C(2)H(2) adducts and a second signal (S(EPR2)) arising from a radical species [Sørlie, M., Christiansen, J., Dean, D. R., and Hales, B. J. (1999) J. Am. Chem. Soc. 121, 9457-9458]. Pressure-dependent studies show that the intensity of these signals has a sigmoidal dependency at low pressures and maximized at 0.1 atm C(2)H(2) with a subsequent decrease in steady-state intensity at higher pressures. Analogous signals are not recognized for the wild-type MoFe protein. Analysis of the principal g-factors of S(EPR2) suggests that it either represents an unusual metal cluster or is a carboxylate centered radical possibly originating from homocitrate. Both S(EPR1) and S(EPR2) exhibit similar relaxation properties that are atypical for S = 1/2 signals originating from Fe-S clusters or radicals and indicate a coupled relaxation pathway. The alpha-Gln(195) MoFe protein also exhibits these signals when incubated under turnover conditions in the presence of C(2)H(4). Under these conditions, additional inflections in the g 4-6 region assigned to ground-state transitions of an S = 3/2 spin system are also recognized and assigned to turnover states of the MoFe protein without C(2)H(4) bound. The structure of alpha-Gln(195) was crystallographically determined and found to be virtually identical to that of the wild-type MoFe protein except for replacement of an NuH-S hydrogen bond interaction between FeMo-cofactor and the imidazole side chain of alpha-His(195) by an analogous interaction involving Gln.

Amino Acid Substitution↗
PubMed2001

C-MYC and IGF-II mRNA-binding protein (CRD-BP/IMP-1) in benign and malignant mesenchymal tumors.

Mouse coding region determinant-binding (mCRD-BP) and human IGF-II mRNA-binding 1 (hIMP-1) proteins are orthologous mRNA-binding proteins that recognize c-myc and IGF-II mRNA, respectively, and regulate their expression posttranscriptionally. Here, we confirm that human CRD-BP/IMP-1 binds to c-myc mRNA and that it is predominantly expressed in fetal tissues. Moreover, hCRD-BP/IMP-1 expression was detected in cell lines of neoplastic origin and in selected primary tumors. In a series of 33 malignant and 10 benign mesenchymal tumors, 73% and 40%, respectively, were found to express hCRD-BP/IMP-1. In particular, expression was significant in 14 Ewing's sarcomas, all of which were positive. The data suggest that hCRD-BP/IMP-1 plays a role in abnormal cell proliferation in mesenchymal tumors.

Amino Acid Motifs↗
PubMed2001

Chronic idiopathic anal pain: analysis of ultrasonography, pathology, and treatment.

PURPOSE: This study was undertaken to analyze whether intra-anal ultrasound examination, anorectal physiologic evaluation, and histopathologic examination in patients with chronic idiopathic anal pain presented any common features and whether the results of different treatment modalities correlated with these findings. METHODS: Eighteen patients who met the criteria for chronic idiopathic anal pain were studied. All had an intra-anal ultrasound examination and a complete anorectal physiologic evaluation. In a selected group of patients, ultrasound-guided biopsy samples were taken from pathological areas in the internal and external sphincter. Treatment consisted of analgesics only in four patients, 0.2 percent nitroglycerin ointment in four, and ultrasound injection of botulin (botulinum toxin, Botox) into the intersphincteric space in nine. Two patients, including one who was previously treated with botulin, ultimately had a colostomy. RESULTS: Four patients were managed satisfactorily on analgesic treatment under the guidance of the hospital's pain clinic. Nitroglycerin ointment resulted in temporary pain relief in one of four patients. Injection of botulin resulted in a permanent improvement in four patients, a temporary improvement in one patient, and no effect in four patients. Two patients had a colostomy, resulting in complete pain relief. The effect or lack of effect of nitroglycerin ointment and botulin was not related to changes in anal pressure. CONCLUSION: Chronic idiopathic anal pain is a condition of unknown origin for which no proven therapy exists. As in other syndromes based on muscular dystonia, some patients may benefit from injection of botulin.

Adult↗
PubMed2001

Complications of dynamic graciloplasty: incidence, management, and impact on outcome.

PURPOSE: Dynamic graciloplasty can improve continence in patients with severe refractory fecal incontinence, but associated morbidity is high. The purpose of this study was to identify complications associated with dynamic graciloplasty and to characterize their treatment and impact on patient outcome. METHODS: In 121 patients enrolled in a prospective trial of 20 centers and eligible for safety analysis, all complications of dynamic graciloplasty were recorded at the time of their occurrence and followed up until resolution. Severe treatment-related complications were defined as those requiring hospitalization or surgical intervention. RESULTS: In 93 patients, 211 complications occurred. Of these, 89 (42 percent) in 61 patients were classified as severe treatment-related complications and resulted from the following: major infection, 19; minor infection, 10; thromboembolic events, 3; device performance and use, 13; pain, 16; noninfectious gracilis problems, 8; noninfectious wound-healing problems, 3; other surgery-related complications, 3. In addition, severe treatment-related complications resulted from constipation in ten and stoma creation or closure in ten. The recovery rate (full or partial) was 87 percent overall, and for severe treatment-related complications, was 92 percent. Of the types of complications, only major infections had an adverse effect on outcome. CONCLUSION: Severe complications occur frequently after dynamic graciloplasty, but are usually treatable. They often require one or more reoperations and can lead to significant delays in completion of therapy. In most cases therapy can be salvaged.

Anal Canal↗
PubMed2001

Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis.

p62 is a RNA-binding protein that was isolated by immunoscreening a cDNA expression library with autoantibodies from patients with hepatocellular carcinoma (HCC). This autoantigen binds to mRNA encoding insulin-like growth factor II, which has been found to be overexpressed in HCC and is tumorigenic in transgenic animals. Immunohistochemical analysis of HCC liver showed that 33% (9 of 27) exhibited readily detectable staining of p62 protein in the cytoplasm of all malignant cells in cancer nodules, whereas it was undetectable in adjacent nonmalignant liver cells. In addition one of two patients with cholangiocarcinoma expressed p62 in malignant bile duct epithelial cells. p62 expression was also detected in scattered cells in cirrhotic nodules in contrast to uniform expression in all cells in HCC nodules. In HCC nodules, p62 mRNA was also detected by reverse transcriptase-polymerase chain reaction analysis. Nine normal adult livers did not contain detectable p62 mRNA or p62 protein whereas five fetal livers were all positive for mRNA and protein. The observations show that p62 is developmentally regulated, expressed in fetal, but not in adult liver, and aberrantly expressed in HCC and could be playing a role in abnormal cell proliferation in HCC and cirrhosis by modulating expression of growth factors such as insulin-like growth factor II.

Adult↗