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Biomedical subjects

C Lund

Publications and source records attributed to C Lund.

At least 19 recordsLinked to original sources

Methylated CpG-containing plasmid activates the immune system.

Bacterial DNA differs from mammalian DNA by the presence of unmethylated cytosine-phosphate-guanosine (CpG) motifs. The immunostimulatory properties of a DNA vaccine have been suspected to be associated with these motifs. The aim of this study was to assess the inactivation of the immunostimulatory potential of a plasmid after methylation of its CpG motifs. We constructed two identical non-coding plasmids, and one of these was de novo methylated on its CG sequences. A single administration of recombinant antigen with methylated or unmethylated CpG-containing plasmid was performed in mice. As expected, only unmethylated CpG-containing plasmid enhanced the specific immune response. However, a study of in vivo activation of Langerhans' cells and analysis of mRNA synthesis indicated that both the plasmids promoted cell emigration and cytokine induction. These data highlight that a methylated CpG-containing plasmid is not inert and carries immunomodulatory properties. The results further emphasize the necessity to definitively identify the mode of action of plasmids used for DNA vaccination.

Animals↗

Analgesic effect of i.v. paracetamol: possible ceiling effect of paracetamol in postoperative pain.

BACKGROUND: Despite the widespread use of paracetamol for many years, the analgesic serum concentrations of paracetamol are unknown. Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied. METHODS: Sixty-four women undergoing laparoscopic sterilization were included in a double-blind, placebo-controlled, randomized study. Patients were given i.v. propacetamol 40 mg kg(-1) (group H), 20 mg kg(-1) (group I), 10 mg kg(-1) (group L) or placebo after surgery. Alfentanil was available via patient-controlled analgesia (PCA) during the 4-h postoperative study period. The patients' self-reported pain was registered on the visual analog scale (VAS). A pharmacokinetic model was fitted to the paracetamol data. RESULTS: One to 3 h after injection of propacetamol the alfentanil consumption was significantly (P = 0.01-0.04) higher in the placebo group compared with groups H, I, and L receiving propacetamol. There were no significant differences between the amounts of alfentanil consumed in groups H, I, and L. Initial VAS-scores were moderate (5.4-6.2), and declined significantly (P < 0.0001) over time, with no difference between groups. Paracetamol followed an open two-compartment model with i.v. administration and first order elimination. The estimated concentrations immediately (t = 0) after injection were 56 mg l(-1) (H), 28 mg l(-1) (I) and 14 mg l(-1) (L). CONCLUSION: We showed a significant opioid-sparing effect of paracetamol in the immediate postoperative period. Pharmacokinetic data were in accordance with other studies. Our results suggest that a ceiling effect of paracetamol may be present at i.v. doses of 5 mg kg(-1), i.e. a serum concentration of 14 mg l(-1), which is a lower dose than previously suggested.

Absorption↗

Delayed incubation as an alternative method to sample storage for enumeration of E. coli and culturable bacteria in water.

The effects of sample storage on enumeration of Escherichia coli in marine bathing water and culturable bacteria in drinking water were evaluated. Results showed that overnight storage at 0-5 degrees C significantly reduced the counts of E. coli in bathing water (p = 0.0001) with a mean reduction of 25%. A similar effect of sample storage was observed for the enumeration of culturable bacteria in drinking water at 22 +/- 2 degrees C for 66 +/- 4 h (p = 0.0074; mean reduction = 25%) or at 36 +/- 2 degrees C for 44 +/- 4h (p = 0.0353; mean reduction = 6%). The use of a delayed incubation method, i.e. overnight storage at 0-5 degrees C of inoculated agar plates prior to incubation, did not significantly affect the counts of culturable bacteria when plates were incubated at 22 + 2 degrees C for 66 +/- 4 h, whereas it resulted in a significant increase of the bacterial numbers when plates were incubated at 36 +/- 2 degrees C for 44 +/- 4 h (p = 0.0002; mean increase = 32%). Based on these results, it is suggested to avoid the use of overnight or longer sample storage for the enumeration of E. coli in bathing water samples, as well as for the enumeration of culturable bacteria in drinking water. The delayed incubation method appears to be a reliable procedure for the enumeration of culturable bacteria and could represent a valid alternative to sample storage in order to overcome problems associated with the performance of bacteriological counts during weekends or statutory holidays. However, a multi-laboratory study is needed to evaluate the reproducibility of the delayed incubation method for the enumeration of culturable bacteria and its possible use for the enumeration of E. coli by membrane filtration.

Environmental Monitoring↗

X-linked recessive Menkes disease: identification of partial gene deletions in affected males.

Menkes disease is an X-linked recessive lethal disorder of copper metabolism, caused by defects in the ATP7A gene. Partial gene deletions comprise about 15% of the mutations causing Menkes disease. We have previously demonstrated identification of partial ATP7A deletions in patients by Southern blot analysis. In the present study, we report the use of three fast and reliable polymerase chain reaction (PCR)-based methods for the identification of partial ATP7A deletions in Menkes disease patients. First we demonstrate the use of multiplex PCR, a fast method for identification and rough localization of partial gene deletions, in which two exons of ATP7A are coamplified. Second, we present PCR amplification of genomic DNA across the deletion junctions, a method enabling identification of the deletion breakpoints and hence the exact size of the deletion. Finally, application of reverse transcription PCR (RT-PCR) for identification and localization of gene deletions at the cDNA level is demonstrated. By studying the mutation at the cDNA level the predicted effect of the mutation on the amino acid sequence and consequently the protein structure and function can be inferred. We demonstrate characterization of partial gene deletions in five patients, and in three of these we were able to determine the breakpoint sequences.

Adenosine Triphosphatases↗

[Accelerated rehabilitation after colon resection].

INTRODUCTION: The stay in hospital after colonic resection is usually 7-12 days, with a complication rate of 20%. A multi-modal rehabilitation regimen, comprising epidural analgesia, early mobilisation, and oral nutrition, reduced the hospital stay to 2-3 days after colonic resection. METHODS: One hundred patients underwent elective colonic resection with a planned postoperative stay of two days in hospital and a regimen with epidural analgesia, oral nutrition, and mobilisation. Anaesthesia, the surgical technique, and nursing care programme were standardised. Postoperative follow-up visits were arranged for day 8 and day 30. RESULTS: The median age was 73 years. Forty patients were at high risk, ASA III-IV. Gastrointestinal function (defecation) occurred within 48 hours, except for five patients, and the median hospital stay was two days. The readmission rate was 18% with no acute, potentially lethal conditions. The total hospital stay was three days. None of the patients had cardiopulmonary complications, except for one patient, who died from cardiac failure 36 hours after surgery. Three patients had anastomotic dehiscence, two of whom were treated conservatively. CONCLUSION: The usual postoperative ileus, "medical complications", and hospital stay were reduced in high-risk patients undergoing colonic resection with a multi-modal rehabilitation programme. These results call for further comparative studies with conventional care programmes and laparoscopic colonic resection.

Adult↗

Fast track hysterectomy.

OBJECTIVE: To identify factors limiting early discharge after laparoscopically assisted vaginal hysterectomy (LAVH) and abdominal hysterectomy, in a fast track setting with emphasis on information, treatment of pain, early mobilization, and early food intake. STUDY DESIGN: A prospective, descriptive study of 32 unselected women allocated to either abdominal hysterectomy (n=16) or LAVH (n=16). The patients received the same information, care, and advice for the perioperative period except for an assumed 1-day hospital stay in the LAVH-group and 2 days in the abdominal group. RESULTS: Patients were discharged median 1 day (1-3) after LAVH and 2 days (2-4) after abdominal hysterectomy. Work was resumed median 23 days after abdominal hysterectomy and 28 days after LAVH (P > 0.05). CONCLUSIONS: The study questions the previously proposed advantages of shortened hospitalization and convalescence after LAVH compared with abdominal hysterectomy. Further studies with active rehabilitation are needed to demonstrate real differences between laparoscopic and open hysterectomy.

Adult↗

Postural stability after inguinal herniorrhaphy under local infiltration anaesthesia.

OBJECTIVE: To investigate postural stability in patients after inguinal herniorrhaphy under local infiltration anaesthesia, to see if the anaesthetics and analgesics used influenced it and therefore hindered early discharge. DESIGN: Open study. SETTING: Teaching hospital, Denmark. SUBJECTS: 55 patients listed for elective inguinal herniorrhaphy. INTERVENTIONS: Preoperative and intraoperative infiltration anaesthesia by bupivacaine 2.5 mg/ml (median dose 41 ml, range 30-84 ml), and sedation with midazolam intraoperatively (median dose 3 mg, range 0-10 mg). Lichtenstein tension-free technique with polypropylene mesh repair (Prolene). Measurement of postural stability before operation and 30 and 60 minutes afterwards using the "Basic Balance Master" system, and balance assessed by visual analogue scale and verbal rating scale. MAIN OUTCOME MEASURES: Postural stability and subjectively assessed balance. RESULTS: Dynamic postural stability was impaired 30 min (p < 0.05), but not 60 minutes postoperatively. All but two patients were discharged shortly after the measurement at 60 minutes, because of pain in one and an attack of asthma in the other. Balance also returned to normal within an hour. CONCLUSION: Objectively measured postural stability and subjectively assessed balance return to normal within 60 minutes after inguinal herniorrhaphy under local infiltration anaesthesia, thereby permitting early discharge.

Adult↗

Ventricular fibrillation during off-pump coronary artery bypass grafting: transcranial Doppler and clinical findings.

A 73-year-old male developed ventricular fibrillation which lasted for 2 min and 24 s, during off-pump coronary artery bypass grafting. Cerebral hemodynamics were assessed by continuous transcranial Doppler monitoring. Ventricular fibrillation resulted in an immediate fall in cerebral blood flow velocities to almost zero with only slight fluctuations. This was then followed by a pronounced reactive hyperperfusion. Cerebral magnetic resonance imaging examinations and detailed neurological and neuropsychological evaluations were performed before and at 3 and 12 months after surgery. No evidence of cerebral damage was found.

Aged↗

Characterization of the hCTR1 gene: genomic organization, functional expression, and identification of a highly homologous processed gene.

The human hCTR1 gene was originally identified by its ability to complement a yeast mutant deficient in high-affinity copper uptake (Zhou, B., Gitschier, J., 1997. A human gene for copper uptake identified by complementation in yeast. Proc. Natl. Acad. Sci. USA 94, 7481-7486). Here, we have determined the DNA sequence of the exon-intron borders of the hCTR1 structural gene and report that the coding sequence is disrupted by three introns, all of which comply with the GT/AG rule. Furthermore, human fibroblasts, transfected with hCTR1 cDNA, were shown to have a dramatically increased capacity for (64)Cu uptake, indicating that the hCtr1 protein is functional in copper uptake in human cells. In contrast, no evidence was found for involvement of the hCTR2 gene product in copper uptake. Finally, we have identified a highly homologous processed pseudogene, hCTR1psi, which was localized to chromosome 3q25/26. The processed gene was found to be transcribed, but due to a frame shift mutation, it only had the potential to encode a truncated protein of 95 amino acid residues, and cells transfected with hCTR1psi DNA showed no increase of (64)Cu uptake.

Amino Acid Sequence↗

Similar splice-site mutations of the ATP7A gene lead to different phenotypes: classical Menkes disease or occipital horn syndrome.

More than 150 point mutations have now been identified in the ATP7A gene. Most of these mutations lead to the classic form of Menkes disease (MD), and a few lead to the milder occipital horn syndrome (OHS). To get a better understanding of molecular changes leading to classic MD and OHS, we took advantage of the unique finding of three patients with similar mutations but different phenotypes. Although all three patients had mutations located in the splice-donor site of intron 6, only two of the patients had the MD phenotype; the third had the OHS phenotype. Fibroblast cultures from the three patients were analyzed by reverse transcriptase (RT)-PCR to try to find an explanation of the different phenotypes. In all three patients, exon 6 was deleted in the majority of the ATP7A transcripts. However, by RT-PCR amplification with an exon 6-specific primer, we were able to amplify exon 6-containing mRNA products from all three patients, even though they were in low abundance. Sequencing of these products indicated that only the patient with OHS had correctly spliced exon 6-containing transcripts. We used two different methods of quantitative RT-PCR analysis and found that the level of correctly spliced mRNA in this patient was 2%-5% of the level found in unaffected individuals. These findings indicate that the presence of barely detectable amounts of correctly spliced ATP7A transcript is sufficient to permit the development of the milder OHS phenotype, as opposed to classic MD.

Adenosine Triphosphatases↗

High-dose rectal and oral acetaminophen in postoperative patients--serum and saliva concentrations.

BACKGROUND: The primary purpose of the study was to examine the absorption of acetaminophen by measuring serum and saliva concentrations produced by a standard postoperative acetaminophen dosing regimen and secondary to examine the correlation between saliva and serum concentrations of acetaminophen after rectal and oral dosing. METHODS: Twenty-four women, aged 18-60 years, scheduled for minor gynaecological laparoscopic surgery were studied. Patients received acetaminophen 2000 mg suppositories after surgery and oral doses of 1000 mg at 4 and 8 h postoperatively. Alfentanil was available via patient-controlled analgesia. Saliva and blood samples were collected postoperatively. RESULTS: At 1, 2, 3, and 4 h after rectal dosing the saliva concentrations (mean+/-SD) were 15.2+/-5.9 micromol/l, 33.7+/-12.5 micromol/l, 45.5+/-19.1 micromol/l, and 55.4+/-23.1 micromol/l, respectively. The serum concentrations at 2 and 4 h were 31.0+/-11.2 micromol/l and 54.8+/-23.8 micromol/l, respectively. Additional oral dosing resulted in saliva concentrations at 5, 8, and 9 h of 99.7+/-49.5 micromol/l, 106.9+/-31.7 micromol/l, and 139.3+/-55.4 micromol/l, respectively, with coincident serum concentrations of 100.1 +/- 50.2 micromol/l, 105.6+/-29.0 micromol/l, and 141.2+/-52.1 micromol/l. After rectal dosing the linear regression resulted in r2=0.96, P<0.001 and saliva/ serum-ratio=0.99. After additional oral dosing the outcome of linear regression was: r2=0.90, P<0.001 and saliva/serum-ratio= 1.00. CONCLUSION: The slow and ongoing absorption process resulting in no maximum concentration within 4 h after administration of 2000 mg acetaminophen suppositories makes this rectal regimen therapeutically irrational for treatment of postoperative pain. The significant ratio and linear correlation between saliva and serum concentrations of acetaminophen suggests that saliva could be used instead of blood to monitor acetaminophen administration in patients.

Absorption↗

A model for estimating mental health service needs in South Africa.

OBJECTIVE: To develop a model for estimating the services and human resources needed to care for people with severe psychiatric conditions in a hypothetical population of 100,000 people in South Africa. METHOD: Annual mental health service needs were estimated in terms of numbers of daily patient visits (DPV) in ambulatory care, the number of beds required, and staffing. Developed within a spreadsheet format, the model allows for the adjustment of key service variables according to estimated or existing service data. RESULTS: At 100% coverage, 87 DPV, 28 acute beds, and 10 medium-long stay beds are necessary for a population of 100,000 people. This would require 35.2 full-time equivalent mental health staff: 21.3 for inpatient care, 12.0 for ambulatory care, and 1.9 for management. CONCLUSION: Because the model can produce a range of service recommendations, the assumptions that inform it should be clearly stated and justified. This method makes the assumptions on which services are planned explicit and allows for a rational approach to decision making.

Adolescent↗

[Reference values of chemical blood parameters in puppies during the first eight weeks of life].

Reference values were determined for blood plasma concentrations of albumin, total protein, glucose, total bilirubin, urea, creatinine, cholesterin, triglycerides, total calcium und anorganic phosphate as well as the activities of alkaline phosphatase, alanine-amino-transferase (ALT) and glutamate-dehydrogenase based on 109-124 healthy puppies at different times (1st-3rd, 8th-10th, 28th-33rd, and 50th-58th day of life). In addition, all the results were calculated separately for the breeds involved in this study (Beagle [n = 34-40], German Shepherd [n = 32-35] and Golden Retriever [n = 43-53]). Furthermore, male and female puppies were compared. All examined parameters showed remarkable dynamics during the suckling period. Often the values exceeded respectively fell below the reference ranges for adult dogs. Significant systematic breed influences as for instance a significantly lower glucose concentration for the German Shepherd puppies were also found for other parameters, especially for alkaline phosphatase and ALT. However, differences between male and female animals were only present sporadically and were of minor clinical relevance. The gathered breed differences show that it is worthwhile not only to acquire age specific reference ranges but also breed specific reference ranges for selected parameters. On the other hand, reference ranges without the definition of the breed can only be used for orientation.

Aging↗

Interrater reliability of a Danish version of the Morgan Russell scale for assessment of anorexia nervosa.

OBJECTIVE: To study the interrater reliability of a Danish version of the Morgan Russell scale for assessment of patients with anorexia nervosa, and subsequently to clarify the existing rating instructions. METHOD: Ten patients undergoing treatment for anorexia nervosa at a regional center participated and had their interview videotaped. Two interviews were reserved for a training phase only. The group of raters comprised eight clinicians, and measures of interrater reliability were computed using intraclass correlation coefficient (ICC). RESULTS: The ICC for the total score was good (0.79), while reliability for the single items varied from poor to excellent (0.14-0.99). Internal consistency as expressed by Cronbach's coefficient alpha was acceptable (0.74). DISCUSSION: The Morgan Russell scale stands out as an easily applied and reliable measure of severity of anorexia nervosa, though the rating instructions need clarification in some items.

Adolescent↗

Neonatal skin care: the scientific basis for practice.

OBJECTIVE: To review the literature addressing the care of neonatal skin. DATA SOURCES: Computerized searches in MEDLINE and CINAHL, as well as references cited in articles reviewed. Key concepts in the searches included neonatal skin differences; neonatal skin and care practices for skin integrity; neonatal skin and toxicity; permeability; and contact irritant sensitization. STUDY SELECTION: Articles and comprehensive works relevant to key concepts and published after 1963, with an emphasis on new findings from 1993 to 1999. One hundred two citations were identified as useful to this review. DATA EXTRACTION: Data were extracted and organized under the following headings: anatomy and physiology of the skin; physiologic and anatomic differences in neonatal skin; nutritional deficiencies; skin care practices; and care of skin breakdown. DATA SYNTHESIS: Newborns' skin is at risk for disruption of normal barrier function because of trauma. In light of available evidence about differences in neonatal skin development, clinical practice guidelines are suggested for baths, lubrication, antimicrobial skin disinfection, and adhesive removal. In addition, basic care practices are suggested for maintaining skin integrity, reducing exposure to potentially toxic substances, and promoting skin health beyond the neonatal period. Preventive care recommendations are made for reducing trauma, protecting the skin's immature barrier function, and promoting skin integrity. CONCLUSIONS: This review generated evidence with which to create a new and comprehensive practice guideline for clinicians. Evaluation of the guideline is under way at 58 U.S. sites.

Baths↗

Prevention and management of infant skin breakdown.

There are anatomic and physiologic differences in the skin of both premature and full-term infants that place them at increased risk for skin injury and breakdown. This article reviews these differences and discusses some of the infant skin care practices that can cause injury to infant skin with preventive strategies identified. Care of skin breakdown is outlined, and topical treatments reviewed in detail. Diaper dermatitis is also discussed with treatment of the underlying causes as well as the goals of treating diaper dermatitis described.

Aging↗

[Amebiasis--a differential diagnosis from inflammatory bowel disease].

Entamoeba histolytica is a very uncommon etiology of travelers diarrhoea, but may be an important differential diagnosis to inflammatory bowel disease. A misdiagnosis of amoebic colitis as inflammatory bowel disease followed by inadvertent treatment with corticosteroids may be fatal. Current techniques for the diagnosis of amoebiasis include stool studies, endoscopic biopsy and serology. Demonstration of haematophagous trophozoites in feces or in tissue biopsy is the definitive method for diagnosis. Unfortunately both methods have many drawbacks. If the specimens are negative, serology can support the diagnosis especially in a non-endemic area where a positive test is highly predictive of current disease.

Aged↗