Uroporphyrinogen decarboxylase gene mutations in Danish patients with porphyria cutanea tarda

Decreased uroporphyrinogen decarboxylase (UROD) activity is a characteristic feature of the most common of the porphyrias, porphyria cutanea tarda (PCT). A subgroup of the clinically overt PCT cases is associated with mutations in the gene encoding UROD and inherited as an autosomal-dominant trait. In this study, DNAs from 53 Danish PCT patients were subjected to genetic analysis for UROD mutations using denaturing gradient gel electrophoresis. Eleven genetic variations, seven of which are possible disease causing, were identified. All but one of these mutations were previously unknown, lending further support to the assumption that PCT is a heteroallelic disease. Only 11% of the examined patients were previously recognized as familial PCT cases. However, possible disease-related UROD mutations were identified in 24% of the examined patients, indicating that genetic analysis of PCT patients may improve differentiation between familial and sporadic PCT cases.     

Entering a World with No Future: A phenomenological study describing the embodied experience of time when living with severe incurable disease

Scand J Caring Sci; 2013; 27; 165–174 A phenomenological study describing the embodied experience of time when living with severe incurable disease This article presents findings from a phenomenological study exploring experience of time by patients living close to death. The empirical data consist of 26 open‐ended interviews from 23 patients living with severe incurable disease receiving palliative care in Norway. Three aspects of experience of time were revealed as prominent: (i) Entering a world with no future; living close to death alters perception of and relationship to time. (ii) Listening to the rhythm of my body, not looking at the clock; embodied with severe illness, it is the body not the clock that structures and controls the activities of the day. (iii). Receiving time, taking time; being offered – not asked for – help is like receiving time that confirms humanity, in contrast to having to ask for help which is like taking others time and thereby revealing own helplessness. Experience of time close to death is discussed as an embodied experience of inner, contextual, relational dimensions in harmony and disharmony with the rhythm of nature, environment and others. Rhythms in harmony provide relief, while rhythms in disharmony confer weakness and limit time.     

Translation of the Manchester Clinical Supervision Scale (MCSS) into Danish and a preliminary psychometric validation

A central challenge for empirical research of clinical supervision is how to measure the effectiveness of clinical supervision. The Manchester Clinical Supervision Scale (MCSS) measures supervisees' perception of the effectiveness of clinical supervision. The aims of this paper were to account for the translation of the MCSS from English into Danish and to present a preliminary psychometric validation of the Danish version of the scale. Methods included a formal translation/back‐translation procedure and statistical analyses. The sample consisted of MCSS scores from 139 Danish mental health nursing staff members. The total MCSS score had good internal consistency, but the analyses identified a number of reliability and consistency issues. The results were compared with other translations of the MCSS and with the reduced version of the MCSS, the MCSS‐26. The discussion indicated that MCSS theoretically refers to a broad conception of supervision, which includes supervision practices ranging from highly formalized events to more frequent ad hoc sessions. The MCSS's intention to measure perceptions of supervisees from this variety of practices may be problematic, and it is suggested that a further reduction of the type of practices MCSS currently aims at measuring could be beneficial.     

Rapid Selection of Plasmodium falciparum Chloroquine Resistance Transporter Gene and Multidrug Resistance Gene-1 Haplotypes Associated with Past Chloroquine and Present Artemether-Lumefantrine Use in Inhambane District,Southern Mozambique

Chloroquine (CQ) use in Mozambique was stopped in 2002 and artemether-lumefantrine (AL) was implemented in 2008. In light of no use of CQ and extensive use of AL, we determined the frequency of molecular markers of Plasmodium falciparum drug resistance/tolerance to CQ and AL in persons living in Linga-Linga, an isolated peninsula and in Furvela village, which is located 8 km inland. The P. falciparum chloroquine resistance transporter gene CVMNK wild type increased in frequency from 43.9% in 2009 to 66.4% in 2010 (P ≤ 0.001), and combined P. falciparum multidrug resistance gene 1 N86-184F-D1246 haplotype increased significantly between years (P = 0.039). The combination of P. falciparum chloroquine resistance transporter gene CVMNK and P. falciparum multidrug resistance gene NFD increased from 24.3% (2009) to 45.3% in (2010, P = 0.017). The rapid changes observed may largely be caused by decreased use of CQ and large-scale use of AL. In the absence of a clear AL-resistance marker and the (almost) continent-wide use of AL in sub-Saharan Africa, and when considering CQ reintroduction, continued monitoring of these markers is needed.     

Survival after jaundice: a prospective study of 1000 consecutive cases

A consecutive series of 1002 jaundiced adult patients covering 23 different causes of jaundice is presented. Patients were followed up for 2 to 7 years. The survival for the 784 patients included during their first episode of jaundice was calculated for each diagnostic category. Examples of decreased survival as compared with the general population were (figures indicate 3 months' and 5 years' survival, respectively): alcoholic cirrhosis 0.81, 0.35; cryptogenic cirrhosis 0.78, 0.32; pancreatic carcinoma 0.54, 0.04; cholangiocarcinoma 0.26, 0.00; and heart failure with liver congestion 0.47, 0.07. Ten of 172 patients with acute viral hepatitis died, 1 of fulminant hepatitis and 9 because of suicide or accidents. Of 105 patients with gallstones 37 died during the study period, but in only 9 of these could death be attributed to the gallstone disease. New diagnostic methods and types of treatment for jaundiced patients have been developed during recent years. To justify fully these diagnostic and therapeutic modalities, knowledge of the prognosis for the various causes of jaundice is essential.     

Can autologous bone culture predict spinal fusion capacity?

The capacity of the individual patient to initiate osteoblast proliferation as a predictor for successful lumbar spinal fusion has not yet been reported. The objectives of this study were, first, to analyze the relationship between in vitro osteoblast proliferation and clinical bony fusion in the individual patient in order to predict the fusion outcome and, second, to measure the effect of preoperative tobacco smoking on osteoblast proliferation. Sixty-one patients (mean age 46 years) underwent posterolateral lumbar fusion in the period 1994–1995. Thirty-eight patients received CD pedicle screw implants and 23 received posterolateral fusions alone. During surgery, autogenous iliac bone was harvested and 1 g of trabecular bone without blood or bone marrow was then isolated for cell culturing. The cultures were classified as excellent (confluence within 4 weeks), good (confluence between 4 and 6 weeks) and poor (no or poor growth). Spine fusion was evaluated by two independent observers from plain anterior-posterior, lateral, and flexion/extension radiographs taken 1 year postoperatively, and the functional outcome was measured by the Dallas Pain Questionnaire (DPQ). Twenty-three patients had excellent, 19 good, and 19 poor in vitro osteoblast proliferation. Bony fusion was obtained in 77% of patients: 83% in the CD instrumentation group and 70% in the non-instrumentation group (NS). There was no significant correlation between osteoblast proliferation and spinal fusion or functional outcomes when analyzing the CD instrumentation and non-instrumentation groups together or separately. Elderly patients had a significantly poorer osteoblast proliferation than younger patients (P < 0.008). Preoperative tobacco consumption had no discernible effect on osteoblast proliferation, and no correlation between smoking and fusion was found. Further refinement of autologous osteoblast culturing may provide a biological tool for selection of patients who require biological enhancement of their bone fusion capacity. The poorer osteoblast proliferation related to advanced age supports the important negative biological influence of age on bony fusion. However, with more sensitive testing and better discrimination, other results are possible – or can in any event not be excluded. Received: 17 April 1998 Revised: 10 September 1998 Accepted: 12 October 1998     

Relevance of neoadjuvant and adjuvant treatment for patients with resectable liver metastases of colorectal carcinoma

Background: Excellent results after resection of colorectal liver metastases are associated with a high rate of recurrence. Influenced by positive results of palliative and adjuvant treatment in advanced cancer, various chemotherapy regimens were evaluated to improve long-term results. Methods: The databases Medline and Cancerlit (1982–1998) gave information about 675 patients who were treated either by means of systemic, intra-arterial, intraportal or intraperitoneal administration before or after liver resection. Results: In general, the feasibility of an adjuvant treatment was tested. Proof has been furnished for the practicability of systemic and arterial therapy and for immunotherapy after liver resection whereas, for peritoneal and portal treatment, further studies are necessary. In a few non-randomised trials, it has been possible to discern a trend towards an improvement due to adjuvant postoperative therapy using historical or matched-pair control groups. Until now, only one of five randomised studies has been published. Six months of postoperative adjuvant intra-arterial treatment using 5-fluorouracil (1000 mg/m² for 5 days every 28 days) and folinic acid (200 mg/m² for 5 days every 28 days) was compared with observation only. Neither in the intention-to-treat nor in the as-treated analysis was median survival time (34.5 months versus 40.8 months and 39.7 months versus 44.8 months, respectively) significantly increased. As neoadjuvant treatment was successful in primary non-resectable patients, this approach is now being tested in resectable patients. Conclusion: Despite several theoretical reasons for post- or preoperative treatment in resectable patients, every approach should be tested using of controlled studies. Received: 2 March 1999 Accepted: 28 June 1999