The outcome of critical illness in decompensated alcoholic liver cirrhosis.

BACKGROUND: The mortality of patients suffering from acute decompensated liver disease treated in the intensive care unit (ICU) varies between 50% and 100%. Previously published data suggest that liver-specific score systems are less accurate compared with the ICU-specific scoring systems acute physiology and chronic health evaluation II (APACHE II) and simplified organ failure assessment (SOFA) in predicting outcome. We hypothesized that in a Scandinavian cohort of ICU patients, APACHE II, SOFA, and simplified acute physiology score (SAPS II) were superior to predict outcome compared with the Child-Pugh score. METHODS: A single-centre retrospective cohort analysis was conducted in a university-affiliated ICU. Eighty-seven adult patients with decompensated liver alcoholic cirrhosis were admitted from January 2007 to January 2010. RESULTS: The patients were severely ill with median scores: SAPS II 60, SOFA (day 1) 11, APACHE II 31, and Child-Pugh 12. Receiver operating characteristic curves area under curve was 0.79 for APACHE II, 0.83 for SAPS II, and 0.79 for SOFA (day 1) compared with 0.59 for Child-Pugh. In patients only in need of mechanical ventilation, the 90-day mortality was 76%. If respiratory failure was further complicated by shock treated with vasopressor agents, the 90-day mortality increased to 89%. Ninety-day mortality for patients in need of mechanical ventilation, vasoactive medication, and renal replacement therapy because of acute kidney injury was 93%. CONCLUSION: APACHE II, SAPS II, and SOFA were better at predicting mortality than the Child-Pugh score. With three or more organ failures, the ICU mortality was > 90%. APACHE II > 30, SAPS II > 60, and SOFA at day 1 > 12 were all associated with a mortality of > 90%. Referral criteria of patients suffering from decompensated alcoholic liver disease should be revised.

Total and cause-specific mortality rates in a prospective study of community-acquired hepatitis C virus infection in northern Norway.

Knowledge of the natural course and especially the total and cause-specific mortality of community-acquired chronic HCV infection is limited. The aims of our study were to determine the total and cause-specific mortality in patients infected with chronic hepatitis C in a community-based setting in northern Norway. This prospective cohort study included 1010 HCV-positive patients diagnosed with recombinant immunoblot assay between 1 January 1990 and 1 January 2000, with a median observation time from diagnosis to follow-up of 7 years. Data were collected from medical records in the period between 1 January 2004 and 30 June 2006. Time and cause of death were ascertained from the Norwegian Causes of Death Register. Age-adjusted death rates and standardised mortality ratios (SMRs) were compared with those of the general Norwegian population. In total, 122 deaths were recorded. The Kaplan-Meier estimate of survival was 88% at 14 years. The SMR in the cohort relative to the general population was 6.66. Most of the excess deaths in both genders were because of liver-related causes, those associated with a drug-using lifestyle and suicide. The statistically significant increase in SMRs ranged from 4.2 for death by cancer in women to 64.6 for liver disease in women. There was no statistically significant increase in SMRs from cardiovascular disease in either gender or from cancer in men. In conclusion, our study shows that the death rate in patients infected with hepatitis C is 6.66 times higher than in the general Norwegian population.

Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels.

BACKGROUND AND PURPOSE: Positive modulators of small conductance Ca(2+)-activated K(+) channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non-excitable cells. The prototype compound 1-EBIO or the more potent compound NS309, do not distinguish between the SK subtypes and they also activate the related intermediate conductance Ca(2+)-activated K(+) channel (IK). This paper demonstrates, for the first time, subtype-selective positive modulation of SK channels. EXPERIMENTAL APPROACH: Using patch clamp and fluorescence techniques we studied the effect of the compound cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) on recombinant hSK1-3 and hIK channels expressed in HEK293 cells. CyPPA was also tested on SK3 and IK channels endogenously expressed in TE671 and HeLa cells. KEY RESULTS: CyPPA was found to be a positive modulator of hSK3 (EC(50) = 5.6 +/- 1.6 microM, efficacy 90 +/- 1.8 %) and hSK2 (EC(50) = 14 +/- 4 microM, efficacy 71 +/- 1.8 %) when measured in inside-out patch clamp experiments. CyPPA was inactive on both hSK1 and hIK channels. At hSK3 channels, CyPPA induced a concentration-dependent increase in the apparent Ca(2+)-sensitivity of channel activation, changing the EC(50)(Ca(2+)) from 429 nM to 59 nM. CONCLUSIONS AND IMPLICATIONS: As a pharmacological tool, CyPPA may be used in parallel with the IK/SK openers 1-EBIO and NS309 to distinguish SK3/SK2- from SK1/IK-mediated pharmacological responses. This is important for the SK2 and SK1 subtypes, since they have overlapping expression patterns in the neocortical and hippocampal regions, and for SK3 and IK channels, since they co-express in certain peripheral tissues.

Prognostic implications of proliferative activity and DNA aneuploidy in Astler-Coller Dukes stage C colonic adenocarcinomas.

Paraffin-embedded surgical specimens from 69 patients who underwent resections of otherwise untreated Dukes stage C adenocarcinoma of the colon were examined for proliferative activity, DNA aneuploidy, DNA index, and proportion of aneuploid cells by flow cytometry. Results were correlated to clinical characteristics of the patients and to overall survival times. DNA aneuploid tumors were identified in 60 cases (87%), diploid tumors in 9 cases (13%). The mean S-phase fraction for all cases was 17.6%, with a standard deviation (SD) of 7.8. In univariate statistical analysis, younger patient age, lower tumor proliferative activity, DNA index less than or equal to 1.2, and presence of only 1-4 lymph nodes with tumor involvement were found to be significant predictors of improved patient survival. In multivariate Cox regression analysis, low tumor proliferative activity, younger patient age, and location of the tumor in the right or transverse colon were found to be significant independent predictors of increased patient survival. When tumor proliferative activity was stratified into statistically defined subgroups, patients with tumors of low proliferative activity (S-phase less than mean - 0.5 SD) had significantly longer survival than patients with tumors of moderate proliferative activity (S-phase value greater than mean - 0.5 SD and less than mean +0.5 SD) or high proliferative activity (S-phase greater than mean +0.5 SD). These results suggest that tumor proliferative activity in Dukes C colon carcinoma may be an important biological factor in determining patient prognosis.

Primary histiocytosis X of the parieto-occipital lobe.

Immunohistochemical and ultrastructural evidence support the concept that histiocytosis X is the result of proliferation of pathological Langerhans' cells. Central nervous system involvement by histiocytosis X has been commonly described in multisystem disease and in association with lytic skull lesions. Unifocal brain involvement by histiocytosis X without concomitant osseous involvement is rare, with only 14 cases reported in the literature to date. Ten of these cases have involved the hypothalamus; the remaining four have involved the frontal lobe (two cases) and the temporal lobe (two cases). The fifth case of extrahypothalamic unifocal histiocytosis X, the first female case, and the first case with parieto-occipital lobe involvement, is reported. Pathology demonstrated infiltration of brain parenchyma by clusters of characteristic histiocytosis X cells with an admixture of morphologically related giant cells, eosinophils, and lymphocytes. Langerhans' granules were identified in the histiocytosis X cells by electron microscopy. Immunohistochemistry showed strong S-100 protein, HLA-DR, and T6 antigen positivity by the histiocytosis X cells. Therapy included complete surgical excision and postoperative radiation therapy for the incompletely excised lesion. Patients with unifocal extrahypothalamic histiocytosis X may have a better prognosis than patients with localized hypothalamic disease.

Does admission to a medical department improve patient life expectancy?

Doubts about the effectiveness of medical care in improving patient health have been raised by epidemiological studies and by studies of geographical variation and inappropriate use of health care. To investigate this problem, the life expectancy gain (LEG) from consecutive admissions to a department of internal medicine during a six-week period was assessed by two expert panels, each consisting of an internist, a surgeon, and a general practitioner. The mean LEG for all admissions was 2.25 years (n = 422). Sixty-one percent had a LEG of 0.10 years or less, while 5% had a LEG of more than 9.98 years. In a probabilistic sensitivity analysis, the mean LEG remained greater than zero under assumptions of overestimated positive LEG and underestimated negative LEG. We conclude that the life expectancy of the majority of the patients was not influenced by the admission, but that a minority had substantial gains, resulting in a high overall mean LEG.

Metastatic renal tumor presenting as ovarian clear cell carcinoma.

Patients with clear cell adenocarcinoma of the kidney often present with metastatic disease, in some cases involving organs in which primary clear cell tumors occur. Under these circumstances, diagnosis of the renal primary tumor may be delayed. Herein we present a case of renal cell carcinoma metastatic to the ovaries initially treated as primary ovarian disease, until the appearance of other metastases prompted the discovery of its true origin. A high index of suspicion and the histologic characteristics of these tumors may allow earlier diagnosis and treatment of a renal primary tumor.

Psoriasis in an unselected series of twins.

The relative importance of genetic factors in the origin, age at onset, clinical type, course, and severity of psoriasis was evaluated on the basis of an unbiased sample of twins, ie, the Danish Twin Register, which covers the total population of twins born in Denmark. All verified and probable cases of psoriasis in twins, born 1891 through 1920, were ascertained. Results are presented of an examination of all members of index pairs in which both partners were alive on a certain date. Fourteen monozygotic and 22 dizygotic, like-sexed pairs were found to include at least one partner with unquestionable psoriasis. Zygosity determination was mainly based on extensive serological examinations. The analyses show that the manifestation of psoriasis depends almost exclusively on the presence of the specific genotype. The age at onset, clinical type, course, and severity are also mainly determined by the genetic constitution. Association with certain HLA antigens of the B series has been confirmed, but the fact that many of the twins (including several of the concordant monozygotic pairs) possess neither of these antigens shows the corresponding genes to be important, but not decisive, elements in the predisposition. We conclude that psoriasis is a genetically determined disorder that may, to a limited extent, be modified by environmental influences.

Effect of anticoagulant therapy on the hypercoagulable state in patients carrying the factor V Arg506Gln mutation.

Resistance to activated protein C, caused by a single point mutation in the factor V gene (Arg506Gln or FV Leiden), is the most prevalent single risk factor associated with venous thromboembolic disease. The aim of this study was to investigate the effectiveness of standard oral anticoagulant therapy (OAT) in patients with the Arg506Gln mutation compared with a matched control group. The study compared selected variables in 27 patients carrying the Arg506Gln mutation with 27 sex- and age-matched controls in steady state oral anticoagulant treatment (OAT). The study showed that similar doses of vitamin K antagonists in carriers and noncarriers suppress and generate a uniform distribution of coagulation markers in steady state OAT. Thus, it seems that OAT with standard treatment doses is just as effective in patients with the Arg506Gln mutation as in comparable controls without the mutation.

Evaluation of a simple dosage scheme for transition from phenprocoumon to warfarin in oral anticoagulation.

Phenprocoumon, whose elimination half-time is 144 hours, has been the traditional oral anticoagulant of choice in Europe. However, today's most widely used drug is warfarin, whose elimination half-time is 40 hours. This study aims to evaluate a method for safe transition from phenprocoumon to warfarin, which is sometimes required. Hence, the large difference in their elimination rates may on occasion lead to serious overdosage upon transition from one drug to the other. According to average equipotent doses, a stepwise increase in warfarin dose was calculated based on the elimination half-times of the two drugs. The dosage scheme was subsequently tested in a pilot study including 35 patients. The conversion scheme was then adjusted based on the results from the pilot study. The new scheme was tested in 69 patients. The transition factor was 2.3, which implies that equipotency was achieved when the warfarin dose was 2.3 times larger than the phenprocoumon dose (in mg). This scheme proved optimal for 75% of the patients. However, the dose had to be adjusted individually in the remaining 25% of the patients to a level corresponding to the measured international normalised ratios. No patients experienced haemorrhages or thromboembolic complications during the period of changeover. In conclusion, the proposed scheme for changing medication from phenprocoumon to warfarin is safe and convenient.

Effectiveness of antihypertensive treatment in chronic renal failure: to what extent and with which drugs do patients treated by nephrologists achieve the recommended blood pressure?

Adequate control of blood pressure (BP) is important to slow the progression of chronic renal failure (CRF). The Joint National Committee (JNC) VI recommends BP <130/85 mmHg, or <125/75 mmHg if urinary protein excretion exceeds 1 g/d. Angiotensin converting enzyme inhibitors (ACE-I) are considered as first-line agents. The current study is a survey of the degree of goal achievement and prescription patterns of antihypertensive (AHT) medication according to the JNC guidelines in clinical nephrology practice. All patients with CRF, not on renal replacement therapy, treated by nephrologists at the University Hospital of North-Norway were included in this retrospective cross-sectional study. Data on protein:creatinine ratio (PC ratio), BP and AHT drugs prescribed were extracted from the hospital's databases and medical records. A total of 144 patients were included. The patients' age was 62+/-16 years and the serum creatinine value was 210+/-92 micromol/l (mean+/-s.d.). In all, 74 patients (51%) had PC ratio < or =1, 36 (25%) >1, and for 34 (24%) PC ratio had not been measured; 23 (31%) of the patients with PC ratio < or =1 had BP < or =130/85 (139+/-21/78+/-12), and 5 (14%) of those with PC ratio >1 had BP < or =125/75 (145+/-22/85+/-14). Failure to achieve the goal was most commonly due to elevated SBP. In all, 55 % of the patients were prescribed ACE-I or angiotensin receptor blocker (ARB). In conclusion, the recommended BP goals may be difficult to achieve for a high proportion of patients in clinical practice due to difficulty in lowering SBP. There is a potential for improved treatment of hypertension in CRF patients, including increased prescription of ACE-I and ARB.

Lipoma of the breast: a diagnostic dilemma.

Lipoma of the breast often causes diagnostic and therapeutic uncertainty. Clinically it may be difficult to distinguish a lipoma from other conditions. Fine-needle aspiration cytology (FNAC) is often not helpful. Both mammography and ultrasound scanning are often negative. For the present study, 108 women with a clinical diagnosis of lipoma were enrolled prospectively. The clinical diagnosis of lipoma was found to be incorrect in 25.0% of these cases. Mammography and ultrasound revealed a lipoma in only 3.0% and 21.0%, respectively. FNAC revealed only fat cells in 74.0% of cases. In all, only 9 patients (11.4%) fulfilled the triple diagnostic criteria, theoretically making tumour excision mandatory in the remaining cases. Our proposal for management is for any clinical diagnosis of lipoma to be confirmed by either FNAC revealing fat cells or a core biopsy consistent with a lipoma. The mammogram and the ultrasound need not necessarily demonstrate a lipoma, but obviously must not show anything to raise the suspicion of malignancy at the site. If these criteria are met it is not necessary to excise the tumour.

Recognition memory and attentional selection: serial scanning is not enough.

In two experiments, using memory sets of up to 10 letters, the response competition paradigm was employed to investigate the extent to which extraneous visual stimuli interfere with or affect the process of memory search. It was assumed that if selective attention could exclude the effect of noise letters from a Sternberg-type memory comparison process, then there would be an increase in intercept for the reaction time-set size functions but no increase in slope. This result was obtained. However, a large difference in response times to both positive and negative set targets was found when the accompanying noise letters indicated a competing response, as opposed to when they indicated the same response as the target. This implies rapid identification of the nature of both target and noise, independent of a serial comparison process. A modification of a dual process model (Juola, Fischler, Wood, & Atkinson, 1971) in which stimuli activate a familiarity value independent of memory search was suggested to account for these results.

Nutritional status at submission for dietetic services and screening for malnutrition at admission to hospital.

This paper presents two studies in a quality management project that aims to diminish malnutrition among hospitalized patients. The objective of study 1 was to investigate what information was available on the nutritional status of patients submitted for dietetic services for reasons other than obesity (n= 167) and of study 2 to evaluate a nine-question screening sheet for malnutrition in patients (n= 115) within 48 h of admission to the hospital. In study 1 sufficient data to evaluate nutritional status was found for 17% of the patients submitted for dietetic services. In study 2 the screening sheet identified 21% of the patients as malnourished and a full nutritional assessment of seven anthropometrical and biochemical measurements 20%. The screening sheet could be simplified to six questions and then had a sensitivity of 0.69, a specificity of 0.91 and a positive predictive value of 0.65. It is concluded that evaluation of nutritional status in hospitalized patients has been disregarded and a simple screening sheet can be used to identify patients in need of further nutritional assessment and treatment.

Screening method evaluated by nutritional status measurements can be used to detect malnourishment in chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate and develop a screening method for malnutrition among patients with chronic obstructive pulmonary disease (COPD). DESIGN: Findings from a screening sheet for malnutrition were compared with results from full nutritional assessment. The screening sheet included 7 questions regarding body mass index, anorexia, loss of weight, and other variables possibly affecting nutritional status. Each answer was assigned a point value, and a total of 4 and 5 points were tested as criterion for malnutrition. Full nutrition assessment included measurements of weight and height (body mass index), serum albumin and prealbumin, total lymphocyte count, triceps skinfold thickness, mid-arm muscle circumference or area, and information on unintentional weight loss. Malnutrition was defined by 3 or more values below reference values. SUBJECTS: Randomly selected patients (n = 34) with a clinical diagnosis of COPD, 15% of eligible patients admitted to the Department of Lung Medicine at National University Hospital, Reykjavik, Iceland, during the time of the study. STATISTICAL ANALYSIS: Sensitivity, specificity, and predictive values were calculated to evaluate the screening sheet. Each of the 7 parameters used in a full nutrition assessment was similarly evaluated as an indicator to predict malnutrition. RESULTS: Full nutrition assessment identified 13 of 34 patients (38%) as malnourished. Using 4 points as a criterion for malnutrition, the screening sheet to be used for patients with COPD resulted in sensitivity of 0.69 and specificity of 0.90. CONCLUSION: The results confirm the frequent finding of malnutrition among patients with COPD and show that a simple screening sheet can be used to identify which patients need further nutrition assessment and treatment.

Analysis of a Danish Caucasian population sample of single locus DNA-profiles. Allele frequencies, frequencies of DNA-profiles and heterozygosity.

The frequency distributions of the length of restriction fragments (HinfI) revealed by RFLP-analysis (restriction fragment length polymorphism) of blood samples from 482 Danish Caucasians using the single locus VNTR (variable number of tandem repeats) probes MS1, MS31, MS43a and YNH24 are reported. From two blood samples three fragments were obtained with MS1. The consistency of the characteristic allele frequency distribution for each probe is exemplified by comparing the accumulated frequency curves obtained with MS43a in samples consisting of 50 and 920 bands, respectively. The distribution of the differences in migration distance for the two fragments of a bandpair was investigated. The results suggest that the high frequency of apparent homozygotes observed is due mainly to coalescence of close heterozygotes. The distribution of frequencies of 437 DNA-profiles is reported.

DNA-profiling of stains in criminal cases: analysis of measurement errors and band-shift. Discussion of match criteria.

DNA-profiling was performed on approximately 600 stains (blood, semen/vaginal secretion, tissue samples and saliva) deriving from criminal investigations. The restriction enzyme was HinfI, and the VNTR (variable number of tandem repeats) probes were MS1, MS31, MS43a and YNH24. DNA-profiles were obtained from 60% of the stains, and matches were seen for 65% of the profiles. The measurement errors and the differences between corresponding fragment lengths of blood and stain profiles were analysed statistically. Distinct band-shifts were observed for approximately 65% of the profiles. For 50% of the profiles, the fragments derived from the stain fragments migrated faster than those from the blood sample, and for 15% of the profiles the stain fragments migrated slower. The difference between the migration distance of the stain and the blood fragments of a given pair of profiles increased with increasing migration distance, i.e. with decreasing fragment length. After correction for this slope the measurement errors were independent of the fragment length, and of the same order of size as for duplicate determinations of fragments from blood samples. The differences between the fragment lengths of corresponding profiles were highly correlated (rho = 0.8). Based on the statistical analysis, different match criteria are discussed and an ellipsoid accept-area is suggested.

The effect of sample size on the estimation of the frequency of DNA-profiles in RFLP-analysis.

Restriction fragment length polymorphism analysis (RFLP-analysis) was carried out on blood samples from 616 unrelated Danish Caucasians. DNA was restricted with Hinf I and analyzed with the single locus variable number tandem repeats (VNTR) probes MS1, MS31, MS43a and YNH24. The effect of the sample size on the estimates of the frequencies of DNA-profiles was investigated using reference samples of 50-1200 bands for each probe. The effects of using the upper confidence limit and a minimum default allele frequency in the calculation of the frequency of the DNA-profile were investigated. It is concluded that very small samples, e.g. 50 individuals, may be used as reference samples in the estimation of the frequency of a DNA-profile. The use of an upper confidence limit was without significant effect, whereas the use of a minimum default allele frequency prevented large underestimates.

Statistical analysis of the measurement errors in the determination of fragment length in DNA-RFLP analysis.

DNA from human whole blood samples was digested with the restriction enzyme HinfI and RFLP analysis performed using the single locus probes MS1, MS31, MS43a and YNH24. The intergel variation of 3291 duplicate measurements of fragment lengths in terms of basepairs was investigated. The difference between two measurements of the same fragment on different gels increased approximately exponentially with increasing fragment length. After transformation of the fragment length into a normalized migration distance it was found that the difference between two transformed measurements was normally distributed with a S.D. (0.70 mm) which was independent of the fragment length. The errors of band 1 and band 2 on the same lane were correlated (r2 = 0.8). It is useful in the calculation of frequencies and in retrieval procedures and also in the calculation of likelihood ratios to be able to use a S.D. which is independent of the fragment length.

Sequencing strategy of mitochondrial HV1 and HV2 DNA with length heteroplasmy.

We describe a method to obtain reliable mitochondrial DNA (mtDNA) sequences downstream of the homopolymeric stretches with length heteroplasmy in the sequencing direction. The method is based on the use of junction primers that bind to a part of the homopolymeric stretch and the first 2-4 bases downstream of the homopolymeric region. This junction primer method gave clear and unambiguous results using samples from 21 individuals with length heteroplasmy in the hypervariable regions HV1, HV2 or both. The method is of special value for forensic casework, because sequencing of both strands of an mtDNA region is preferable in order to reduce ambiguities in sequence determination.