Showing papers by "Haukeland University Hospital published in 2003"

Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration

Abstract: The present study examined the extent and distribution of lymphocyte infiltration in demyelinated lesions in the cerebral cortex of multiple sclerosis (MS) patients. Tissue sections from the brain of 10 MS patients and five patients without neurological disease were double labeled for myelin basic protein and the lymphocyte markers CD3, CD4, CD8, CD45RO, and CD20. The highest density of CD3-positive T cells was found in MS white matter lesions (40.4/10 high power fields (hpf)). Fewer T cells were detected in cortical lesions that extended through both white and gray matter (12.1/10 hpf; P < 0.001). The lowest number of T cells was detected in intracortical demyelinated lesions (1.1/10 hpf). This was equal to the lymphocyte density in nondemyelinated cerebral cortex within the same tissue block (1.1/10 hpf) or cerebral cortex in control brains (1.8/10 hpf). A similar distribution was found using the CD4, CD8, and CD45RO markers. CD20-positive B cells were scarce in all specimens examined. These data indicate that areas of intracortical demyelination in chronic MS are not associated with an increased number of lymphocytes, or an altered distribution of lymphocyte subsets, when compared with control areas in MS and control patients. This finding indicates that the extent of lymphocyte infiltration in MS lesions is dependent on lesion location.

Antibiotic prophylaxis in total hip arthroplasty: effects of antibiotic prophylaxis systemically and in bone cement on the revision rate of 22,170 primary hip replacements followed 0-14 years in the Norwegian Arthroplasty Register

Abstract: We studied the effects of antibiotic prophylaxis, systemically and in bone cement, on the revision rate of cemented total hip arthroplasties (THAs) in data from the Norwegian Arthroplasty Register during the period 1987-2001. To have comparable groups, only THAs performed because of primary osteoarthritis, using cemented implants with documented good results, and high-viscosity cement were included. If systemic antibiotic prophylaxis had been given, only operations with cephalosporin or penicillin were selected. Cox-estimated survival relative revision risks (RR) are presented with adjustment for differences among groups in gender, age, cement brand, type of systemic antibiotic prophylaxis, type of prosthesis, type of operating room, and duration of the operation. Of 22,170 THAs studied, 696 THAs (3.1%) were revised, 440 (2.0%) for aseptic loosening and 102 (0.5%) for deep infection. We found the lowest risk of revision when the antibiotic prophylaxis was given both systemically and in the cement (15,676 THAs). Compared to this combined regime, patients who received antibiotic prophylaxis only systemically (5,960 THAs) had a 1.4 times higher revision rate with all reasons for revision as endpoint (p = 0.001), 1.3 times higher with aseptic loosening (p = 0.02) and 1.8 times higher with infection as the endpoint (p = 0.01). With the combined antibiotic regime, the results were better if antibiotics were given 4 times on the day of surgery (2,194 THAs), as compared to once (1,424 THAs) (p < 0.001), twice (2,680 THAs) (p < 0.001), or 3 times (5,522 THAs) (p = 0.02). Those who received systemic prophylaxis a single day 1, 2 or 3 times, as compared to 4 times, had a revision rate 1.8-3.5 times higher with all reasons for revision as endpoint, 1.5-3.1 times higher with aseptic loosening, and 2.7-6.8 times higher with infection. When we compared systemic prophylaxis 4 times in 1 day, no further improvement resulted in those given systemic prophylaxis for 2 days (1,928 THAs) or 3 days (717 THAs). In a subset of data including only the Charnley prosthesis, we obtained similar results. This observational study shows that the best results were recorded when antibiotic prophylaxis was given both systemically and in the bone cement, and if the systemic antibiotic was given 4 times on the day of surgery.

Performance on the dementia rating scale in Parkinson’s disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer’s disease

Abstract: Background: The relation between dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) is unknown. Objectives: To compare the cognitive profiles of patients with DLB and PDD, and compare those with the performance of patients with a subcortical dementia (progressive supranuclear palsy) and a cortical dementia (Alzheimer’s disease). Design: Survey of cognitive features. Setting: General community in Rogaland county, Norway, and a university dementia and movement disorder research centre in the USA. Patients: 60 patients with DLB, 35 with PDD, 49 with progressive supranuclear palsy, and 29 with Alzheimer’s disease, diagnosed by either standardised clinical procedures and criteria (all PDD and Alzheimer cases and 76% of cases of progressive supranuclear palsy), or necropsy (all DLB cases and 24% of cases of progressive supranuclear palsy). Level of dementia severity was matched using the total score on the dementia rating scale adjusted for age and education. Main outcome measures: Dementia rating scale subscores corrected for age. Results: No significant differences between the dementia rating scale subscores in the PDD and DLB groups were found in the severely demented patients; in patients with mild to moderate dementia the conceptualisation subscore was higher in PDD than in DLB (p = 0.03). Compared with Alzheimer’s disease, PDD and DLB had higher memory subscores (p < 0.001) but lower initiation and perseveration (p = 0.008 and p=0.021) and construction subscores (p = 0.009 and p = 0.001). DLB patients had a lower conceptualisation subscore (p = 0.004). Compared with progressive supranuclear palsy, PDD and DLB patients had lower memory subscores (p < 0.001). Conclusions: The cognitive profiles of patients with DLB and PDD were similar, but they differed from those of patients with Alzheimer’s disease and progressive supranuclear palsy. The cognitive pattern in DLB and PDD probably reflects the superimposition of subcortical deficits upon deficits typically associated with Alzheimer’s disease.

Femoral head size is a risk factor for total hip luxation: a study of 42,987 primary hip arthroplasties from the Norwegian Arthroplasty Register.

Abstract: On the basis of the Norwegian Arthroplasty Register, which has recorded nearly all primary hip prostheses and revisions in Norway since 1987, we studied risk factors for prosthesis luxation leading to revision. 7 prosthesis brand combinations used in 42,987 primary operations were included from 1987-2000. We found that femoral head size was an important risk factor; 28 mm heads led to revision more often than 32 mm ones (failure rate ratio (FRR) 4.0, 95% confidence interval (CI) 2.2-7.3). Charnley (22 mm head) performed equally well or better than the 28 mm heads. The Exeter stem and cup is the type of prosthesis on the Norwegian market with more than two femoral head sizes (26, 28, 30, 32 mm) and 26 mm heads led to revision due to luxation significantly more often than 30 mm heads (FRR 4.1, 95%CI 2.2-8.1). Old age, preoperative diagnosis, and choice of pros- thesis brand combination were also important factors affecting the revision rate due to luxation. A posterior approach increased the risk of revision more than a lateral one (FRR 1.9, 95%CI 1.4-2.5). Gender, trochan- teric osteotomy and duration of the operation did not affect the results. 

HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects

Abstract: HAMLET (human α-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models, on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells, HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei, where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of α-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

Combined loss of PTEN and p27 expression is associated with tumor cell proliferation by Ki-67 and increased risk of recurrent disease in localized prostate cancer.

Abstract: Purpose: Recent experimental work indicates a major role for PTEN and p27 in prostate cancer. The combined loss of PTEN and p27 was found to strongly increase the development of prostatic carcinomas in an animal model, and a prognostic value in human tumors was postulated. The purpose of our study was to examine the impact of PTEN and p27 on prognosis in a series of prostate cancer patients, using high-density tissue microarray technology for expression profile analysis of PTEN, p27, and tumor cell proliferation. Experimental Design: The expression of PTEN and p27 was examined in primary prostatic carcinomas from 104 patients treated with radical prostatectomy and with complete follow-up available. Using high-throughput tissue microarrays, the expression of PTEN and p27 was examined by immunohistochemistry, and the results were related to clinicopathological variables, tumor cell proliferation (Ki-67), and time to disease progression. Results: PTEN was negative in 28 of 103 tumors (27.2%), and median p27 expression was 64%. Combined loss of PTEN and p27 expression defined a group of 18 tumors (17.5%) associated with increased tumor diameter, seminal vesicle invasion, increased pathological stage, and elevated tumor cell proliferation by Ki-67. Cox regression analysis revealed that loss of PTEN/p27 expression and histological grade were both independent predictors of time to biochemical failure and clinical recurrence. Conclusions: Our findings strongly support the importance of PTEN and p27 for the progression of human prostate cancer because loss of PTEN/p27 expression was associated with adverse pathological parameters, tumor cell proliferation, and increased risk of recurrence.

Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial.

Abstract: The physiological role of dehydroepiandrosterone (DHEA) is not well understood, but studies suggest positive effects on subjective health and bone metabolism. We have conducted a clinical trial with DHEA replacement in adrenal failure with the primary aim of evaluating effects on subjective health status and sexuality. Thirty-nine women with adrenal failure were randomized to 9 months of treatment with 25 mg DHEA (n = 19) or placebo (n = 20). Treatment effects were assessed by validated questionnaires of subjective health and sexuality. DHEA replacement yielded a wide variation of effects on the subjective health scales, which were not different from the effects of placebo. Almost all patients receiving DHEA obtained normal androgen levels. Eighty-nine percent of the patients receiving DHEA experienced side-effects, in particular increased sweat odor and scalp itching. DHEA replacement did not significantly change the levels of blood lipids, IGF-I, and markers of bone metabolism. In conclusion, we do not find evidence of beneficial effects of DHEA on subjective health status and sexuality in adrenal failure. However, DHEA may be beneficial for subgroups of patients with adrenal failure, but these remain to be identified. Premenopausal androgen levels can be restored with 25 mg DHEA daily in most female patients, but side-effects are frequent.

Attention profile in schizophrenia compared with depression: differential effects of processing speed, selective attention and vigilance.

Abstract: Objective: The aim of the study is to investigate whether subjects with schizophrenia and major depression display attention deficits for different reasons. Method: Subjects with schizophrenia (n = 53), recurrent major depression (n = 50) and normal controls (n = 50) were administered with 11 measures of processing speed, selective attention and vigilance. Indices of basal speed, speeded attention, non-speeded attention and vigilance were computed. Results: Both clinical groups were impaired on all chronometric tests. The schizophrenic subjects were also more impaired on speeded attention compared with basal processing speed. Only the schizophrenics were impaired on the non-speeded measures of selective attention. Compared with the schizophrenics, the depressives showed a decrement in vigilance. Conclusion: Reduced performance on attention tests in major depression is because of a non-specific speed reduction and loss of vigilance consistent with lack of effort. In addition to generally impaired processing speed, the schizophrenic subjects exposed a deficit in selective attention, indicating executive dysfunction.

TP53 gene mutations predict the response to neoadjuvant treatment with 5-fluorouracil and mitomycin in locally advanced breast cancer.

Abstract: Purpose: Recent studies have found an association between certain TP53 mutations and resistance to anthracycline-based primary medical therapy in breast cancer. The purpose of this study was to investigate whether TP53 mutational status also might influence the response to a non-anthracycline-containing regimen in primary breast cancer. Experimental Design: Thirty-five patients with locally advanced breast cancer were investigated for TP53 mutations before receiving combination chemotherapy with 5-fluorouracil (1000 mg/m 2 on days 1 and 2) and mitomycin (6 mg/m 2 on day 2), administered every 3 weeks for 2–10 cycles in the neoadjuvant setting. Results: Mutations in the TP53 gene, in particular those affecting loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy ( i.e. , increase in the diameter product of tumor lesion by ≥25%; P = 0.177 for all mutations and P = 0.006 for those affecting L2/L3 domains, respectively). No statistically significant correlation between TP53 LOH and response to therapy was seen. Conclusion: This study revealed a significant association between lack of response to 5-fluorouracil and mitomycin and mutations affecting the L2/L3 domains of the p53 protein. Together with our previous finding that such mutations predict resistance to weekly doxorubicin, our data suggest that mutations affecting this particular domain of the p53 protein may cause resistance to several different cytotoxic compounds applied in breast cancer treatment.

Exposure therapy and sertraline in social phobia: I-year follow-up of a randomised controlled trial

Abstract: Background Maintenance of treatment effect is important for the choice of treatment for social phobia. Aims To examine the effect of exposure therapy and sertraline 28 weeks after cessation of medical treatment. Method In this study 375 patients with social phobia were randomised to treatment with sertraline or placebo for 24 weeks, with or without the addition of exposure therapy. Fifty-two weeks after inclusion, 328 patients were evaluated by the same psychometric tests as at baseline and the end of treatment (24 weeks). Results The exposure therapy group and the placebo group had a further improvement in scores on social phobia during follow-up: mean change in the Clinical Global Impression — Social Phobia overall severity score was 0.45 (95% CI 0.16-0.65, P < 0.01) for the exposure group, and 0.25 (95% CI 0.00-0.48, P < 0.05) for the placebo group. At week 52 the sertraline plus exposure group and the sertraline-alone group had a significant deterioration on the 36-item Short Form Health Survey compared with exposure alone. Conclusions Exposure therapy alone yielded a further improvement during follow-up, whereas exposure therapy combined with sertraline and sertraline alone showed a tendency towards deterioration after the completion of treatment.

Factors affecting general practitioners' decisions about plain radiography for back pain: implications for classification of guideline barriers – a qualitative study

Abstract: Background General practitioners often diverge from clinical guidelines regarding spine radiography. This study aimed to identify and describe A) factors general practitioners consider may affect their decisions about ordering plain radiography for back pain and B) barriers to guideline adherence suggested by such factors.

Childhood Fractures in Bergen, Norway: Identifying High-risk Groups and Activities

Abstract: In 1998 the authors conducted a prospective registration of children younger than 16 presenting with a new traumatic fracture in the city of Bergen, Norway In this epidemiologic study, the authors registered a total of 1725 fractures in children; the fracture incidence was 245 per 10,000 children below the age of 16 One fifth needed reduction, and the distal radius was the most common fracture site (27%) Activities associated with fracture were mostly soccer and bicycling, but compared with the total number of injuries associated with each activity, we found a doubled risk of fractures during rollerblading/skating or snowboarding (60%) compared with playing soccer (38%) or bicycling (33%) Scaphoid fracture, an infrequent fracture in children, was seen in 9% of all fractures due to rollerblading/skating There was a doubled risk of fracture in boys aged 13 to 15 compared with their female peers To make fracture prevention more efficient, it should be targeted at this risk group and these high-risk activities Protection of the wrist region might prevent the most common fractures

Flt3-mediated signaling in human acute myelogenous leukemia (AML) blasts: a functional characterization of Flt3-ligand effects in AML cell populations with and without genetic Flt3 abnormalities

Abstract: BACKGROUND AND OBJECTIVES: Intracellular signaling initiated via Flt3 seems important in both leukemogenesis and chemosensitivity in acute myelogenous leukemia (AML). Flt3 is activated by binding of its natural Flt3-ligand (Flt3-L), but Flt3 genes with internal tandem duplications (Flt3-ITD) or Asp(D)-835 point mutations encode molecules with constitutive activation. The aim of this study was to compare functional effects of exogenous Flt3-L on AML blast populations with and without genetic Flt3 abnormalities. DESIGN AND METHODS: Native AML blasts were derived from 64 consecutive patients with high blast counts in peripheral blood, and in vitro models were used to characterize the Flt3-L effects. RESULTS: The Flt3 protein levels showed a similar wide variation between AML blast populations with and without genetic Flt3 abnormalities. Flt3-L was an autocrine growth factor only for 2 patients. Flt3-ITD+ AML cells had lower responsiveness to exogenous cytokines than cell populations without Flt3 abnormalities, but exogenous Flt3-L increased blast proliferation both for patients without Flt3 abnormalities and patients with Flt3-ITD as well as D835 mutations. This enhancement was observed even in the presence of other exogenous cytokines and included clonogenic AML progenitors. Flt3-L inhibited proliferation only for 1 patient, but had divergent effects on AML blast cytokine release. Flt3-L affected AML blast differentiation (inhibition of erythroid colonies, increased neutrophil granulation) only in a minority of patients, whereas it had an anti-apoptotic effect for a larger subset of patients. INTERPRETATION AND CONCLUSIONS: Intracellular signaling initiated by Flt3 ligation modulates the functional phenotype for native human AML blasts both with and without genetic Flt3 abnormalities.

Localization of a Gene for Migraine without Aura to Chromosome 4q21

Abstract: Migraine is a common form of headache and has a significant genetic component. Here, we report linkage results from a study in Iceland of migraine without aura (MO). The study group comprised patients with migraine recruited by neurologists and from the registry of the Icelandic Migraine Society, as well as through the use of a questionnaire sent to a random sample of 20,000 Icelanders. Migraine diagnoses were made and confirmed using diagnostic criteria established by the International Headache Society. A genomewide scan with multipoint allele-sharing methods was performed on 289 patients suffering from MO. Linkage was observed to a locus on chromosome 4q21 ( LOD = 2.05 ; P =.001). The locus reported here overlaps a locus (MGR1) reported elsewhere for patients with migraine with aura (MA) in the Finnish population. This replication of the MGR1 locus in families with MO indicates that the gene we have mapped may contribute to both MA and MO. Further analysis indicates that the linkage evidence improves for affected females and, especially, with a slightly relaxed definition of MO ( LOD = 4.08 ; P =7.2×10 −6 ).

Contemporary understanding and management of reflux and constipation in the general population and pregnancy: a consensus meeting.

Abstract: Summary Background : Gastro-oesophageal reflux disease (GERD) and constipation have a major impact on public health; however, the wide variety of treatment options presents difficulties for recommending therapy. Lack of definitive guidelines in pharmacy and general practice medicine further exacerbates the decision dilemma. Aims : To address these issues, a panel of experts discussed the principles and practice of treating GERD and constipation in the general population and in pregnancy, with the aim of developing respective treatment guidelines. Results : The panel recommended antacids ‘on-demand’ as the first-line over-the-counter treatment in reflux, and as rescue medication for immediate relief when reflux breaks through with proton pump inhibitors. Calcium/magnesium-based antacids were recommended as the treatment of choice for pregnant women because of their good safety profile. In constipation, current data do not distinguish a hierarchy between polyethylene glycol (PEG)-based laxatives and other first-line treatments, although limitations are associated with stimulant- and bulk-forming laxatives. Where data are available, PEG is superior to lactulose in terms of efficacy. In pregnancy, PEG-based laxatives meet the criteria for the ideal treatment. Conclusions : The experts developed algorithms that present healthcare professionals with clear treatment options and management strategies for GERD and constipation in pharmacy and general practice medicine.

Variants of developmental genes (TGFA, TGFB3, and MSX1) and their associations with orofacial clefts: a case-parent triad analysis.

Abstract: We selected 262 case-parent triads from a population-based study of orofacial clefts in Norway, and examined variants of developmental genes TGFA, TGFB3, and MSX1 in the etiology of orofacial clefts. One hundred seventy-four triads of cleft lip cases (CL±P) and 88 triads of cleft palate only cases (CPO) were analyzed. There was little evidence for an association of any of these genes with CL±P. The strongest association was a 1.7-fold risk with two copies of the TGFB3-CA variant (95% CI=0.9–3.0). Among CPO cases, there was a 3-fold risk with two copies of the TGFA TaqI A2 allele, and no increase with one copy. Assuming this to be a recessive effect, we estimated a 3.2-fold risk among babies homozygous for the variant (95% CI=1.1–9.2). Furthermore, there was strong evidence of gene-gene interaction. While there was only a weak association of the MSX1-CA variant with CPO, the risk was 9.7-fold (95% CI=2.9–32) among children homozygous for both the MSX1-CA A4 allele and the TGFA A2 allele. No association of CPO with the TGFA variant was seen among the other MSX1-CA genotypes. In conclusion, no strong associations were found between CL±P and variants at these three genes. There was a possible recessive effect of the TGFA TaqI variant on the risk of CPO, with a 3-fold risk among children homozygous for the variant. The effect of this TGFA genotype was even stronger among children homozygous for the MSX1-CA A4 allele, raising the possibility of interaction between these two genes. Genet Epidemiol 24:230–239, 2003. © 2003 Wiley-Liss, Inc.

Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T lymphocyte-associated antigen 4, and programmed cell death 1 in primary Sjögren's syndrome.

Abstract: Objective To assess salivary gland tissues obtained from patients with primary Sjogren's syndrome (SS) for the gene expression profile of the candidate genes TNFRSF6 (Fas), TNFSF6 (FasL), SSA1 (Ro52α and the splice variant Ro52β), SSB (La), CTLA4, PDCD1 (PD-1), and ORM2, which were selected on the basis of their putative participation in salivary gland inflammation. Methods Quantitative real-time reverse transcriptase–polymerase chain reaction (RT-PCR) was used to examine the expression of messenger RNA (mRNA). Tissue localization of the expressed proteins was detected by immunohistochemistry. Results Expression of mRNA was increased for Fas (5.1-fold; P < 0.001), FasL (8.8-fold; P < 0.05), cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) (11.2-fold; P < 0.01), programmed cell death 1 (PD-1) (15.2-fold; P < 0.05), Ro52α (3.0-fold; P < 0.01), La (2.3-fold; P < 0.05), and orosomucoid 2 (ORM2) (4.4-fold; P < 0.05) in patients compared with controls when GAPDH was used as endogenous standard in duplex runs. In single runs using 2 other endogenous standards (18S and β-actin), statistically significant differences between patients and controls were confirmed for expression of Fas, FasL, CTLA-4, and PD-1, but this difference was not observed for Ro52α, La, and ORM2. Expression of Ro52β mRNA was similar in patients and controls. Conclusion The present study demonstrates a substantial increase in expression of the negative regulator molecules PD-1 and CTLA-4 and the apoptotic signal molecules Fas and FasL in patients with primary SS compared with controls, which corresponded to the immunomorphologic pattern. The results strongly indicate that these molecules have central roles in the inflammatory process in the salivary glands of patients with primary SS.

Exploring the Effects of Methylenetetrahydrofolate Reductase Gene Variants C677T and A1298C on the Risk of Orofacial Clefts in 261 Norwegian Case-Parent Triads

Abstract: Folic acid and the methylenetetrahydrofolate reductase (MTHFR) gene have both been implicated in the etiology of orofacial clefts. The authors selected 261 case-parent triads (173 cases with cleft lip with or without cleft palate (CL/P) and 88 cases with cleft palate only (CPO)) from a Norwegian population-based study of orofacial clefts (May 1996-1998). A case-parent triad design was used to examine whether MTHFR variants C677T and A1298C, and their haplotypes, are risk factors for orofacial clefts. Among CL/P cases, the child's genotype at C677T or A1298C did not influence the risk. However, children of mothers carrying the C677T variant allele had a lower risk of CL/P. For CPO, children carrying the C677T variant allele had about a twofold increased risk, whereas the mother's genotypes did not contribute to the risk. The haplotype-based transmission/disequilibrium test showed that except for 677T/1298A (p = 0.06), none of the other haplotypes showed evidence of excess transmission to the offspring. The authors also explored interaction of C677T with maternal use of folic acid among children with CPO. Surprisingly, the risk associated with the child's carrying either CT or TT was higher (fourfold) when the mother used folic acid. These findings suggest a possible role of MTHFR and folic acid in the causation of orofacial clefts, but the strength and direction of these effects remain to be clarified.

CSF shunt infections in children: experiences from a population-based study.

Abstract: The objective was to identify risk factors for shunt infections, and establish the rate of infection for shunt procedures carried out under standardized conditions in a well-defined population. All (407) paediatric shunt operations (primary and revisions) performed within a total population of 630000 inhabitants between January 1, 1986 and December 31, 1996, were analysed retrospectively. 11 shunt infections were diagnosed in 10 patients, giving an overall infection rate of 2.7% per procedure and 6.2% per patient. Infections were significantly correlated with age, type of operation, and a etiology of hydrocephalus. Thus, infections occurred more frequently during the first 6 months of life, more often following primary shunt insertions compared with revisions, and children with myelomeningocele had a higher infection risk than children with hydrocephalus due to other causes. There was a highly significant male preponderance in the patient material. Conclusion: The overall infection rate was relatively low. The risk factors for shunt infections appear to relate to epidemiological characteristics rather than to surgical factors.

Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease.

Abstract: Background: Iron deficiency anaemia is a frequent complication of Crohn disease. Treatment with ferrous iron (Fe[Formula: See Text]) compounds is often unsatisfactory and is associated with gastrointestinal side effects. Theoretically, oral iron supplementation may even be harmful, because iron may reinforce intestinal inflammation by catalysing production of reactive oxygen species. We investigated the effect of ferrous iron on disease activity and plasma antioxidant status in patients with active Crohn disease. Methods: Ten patients with Crohn disease and iron deficiency and 10 healthy controls were given ferrous fumarate 120 mg for 7 days. The Crohn Disease Activity Index, gastrointestinal complaints and blood samples for antioxidant status, anaemia, inflammation and iron absorption were investigated on day 1 and day 8. Results: During 1 week of ferrous fumarate supplementation, the Crohn Disease Activity Index tended to increase (P = 0.071). Patients experienced aggravation of diarrhoea, abdominal pai...

Long-lasting cognitive impairment in unipolar major depression: a 6-month follow-up study

Abstract: The aim of the study was to investigate cognitive impairment in major depression both acutely and after 6 months. All patients were investigated within a neurocognitive experimental setting at two testing sessions: at inclusion and after 6 months. Automatic and effortful information processing was investigated with a visual search paradigm. Twenty-one patients with recurrent major depression according to DSM-IV and a Hamilton Depression Rating Scale score >18 were included in the study. Healthy subjects, matched for age and gender, were used as a control group. The results showed that the depressed patients performed equal to the control group on trials requiring automatic information processing at both sessions. However, the patients were impaired compared to the control group on trials requiring effortful information processing, also at both sessions. The depressed patients showed no improvement in cognitive performance from test 1 to test 2. The results indicate that the depressed patients had an impaired performance for effortful, but not automatic, visual search performance, and that the impairment remained after 6 months, despite significant improvement in their depression scores.

Follow-up after intensive care: a single center study.

Abstract: To study health problems, quality of life, functional status, and memory after intensive care. Adult patients (n=346) discharged from a university hospital ICU. Prospective cohort study. Follow-up patients were found using the ICU database and the Peoples Registry. Quality of life (QOL) was measured with the Short Form 36 (SF-36) 6 months after ICU discharge. Semi-structured interviews, questionnaires, Glasgow Outcome Score (recovery), and Karnofsky Index (functional status) were used at consultations 7–8 months after ICU discharge. The SF-36 response rate was 64.5%, with scores significantly lower than population scores. Consultation patients (n=136) did not differ from the rest (n=210) regarding age, SAPS II scores, length of stay (LOS), and reasons for ICU admission. At follow-up 67.6% of consultation patients continued most activities, 75% looked after themselves, and 64.7% were non-workers, compared to 40.4% before the ICU admission. During and after the ICU stay, 40% lost more than 10 kg body weight. Fifty-eight (43%) could not remember anything from their ICU stay. At follow-up only 22 (16%) could remember having received information during their ICU stay. Three patients needed referral to other specialities. We should focus more on optimizing symptom management and giving repeated information after ICU discharge. Nutritional status and weight loss is another area of concern. More research is needed to find out how the broad range of psychosocial and physical problems following an ICU stay relates to the stay.