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- Chelban, V., et al.
(författare)
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PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation
- 2019
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:2, s. 225-240
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
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- Heimer, G, et al.
(författare)
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Effects of vaginally delivered estrogens
- 1996
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. Supplement. - 0300-8835. ; 163, s. 1-2
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Atrophic condition in the vagina and lower parts of the urethral tract are common in elderly women. From population based surveys it has been estimated that 40% or more of women over 60 complain of insufficient control of micturation. In addition, lower urinary tract infections are common in this age group and recurrent cystitis is a scourge for many women (1, 2). Vaginal problems such as vaginal dryness, dyspareunia as well as infectious and non infectious disorders in the vagina may be even more common in elderly women (3) Vasomotor symptoms such as sweats and hot flushes commonly commence around the time of the menopause. In the majority of cases urogenital dysfunction does not become a problem until a decade later. Endogenous estrogens decline during the climacteric and the fall of estradiol levels from the time of onset of vasomotor symptoms until commencement of urogenital problems cannot be disregarded. In other words, it seems as if urogenital integrity can be maintained at lower estrogen levels than those required to resist vasomotor symptoms and conserve bone mass. Further evidence for this concept is achieved from numerous clinical studies in which various estrogens have been administered both orally and vaginally to elderly women with signs of urogenital atrophy which have resulted in amelioration. Such an alleviation of urogenital symptoms can be achieved without provoking endometrial growth.
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- Heimer, G, et al.
(författare)
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Kvinnomisshandel-den tysta epidemin.
- 1999
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Ingår i: Särtryck ur Nordisk Kriminalkrönika. ; , s. 32-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Heimer, G, et al.
(författare)
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Mäns våld mot kvinnor
- 2004
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Ingår i: Utsatta och sårbara brottsoffer. ; , s. 221-239
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Lundgren, E, et al.
(författare)
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Slagen Dam
- 2001
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Bok (övrigt vetenskapligt/konstnärligt)
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- Söderblom, T., et al.
(författare)
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Alarming spread of vancomycin resistant enterococci in Sweden since 2007
- 2010
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Ingår i: Eurosurveillance. - 1025-496X .- 1560-7917. ; 15:29
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Tidskriftsartikel (refereegranskat)abstract
- The total number of persons infected or colonised with vancomycin-resistant enterococci mandatorily reported to the Swedish Institute for Infectious Disease Control increased dramatically during 2007 and 2008. During a period of twenty months from 1 July 2007 to 28 February 2009, a total of 760 cases were reported compared with 194 cases reported during the entire period from 2000 to 2006. This rise was mainly attributed to a wide dissemination of vancomycin resistant enterococci which started in a number of hospitals in Stockholm in the autumn of 2007 and was followed by dissemination in various healthcare facilities (hospitals and homes for the elderly) in a further two Swedish counties in 2008. The majority of the cases (97%) were acquired in Sweden and among these, healthcare-acquired E. faecium vanB dominated (n=634). The majority of these isolates had identical or closely related pulsed-field gel electrophoresis patterns indicating clonal dissemination in the affected counties. The median minimum inhibitory concentration of vancomycin was 32 mg/L (ranging from 4 to > 128 mg/L) and of teichoplanin 0.12 mg/L (ranging from 0.06 to 0.25 mg/L). Particular emphasis was placed on countermeasures such as screening, contact tracing, cleaning procedures, education in accurate use of infection control practices as well as increasing awareness of hygiene among patients and visitors. With these measures the dissemination rate decreased substantially, but new infections with the E. faecium vanB strain were still detected.
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