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- Abdelmagid, N., et al.
(författare)
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The Calcitonin Receptor Gene Is a Candidate for Regulation of Susceptibility to Herpes simplex Type 1 Neuronal Infection Leading to Encephalitis in Rat
- 2012
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Ingår i: Plos Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex encephalitis (HSE) is a fatal infection of the central nervous system (CNS) predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s) regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL), Hse1, on rat chromosome 4 (confidence interval 24.3-31 Mb; LOD score 29.5) governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr) as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development.
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| 2. |
- Abdelmagid, N., et al.
(författare)
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Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex encephalitis (HSE) is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats) with the asymptomatic infection of BN (Brown Norway). Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains), displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus) named Hse6 towards the end of chromosome 4 (160.89-174Mb) containing the Vwf (von Willebrand factor) gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism). Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008) after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.
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| 4. |
- Gnann, J. W., et al.
(författare)
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Herpes Simplex Encephalitis: Lack of Clinical Benefit of Long-term Valacyclovir Therapy
- 2015
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 61:5, s. 683-691
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Tidskriftsartikel (refereegranskat)abstract
- Background. Despite the proven efficacy of acyclovir (ACV) therapy, herpes simplex encephalitis (HSE) continues to cause substantial morbidity and mortality. Among patients with HSE treated with ACV, the mortality rate is approximately 14%-19%. Among survivors, 45%-60% have neuropsychological sequelae at 1 year. Thus, improving therapeutic approaches to HSE remains a high priority. Methods. Following completion of a standard course of intravenous ACV, 87 adult patients with HSE (confirmed by positive polymerase chain reaction [PCR] for herpes simplex virus DNA in cerebrospinal fluid) were randomized to receive either valacyclovir (VACV) 2 g thrice daily (n = 40) or placebo tablets (n = 47) for 90 days (12 tablets of study medication daily). The primary endpoint was survival with no or mild neuropsychological impairment at 12 months, as measured by the Mattis Dementia Rating Scale (MDRS). Logistic regression was utilized to assess factors related to the primary endpoint. Results. The demographic characteristics of the 2 randomization groups were statistically similar with no significant differences in age, sex, or race. At 12 months, there was no significant difference in the MDRS scoring for VACV-treated vs placebo recipients, with 85.7% and 90.2%, respectively, of patients demonstrating no or mild neuropsychological impairment (P = .72). No significant study-related adverse events were encountered in either treatment group. Conclusions. Following standard treatment with intravenous ACV for PCR-confirmed HSE, an additional 3-month course of oral VACV therapy did not provide added benefit as measured by neuropsychological testing 12 months later in a population of relatively high-functioning survivors.
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| 10. |
- Hjalmarsson, A, et al.
(författare)
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Encephalitis after influenza in Sweden 1987-1998: a rare complication of a common infection
- 2009
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Ingår i: European neurology. - : S. Karger AG. - 1421-9913 .- 0014-3022. ; 61:5, s. 289-294
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the incidence of influenza-related encephalitis in Sweden during 11.5 years. Studies from Japan report an increased incidence of influenza-related encephalitis/encephalopathy. Few other studies are available. We conducted a retrospective register-based study on the Swedish National Inpatient Register, which covers all Swedish hospitals. In 1987–1998, a total number of 14,250 hospitalized individuals had an influenza diagnosis (population incidence: 137 per million personyears). In-hospital mortality was 4.1%. Using three different approaches, only 21 cases of influenza-related encephalitis were found, corresponding to a rate of 1.5 per 1,000 hospitalized persons with an influenza diagnosis (population incidence 0.21 per million person-years). We conclude that encephalitis following influenza occurs rarely, or is an infrequently recognized, diagnosed or reported complication. The cases we studied in detail have all recovered without sequels.
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| 13. |
- Laszlo, Sofia, et al.
(författare)
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Proximal Hamstring Tendon Avulsions : A Survey of Orthopaedic Surgeons' Current Practices in the Nordic Countries
- 2022
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Ingår i: SPORTS MEDICINE-OPEN. - : Springer. - 2199-1170 .- 2198-9761. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Evidence guiding the decision on whether to treat proximal hamstring tendon avulsions (PHA) operatively or non-operatively is very limited. The aim of this study was to identify the current practices and the rationale behind PHA treatment decisions in the Nordic countries. Methods A survey was sent to orthopaedic surgeons in Sweden, Norway, Finland and Denmark. The study population consisted of responding surgeons with exposure to surgical treatment of PHA (n = 125). The questions covered surgeon and unit characteristics, and surgeons' understanding of the evidence for treatment, and they explored which patient and injury factors influence treatment allocation. Results Although some surgeons indicated a preference for one of the treatments, 84% stated that the treatment decision was based on patient and injury-related factors. Severe obesity, drug abuse, a sedentary lifestyle, age > 60 years and delayed diagnosis (> 6 weeks) were considered contraindications to surgical treatment. Also, there was agreement that patients expressing a preference for non-operative treatment should not be operated. Complete avulsions with tendon dislocation >= 2-3 cm on MRI were relative indications for surgical treatment. The majority of surgeons did not believe that operatively treated patients did better than non-operatively treated patients and experienced that patients, generally, were satisfied with the treatment result, regardless of the type of treatment. Most surgeons had experienced significant complications to operative treatment. Conclusion Current practices varied among different units, and despite the lack of evidence for their prognostic value, several factors were inconsistently being used as decision modifiers when selecting patients for surgical treatment.
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- Pihl, Elsa, et al.
(författare)
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At mid- to long-term follow-up after proximal hamstring tendon avulsion; there was greater fatty infiltration, muscle atrophy and strength deficit in the hamstring muscles of the injured leg than in the uninjured leg
- 2023
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Ingår i: Journal of Orthopaedic Surgery and Research. - : BioMed Central (BMC). - 1749-799X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundProximal hamstring tendon avulsions (PHAs) may be treated nonoperatively or operatively. Little is known about the result of the injury, and its treatment, on the quality and function of the hamstring muscle after healing and rehabilitation. We hypothesized that the injured leg would have greater fatty infiltration and atrophy than the uninjured leg at follow-up and that these findings would correlate to muscle weakness.MethodsIn a cross-sectional cohort study, 48 patients treated for PHA, either operatively or nonoperatively, were re-examined 2-11 years post-treatment. We measured muscle strength with isokinetic strength tests, and muscle volume and fatty infiltration with MRI.Primary outcomes were hamstring muscle quality, quantified by outlining the cross-sectional area slice-by-slice, and the degree of fatty infiltration estimated using the Goutallier grading method. Secondary outcome was concentric isokinetic hamstring muscle strength measured using BioDex at 60 degrees/sec and tendon attachment assessed on MRI. Comparisons with the outcomes of the uninjured leg were made.ResultsThe total hamstring muscle volume was on average reduced by 9% (SD +/- 11%, p < 0.001) compared to that of the uninjured leg. Fatty infiltration was significantly more severe in the injured hamstrings than in the uninjured hamstrings (p < 0.001). This was also true when only analyzing operatively treated patients. The reduction in muscle volume and increase in fatty infiltration correlated significantly (r = 0.357, p = 0.013), and there was also a statistically significant correlation with muscle atrophy and reduction in isokinetic strength (r = 494, p < 0.001).ConclusionPHA injuries result in fatty infiltration and muscle atrophy and the muscle quality impairment correlates with residual muscle weakness.
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| 15. |
- Pihl, Elsa, et al.
(författare)
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Exploring the Perth Hamstring Assessment Tool and Lower Extremity Functional Scale in a Proximal Hamstring Avulsion Cohort : A Cross-sectional Study
- 2021
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Ingår i: American Journal of Sports Medicine. - : Sage Publications. - 0363-5465 .- 1552-3365. ; 49:7, s. 1732-1740
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Tidskriftsartikel (refereegranskat)abstract
- Background: The goal of treatment for a proximal hamstring avulsion (PHA) is an objectively restored muscle and a subjectively satisfied, pain-free patient at follow-up. Different self-reported and performance-based outcome measures have been used to evaluate recovery, but their validity is poorly investigated. Purpose: To investigate (1) the correlation between the commonly used self-reported outcome measurements, the Perth Hamstring Assessment Tool (PHAT) and the Lower Extremity Functional Scale (LEFS); (2) to what extent these scores can be explained by physical dysfunction as measured by performance-based tests; (3) whether performance-based tests can discriminate between the injured and uninjured extremity; and (4) which activity limitations are perceived by patients several years after the injury. Study design: Cohort study (Diagnosis); Level of evidence, 3. Methods: We included a consecutive series of patients treated for or diagnosed with PHA in our department between 2007 and 2016 having at least 2 tendons avulsed from the ischial tuberosity. Participants attended 2 study visits, answered questionnaires (PHAT, LEFS, and Patient-Specific Functional Scale [PSFS]), and performed physical performance-based tests (single-leg hop tests, single-step down test, and isometric and isokinetic strength tests). Results: A total of 50 patients were included (26 men [52%], 24 women [48%]; mean age, 50.9 years [SD, 9.8 years]). The mean follow-up time was 5.5 years (SD, 2.7 years), and 74% had been surgically treated. The correlation between PHAT and LEFS was strong (r = 0.832) and statistically significant (P < .001). Seven of the performance-based tests exhibited a statistically significant but weak correlation with LEFS (0.340-0.488) and 3 of the tests to PHAT (-0.304 to 0.406). However, only peak torque could significantly discriminate between the extremities. The activity limitation most commonly mentioned in PSFS was running (16 patients [32%]). Conclusion: Although PHAT and LEFS correlated strongly, the correlations between functional tests and the patient-reported outcome scores were weak, and most functional tests failed to discriminate between the injured and uninjured lower extremity in patients with PHA 5 years after injury. In general, patients alleged few activity limitations, but running difficulty was a common sequela after PHA.
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| 19. |
- Skoldenberg, B
(författare)
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Herpes simplex encephalitis
- 1996
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Ingår i: Scandinavian journal of infectious diseases. Supplementum. - 0300-8878. ; 100, s. 8-13
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Tidskriftsartikel (refereegranskat)
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