Leif Svensson

Eccentric Training of the Gastrocnemius-Soleus Complex in Chronic Achilles Tendinopathy Results in Decreased Tendon Volume and Intratendinous Signal as Evaluated by MRI

Background Satisfactory treatment results have been reported after eccentric calf muscle strength training in patients with chronic Achilles tendinopathy. Hypothesis Magnetic resonance imaging may be a useful adjunct in the evaluation of the effect of 3 months of eccentric calf muscle strength training. Study Design Prospective cohort study. Methods Using magnetic resonance imaging, the Achilles tendons were investigated in 25 patients (16 men and 9 women) ranging in age from 28 to 70 years (median, 51 years) before and after training. Five different magnetic resonance imaging sequences were used. Tendon volume and mean intratendinous signal were calculated using a new seed-growing technique showing 99.3% and 96.6% intraobserver reliability, respectively. The clinical outcome was categorized according to pain level and performance using a questionnaire completed by the patient. Results The eccentric training resulted in a 14% (mean) decrease of tendon volume measured on T1-weighted images, from 6.6 ± 3.1 cm3 to 5.8 ± 2.3 cm3 (P < .05). The intratendinous signal in the symptomatic Achilles tendon measured on proton density-weighted images decreased 23% (mean), from 227 ± 77 signal units to 170 ± 83 signal units (P < .05). The gadolinium contrast agent-enhanced images did not add further value compared with other sequences. Clinical Outcome The clinical outcome was categorized as excellent in 10, good in 3, fair in 5, and poor in 8 patients. The [. Delta]signal correlated significantly with the pain level (P < .05). Conclusions Eccentric training resulted in decreased tendon volume and intratendinous signal and was correlated with an improved clinical outcome. Magnetic resonance imaging techniques can be used as an adjunct to clinical evaluation by monitoring morphologic effects in clinical treatment studies of Achilles tendinopathy.

Platelet concentrates in an additive solution prepared from pooled buffy coats : in vivo studies

Leukocyte‐depleted platelet concentrates were prepared from pools of 4 buffy coats on the day after blood collection (BC‐PC). The storage medium was composed of citrate phosphate dextrose plasma and a platelet‐additive solution. Autologous transfusions of 111In‐labelled platelets in 9 healthy volunteers were performed on the day of preparation (day 1) and on day 5. The recovery was 54.6±8.7 (day 1) and 51.9±10.4% (day 5), T1/2 was 101±28 and 61±9 h, respectively. The survival was 8.3±1.7 and 5.7±1.0 days, respectively, using linear plot, and 7.8±2.0 and 5.8±0.5 days using the multiple hit method. In a prospective clinical study a comparison of the corrected posttransfusion increments was made between BC‐PCs and apheresis‐PCs, and between fresh (1–2 days) and stored (3–5 days) preparations. No difference was found between BC‐PCs and apheresis PCs. However, fresh BC‐PCs gave higher increments than stored BC‐PCs. A slight numerical difference between fresh and stored apheresis‐PCs was not statistically significant. It is concluded that the BC‐PC method results in platelets of equal quality to apheresis‐PC.

Imaging markers of mild cognitive impairment: Multivariate analysis of CBF SPECT

This study aimed to investigate cross-sectional and longitudinal changes of regional cerebral blood flow (rCBF) in preclinical dementia using single photon emission computed tomography (SPECT). SPECT and cognitive function were investigated in 39 mild cognitive impairment (MCI) subjects and 20 age-matched controls. All subjects were followed longitudinally 19 months on average, 16 MCI subjects progressed to Alzheimers disease (AD), who were retrospectively defined as progressive mild cognitive impairment (PMCI) at baseline and 23 MCI subjects remained stable and were defined as stable mild cognitive impairment (SMCI) at baseline. SPECT was performed both at the initial investigation and at follow-up. Image data were analyzed using multivariate analysis, SPM and volume of interest (VOI)-based analysis. Significant covariate patterns were derived, which differentiate among PMCI, SMCI and controls at baseline as well as describe the longitudinal progression of PMCI. The combined SPECT and neuropsychology increased the diagnostic accuracy of PMCI at baseline. SPECT and neuropsychological testing can be used objectively for both baseline diagnosis and to monitor changes in brain function during very early AD.

In vitro and in vivo effects of potassium and magnesium on storage up to 7 days of apheresis platelet concentrates in platelet additive solution.

Background and Objective  Prolonged storage of platelets up to 7 days provides improved availability, logistical management and decreased wastage. Beside methods of bacterial detection, addition of magnesium and potassium to the platelet storage solution (SSP+) may further improve the quality of platelets with extended storage.

Plasma levels of 24S-hydroxycholesterol reflect brain volumes in patients without objective cognitive impairment but not in those with Alzheimer's disease.

OBJECTIVES Cholesterol has been linked to Alzheimers disease (AD) and plasma 24S-hydroxycholesterol (24OHC) has been suggested as a surrogate marker for brain cholesterol metabolism. This study investigates the relation of 24OHC as well as markers of extracerebral cholesterol homeostasis (lanosterol, lathosterol, cholesterol, LDL-C, HDL-C and 27-hydroxycholesterol) with brain volumes in memory clinic patients. METHODS 96 patients (33 with subjective cognitive impairment--SCI; 36 with mild cognitive impairment--MCI; 27 with AD) referred to the Memory Clinic at Karolinska University Hospital, Sweden. Plasma assessments were done by isotope dilution-mass spectrometry. MRI measurements were done using custom-made software BMAP (imaging laboratory, Karolinska Institutet), running on HERMES platform. RESULTS Ratios of 24-hydroxycholesterol, 27-hydroxycholesterol, lanosterol and lathosterol to cholesterol (R_24OHC, R_27OHC, R_lanosterol and R_lathosterol) were significantly lower in patients with AD. In the whole population, after controlling for age, sex, APOE genotype and statins, R_24OHC was positively related to gray matter (GM) fraction. However, when groups were considered separately, the relation to GM volume, GM and parenchymal fractions was significant in the SCI group only (p<0.05). There was a significant positive association between cholesterol and white matter (WM) volume, WM and parenchymal fractions in patients with AD. CONCLUSIONS Plasma R_24OHC was lower in patients with AD, but R_24OHC was significantly related to brain volumes in the control group only. One reason may be the previously demonstrated abnormal expression of cholesterol 24S-hydroxylase in astrocytes in AD, which may limit the usefulness of this plasma marker in this specific disease. The findings on cholesterol agree with previous reports of decreasing plasma cholesterol levels in AD patients, suggesting a CNS-mediated effect on extracerebral cholesterol homeostasis.

Caudate Nucleus Volumes in Frontotemporal Lobar Degeneration: Differential Atrophy in Subtypes

BACKGROUND AND PURPOSE: Frontostriatal circuits involving the caudate nucleus have been implicated in frontotemporal lobar degeneration (FTLD). We assessed caudate nucleus volumetrics in FTLD and subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 27) and subjects with Alzheimer disease (AD, n = 19). MATERIALS AND METHODS: Diagnoses were based on accepted clinical criteria. Manual volume measurement of the head and body of the caudate, excluding the tail, was conducted on T1-weighted brain MR imaging scans, using a published protocol, by a single analyst blinded to the diagnosis. RESULTS: Paired t tests (P < .05) showed that the right caudate nucleus volume was significantly larger than the left in controls and PNFA. No hemispheric asymmetry was found in AD, FTD, and SD. Across the groups, there was a positive partial correlation between the left caudate nucleus volume and Mini-Mental State Examination (MMSE) scores (r = 0.393, n = 76, P = .001) with higher left caudate volumes associated with higher MMSE scores. Multivariate analysis of covariance was used to assess the statistical significance between the subject groups (AD, FTD, SD, PNFA, and controls) as independent variables and raw right/left caudate volumes at the within-subject level (covariates: age and intracranial volume; P < .05). Control volume was largest, followed by AD (93% of control volume), SD (92%), PNFA (79%), and FTD (75%). CONCLUSIONS: Volume of the head and body of the caudate nucleus differs in subtypes of FTLD, due to differential frontostriatal dysfunction in subtypes being reflected in structural change in the caudate, and is correlated with cognition.

Volumetrics of the caudate nucleus: Reliability and validity of a new manual tracing protocol

Our aim was to develop a reliable and valid manual segmentation protocol for tracing the caudate nucleus in MRI for volumetric and, potentially, shape analysis of the caudate. Using the protocol, two inter- and intra-rater reliability studies were conducted using five different raters on two different image analysis platforms (ANALYZE, Mayo Biomedical Imaging Resource, Rochester MN, USA, and HERMES, Nuclear Diagnostics AB, Stockholm, Sweden). Reference images for the detailed protocol are described. Two studies were performed. In study 1, the intra-rater class correlation ICC(1,1) for an experienced rater (JCLL) using this protocol for caudate nucleus volumes was evaluated by repeating right and left caudate measurements on 10 scans (20 comparisons) and was 0.972. The inter-rater class correlation ICC(1,k) with OL was 0.922 on 5 scans (10 comparisons) and with BL was 0.960 on 5 scans (10 comparisons). In study 2, VT obtained an intra-rater class correlation of 0.9 on 5 scans (involving 10 comparisons, e.g. right and left caudate). The inter-rater class correlation ICC(1,k) was 0.988 on 5 scans (again involving 10 comparisons) with EM. We therefore developed a novel, reliable and reference image-based, method of outlining the caudate nucleus on axial MRI scans, usable in two different image analysis laboratories, across two different sets number of tracers reliably, and across software platforms. This method is therefore potentially usable for any image analysis package capable of displaying and measuring outlined voxels from MRI brain scans.

Evaluation of platelets prepared by apheresis and stored for 5 days. In vitro and in vivo studies.

To evaluate the effect of storage on apheresis platelets collected with a closed‐system blood cell separator, an in vitro investigation was performed, with measurements of pH, lactate, ATP, the ratio of ATP to the total adenine nucleotide content, and adenylate kinase. Unmodified apheresis platelets and apheresis platelets with plasma added were compared with conventional platelets stored in PL‐1240 or PL‐732 plastic containers. During 6 days of storage, there were similar changes in all variables with one exception: the extracellular activity of adenylate kinase was lower in apheresis platelets with plasma than in the other three groups (p < 0.01). In vivo studies were carried out with 111Indium‐labeled autologous platelets in eight volunteers. Apheresis platelets with 100 mL of plasma added were stored in two 1000‐mL containers (PL‐732) at 22° C during agitation. Platelets from one of the containers were labeled with 111Indium and transfused into the volunteer within 24 hours. Platelets from the other container were labeled after 5 days of storage and transfused into the same donor. There were no significant differences between apheresis platelets stored for 1 day and those stored for 5 days: the mean percentage of recovery was 58.4 and 57.6 percent, t½ was 69 and 67 hours, and the survival time was 5.5 and 5.6 days, respectively.

Paired in vitro and in vivo comparison of apheresis platelet concentrates stored in platelet additive solution for 1 versus 7 days

BACKGROUND:  To improve clinical access to platelet concentrates (PCs), prolonging the storage period is one alternative, provided that they are free from bacteria. The quality of platelets (PLTs) stored for 1 versus 7 days was compared by in vitro analyses and in vivo recovery and survival in blood donors.

Lymph Drainage Studied by Lymphoscintigraphy in the Arms after Sentinel Node Biopsy Compared with Axillary Lymph Node Dissection Following Conservative Breast Cancer Surgery

Purpose: To investigate lymphatic drainage as measured by lymphoscintigraphy in the arms of patients undergoing either sentinel lymph node biopsy (SNB) or axillary lymph node dissection (ALND). Material and Methods: From January 2001 to December 2002, 30 patients with unilateral invasive breast carcinoma underwent breast-conserving surgery with SNB and 30 patients with ALND. All patients received radiotherapy to the breast. Lymphoscintigraphy was performed, and skin circulation, skin temperature, and arm volume were measured 2–3 years after radiotherapy. Results: None of the 30 patients who underwent SNB showed any clinical manifestation of lymphedema. Of the 30 patients undergoing ALND, six (20%) had clinical lymphedema, with an arm volume that was >10% larger on the operated than on the non-operated side (P<0.01). Scintigraphically, visual analysis revealed lymphatic dysfunction in three patients, manifested as forearm dermal back flow. Two of these patients also had an increased arm volume. Quantitative analysis showed no differences between the groups, apart from a smaller amount of isotope in the axilla in the ALND group. There was no difference in skin circulation or skin temperature. Conclusion: Our study shows that lymph drainage in the operated arm compared with the non-operated arm was less affected by SNB than by ALND, and that morbidity associated with SNB was lower than with ALND. However, the results do not confirm our hypothesis that lymphoscintigraphy can reveal differences in lymph circulation that are not evident clinically in the form of manifest lymphedema. The most sensitive clinical method of assessing lymph drainage seems to be measurement of arm volume.