Publications by authors named "Katri Kivinen"

10 Publications

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Patient education in relation to informational needs and postoperative complications in surgical patients.

Int J Qual Health Care 2020 Apr;32(1):35-40

Hospital District of Satakunta.

Objective: To study surgical patients' informational expectations and the level of received knowledge at the time of hospital discharge. To examine if there is an association with postoperative complications and the patient´s level of received knowledge.

Design: Comparative descriptive design.

Setting: The data on patients admitted for non-cardiac surgery were collected in three phases during an eight-month period.

Participants: 258 in-ward non-cardiac general surgery and orthopedic surgery adult patients.

Interventions: Questionnaires before admission (knowledge expectations) and at discharge (received knowledge). A telephone interview 30 days after discharge.

Main Outcome Measures: Received knowledge (as much or more / less) compared to expectations, and its association with post-discharge complications.

Results: There were differences between patient groups in their perception of receiving enough knowledge and they were connected to gender (male vs. female OR 2.67, 95% CI 1.55-4.60, P = 0.0004) and procedure (elective orthopedic implant surgery vs. elective minor orthopedic and hand surgery: OR 3.25, 95% CI 1.72-6.17, P = 0.0003). Patients who received less knowledge than expected had more postoperative complications than those who received sufficient (as much or more than expected) information.

Conclusions: Patients differ in terms of informational needs, and preoperative education prepares the patient for the information provided postoperatively. Patient education may have an influence on recovery from surgery.
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April 2020

Fat Grafting Can Induce Browning of White Adipose Tissue.

Plast Reconstr Surg Glob Open 2018 Jun 19;6(6):e1804. Epub 2018 Jun 19.

Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland.

Background: Fat grafting is commonly used when treating soft-tissue defects. However, much of the basic biology behind fat transfer is still uncovered. Adipocytes can be divided into energy storing white and energy burning brown adipose cells. It is now well known, that also adult humans have metabolically active brown adipose tissue (BAT) within white adipose tissue (WAT). Previously our group showed that transfer of metabolically inactive WAT into a new environment increased the metabolic activity of the fat grafts to resemble the activity in the recipient site and that different WAT depots have variation in the metabolic activity. This led us to speculate, whether the metabolic increase of the graft is a result of "browning" of the transferred WAT toward beige adipose tissue.

Methods: We investigated the metabolic and histological characteristics and BAT marker gene expression in different types of WAT grafts placed either in subcutaneous or muscle tissue in mice. Metabolic activity of the grafts was investigated by FDG-PET/CT at 4- and 12-week time-points.

Results: The glucose uptake of all transferred fat types was increased when compared with respective control WAT regardless of transfer location. gene and protein expression was increased in 4 of 15 intramuscularly placed fat graft samples and showed histological resemblance to BAT with multilocular cells.

Conclusions: Grafting of metabolically inactive fat intramuscularly may induce browning of fat grafts toward more active beige adipose tissue. This opens up new research areas in exploiting fat grafting in metabolic diseases.
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June 2018

Acute Lymphoblastic Leukemia With INPP5D-ABL1 Fusion Responds to Imatinib Treatment.

J Pediatr Hematol Oncol 2019 10;41(7):e481-e483

Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital.

We describe a patient with Down syndrome whose precursor B-cell acute lymphoblastic leukemia cells expressed INPP5D-ABL1 fusion gene that resulted in a reciprocal chromosome translocation t(2;9)(q27;q34). The fusion gene was present as a small subclone in the primary disease but was first identified at relapse when the subclone had expanded into a major clone. At relapse, the patient responded poorly to conventional induction chemotherapy but a transient morphologic remission was achieved after administration of imatinib monotherapy. This case demonstrates a pathway to relapse in a Down syndrome patients with acute lymphoblastic leukemia through a rare fusion event. It highlights the significance of minor subclonal events in therapy resistance and the opportunity provided for targeted therapy.
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October 2019

Season of death and nigral neuronal density in a high-latitude region.

Neuropathol Appl Neurobiol 2019 04 21;45(3):314-317. Epub 2018 May 21.

Department of Neurology, University of Turku, Turku, Finland.

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April 2019

Somatostatin receptor 2A in gliomas: Association with oligodendrogliomas and favourable outcome.

Oncotarget 2017 Jul;8(30):49123-49132

Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland.

Somatostatin receptor subtype 2A (SSTR2A) is a potential therapeutic target in gliomas. Data on SSTR2A expression in different glioma entities, however, is particularly conflicting. Our objective was to characterize SSTR2A status and explore its impact on survival in gliomas classified according to the specific molecular signatures of the updated WHO classification. In total, 184 glioma samples were retrospectively analyzed for SSTR2A expression using immunohistochemistry with monoclonal antibody UMB-1. Double staining with CD68 was used to exclude microglia and macrophages from analyses. SSTR2A staining intensity and its localization in tumor cells was evaluated and correlated with glioma entities and survival. Diagnoses included 101 glioblastomas (93 isocitrate dehydrogenase (IDH) -wildtype, 3 IDH-mutant, 5 not otherwise specified (NOS)), 60 astrocytomas (22 IDH-wildtype, 37 IDH-mutant, 1 NOS), and 23 oligodendrogliomas (19 IDH-mutant and 1p/19q-codeleted, 4 NOS). SSTR2A expression significantly associated with oligodendrogliomas (79% SSTR2A positive) compared to IDH-mutant or IDH-wildtype astrocytomas (27% and 23% SSTR2A positive, respectively), and especially glioblastomas of which only 13% were SSTR2A positive (p < 0.001, Fisher's exact test). The staining pattern in glioblastomas was patchy whereas more homogeneous membranous and cytoplasmic staining was detected in oligodendrogliomas. Positive SSTR2A was related to longer overall survival in grade II and III gliomas (HR 2.7, CI 1.2-5.8, p = 0.013). In conclusion, SSTR2A expression is infrequent in astrocytomas and negative in the majority of glioblastomas where it is of no prognostic significance. In contrast, oligodendrogliomas show intense membranous and cytoplasmic SSTR2A expression, which carries potential diagnostic, prognostic, and therapeutic value.
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July 2017

Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease.

Neurology 2017 Apr 10;88(15):1461-1467. Epub 2017 Mar 10.

From the Division of Clinical Neurosciences (L.S., J.J., V.K.), Turku University Hospital, Turku, Finland; Department of Neurology (L.S., J.J., V.K.) and Turku PET Centre (J.J., T.N., V.K.), University of Turku; and Departments of Pathology (K.K., M.G.) and Clinical Physiology and Nuclear Medicine (T.N.), Turku University Hospital and University of Turku, Finland.

Objective: To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD).

Methods: Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)-positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest-based and voxel-based analyses.

Results: Mean putamen SBR did not correlate with the number of substantia nigra TH-positive ( = -0.11, = 0.66) or neuromelanin-containing ( = -0.07, = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included.

Conclusions: This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.
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April 2017

Uptake of [F]EF5 as a Tracer for Hypoxic and Aggressive Phenotype in Experimental Head and Neck Squamous Cell Carcinoma.

Transl Oncol 2014 May 23. Epub 2014 May 23.

MediCity Research Laboratory, Turku PET Centre, University of Turku, Turku, Finland; Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland. Electronic address:

Purpose: This study aims to investigate whether the uptake of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide ([F]EF5) and 2-deoxy-2-[F]fluoro-d-glucose ([F]FDG) is associated with a hypoxia-driven adverse phenotype in head and neck squamous cell carcinoma cell lines and tumor xenografts.

Methods: Xenografts were imaged in vivo, and tumor sections were stained for hypoxia-inducible factor 1α (Hif-1α), carbonic anhydrase IX (CA IX), and glucose transporter 1 (Glut-1). Tracer uptakes and the expression of Hif-1α were determined in cell lines under 1% hypoxia.

Results: High [F]EF5 uptake was seen in xenografts expressing high levels of CA IX, Glut-1, and Hif-1α, whereas low [F]EF5 uptake was detected in xenografts expressing low amounts of CA IX and Hif-1α. The uptake of [F]EF5 between cell lines varied extensively under normoxic conditions. A clear correlation was found between the expression of Hif-1α and the uptake of [F]FDG during hypoxia.

Conclusions: The UT-SCC cell lines studied differed with respect to their hypoxic phenotypes, and these variations were detectable with [F]EF5. Acute hypoxia increases [F]FDG uptake in vitro, whereas a high [F]EF5 uptake reflects a more complex phenotype associated with hypoxia and an aggressive growth pattern.
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May 2014

Analysis of fat graft metabolic adaptation and vascularization using positron emission tomography-computed tomographic imaging.

Plast Reconstr Surg 2014 Feb;133(2):291-299

Turku, Kuopio, and Helsinki, Finland From the Departments of Plastic and General Surgery and Pathology, Turku University Central Hospital; Turku PET Centre, University of Turku; the Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Kuopio; and the Cleft Unit, Department of Plastic Surgery, Helsinki University Hospital.

Background: Fat tissue transfer is commonly used for different soft-tissue defects in surgery. The immediate result of these operations is often good, but the long-term result is unfortunately unpredictable. The authors used an experimental model to evaluate the vascularization, survival, and metabolic changes after free fat transfer and the impact of proangiogenic therapy on these processes.

Methods: Fat was collected from the mouse epididymal region and placed into the subcutaneous tissue of the forehead. Fat grafts were treated with proangiogenic vascular endothelial growth factor (VEGF)-A (n = 9) or the control vector (n = 9). Metabolic activity and fat graft volume were investigated by positron emission tomography-computed tomography at 4 weeks and at 12 weeks. Histologic analysis was performed at 12 weeks.

Results: The glucose metabolism (fluorodeoxyglucose uptake) of the transferred epididymal fat was higher than in the epididymal fat before transplantation in both study groups (VEGF-A and control) and resembled that of normal subcutaneous fat. VEGF-A therapy enhanced the survival and capillary density of the transferred fat after surgery.

Conclusions: Transfer of the metabolically inactive (epididymal) fat into a new environment modulated the metabolic activity of the fat grafts to resemble the situation in the recipient site. These novel findings support the clinical use of free fat grafts in various anatomical regions and tissue types. Proangiogenic VEGF-A therapy enhanced the vascularization and survival of the free fat grafts.
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February 2014

Silencing of Nuclear Mitotic Apparatus protein (NuMA) accelerates the apoptotic disintegration of the nucleus.

Apoptosis 2010 Aug;15(8):936-45

Department of Pathology, University of Turku, Finland.

One main feature of apoptosis is the sequential degradation of the nuclear structure, including the fragmentation of chromatin and caspase-mediated cleavage of various nuclear proteins. Among these proteins is the Nuclear Mitotic Apparatus protein (NuMA) which plays a specific role in the organization of the mitotic spindle. The exact function of NuMA in the interphase nucleus is unknown, but a number of reports have suggested that it may play a role in chromatin organization and/or gene expression. Here we show that upon cleavage in apoptotic cells, the N-terminal cleavage fragment of NuMA is solubilized while the C-terminal fragment remains associated with the condensed chromatin. Using pancaspase inhibitor z-VAD-fmk and caspase-3 deficient MCF-7 cells, we further show that the solubilization is dependent on caspase-mediated cleavage of NuMA. Finally, the silencing of NuMA by RNAi accelerated nuclear breakdown in apoptotic MCF-7 cells. These results suggest that NuMA may provide structural support in the interphase nucleus by contributing to the organization of chromatin.
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August 2010

Caspase-3 is required in the apoptotic disintegration of the nuclear matrix.

Exp Cell Res 2005 Nov 30;311(1):62-73. Epub 2005 Sep 30.

Department of Pathology, University of Turku, MediCity Research Laboratory, Tykistökatu 6 A, 4th floor, FIN-20520 Turku, Finland.

Apoptotic breakdown of cellular structures is largely mediated by caspases. One target of degradation is a proteinaceous framework of the nucleus termed the nuclear matrix. We compared the apoptotic changes of the nuclear matrix in staurosporine-treated caspase-3-deficient MCF-7 cells transfected with intact CASP-3 gene (MCF-7c3) or an empty vector (MCF-7v) as a control. Nuclear Mitotic Apparatus protein (NuMA), lamin A/C and lamin B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. In both cell lines, staurosporine induced rapid cytoplasmic shrinkage and partial chromatin condensation. MCF-7c3 cells formed apoptotic bodies, whereas MCF-7v cells did not. NuMA and lamins were actively cleaved in MCF-7c3 cells following caspase-3 activation, but only minimal or no cleavage was detected in MCF-7v cells. Interestingly, lamin B but not lamin A/C was relocated into cytoplasmic granules in apoptotic MCF-7v cells. Pancaspase inhibitor, z-VAD-fmk, prevented the apoptotic changes, while caspase-3 inhibitor, z-DEVD-fmk, induced lamin B granules in both cell lines. These results show that caspase-3 is involved in the cleavage of NuMA and lamins either directly or by activating other proteases. This may be essential for disintegration of the nuclear structure during apoptosis.
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November 2005