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Kokki H.,Kuopio University Hospital
Paediatric Anaesthesia | Year: 2012

Summary Every anesthetist should have the expertise to perform lumbar puncture that is the prerequisite to induce spinal anesthesia. Spinal anesthesia is easy and effective technique: small amount of local anesthetic injected in the lumbar cerebrospinal fluid provides highly effective anesthesia, analgesia, and sympathetic and motor block in the lower part of the body. The main limitation of spinal anesthesia is a variable and relatively short duration of the block with a single-injection of local anesthetic. With appropriate use of adjuvant or combining spinal anesthesia with epidural anesthesia, the analgesic action can be controlled in case of early recovery of initial block or in patients with prolonged procedures. Contraindications are rare. Bleeding disorders and any major dysfunction in coagulation system are rare in children, but spinal anesthesia should not be used in children with local infection or increased intracranial pressure. Children with spinal anesthesia may develop the same adverse effects as has been reported in adults, but in contrast to adults, cardiovascular deterioration is uncommon in children even with high blocks. Most children having surgery with spinal anesthesia need sedation, and in these cases, close monitoring of sufficient respiratory function and protective airway reflexes is necessary. Postdural puncture headache and transient neurological symptoms have been reported also in pediatric patients, and thus, guardians should be provided instructions for follow-up and contact information if symptoms appear or persist after discharge. Epidural blood patch is effective treatment for prolonged, severe headache, and nonopioid analgesic is often sufficient for transient neurological symptoms. © 2011 Blackwell Publishing Ltd.

Kokki H.,Kuopio University Hospital
Pediatric Drugs | Year: 2010

The NSAID ketoprofen is used widely in the management of inflammatory and musculoskeletal conditions, pain, and fever in children and adults. Pharmacokinetic studies show that drug exposure after a single intravenous dose is similar in children and adults (after dose normalization), and thus similar mgkg bodyweight dosing may be used in children and adults. Ketoprofen crosses the blood-brain barrier and therefore has the potential to cause central analgesic effects.Ketoprofen has been investigated in children for the treatment of pain and fever, peri- and postoperative pain, and inflammatory pain conditions. The results of four clinical trials in febrile conditions with the oral syrup formulation indicate that ketoprofen is as effective as acetaminophen (paracetamol) and ibuprofen, allowing children to rapidly return to daily activities with improvements in sleep quality and appetite. Studies of ketoprofen in the management of postoperative pain indicate that ketoprofen is a highly effective analgesic when administered perioperatively for a variety of surgical types, by a variety of routes, and whether given preoperatively or postoperatively. For adenoidectomy, intravenous ketoprofen provided superior postoperative analgesic efficacy compared with placebo. Analgesic efficacy was similar with intravenous, intramuscular, or rectal routes of administration, but oral administration just before surgery was inferior to intravenous administration in this setting. In patients undergoing a tonsillectomy, intravenous ketoprofen was superior to intravenous tramadol in terms of the need for postoperative rescue analgesia, but did not remove the need for rescue opioid therapy in these patients. Intravenous ketoprofen had superior postoperative analgesic efficacy to placebo when given as an adjuvant to epidural sufentanil analgesia after major surgery. Oral ketoprofen has shown efficacy in the treatment of juvenile rheumatoid arthritis.Ketoprofen is generally well tolerated in pediatric patients. Most of the adverse events reported are mild and transient, and are similar to those observed with other NSAIDs. Long-term tolerability has not yet been fully established in children, but data from three studies in >900 children indicate that oral ketoprofen is well tolerated when administered for up to 3 weeks after surgery.In conclusion, ketoprofen is effective and well tolerated in children for the control of post-surgical pain and for the control of pain and fever in inflammatory conditions. © 2010 Adis Data Information BV. All rights reserved.

Riikonen R.S.,Kuopio University Hospital
European Journal of Paediatric Neurology | Year: 2010

The following aspects are reviewed: Does the aetiology influence the outcome of infantile spasms? Does the treatment influence the outcome? Can the outcome be predicted? Can we improve the prognosis? Favourable factors are the following: cryptogenic aetiology, age at onset ≥4 months, absence of atypical spasms and partial seizures, and absence of asymmetrical EEG abnormalities, short treatment lag, and an early and sustained response to treatment. Not only patients with a cryptogenic aetiology have a favourable outcome. We can already at the first clinical evaluation tell the parents if the prognosis looks favourable. The final goal of the treatment is improved mental outcome. Steroids and vigabatrin are the first-line drugs for infantile spasms in Europe. In a prospective study from the United Kingdom short-term outcome was better with hormonal than with vigabatrin therapy (tuberous sclerosis excluded). However, the numbers of patients who were seizure-free at 3-4 months in different studies have been very similar. Moreover, an early response to treatment seems to be of predictive value for the cognitive outcome in children with cryptogenic spasms. The long-term outcome is known only after hormonal therapy. The side effects of steroids are usually treatable and reversible. In Finland ACTH therapy is given at the minimum effective dose and for the minimum effective time with minimal side effects. The risks of VGB are irreversible visual field defects. As of yet there is no method to examine the visual fields in patients with infantile spasms. Early treatment of infantile spasms seems to be important. Prevention of infantile spasms with some aetiological groups might be possible. © 2009 European Paediatric Neurology Society.

Jantunen E.,Kuopio University Hospital
Expert Opinion on Biological Therapy | Year: 2011

Introduction: More than 98% of autologous stem cell transplants are now performed with the support of mobilized blood stem cells, and the proportion of allogeneic blood stem cell transplants has risen to more than 70%. Blood stem cell mobilization strategies are therefore important components of all transplant programs. Areas covered: Stem cell mobilization strategies are evaluated based on current literature, with special focus on the use of plerixafor, a CXCR4 chemokine receptor antagonist. Mobilization methods in autologous settings include the use of G-CSF alone or following chemotherapy (chemomobilization), and the use of G-CSF alone in allogeneic transplants. A combination of G-CSF + plerixafor has been shown to be effective in patients who have failed a previous mobilization. This combination has also been found to be superior to G-CSF alone in Phase III studies in myeloma and non-Hodgkin lymphoma patients as the first-line mobilization. Expert opinion: Addition of plerixafor to chemomobilization or G-CSF mobilization may be more cost-effective than its routine use, and it is worth considering in predicted or proven poor mobilizers. Novel mobilization strategies have allowed more successful stem cell collection in autologous setting, although the effect of plerixafor on graft content and long-term patient outcomes needs further investigation. © 2011 Informa UK, Ltd.

Julkunen P.,Kuopio University Hospital
Journal of Neuroscience Methods | Year: 2014

Background: Navigated transcranial magnetic stimulation (nTMS) is used for locating and outlining cortical representation areas, e.g., of motor function and speech. At present there are no standard methods of measuring the size of the cortical representation areas mapped with nTMS. The aim was to compare four computation methods for estimating muscle representation size and location for nTMS studies. New method: The motor cortex of six subjects was mapped to outline the motor cortical representation of hand muscles. Four methods were compared to assess cortical representation size in nTMS. These methods included: (1) spline interpolation method, (2) convex hull method, which outlines all positive motor responses, (3) Voronoi tessellation method, which assigns a specific cortical area for each stimulus location, and (4) average point-area method, which computes an average representation area for each stimulus with the assumption of evenly spaced stimulus locations, i.e., the use of a grid. Results: All applied methods demonstrated good repeatability in measuring muscle representation size and location, while the spline interpolation and the convex hull method demonstrated systematically larger representation areas (p< 0.05) as compared to the average point-area method. Spline interpolation method demonstrated the best repeatability in location. Comparison with existing methods: Unlike the previous methods, the presented methods can be applied for the estimation of the representation area of nTMS-induced activation without the use of an evenly spaced stimulus grid. Conclusions: The spline interpolation method and the Voronoi tessellation method could be used for evaluating motor cortical muscle representation size and location with nTMS, e.g., to study cortical plasticity. © 2014 Elsevier B.V.

Jouppila-Matto A.,Kuopio University Hospital
BMC cancer | Year: 2011

Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, TWIST and SNAI1, are fundamental in regulating EMT. Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas. Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively). TWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome.

Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of peripheral T-cell lymphomas with a poor prognosis. Autologous stem cell transplantation (ASCT) was retrospectively evaluated as a consolidation or salvage strategy for EATL. The analysis included 44 patients who received ASCT for EATL between 2000 and 2010. Thirty-one patients (70%) were in first complete or partial remission at the time of the ASCT. With a median follow-up of 46 months, relapse incidence, progression-free survival, and overall survival were 39%, 54%, and 59% at 4 years, respectively, with only one relapse occurring beyond 18 months posttransplant. There was a trend for better survival in patients transplanted in first complete or partial remission at 4 years (66% vs 36%; P = .062). ASCT is feasible in selected patients with EATL and can yield durable disease control in a significant proportion of the patients.

Laakso M.,Kuopio University Hospital | Kuusisto J.,Kuopio University Hospital
Nature Reviews Endocrinology | Year: 2014

The prevalence of diabetes mellitus will likely increase globally from 371 million individuals in 2013 to 552 million individuals in 2030. This epidemic is mainly attributable to type 2 diabetes mellitus (T2DM), which represents about 90-95% of all cases. Cardiovascular disease is the leading cause of mortality among individuals with diabetes mellitus, and >50% of patients will die from a cardiovascular event - especially coronary artery disease, but also stroke and peripheral vascular disease. Classic risk factors such as elevated levels of LDL cholesterol and blood pressure, as well as smoking, are risk factors for adverse cardiovascular events in patients with type 1 diabetes mellitus (T1DM) and T2DM to a similar degree as they are in healthy individuals. Patients with T1DM develop insulin resistance in the months after diabetes mellitus diagnosis, and patients with T2DM typically develop insulin resistance before hyperglycaemia occurs. Insulin resistance and hyperglycaemia, in turn, further increase the risk of adverse cardiovascular events. This Review discusses the mechanisms by which T1DM and T2DM can lead to cardiovascular disease and how these relate to the risk factors for coronary artery disease. © 2014 Macmillan Publishers Limited.

Kuusisto J.,Kuopio University Hospital
Current cardiology reports | Year: 2013

Type 2 diabetes increases the risk of cardiovascular disease (CVD) from two- to four-fold. In our large Finnish population-based study published in 1998 subjects with medication for type 2 diabetes had as high a risk of fatal and nonfatal myocardial infarction (MI) during the 7- year follow-up as non-diabetic subjects with a prior MI, suggesting that type 2 diabetes is a CVD equivalent. In another large study, including all 3.3 million residents of Denmark, subjects requiring glucose-lowering therapy exhibited a CVD risk similar to that of non-diabetic subjects with a prior MI. Subsequent studies have not systematically replicated aforementioned results. Some studies have supported the concept that type 2 diabetes is a CVD equivalent only in some subgroups, and many studies have reported negative findings. This is likely to be due to many differences across the studies published, for example ethnicity, gender, age and other demographic factors of the populations involved, study design, validation of diabetes status and CVD events, statistical analyses (adjustments for confounding factors), duration of diabetes, and treatment of hyperglycemia among diabetic participants. Varying results reflect the fact that not all diabetic patients are at a similar risk for CVD. Therefore, CVD risk assessment and the tailoring of preventive measures should be done individually, taking into consideration each patient's long-term risk of developing cardiovascular events.

Background/Aims: Unverricht-Lundborg disease (EPM1) is caused by mutations in the cystatin B (CSTB) gene. Most patients are homozygous for the expanded dodecamer repeat mutation alleles, but 9 other EPM1-associated mutations have also been identified. We describe the clinical, cognitive and imaging characteristics of 5 Finnish EPM1 patients who are compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutations. Methods: Five compound heterozygous patients and 21 patients homozygous for the expansion mutation, participating in an ongoing nationwide clinical and molecular genetics study, were evaluated using the Unified Myoclonus Rating Scale test and comprehensive neuropsychological testing. All patients underwent MR imaging. The MR data were also compared with those of 24 healthy control subjects. Results: Age at onset of symptoms was significantly lower in the compound heterozygotes than in the homozygous EPM1 patients. They also had severer myoclonus and drug-resistant tonic-clonic seizures. Moreover, they had lower cognitive performance. In MRI a voxel-based morphometry analysis of primary and premotor cortex, supplementary motor cortex and thalami revealed gray matter volume loss when compared with the healthy controls, similar to patients homozygous for the expansion mutation. Conclusion: Patients compound heterozygous for the dodecamer repeat expansion and the c.202C>T mutations seem to have a severer form of EPM1 than patients homozygous for the expansion mutation. These findings have implications for counseling of EPM1 patients with different genetic defects. Copyright © 2011 S. Karger AG, Basel.

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