1. |
- Persson, Bertil R
(författare)
-
A STORY ABOUT SCHIZOPHRENIA IMAGING AND METABOLISM
- 2023. - 1
-
Bok (refereegranskat)abstract
- After initial studies in the years 1960-62 in chemistry, mathematics andphysics, my scientific career in medical imaging began in 1963. My qualificationsin chemistry then came in handy when the Nordics' first gamma camera installedin Lund. Around the same time, the discovery of a radioactive isotope of a newelement Technetium-99m showed suitable for use with the gamma camera.My task became to produce Technetium-99m radiopharmaceuticals appliedfor use on patients. The gamma camera images with Technetium-99m were athousand times better than the old scintigraphy with 198Au and 131I.This was the beginning to my involvement in medical imaging diagnostics,which in 1981 by unfathomable ways led to my engagement in nuclear magneticresonance imaging MRI.In 1963, I managed together with my skilful collaborators in Lund to build thefirst MR scanner in Scandinavia. I nurtured a hypothesis that the soul could bemirrored with the structure of water in the brain, which the NMR relaxation of theprotons could reveal. Thus, imaging nuclear spin resonance might be able toimage the soul, which I thought should be there somewhere within us. However,it was mostly something about what my co-workers joked.That became a dream until 2015 when a 7-tesla MRI device came to Lund.Then the opportunities opened up to in vivo studies of the chemistry of the brain.This stimulated my visions of the chemistry of the soul and led to my involvementin studying brain imaging of patients with Schizophrenia that is the subject of thisbook:A Story about Schizophrenia Imaging and Metabolism.Dedicated to someone with that diagnose!The first Chapter deals with nuclear medicine imaging of Schizophrenia thatstarted in the early 1970s in Lund by David Ingvar and Göran Franzén. Theycarried out pioneering work with radioactive isotopes to image the brain's regionalblood flow in Schizophrenic patients.The introduction of SPECT with Technetium-99m radiopharmaceuticals suchas e.g. 99mTc-HMPAO simplified the procedure of examining the relationshipsbetween rCBF, psychopathology and effects of neuroleptic therapy.The introduction of positron emission tomography PET was a furtherimprovement in nuclear medicine methods. 18F-FDG PET studies of Schizophrenia show that patients with Schizophrenia have reduced brainmetabolism in several brain regions.The second chapter describes how it all began with the introduction tomagnetic resonance imaging. Then follows a review of how the various magneticresonance methods apply to Schizophrenia.Structural brain imaging studies sMRI performed on Schizophrenic patientstend to focus on changes in anatomy and volume of different brain regions.Altered gyrification in the Insula and Orbitofrontal Cortex appears to be a goodmarker for disturbances in the early neuronal development in Schizophrenia.Additional evaluation of CSF flow dynamics in the aqueduct could strengthenthe knowledge about the pathophysiology in both diagnostics and treatment ofpatients with Schizophrenia.Functional ƒMRI reflects changes in discrete neural circuits and may be auseful tool for defining subgroups within the clinically defined syndrome ofSchizophrenia.Diffusion tensor imaging DTI and its combination with magnetic transferimaging MTI, show higher extracellular concentrations of free water, indicatingthe presence of neuro inflammation in Schizophrenia.The method of nuclear magnetic resonance (NMR) spectroscopy of the humanbrain developed to become a user-friendly tool for chemistry of the brain. An invivo 1H-NMR spectrum measured from the human brain at seven tesla (7 T)provide reliable quantification of more than fifteen different metabolites.The third chapter review the main metabolic pathways in the brain ofimportance for Schizophrenia.1H-MRS shows that all Schizophrenia patients had a significantly lowerconcentration-ratio of N-AcetylAspartic acid (NAA) to Creatine in the frontallobe than the controls.Significantly, lower concentration-ratio of gamma-aminobutyric acid GABAto Creatine (Cr) appeared in the prefrontal cortex of patients with Schizophreniacompared to healthy controls.The results of 1H-MRS also indicate that significantly lower Glutamateconcentrations in the Hippocampus in Schizophrenia are associated with thepathophysiology of Schizophrenia.Activation of the Tryptophan metabolism (TRYCAT) pathway appears to beinvolved in the pathophysiology of Schizophrenia. Patients with Schizophreniaseems to have significantly lower serum levels of Kynurenic-acid (KYNA), whichdampens the effect of the -7nicotinic-acetyl-choline receptor (7nAChR) and/orthe N-methyl-D-Aspartate receptor (NMDAR). he dysfunction of those receptors seems to contribute to cognitive impairment in Schizophreniamotivating new therapeutic strategies targeting brain Kynurenic Acid synthesis.The forth chapter review indications that other metabolite markers couldpromote Schizophrenia diagnosis and treatment follow-up.Out of twenty-two marker, metabolites studied, Citrate, Palmitic acid, Myoinositoland Allantoin exhibit the best ability for completely separateSchizophrenic patients from matched healthy controls, and may be usefulbiomarkers to monitor therapeutic efficacy.Lund 2023-10-12Bertil RR Persson PhD, MD.h.c, Professor Emeritus
|
|
2. |
- Persson, Bertil R
(författare)
-
Electro-Pulse-Enhanced Cancer Therapy
- 2020. - 1
-
Bok (refereegranskat)abstract
- Den här boken är en sammanfattning av mina 30 års erfarenhet av Electro-Pulse-Enhanced-Therapy vid behandling av maligna tumörer.Det första kapitlet är en kort historia över upptäckterna som ledde till klinisk användning av Electro-Pulse-Enhanced Cancer-terapi (EpECT). Redan i slutet av 1960-talet fann Sale att effekten av att inducera korta elektriska pulser på biologiska cellmembran gjorde dem övergående permeabla utan att skada membranstrukturerna. På 1970-talet, Zimmermann, observerade att röda blodkroppar började förlora hemoglobin efter exponering för ett pulserande elektriskt fält som överskred ett visst tröskelvärde. Exponering för korta elektriska pulser med amplituder mellan 4 och -6 kV / cm resulterade i att cellerna smälte samman till större celler innehållande flera kärnor. På 1980-talet demonstrerade Neumann och Wong att elektrisk fältmedierad överföring av DNA till celler är en praktisk teknik, enkel och lätt att applicera för DNA-transfektion. Okino och Mohri rapporterade 1987 möjligheten att använda elektroporeringseffekten för förbättrad transport av cancerläkemedlet Bleomycin över cellmembranet. Den första kliniska prövningen med EECT utfördes på tumörer i huvud och nacke av L. Mir och kollegor i Frankrike 1991.Det andra kapitlet beskriver de elektrokemiska och biofysiska principerna för verkan av applicerade högspännings elektriska pulser applicerade på mänskliga celler och vävnader. Skapandet av kanaler i cellmembranet, vanligtvis kallat elektroporation, är det viktigaste fenomenet som beaktas vid elektroförbättrad kemoterapi. Emellertid kan elektrokemiska processer också vara inblandade.Mitt yrke är inom medicinsk strålningsfysik, där strålningsdosimetri är den mest kritiska frågan inom strålterapi. Således ansåg jag det viktigt att med säkerhet veta hur mycket energi som levereras till patienten även i eElectro-pulsförbättrad cancerbehandling.Det tredje kapitlet beskriver mätningen av förändringen i vävnadens elektriska impedans som ett utmärkt sätt att uppskatta energin som levereras till vävnaden genom exponering för elektriska högspänningspulser.En annan gren av mitt yrke är användningen av radioaktiva läkemedel för att studera morfologi och funktion hos olika mänskliga organ. Således beskriver det fjärde kapitlet användningen av radioaktivt märkta läkemedel och gammakameraregistrering för att utforska det ökade läkemedelsintaget efter exponering för elektriska pulser. Multivariata statistiska metoder används för att förutsäga beroendet av läkemedelsupptagning i den exponerade och icke-exponerade vävnaden på olika variablerI det femte kapitlet sammanfattas resultaten från de många prekliniska studierna av Eelectro-pPulse Enhanced Ccancer-terapi sammanfattas. Bleomycin och Cis-platina är de läkemedel som huvudsakligen används i kliniska tillämpningar av Electro-Pulse Enhanced Chemotherapysuch-terapi. Resultaten av omfattande prekliniska studier har visat sig indikera lovande kombinationer av elektro-pulskemoterapi med etablerade immunterapi- och strålterapiregimer.Som nämnts ovan utfördes den första kliniska prövningen med användning av Bleomycin och elektrisk pulsbehandling (kallad "elektrokemoterapielektro-kemoterapi" (ECT)) på huvud- och nacktumörer av Mir och kollegor i Frankrike 1991. Under de följande åren (upp fram till 2018) har kliniska prövningar behandlats hittills (2018) mer än 1500 patienter behandlats med antingen malmig malmom, Kaposis sarkom, bröstcancer, skivepitelcancer, eller Bbasal Cell Carcinoma. Det sjätte kapitlet granskar och analyserar de kliniska resultaten av dessa prövningar, med hjälp av granskade och analyserade i följande kapitel är mycket utmanande i det sjätte kapitlet. Resultaten av publicerade kliniska prövningar har sammanfattats och analyserats med multivariata metoder, såsom huvudansvarig huvudkomponentkomponentanalysanalys.I det sjunde avsnittet diskuteras de säkerhetsproblem som måste beaktas vid behandling av patienter med allierade högspänningsimpulser. till patienter. Den åttonde och sista delen av boken presenterar en sammanfattning av mina potentiella nya dimensioner inom elektroelektro-puls pulsförbättrad förbättrad cancerterapi.
|
|
3. |
- Persson, Bertil R
(författare)
-
Global distribution of 7Be, 210Pb and, 210Po in the surface air (with Appendix A-E)
- 2016
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- In the effort of modelling the global distribution 7Be, 210Pb and 210Po in surface air, the results from exploration of radioactivity exploration from the Arctic to the Antarctic during 1980 to 1996 are compiled with the results reported by other authors. Partial least square regression modelling PLS-regression, predict missing 7Be, 210Pb and 210Po values of air concentration or annual deposition. All available data of air concentration and deposition, of these radionuclides are then correlated with geophysical parameters. The results indicate that the global latitudinal distribution of 7Be air concentration was rather flat, with an overall global average of 4.2 (SE 0.4) mBq.m-3, although with a slight dip at the equator and decrease towards high latitudes. The corresponding latitudinal distribution was also flat, and decreased slightly at high and low altitudes, with overall global average of 7Be annual deposition was 1500 (SE 100) Bq.m-3.a-1. The 7Be deposition rate estimated from reported annual mean air concentration and annual deposition is 13.4 +/- 1.7 (SE) mm.s-1. By using PLS-r modelling of either air concentrations or annual depositions, the average deposition rate of 7Be was estimated to 12.3 +/- 1.6 (SD) mm.s-1. The 7Be deposition-rate don´t vary significantly with longitude, latitude or geometrical average year of sampling date. Linear regression with height, however, is negative with a coefficient of - 0.02. At sea level, the 7Be deposition-rate was estimated to 13 mm.s-1, while at a height of 800 m it was predicted to be 7 mm.s-1. The 16 values of 7Be deposition rate, reported in the literature, are widely scattered (SD = 18) with an average of about 18 mm.s-1. The latitudinal distribution of the activity concentration of 210Pb in air showed a maximum of about 600 +/- 200 micoBq.m-3 around 45 oN with a steady decrease towards higher and lower latitudes. Minimum values of 400 micoBq.m-3 and 80 micoBq.m-3 were estimated at 90 oN and at 90 oS respectively. The latitudinal distribution of all 210Pb air concentration values (micoBq.m-3) is given by the following equation: log10[210Pb] = 2.52 + 0.0083·(Latitude) - 9.87.10-5· (Latitude)2. The latitudinal distribution of all 210Pb annual deposition values (Bq.m-2.a-1) showed a maximum of about 200 +/- 100 Bq.m-2.a-1 around 45 oN, with a steady decrease towards higher and lower latitudes. A minimum of 100 Bq.m-2.a-1 was predicted at 90 oN, although a value of 17 +/- 4 Bq.m-2.a-1 has been recorded at 84.4 oN 2.3 oW. At 90 oS the predicted 210Pb annual deposition was 3 Bq.m-2.a-1. The 210Pb deposition rate was estimated 12.5 +/- 0.7 mm.s-1 with no significant variation with latitude, height, or average of interval of sampling date. With longitude, however, the 210Pb deposition rate varied significantly (linear k=0.02) R=0.99. The values of 210Po air concentration around 20 - 45 oN ranged between 50 – 1000 micoBq.m-3 with a mean of 200 micoBq.m-3, and the 210Po annual deposition ranged between 20-800 Bq.m-2.a-1 with a mean of 100 Bq.m-2.a-1. The longitudinal distribution of the 210Po/210Pb activity ratios follow a narrow linear relation from 0.2 at 90 oW to 1.0 at 170 oE. While the 210Po air concentration and annual deposition are widely distributed along the longitudes with a slight decrease west of the Greenwich meridian.
|
|
4. |
- Persson, Bertil R, et al.
(författare)
-
II INTERNATIONAL CONFERENCE ONRADIOECOLOGICAL CONCENTRATION PROCESSES : II INTERNATIONAL CONFERENCE 50 years later
- 2016
-
Bok (refereegranskat)abstract
- From the 6th to the 9th of November 2016, in the meeting hall of Centro Nacional de Aceleradores(University of Seville, Seville, Spain) took place the “II International Conference onRadioecological Concentration Processes (50 years later)” under the joint organization of theUniversities of Seville (Spain) and Gothenburg (Sweden). With this event, the organization try tocommemorate the fifty years anniversary of the first Radioecological Concentration ProcessesConference hold in Stockholm, which is recognized as an extremely important event whichcontributed to the birth of the modern radioecology: In the pioneer 1966 conference, more than 100communications were presented and a good number of participants played afterwards an essentialrole in the development and growing of the radioecology as scientific discipline.The first conference had as a main motivation the dissemination of the radioecological studiesappearing at that time associated to the nuclear weapon tests performed by USA and the formerUSSR at the end of the 1950s or beginning of the 1960s. Since then, a lot of anthropogenicemissions of radioactivity (provoked or accidental) have occurred, being remarkable at the dates ofthis II edition the 30 years passed since the Chernobyl accident and the 5 years passed from theFukushima accident. In addition, the emergence of new analytical techniques has made possible toextend the radioecological studies to new radionuclides and environmental compartments.With this II edition of the Conference, the promotors have tried to obtain information about theactual status of the radioecology over the world, to evaluate the advances reached during the lastyears and to plan the development of some priority research lines to be followed along the first halfof the XXI century. Just thinking in the future of the radioecology, special efforts were devoted tostimulate the active participation, through presentation of communications, of young researchers.
|
|
5. |
- Persson, Bertil R
(författare)
-
“More Probable than Unlikely” - : A Tale of the Blood-Brain Barrier and Mobile Communication. Dedicated to Leif G, Salford on his 80th birth day 2021-12-07.
- 2021
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Our team of the clinical researchers in Lund, Sweden, found that electromagnetic radiation, such as those used in mobile communications, even at shallow power values, cause users’ blood albumin to leak through the blood-brain barrier “BBB” into the brain tissue. The BBB is supposed to protect the brain against unwanted and toxic molecules potentially present in the blood, to transfer to the brain tissue. However, our team in Lund found that after exposure of rats to the radiation from mobile telephones, albumin in the blood leak into the brain and accumulates in neurons and glial cells.This matter would be of interest not only for researchers but also for radiation safety authorities and organizations worldwide as well as the general public. The studies performed at the Lund University by: Neurosurgeons: Leif Salford MD, PhD professor em., Henrietta Nittby MD, PhD,Neuropathologist: Arne Brun MD, PhD professor emeritus, Medical Physicist: Bertil RR Persson PhD MDhc prof. em., Jacob Eberhardt PhD, Electric engineer: Lars Malmgren Techn. Dr.
|
|
6. |
- Persson, Bertil R, et al.
(författare)
-
Radioactivity Exploration from the Arctic to the Antarctic
- 2016
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- This book is dedicated to professor emeritus Bengt Forkman (Nuclear Physics, Lund University) who in 1979 took the initiative to arrange an environmental radioactivity research program for the Ymer-80 expedition. He engaged his old friend Bertil Persson whom he during the 1960th inspired to university studies in Lund who just been promoted to professor of Radioecology at the Swedish University of Agricultural Sciences in Uppsala. Bertil Persson was tutor for Elis Holm at Lund University, who for his thesis was engaged in radiochemical analysis of plutonium isotopes in the environment. Elis Holm became deeply involved in management of Ymer-80 and all the following expeditions as well. We found a superior talent for the logistics in Kjell-Åke Carlsson (who was mechanical engineer at the department of radiation physics at Lund University). Without him, we would not have been able to solve all the thousands of practical issues and contacts with authorities and sponsors. He also contributed with the diaries extensive photographic and video documentation of all the expeditions. We have together compiled this book although several others were partly engaged in the various expeditions to whom we are deeply thankful for their contributions. They will appear as contributors in the separate parts of this book: 1. Ymer-80 (Bengt Forkman, Boel Forkman, Lars Ahlgren (diseased) 2. Swedarp 1988-1989 (Per Roos, Birgitta Roos) 3. Arctic Ocean 1991 4. Tundra Expedition 5. Arctic Ocean 1996 (Dan Josefsson, Mats Ericsson) Our first Arctic expedition “Ymer-80” was conducted during the period June 23 - 0ctober 6 1980, to commemorate the discovery of the Northeast Passage by Adolf Erik Nordenskiöld in 1878-1880. The vessel used for the expedition was the Swedish icebreaker, M/S Ymer. The use of such a heavy icebreaker made areas permanently covered with ice accessible to extensive scientific activity by various research teams. The aim of our radio-ecological research was to investigate present levels and sources of both natural and man-made radioactivity in the Arctic air and marine environment, and to study the pathways and distribution of these radionuclides in different compartments. Apart from caesium and plutonium isotopes, we also investigated natural radioactive elements, such as uranium and thorium in water, as well as radon and radon daughters in the air (Holm et al., 1983, Samuelsson et al., 1986). In the Arctic water samples were collected between 57°N to 82.8 °E, and enhanced levels of 137Cs was found along the Norwegian coast caused by 137Cs released from European nuclear fuel reprocessing facilities spread by the Gulf Stream along the Norwegian coast. We also found hot spot of plutonium in the Arctic Ocean. During the expedition, far out in the ice. Far out in the Arctic ice Bertil Persson received a call on short wave radio from the Chancellor of Lund University, Håkan Westling, who asked if he would accept promotion as professor in Medical radiation Physics and Head of Radiation Physics at Lund University Hospital. The answer was “Yes”, and so the exploration of environmental radioactivity proceeded. The second expedition “Swedarp” took place during Nov 1988 to Feb 1989. The research platform was the ship, M/S Stena Arctica, with air-sampling device installed on board. We started from Gothenburg (67.4oN; 12oE) with the first destination Montevideo (34.8oS; 56.2oW). From Montevideo, we continued to the Swedish permanent base “Svea” at the North shelf of Antarctica. After unloading supply and equipment for the continental research group, the ship continued to the Argentinean base “Marambio”. The expedition members were allowed to visit “Paulet Island” with the remains of the stone-hut, built by the Swedish captain Carl Anton Larsen and his crew during 1903-04, after that their vessel "Antarctic" was shattered by the ice masses in the Weddell Sea and sank. The third expedition in 1991 was to the Arctic Ocean with the Swedish icebreaker M/S Oden. The research program was focused on oceanography and geology in the western parts of the Eurasian Basin, the north west Markov Basin and parts of the Barents sea (Josefsson, 1998 , Roos et al., 1998). By using pumps of the ship, samples of surface-water, were collected and processed in 200 l vessels in our laboratory accommodated in a container on board. The forth expedition was the joint Swedish-Russian “Tundra Ecology-94” expedition during 1994 with the Russian ice-breaking research vessel R/V Akademik Fedorov a platform, along a coastline of 3500 km-from the Kola Peninsula 10°E to Kolyuchinskaya Bay 173°E. Air sampling was performed during the route along the Norwegian and North Siberian coastlines and water samples were collected from the vessels cooling water system. Continuous sampling of caesium took place with a separate pump and a pipe hanging from the rail. Finally, in 1996 we returned to the Arctic Ocean with the Swedish icebreaker M/S Oden. This expedition focused on studying the distribution of radionuclides in different water masses of the central Arctic Ocean. The expedition crossed the Barents Sea, entered the Nansen Basin at the St. Anna Trough, and continued north across the Amundsen Basin. The main part of the expedition was concentrated on the north Lomonosov Ridge and the return route passed the North Pole and went south along 10 oE towards Svalbard. Water samples from the surface and subsurface layers, as well as bottom sediments, were collected for analysis of fission products and transuranic elements in seawater and sediment.
|
|
7. |
- Persson, Bertil R, et al.
(författare)
-
Radioactivity Exploration : From the Arctic to the Antarctic
- 2017
-
Bok (refereegranskat)abstract
- This book is dedicated to professor emeritus Bengt Forkman (Nuclear Physics, Lund University) who in 1979 took the initiative to arrange an environmental radioactivity research program for the Ymer-80 expedition. He engaged his old friend Bertil Persson whom he during the 1960th inspired to university studies in Lund and who 1980 has been promoted to professor of Radioecology at the Swedish University of Agricultural Sciences in Uppsala, Sweden. Bertil Persson was tutor for Elis Holm at Lund University, who for his thesis was engaged in radiochemical analysis of plutonium isotopes in the environment. Elis Holm became deeply involved in Ymer-80 and management of all the following expeditions as well. We found a superior talent for the logistics in Kjell-Åke Carlsson (who was mechanical engineer at the department of radiation physics at Lund University). Without him, we would not have been able to solve all the thousands of practical issues and contacts with authorities and sponsors. He also contributed with the diaries extensive photographic and video documentation of all the expeditions. Unfortunately he died in October 2016 just as we finished the first draft of the manuscript to this book, that here is published to his memory.
|
|
8. |
|
|