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T Carlsson

Publications and source records attributed to T Carlsson.

At least 19 recordsLinked to original sources
PubMed2006

Continuous exposure to glial cell line-derived neurotrophic factor to mature dopaminergic transplants impairs the graft's ability to improve spontaneous motor behavior in parkinsonian rats.

Functional recovery following intrastriatal transplantation of fetal dopaminergic neurons in animal models of Parkinson's disease is, at least in part, dependent on the number of surviving dopaminergic neurons and the degree of graft-derived dopaminergic reinnervation of the host striatum. In the present study, we analyzed whether continuous exposure of glial cell line-derived neurotrophic factor (GDNF) to mature dopaminergic grafts could further boost the functional outcome of widespread intrastriatal dopaminergic grafts. Rats with dopamine-denervating lesions received multiple intrastriatal transplants of fetal dopaminergic cells and graft-induced behavioral effects were analyzed in drug-induced and spontaneous motor behaviors. At three months after grafting, animals received intrastriatal injections of recombinant lentiviral vectors encoding for either human GDNF or the green fluorescent protein. Continuous exposure of GDNF to the grafts did not boost the functional recovery beyond what was observed in the control animals. Rather, in some of the spontaneous motor behaviors, animals in the GDNF-group showed deterioration as compared with control animals, and this negative effect of GDNF was associated with a down-regulation of the tyrosine hydroxylase enzyme. Based on these and our earlier results, we propose that intrastriatal administration of GDNF at the time of or shortly after grafting is highly effective in initially promoting the cell survival and fiber outgrowth from the grafts. However, once the grafts are mature, GDNF's ability to boost dopaminergic neurotransmission follows the same dynamics as for the native nigral dopaminergic neurons, which appears to be dependent on the concentration of GDNF. Since rather low doses of glial cell line-derived neurotrophic factor at nanogram levels appear to saturate these effects, it may be critical to adjust GDNF levels using tightly regulated gene expression systems.

Analysis of Variance↗
PubMed2006

Pegylated interferon and ribavirin treatment for hepatitis C in haemodialysis patients.

Standard therapy for chronic hepatitis C (HCV) is pegylated interferon in combination with ribavirin. There is limited experience with either drug in dialysis [end stage renal disease (ESRD)]. Six haemodialysis patients, four with HCV genotype 1, one with genotype 4 and one genotype 2 were treated with pegylated interferon-alfa-2b (n = 4) and pegylated interferon-alfa-2a (n = 2) for 24-48 weeks according to genotype with a dose of 50 or 135 mug/week respectively. All patients were given reduced ribavirin doses, initially 200-400 mg/day. Ribavirin trough plasma concentrations were measured with a HPLC method previously developed for earlier treatment studies, aiming at a target concentration of 10-15 micromol/L. Interferon related side-effects were common, in one patient peg-alfa-2b was permanently reduced to 50 mug every 9-10 days with improvement in tolerance. Average ribavirin dose was 170-300 mg/day. Ribavirin-induced anaemia was treated with high doses of erythropoietin and low doses of iron. Blood-transfusions were not needed. All patients became HCV-RNA-PCR negative during treatment which was completed or nearly completed in four patients. One patient terminated therapy prematurely due to pronounced interferon related side-effects and another died of myocardial infarction probably not related to therapy. Three patients have remained HCV-RNA negative with extended follow-up, two of whom have had a successful kidney transplant. Pegylated interferons are likely to become a valuable addition for HCV therapy in ESRD and are possible to combine with ribavirin. However the pharmacokinetics and tolerability of both peg-alfa-2a and 2b need to be studied more closely in prospective studies before definite dosing recommendations can be made.

Adult↗
PubMed2005

Hepatitis C virus RNA kinetics during the initial 12 weeks treatment with pegylated interferon-alpha 2a and ribavirin according to virological response.

SUMMARY: To optimize treatment of chronic hepatitis C early identification of patients who will not achieve a sustained virological response (SVR) is desirable. We investigated hepatitis C virus (HCV) RNA kinetics at day 1 (in 15 patients; genotypes 1 and non-1, 9 and 6 respectively) at weeks 1, 4 and 12 (in 53 patients; genotypes 1 and non-1, 19 and 34, respectively) during treatment with pegylated interferon alpha-2a and ribavirin. Patients with SVR had a significantly more pronounced mean log10 decline from baseline in HCV RNA levels at weeks 1 and 4 compared with patients who failed to achieve SVR (1.99 vs 0.85 at week 1, P = 0.0003 and 2.89 vs 1.72 at week 4, P = 0.0159), whereas no difference was noted after day 1. For patients with a 2-log10 decrease in HCV RNA levels at day 7, the positive predictive value (PPV) for a SVR was 92%, whereas week 12 was the best time point for predicting a later nonresponse [negative predictive value (NPV) 92%] in patients failing to achieve a 2-log10 drop. For patients with genotype non-1 and a 2-log10 decrease in HCV RNA levels the PPV for a SVR was 89% week 1, and 79% weeks 4 and 12. The corresponding NPV for patients with genotype non-1 were 43, 40 and 100% respectively. During treatment with pegylated interferon alpha-2a plus ribavirin the HCV RNA decline at week 1 was an accurate predictor of SVR in patients who had achieved a 2-log10 drop in HCV RNA levels, whereas the lack of such decline week 12 was an accurate marker of a nonresponse.

Adult↗
PubMed2002

Viral kinetics and treatment response in patients with hepatitis C during induction and standard interferon therapy in combination with ribavirin.

BACKGROUND: The early decline of hepatitis C virus (HCV) RNA levels during therapy may predict the outcome and can be utilized to improve treatment regimens. We studied the HCV RNA levels during induction and standard interferon (IFN) and ribavirin treatment. METHODS: Patients received IFN 3 MU daily for 14 days followed by 3 MU three times a week (induction group; n = 10), or IFN 3 MU three times a week from start (standard group; n = 21), in combination with ribavirin 1000-1200 mg/day. HCV RNA was quantified day 0, 1, 2, 3, 7, 14, 28, 56 and 84 during treatment, and tested qualitatively at the end of treatment and at follow-up. RESULTS: The initial viral load decline was more pronounced in the induction group, and in patients infected with genotype non-1. The sustained response rate was not significantly different between the study groups. At day 1, the mean viral load decline from baseline was significantly greater in patients who became sustained responders than in those who became non-responders; 1.4 log (96%) versus 0.3 log (55%) (P < 0.05). All sustained responders had a viral load decline of at least 0.7 log (79%) after the first IFN dose. CONCLUSIONS: Our short-term induction treatment did not improve the long-term treatment outcome significantly, although a trend was seen. An absent or low initial viral load decline can be used to predict non-response in the individual patient.

Adult↗
PubMed2001

Hepatitis C virus kinetics during induction and standard 3 times a week interferon-alpha therapy.

We studied HCV kinetics during the first 84 d of interferon-alpha (IFN) treatment. IFN was administered either at a dose of 3 million units daily for the first 14 d and thereafter 3 times per week (t.i.w.) (induction treatment), or at a dose of 3 million units t.i.w. throughout (standard treatment). No patient had received HCV treatment previously, and all had a pretreatment viral load of < 1.2 x 10(6) IU/ml at screening. Ten patients were given induction treatment and 21 received the standard t.i.w. regimen. Twenty patients were infected with genotype 1. At Day 2, the median HCV RNA level in the induction group was significantly lower compared to that of the standard treatment group. This significant difference persisted during the study period for patients infected with genotype 1, but was not maintained from Day 14 onwards for patients with genotype non-1. At Day 84, 80% (8/10) of patients in the induction group, compared to 16% (3/19) in the standard treatment group, had undetectable (< 600 IU/ml) HCV RNA levels (p < 0.05). We conclude that induction treatment resulted in a significantly greater decline in HCV RNA levels than standard treatment.

Adult↗
PubMed2000

HCV RNA levels during therapy with amantadine in addition to interferon and ribavirin in chronic hepatitis C patients with previous nonresponse or response/relapse to interferon and ribavirin.

Interferon (IFN) alpha in combination with ribavirin (RIB) is standard therapy for patients with chronic hepatitis C virus (HCV) infection. However, many patients do not respond with sustained HCV clearance to this therapy. At present, no accepted treatment strategy exists for these patients. Recent preliminary data have suggested that amantadine (AMA) is effective against HCV infection. In a pilot study, we treated 13 nonresponders and 10 response/ relapsers to previous IFN/RIB therapy with AMA 200 mg per day in combination with IFN 3 MU thrice weekly, and RIB 1000 mg per day for 24 weeks, with a 24-week follow-up period after end-of-treatment. At the end-of-treatment, 1 previous nonresponder and 5 previous response/relapsers were HCV RNA negative. At the end of follow-up, only 1 previous response/relapser remained HCV RNA negative and had a sustained response. During therapy, serum HCV RNA became undetectable in 4 previous nonresponders, of whom 3 had a breakthrough at week 24. Twenty-one patients continued therapy without dose reductions. One patient discontinued therapy prematurely due to sleeping disturbances, and another patient was withdrawn from therapy due to heavy alcohol intake. We conclude that the addition of AMA to IFN and RIB was well tolerated but had little, if any, impact on HCV RNA eradication in nonresponders or response/relapsers to previous IFN/RIB combination therapy.

Adult↗
PubMed1999

The anti-HBs response after 2 different accelerated intradermal and intramuscular schemes for hepatitis B vaccination.

To study early seroconversion rates after hepatitis B vaccination intramuscular (i.m.) and low-dose intradermal (i.d.) vaccination was compared when given either according to the registered 0, 4, 8 weeks scheme (scheme A), or to an accelerated 0, 2, 6 weeks scheme (scheme B). Medical staff received either 2 microg i.d. or 20 microg i.m. of a recombinant hepatitis B vaccine, in a non-randomized open trial. Two weeks after the third dose i.m. vaccinees overall had significantly higher rates of protective anti-HBs levels (anti-HBs > or = 10 IU/I), (23/30, 77%) compared with i.d. vaccinees (75/166, 45%) (p < 0.001). We conclude that when rapid protection against hepatitis B virus (HBV) infection is desirable, such as for post-exposure prophylaxis, an accelerated low-dose i.d. vaccination schedule cannot be used.

Administration, Cutaneous↗
PubMed1999

Theoretical model for layer rotations in smectic-A* liquid crystals subject to asymmetric electric fields.

Recently, observations of the rotation of smectic layers under certain experimental conditions have been reported in the literature. In this work, the mechanism of such rotations in chiral smectic-A* liquid crystals under the action of asymmetric, periodic electric fields is studied theoretically. The general conditions for layer rotations have been established using symmetry arguments, and a generalized dynamical theory of the chiral smectic-A* phase, coupling layer rotations and the electroclinic effect, has been developed. The theory is applied in the specific case when an asymmetric sawtooth electric field is applied over the system, and the dependence of the average angular velocity of the smectic layers on the relevant material constants of the liquid crystal and experimental control parameters is calculated. By rewriting the final equations into dimensionless form, it is demonstrated that the system exhibits a universal behavior, reducing the number of independent material constants and control parameters considerably.

Journal Article↗
PubMed1998

N-terminal proANF in acute atrial fibrillation: a biochemical marker of atrial pressures but not a predictor for conversion to sinus rhythm. Digitalis in Acute Atrial Fibrillation (DAAF) Trial group.

BACKGROUND: Atrial filling pressures are increased in acute atrial fibrillation, which stimulates the release of atrial natriuretic factor pro-hormone, proANF. METHODS: In a randomized trial comparing digoxin with placebo in 216 patients, we investigated whether the baseline plasma level of N-terminal proANF is a predictor for conversion to sinus rhythm and the relation among N-terminal proANF, conversion to sinus rhythm, and changes in heart rate. RESULTS: N-terminal proANF was increased at baseline and decreased significantly in patients converting to sinus rhythm, whereas it was mainly unchanged in nonconverters. N-terminal proANF was not a predictor of conversion to sinus rhythm. A relation was found between relative changes in heart rate and N-terminal proANF in nonconverters. CONCLUSION: The level of N-terminal proANF does not predict conversion to sinus rhythm, which indicates that hemodynamics per se is not important. There is a correlation between relative changes in heart rate and N-terminal proANF in nonconverters.

Acute Disease↗
PubMed1997

Interferon-alpha 2b treatment in hepatitis B carriers. Effect on hepatitis B virus DNA levels in children infected with different genotypes.

Eleven hepatitis B virus (HBV) carrier children, infected with genotypes A-D, were treated with interferon-alpha. Two children had a sustained loss of hepatitis B e-antigen and HBV DNA. They were infected with the non-Asian genotypes A and D, and had low HBV DNA and high ALT levels in serum before treatment. However, HBV DNA titres decreased during treatment also in children infected with the East-Asian genotypes B and C.

Adolescent↗
PubMed1996

Use of an enzyme thermistor for semi-continuous blood glucose measurements.

A method to monitor glucose in whole blood is presented. The aim of the project was to develop a prototype for a bedside monitor system for semi-continuous monitoring of the blood glucose concentration, requiring only one calibration. This was made possible by using the special advantage of the thermal sensor technique in combination with the adjustment of flow. The glucose concentration was determined from the difference between the sensor response and an estimated background signal. Using standard addition technique, calibration factors for background and sensitivity were set and remained unchanged during the monitoring. The background signal was 45 +/- 8 mV (mean +/- S.D., n = 8) and the sensitivity was 28 +/- 1 mV/mmol (mean +/- S.D., n = 4). Recovery in whole blood was 90-98% (mean 94%, n = 12). With an injection interval of 3 min the precision with the sensor was < 3% over more than 100 blood samples. Response time was about 60 s. The calculated glucose values correlated, r = 0.98, with the values obtained with an YSI glucose analyser (Yellow Springs Instruments. Yellow Springs, OH, USA), over the range 2-20 mmol/l.

Biocompatible Materials↗
PubMed1996

Homeopathic Resistant Malaria.

Multiresistant Plasmodium falciparum malaria is a major threat to travelers to subSaharan Africa. However, even if chemoprophylaxis does not prevent clinical malaria in some individuals, it does lead to a reduction in the severity of the disease.1 In Sweden, we have recently seen five patients with malaria (three due to P. ovale and two due to P. falciparum) who have used homeopathic drugs for prophylaxis during visits to West Africa. We are concerned about this incidence and afraid that reduced confidence in modern medical malaria prophylaxis will encourage some individuals to try totally ineffective alternatives. Three women (57, 40, and 39 years old) visited Guinea Conacry in January 1995 as members of a group of 24 persons learning about African dances. The 57-year-old woman took mefloquine irregularly but vomited each time after intake. She also used Spenglersan M, which is a homeopathic drug that is administered (one drop daily in the bend of the arm) as malaria prophylaxis. The two other women used Spenglersan M only. They all fell ill with P. ovale malaria despite ongoing intake. Spenglersan M is said to contain both antigen from P. falciparum and antibodies against the parasite diluted to 1:1,000,000,000 concentration. The fourth case was a 26-year-old man who visited Ghana and Burkina Faso in October and November 1994. He used China D-6 for prophylaxis. This is a homeopathic preparation of the bark from the cinchona tree. Not even trace amounts of quinine were found in the tablets with a very sensitive high-performance liquid chromatographic method.2 Four days after returning from Africa he fell ill with P. falciparum malaria and received sulphadoxine-pyrimethamine treatment. After clinical relapse (RI), mefloquine was given and the patient was eventually cured. The fifth case was a 34-year-old woman admitted to hospital because of P. falciparum malaria after a visit to Guinea Conacry in January 1995. She had taken a homeopathic drug, Charaka comp 118, as prophylaxis. The drug is said to contain different extracts from herbs diluted 30 times. At first she refused to stay in hospital, but 2 days later she was readmitted and treated in the intensive care unit because of severe malaria with hypotonia and anemia. She had hyperparasitemia with 23% infected erythrocytes. Exchange transfusion was done, quinine was given, and the patient recovered without sequelae. The mortality is about 1% in people with P. falciparum infection.3 We therefore urge the readers to stand up against the dangerous use of homeopathic drugs and instead motivate travelers to use protective malaria prophylaxis.

Journal Article↗