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Biomedical subjects

G Carlsson

Publications and source records attributed to G Carlsson.

At least 19 recordsLinked to original sources
PubMed2006

Assignment of the gene locus for severe congenital neutropenia to chromosome 1q22 in the original Kostmann family from Northern Sweden.

Autosomal recessive severe congenital neutropenia (SCN) or Kostmann syndrome is characterised by reduced neutrophil counts and subsequent recurrent bacterial infections. The disease was originally described in a large consanguineous pedigree from Northern Sweden. A genome-wide autozygosity scan was initiated on samples from four individuals in the original pedigree using high density single nucleotide polymorphism (SNP) genotyping arrays in order to map the disease locus. Thirty candidate regions were identified and the ascertainment of samples from two additional patients confirmed a single haplotype with significant association to the disorder (p<0.01) on chromosome 1q22. One affected individual from the original Kostmann pedigree was confirmed as a phenocopy. The minimal haplotype shared by affected individuals spans a candidate region of 1.2 Mb, containing several potential candidate genes.

Chromosome Mapping↗
PubMed2005

Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF.

BACKGROUND: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.

Adult↗
PubMed2004

Synthetic musk toxicity to early life stages of zebrafish (Danio rerio).

Synthetic musk substances have been found in a number of environmental samples. Some of these chemicals have been detected in concentrations above 1 microg/L in water, which raises concern about possible effects on aquatic life. The toxicity of four synthetic musks, 4-tert-butyl-2,6-dimethyl-3,5-dinitrophenylethanone (musk ketone), 1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene (musk xylene), 1-(5,6,7,8-tetrahydro-3,5,5,6,8,8-hexamethyl-2-naphthalenyl)ethanone (AHTN, tonalide) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-[g]-2-benzopyrane (HHCB, galaxolide), were studied in zebrafish by the use of two different early life-stage methods. In the first method, specific developmental characteristics during the first 48 hours were studied. In the second method, hatching and survival times were studied on eggs and larvae. The results on heart rate in the first test gave the following LOECs: musk ketone 10 microg/L, musk xylene and AHTN 33 microg/L, and HHCB showed no effect up to 1000 microg/L. In the study of survival time, LOEC for musk ketone was 100 microg/L, for musk xylene 33 microg/L, and AHTN gave no effect on survival time up to 100 microg/L. The LOECs for musk ketone, musk xylene, and AHTN in this study are in the range of what has been measured in sewage effluents and recipients, and consequently these substances may have adverse impact on wild fish.

Animals↗
PubMed2004

Visual attention in young adulthood after cardiopulmonary resuscitation at birth or being born small for gestational age.

The Posner cue-target paradigm for the study of shifts in visual attention was used to assess focused attention and shifts in attention in 43 young adults, 19 to 28 years of age, who had been in need of cardiopulmonary resuscitation at birth because of perinatal asphyxia (n=31) or who were born small for gestational age (n= 12). Their performances were compared to that of 18 control subjects. The subjects resuscitated at birth were divided into two groups, mild and moderate, according to neurological symptoms during the neonatal course. An expected significant main effect by block of trials and conditions was found, with general decrease in reaction times from Blocks 1 to 5 and with slowest reaction times to an invalid cue and fastest to a valid one. No group differences were statistically significant, but the moderate asphyxia and the groups small for gestational age had longer average reaction times on all test conditions than control subjects, implying that those who showed the most severe pre- or neonatal complications also were most affected in attentional functions.

Adult↗
PubMed2002

Follow-up into young adulthood after cardiopulmonary resuscitation in term and near-term newborn infants. I. Educational achievements and social adjustment.

AIM: Long-term sequelae after perinatal asphyxia have generally been assessed at preschool or school age. The aim of the study was to confirm the hypothesis that there could be impairment of cognitive and memory functions that does not become apparent until education and adult life impose special demands. METHODS: Seventy-one term or near-term newborns in need of cardiopulmonary resuscitation because of presumed perinatal asphyxia were investigated with evoked EEG potentials during the first week of life and were investigated at a follow-up clinic until 18 mo of age. At that time 12 subjects showed signs of neuro-developmental impairment. The remaining 59 were considered healthy. They were contacted at young adult age and given a questionnaire containing questions about type of education, need for extra support at school, present activity/employment, living conditions, spare-time activities and self-estimation of health. RESULTS: Thirty-five control subjects were approached at the same time. From the group that was resuscitated at birth, 53 questionnaires were returned and 30 from the control group. Although the resuscitated subjects had signs of both encephalopathy and pathologic evoked responses during their neonatal period, the questionnaire revealed that they had coped with school equally as well as their peers, that the rate of entering university studies was the same and that living conditions were similar between the groups. CONCLUSION: These individuals who were resuscitated at birth and who demonstrated various degrees of neonatal encephalopathy suffered either brain injury that could be diagnosed at 18 mo of age or managed as well as their non-resuscitated peers in terms of educational achievement and social adjustment at young adult age.

Asphyxia Neonatorum↗
PubMed2002

Follow-up into young adulthood after cardiopulmonary resuscitation in term and near-term newborn infants. II. Neuropsychological consequences.

AIM: Brain injury after neonatal cardiopulmonary resuscitation in the term baby is often described as an all-or-nothing phenomenon, but little is known about possible late cognitive consequences. The aim of this study was therefore to investigate whether children who needed cardiopulmonary resuscitation because of presumed mild and moderate intra-partum asphyxia with no evidence of neurological impairments at 18 mo of age may display neuropsychological impairments later in life. METHODS: A long-term follow-up of young adults was carried out. A blinded comprehensive neuropsychological assessment of the main aspects of cognitive functions was made. The subjects who were resuscitated were divided into two groups according to the clinical course: 20 cases with mild asphyxia and 11 cases with moderate asphyxia, all followed prospectively and compared with 18 healthy controls. The 31 subjects were born at term or near-term and selected randomly from 59 infants born in 1969-1978 at Sahlgren's Hospital, Göteborg. All infants with early neurological impairments were excluded. RESULTS: No major differences could be established between the two clinical groups and normal controls in any aspects of cognitive function or intelligence. All the groups performed within the normal range in all tests. A tendency toward minor deficits in verbal ability in the mild group compared to the controls was found. Only one subject had a clear, defined memory deficit. CONCLUSIONS: Infants who underwent cardiopulmonary resuscitatation at birth without neurological deficits at 18 mo of age did not show any cognitive deficits or neuropsychological impairments in adulthood even though inferior performance on some verbal subtests was observed compared to the control group.

Asphyxia Neonatorum↗
PubMed2002

Large variability in performance IQ associated with postnatal morbidity, and reduced verbal IQ among school-aged children born preterm.

AIM: To assess cognitive ability in a population-based group of prematurely born school-aged children and to relate these findings to postnatal morbidity. METHOD: The study group consisted of a cohort of 51 children born preterm, 43 (26 boys, 17 girls) of whom were available for psychological evaluation At evaluation, their median age was 10 y (range 8-11 y). They were all born between 1988 and 1991, with gestational age less than 29 wk (median 27, range 24-28). Their median birthweight was 1060g (range 450-1450). The Wechsler Intelligence Scale for Children (WISC-III) was used, and the test results were compared with those of a standardized, age-matched, normative group of children. RESULTS: Thirteen children (30%) performed below average [intelligence quotient (IQ) < 80] for Full Scale IQ (FSIQ). Thirty-six children had a Verbal IQ (VIQ) below the mean value of 100 [84%, 95% confidence interval 73-95%], p < 0.0001. The Performance IQ (PIQ) was within the expected range of a normal population, although a large variability was observed. Discrepancies between VIQ and PIQ of more than 15 IQ units were found in 42% of the children. High postnatal morbidity (days with assisted ventilation, number of blood transfusions) and low birthweight standard deviation scores (SDS) were associated with lower PIQ than VIQ, while low postnatal morbidity and high birthweight were associated with higher PIQ than VIQ. CONCLUSION: This cohort of preterm children had reduced overall verbal capacity independent of morbidity, and a large variability in performance capacity that was associated with postnatal morbidity. The findings suggest that there are different mechanisms influencing the outcome of verbal and performance capacity in preterm children.

Blood Transfusion↗
PubMed2001

Effects of 5-fluorouracil on mitogen-induced costimulatory capacity of accessory cells from rat oral mucosa and dental pulp.

The present study was designed to investigate the effect of the antimetabolite 5-fluorouracil (5-FU) on the capacity of the oral epithelium and the dental pulp to induce a mitogen-driven T-cell proliferation. Inbred Lewis rats were given 6 i.v. injections of 5-FU (30 mg/kg or 50 mg/kg) over a period of 8 days. Suspensions of oral epithelial and dental pulpal cells were prepared. The costimulatory capacity of the accessory cells from treated animals was monitored by their ability to induce a mitogen (ConA)-mediated proliferation of T cells isolated from regional lymph nodes of untreated animals. Accessory epithelial cells from rats treated with the high dose of 5-FU, but not the low dose, induced a decreased T-cell proliferation compared to controls. Accessory pulpal cells from rats, treated with 30 mg/kg or 50 mg/kg of 5-FU, induced a lower T-cell proliferation. When MHC class II molecule depleted T-cell suspensions from lymph nodes of 5-FU-injected animals were incubated with ConA, a significant proliferative response was observed. This finding correlated with an increase of MHC class II molecule expressing cells detected after incubation, although no such cells were observed immediately following the initial purification step of T cells. This finding demonstrates that the accessory cells could partly restore their expression of MHC class II molecules during incubation. The results of the study suggest that the function of immunocompetent cells of the oral mucosa and dental pulp is influenced by treatment with 5-FU and that the function of accessory cells of the pulp is affected more than the function of accessory cells derived from the oral mucosa.

Animals↗
PubMed2001

Age effects in dichotic listening to consonant-vowel syllables: interactions with attention.

A relatively large sample of individuals (N = 240) ranging from 7 to 70 years were studied with the dichotic listening (DL) technique as a measure of language lateralization. Two questions were asked: (a) Is there a developmental effect for the right-ear advantage (REA) with age? (b) Is there a developmental effect for attentional modulation of the REA? The participants were all right-handed, healthy individuals tested in Sweden and Norway. The stimuli were dichotic presentations of consonant-vowel (CV) syllable pairs. There were 3 different attentional conditions: nonforced (NF) attention, with no specific instructions about focusing of attention; forced-right (FR) attention, with instructions to focus attention on the right-ear stimulus; and forced-left (FL) attention, with instructions to focus attention on the left-ear stimulus. The results showed a REA in all age groups, except for the 9-year-olds, in the NF condition. In the FR condition, all age groups showed a REA. The youngest age groups did not, however, increase the REA to the same degree as the older age groups, as indicated by the significant age x ear interaction. In the FL condition, all age groups, with the exception of the youngest groups, showed a left-ear advantage (LEA). It is concluded that the REA effect in DL is subject to developmental effects and that attentional effects on laterality also develop with increasing age.

Adolescent↗
PubMed2001

Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original "Kostmann family" and a review.

UNLABELLED: In 1956 Rolf Kostmann reported on six children with severe neutropenia associated with a block in myelopoiesis at the promyelocyte/myelocyte stage and an autosomal recessive inheritance. He named the new syndrome infantile genetic agranulocytosis. Today it is known as Kostmann's syndrome or severe congenital neutropenia. In 1975 an additional 10 cases from northern Sweden were published. This article reports on the only long-term survivor from the 1975 report plus another five patients born after 1975 who belong to the original "Kostmann family". Treatment and survival have changed dramatically since Kostmann's first publication. In the pre-antibiotic era, Kostmann's syndrome was inevitably fatal during the first year of life. CONCLUSION: Since the introduction of recombinant human granulocyte colony-stimulating factor (G-CSF) about 10 y ago, most patients now enjoy a normal life span and a greatly improved quality of life. Although the threat of death has disappeared, patients still have problems with infections, especially chronic gingivitis and periodontitis. In other groups of severe neutropenia, not related to the original "Kostmann family", an increased incidence of myeloid leukaemia has been observed. However, in this small cohort none of the children on chronic G-CSF therapy have developed malignancies.

Adolescent↗
PubMed2001

The effect of desmopressin on short-term memory in children with primary nocturnal enuresis.

PURPOSE: The use of desmopressin in patients with primary nocturnal enuresis is based on the hypothesis of a nocturnal lack of endogenous arginine vasopressin. However, in addition to the kidney, other targets of desmopressin are known. Therefore, we examined whether the administration of desmopressin influences central nervous function in children with primary nocturnal enuresis. MATERIALS AND METHODS: Our prospective, randomized, double-blind, placebo controlled cross-over study was performed on 40 children with nocturnal enuresis. Patients were randomly assigned to receive either 20 microg. desmopressin intranasally or 0.9% saline solution. Each group comprised 19 and 21 to children, respectively. After 2 weeks the groups were switched. The children were tested for short-term memory and reaction time to both treatments. Statistical analysis was done using the Wilcoxon matched pairs test. RESULTS: Median patient age was 8.0 years (range 6 to 13). During desmopressin treatment children in both groups had a significant decrease of wet nights (5.3 to 3.2 per week). In contrast to reaction time, short-term memory was significantly different between both groups (p <0.05). CONCLUSIONS: Our results demonstrate an increase in short-term memory after desmopressin treatment in children with nocturnal enuresis. This finding indicates the central nervous system as a target involved in the pathogenesis of nocturnal enuresis as well as the therapeutic benefit of desmopressin treatment.

Adolescent↗
PubMed2000

A pharmacokinetic study of 5-FU/leucovorin and alpha-interferon in advanced cancer.

The present study was designed to study 5-FU pharmacokinetics after interferon. Weekly bolus 5-FU (500 mg/m2), immediately followed by leucovorin (60 mg/m2) was given in 14 weekly cycles to 55 gastrointestinal and breast cancer patients. Interferon-alpha was given on days 2, 4 and 6, starting from cycle 2 at a dose of 0.5 million units (MU) and stepwise increased to 12 MU in cycles 12 and 13. Five patients could not tolerate the treatment even at the lowest dose of interferon and 22 patients were unavailable for the pharmacokinetic analysis because of dose reductions of 5-FU. Five patients were able to follow the protocol to 12 MU, whereas most patients were unable to continue owing to toxicity. 5-FU pharmacokinetics was analysed every second cycle. Peak concentration and AUC were increased after 12 MU of interferon, but no other significant influence of interferon on pharmacokinetic parameters of 5-FU was observed.

Adult↗
PubMed2000

Evaluation of solid-phase microextraction for the study of protein binding in human plasma samples.

Solid-phase microextraction (SPME) in combination with capillary gas chromatography and a nitrogen-phosphorous detector is used to study protein binding in human plasma samples. Local anesthetics of the amide-type (ropivacaine, bupivacaine, mepivacaine, prilocaine, and lidocaine) are used as model compounds in this evaluation. Carbowax/divinylbenzene (CW/DVB), polyacrylate, and polydimethylsiloxane fibers are tested. Sampling on CW/DVB fibers give the highest recovery in plasma samples compared with other fibers. Ultrafiltrate spiked with each of the substances is used for the construction of calibration curves. The protein binding is investigated at four different total concentrations from 0.5 to 15.0 microM. The degree of protein binding increases when the solute concentration decreases. Protein binding of the five solutes is investigated at four pH levels (6.4, 7.4, 8.4, and 9.4). It is found that protein binding increased with increasing pH. The influence of temperature variation (from 32 degrees C to 40 degrees C) on protein binding is also investigated. The protein binding decreases when the temperature increases. The methodology is validated and good correlation and precision are obtained. Back-calculated quality control samples give accuracy within 20% of theoretical values for all five substances. This study shows that SPME as a sample-preparation method gives the same protein binding for the studied local anesthetics as that achieved using earlier presented methods.

Anesthetics, Local↗
PubMed2000

Neuropsychological long-term outcome of rolandic EEG traits.

BACKGROUND: Long-term outcome of rolandic epilepsy (RE) is associated with a diversity of neuropsychological deficits in childhood, although RE is historically considered as a benign epileptic disorder. Dyslexia and other developmental disorders are associated with rolandic EEG traits. AIM: To investigate if there is an association between the manifestation of a specific EEG trait of RE and dyslexia. If the EEG traits are causing dyslexia, the cognitive deficits are supposed to be normalised after the EEG trait have resolved. METHOD: Thirty adolescents and young adults, who had previously received a diagnosis of dyslexia by standard criteria, were included. Fifteen probands (mean age = 15.9) with dyslexia and rolandic EEG traits were compared with 15 age- and sex-matched controls (mean age = 16.0) with normal EEG. RESULTS: There were no statistical differences between the groups according to intelligence (Verbal IQ, Performance IQ and Arithmetical IQ) or spelling ability. However, there was a significant difference between the groups in reading ability of non-related words with the group without RE performing better than the group with RE (p < 0.01). Attentional shifts in dichotic listening with forced or directed attention are generally found in 50-60% in normative samples. However, the present date suggest an impaired attentional shift in dichotic listening test for both groups. Only one third was able to modulate their ear-preference. There were no group differences. CONCLUSION: In general, both dyslectic groups did not show significant neuropsychological deficits as compared to standard controls. However, there were more reading errors and a tendency to attention impairments in the group with rolandic EEG trait as compared to the dyslectic group with normal EEG. Possible pathogenic factors are discussed.

Adolescent↗
PubMed1998

Chemical stability and human plasma pharmacokinetics of reduced folates.

The in vitro stability and plasma pharmacokinetics of 5,10-methylenetetrahydrofolic acid (CH2FH4), tetrahydrofolic acid (FH4), 5-methyltetrahydrofolic acid (CH3FH4), and 5-formyltetrahydrofolic acid (5-CHOFH4) were studied in view of their potential usefulness in cancer chemotherapy. Analysis of reduced folates was done on a high-performance liquid chromatography (HPLC) system. The high sensitivity of FH4 and CH2FH4 to oxidation can be circumvented by use of high concentrations of the folates, addition of ascorbate, and by thorough exclusion of atmospheric O2. Intravenous injection of 200 mg FH4 or CH2FH4 resulted in average peak concentrations of 69.2 +/- 3.2 nmol/ml and 46.3 +/- 2.6 nmol/ml, respectively. The plasma concentration curves support the concept that these highly oxygen-sensitive reduced folates can be reliably administered as pharmaceuticals to cancer patients through the use of a suitable air-occlusive system for their preparation and administration.

Colorectal Neoplasms↗
PubMed1997

Dichotic-listening performance and intracarotid injections of amobarbital in children and adolescents. Preoperative and postoperative comparisons.

BACKGROUND: Dichotic listening (DL) to consonant-vowel syllables is frequently used in clinical and experimental studies of brain laterality. However, the paradigm of consonant-vowel syllables has not been thoroughly validated through a comparison with injections of amobarbital sodium (Amytal). OBJECTIVE: To validate the DL test for hemisphere dominance preoperatively vs postoperatively with the results from intracarotid injections of amobarbital (i.e., the Wada test) in epileptic children and adolescents. DESIGN AND MAIN OUTCOME MEASURES: Patients were tested with DL preoperatively and at 6-month follow-up. Correct reports in the DL tests were entered in a stepwise discriminant analysis for calculation of correct classification of hemisphere dominance with the results from the injections of amobarbital as the grouping variable. Correct reports from the right and left ears on the consonant-vowel DL test were compared preoperatively and postoperatively, separated for the subjects with regard to language dominance in the left and right hemispheres. SETTING: The Department of Pediatrics, Ostra Hospital, University of Göteborg, Göteborg, Sweden. PATIENTS: Thirteen children and adolescents between the ages of 10 and 19 years, who were surgically treated for resistant epilepsy, were included in the study. The operated area corresponded with morphological changes and functional dysfunctions according to findings from computed tomography, magnetic resonance imaging, single photon emission computed tomography, and electroencephalography. RESULTS: The results of the Wada tests revealed that 10 subjects had left hemisphere language dominance, with 3 subjects having right hemisphere language dominance. All 3 subjects with right hemisphere language dominance showed a left ear advantage on the DL test preoperatively and postoperatively, with 8 and 7 of the 10 subjects with left hemisphere dominance showing a right ear advantage, preoperatively and postoperatively, respectively. However, according to discriminant analysis, knowledge of the DL performance led to a correct classification according to the Wada test results in 12 (92%) of the 13 subjects. CONCLUSIONS: A quantitative classification procedure like discriminant analysis may be more sensitive when predicting hemisphere speech dominance from DL data than a qualitative procedure based on the ear advantage dichotomy. The ear advantage dichotomy may actually introduce arbitrary left-right categories that do not correspond to the actual clustering of the data.

Adolescent↗
PubMed1997

Mutations in the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia.

Previously, nonsense mutations in the gene encoding the granulocyte colony-stimulating factor receptor (G-CSF-R) have been described in three patients with severe congenital neutropenia (SCN) (Proc Natl Acad Sci USA 1994; 91: 4480; New Engl J Med 1995; 333: 487). The mutations resulted in the truncation of the carboxy-terminal region of G-CSF-R essential for transduction of maturation signals. Two of these patients developed acute myeloblastic leukemia (AML). We present the results of a search among 20 additional cases of congenital neutropenia (CN) and SCN for the presence of mutations in the cytoplasmic domain of G-CSF-R. This series includes patients with familial and nonfamilial forms of CN and SCN. Mutations in the G-CSF-R gene were found in two new SCN cases. These mutations were nonsense mutations, located in the same cytoplasmic region of G-CSF-R as those found earlier, resulting in the truncation of the C-terminus. Both of these patients developed AML. None of the other patients showed clinical symptoms or cytogenetic features indicative of AML or progression to leukemia. The analysis in this extended series of patients thus has revealed five SCN cases with G-CSF-R mutations, four of whom developed AML. These results add support to the notion that mutations in the G-CSF-R gene, affecting the maturation signaling function of the receptor, define a distinct subgroup of SCN with increased susceptibilty to AML.

Adolescent↗