Search PubMed⌕ Search

Biomedical subjects

P Carlsson

Publications and source records attributed to P Carlsson.

At least 73 records · Page 4Linked to original sources

Differential activation of lung-specific genes by two forkhead proteins, FREAC-1 and FREAC-2.

We describe the cDNA sequences for two human transcription factors, Forkhead RElated ACtivator (FREAC)-1 and -2, that belong to the forkhead family of eukaryotic DNA binding proteins. FREAC-1 and -2 are encoded by distinct genes, are almost identical within their DNA binding domains and in the COOH termini, but are otherwise divergent. Cotransfections with a reporter carrying FREAC binding sites showed that both proteins are transcriptional activators, and deletions located the activation domains to the COOH-terminal side of the forkhead domains. Expression of FREAC-1 and FREAC-2 is restricted to lung and placenta. We show that the promoters of genes for lung-specific proteins such as pulmonary surfactant proteins A, B, and C (SPA, SPB, and SPC) and the Clara cell 10-kDa protein (CC10) contain potential binding sites for FREAC-1 and FREAC-2. DNaseI footprinting verified that FREAC proteins bind to the predicted sites in the CC10 and SPB promoters. While an SPB promoter construct could be transactivated by both FREAC-1 and FREAC-2, CC10 was only activated by FREAC-1. Efficient activation of CC10 by FREAC-1 is shown to be specific for a lung cell line with Clara cell characteristics (H441) and to involve a region of the FREAC-1 protein unable to activate in other cell types.

Amino Acid Sequence↗

Severity of a case for outcome assessment in health care--definitions and classification of instruments.

Severity of a case is one of the ingredients in management systems. Severity adjustment systems have limitations, and confusion and diversity characterize definitions of severity of a case. These facts may be a consequence of lack of conceptual knowledge. Based on a holistic theory of health, we introduce a definition of severity of a case from a patient perspective. Here severity is characterized as having two basic components: disease severity and illness severity; and five dimensions: suffering, disabilities, risk of suffering, risk of disabilities and risk of death. A classification of instruments as measures of severity dimensions is presented. This classification is based on definition and application criteria. The article's main contribution is to combine theoretical and practical knowledge about severity of a case, which may empower implementations of outcome management systems in health care.

APACHE↗

Linearity of sound transmission through the human skull in vivo.

The linearity of sound propagation through the human skull was investigated. One male subject, equipped with bilateral skin-penetrating titanium fixtures for attachment of bone-anchored hearing aids, was studied thoroughly. Three different methods were used: comparison of the frequency response functions estimated at different signal levels (using stepped sine as well as random noise), comparison of the coherence function at different signal levels (using random noise), and the Hilbert transform of the estimated frequency response function. Frequencies from 0.1 to 10 kHz and signal levels up to 77 dB HL at discrete frequencies were used. No indication of any significant nonlinear behavior was found with the three methods used.

Bone Conduction↗

An estimate of the life-time cost of surgical treatment of patients with benign prostatic hyperplasia in Sweden.

Two clinical series (n = 96 + 90) and one record-linkage study (n = 492) were used for estimation of the health care utilization for the treatment of BPH patients, mainly by TURP, in Sweden during one year before and 5-7 years after surgery. The total cost for a single patient amounted to ca. 33000 SEK in 1900 prices (5850 USD). Costs for surgery dominated and for a TURP amounted to about 70% of the Total. The costs during one year preoperatively and 5 years postoperatively each amounted to 15% of the total costs. In the present study the outcome of surgery was similar to other reports from the same period. The surgical mortality was 0.4% and the readmission rate because of complications of surgery or manifestations of BPH was 25% after 7 years of observation. Of the patients 11% were reoperated on within 7 years. When transurethral resection of the prostate (TURP) replaced open surgery in Sweden during the 1970's it had several of the attributes of the new methods introduced for treatment of benign prostate hyperplasia (BPH) currently in use. However, the spread of TURP resulted in wider indications for surgery and an increase in the total number of surgical procedures. An important argument for the adoption of the new, less invasive methods for treatment of BPH is the lower cost. To make a fair comparison of the costs of different methods for treatment of BPH the long-term costs have to be included in the calculation.

Aged↗

Extracorporeal shock-wave lithotripsy of gallbladder stones: an alternative for the selected few.

OBJECTIVE: To define selection criteria for optimal outcome of ESWL with oral litholysis (ursodeoxycholic acid) for gallbladder stones. DESIGN: Prospective study. SETTING: University hospital, Sweden. SUBJECTS: 145 patients with symptomatic gallbladder stones occupying a maximum of half the fasting gallbladder volume and gallbladder opacification at oral cholecystography. MAIN OUTCOME MEASURES: Three-year stone clearance rates in relation to initial stone burden, occurrence of calcified stones, and degree of gallbladder opacification at cholecystography. RESULTS: At all times clearance rates according to life table analysis were significantly higher for patients whose stone volume was < or = 4.2 ml (corresponding to one stone with a diameter of < or = 2.0 cm) (83% at 3 years) than for patients whose stone volume was > 4.2 ml (67% at 3 years), and patients with one stone had significantly higher clearance rates (88% at 3 years) than patients with multiple stones (58% at 3 years). Of all patients treated for gallbladder stones during one year, 25/194 (13%) had a stone volume of < or = 4.2 ml and 16/194 (8%) a solitary stone with volume < or = 4.2 ml. Neither the degree of gallbladder opacification nor the occurrence of calcified stones influenced clearance rates. CONCLUSION: ESWL may be an alternative to surgery in the few patients whose stone volume is roughly 4 ml or less and preferably have only one stone. Gallbladder function and patency of the cystic duct are poorly evaluated by oral cholecystography.

Adult↗

Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12).

The forkhead family of transcription factors has been shown to be involved in the regulation of embryonic development in organisms from Drosophila to humans. Genes encoding forkhead proteins are also emerging as a new class of oncogenes with relevance for human cancer. We have used a combination of fluorescence in situ hybridization and somatic cell hybrids to map the chromosomal localizations of five previously cloned human forkhead genes, freac-1, -3, -4, -5, and -6. (HGMW-approved symbols FKHL5, FKHL7, FKHL8, FKHL9 and FKHL10). We also report the sequence and the chromosomal position of a novel human forkhead gene, freac-8 (FKHL12). The freac genes have been localized to the following positions: freac-1, 16q24; freac-3, 6p25; freac-4, 5q12-q13; freac-5, 9 pericen; freac-6, 5q34, and freac-8, 1p32.

Amino Acid Sequence↗

Selection of high-affinity binding sites for sequence-specific, DNA binding proteins from random sequence oligonucleotides.

We describe a rapid and sensitive method to isolate sets of high-affinity binding sites for sequence-specific DNA binding proteins. The DNA binding domain of the protein is expressed in Escherichia coli as a fusion with glutathione S-transferase (GST). Binding reactions are set up with total soluble extract from induced bacteria and a double-stranded oligonucleotide for which the central 32 bp have been randomized. To ensure stringent conditions, binding is done in the presence of high levels of poly(dI:C). The GST fusion protein is recovered by the addition of glutathione-Sepharose. Following extensive washing of the Sepharose beads, the bound oligonucleotides are rescued by polymerase chain reaction amplification. The amplified material is used in the next cycle of selection and amplification. Approximately five cycles are needed to obtain a pure population of high-affinity sites, which are then cloned and sequenced. This procedure should be applicable to any sequence-specific DNA binding protein for which the cDNA is available and which can be expressed in bacteria in a functional form.

Base Sequence↗

Cost-effectiveness analysis in early detection of prostate cancer: an evaluation of six screening strategies in a randomly selected population of 2,400 men.

Based on the findings in an early detection study for prostate cancer [Gustafsson et al.: J Urol 148:1827-1831, 1992] using digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate-specific antigen (PSA), a cost-effectiveness analysis was performed based on 6 screening strategies, namely: 1) DRE of all individuals; 2) TRUS of all individuals; 3) DRE, TRUS, and PSA analysis followed by reexamination of individuals with PSAs > or = 7 ng/ml; 4) DRE of individuals with PSAs of > or = 4 ng/ml; 5) TRUS of individuals with PSAs of > or = 4 ng/ml; 6) DRE and PSA analysis followed by TRUS on individuals with PSAs > or = 4 ng/ml. The detection rates of prostate cancer using these 6 strategies were 2.4%, 3.3%, 3.6%, 2.0%, 2.6%, and 3.2%, respectively. Except for costs per detected cancer, costs were also calculated per detected small cancer (< or = 1.5 cm) and per detected cancer treated for cure. The cost calculations were based on total costs, i.e., direct plus indirect costs. When the 6 strategies were compared, taking into account the detection rate of cancers treated for cure and cost-effectiveness with respect to cancers treated for cure, strategies 1), 2), 3), and 4) were ruled out as less favorable than the remaining 2 strategies. TRUS of individuals with PSAs > or = 4 ng/ml (strategy 5) was the most cost-effective strategy and detected 80% of the cancers actually treated for cure. Screening with DRE and PSA analysis followed by TRUS of individuals with PSAs > or = 4 ng/ml (strategy 6) had a somewhat lower cost-effectiveness, but detected 90% of the cancers treated for cure.

Aged↗

Force threshold for hearing by direct bone conduction.

The bone-anchored hearing aid is connected, by means of a skin-penetrating bayonet coupling, to an implanted titanium fixture. Hence, direct bone conduction (dbc) excitation is used. Since no international standard of audiometric zero for dbc force threshold exists, it is of general interest to determine the dbc force threshold for normal hearing subjects. Two different methods have previously been applied to estimate the relation between bone conduction (bc) and dbc thresholds. One preliminary problem was to make a measurement of the output-force level of dbc transducers, which is equivalent to the situation in situ. A skull simulator, TU-1000, has been designed for measuring the output-force level of dbc transducers. The skull simulator does, in an adequate way, reflect the mechanical point impedance of the human skull. This opportunity to determine equivalent dbc force thresholds has motivated the present study in which a linear relation between the dbc force threshold and the bc force threshold was estimated. The estimate found in the present study conforms fairly well with the two previously found estimates. It is suggested that the estimate found in the present study be used as the reference equivalent threshold force level for dbc.

Adolescent↗

Effects on demineralization of enamel by fluoridated sucrose: a pilot study in an in situ caries model.

Blocks of human enamel, placed in removable partial dentures, were allowed to acquire natural plaque for seven days and were exposed extra-orally to a cariogenic challenge by repeated periods in a fluoride-sucrose solution. As a control, enamel blocks were exposed extra-orally to a sucrose solution. After two weeks of cariogenic challenge, the blocks were examined for mineral loss by quantitative microradiography on thin sections of the enamel. The results from six subjects showed that no significant effect on demineralization could be detected by the addition of fluoride corresponding to fluoride/sugar content of 1 mg/kg, 5 mg/kg, or 10 mg/kg (dry weight). One subject did not develop lesions at all, either with fluoride-sucrose or with sucrose exposure alone.

Analysis of Variance↗

Estimated total costs of treating benign prostatic hyperplasia in Sweden.

New surgical methods and safe effective drugs for treating benign prostatic hyperplasia (BPH) have been introduced in recent years. The long-term effects of these measures and the patient categories for which each is best suited are not as yet known. Amid rapid changes in treatment policy, our study aims to establish a frame of reference in Sweden for the costs of treating BPH. In 1988 most treatment of BPH was surgical, with "watchful waiting" or indwelling urethral catheter as alternatives. Transurethral resection was the main surgical method. The costs of treating BPH in 1988 were calculated with a "prevalence" and an "incidence" approach. Direct costs accounted for 80-85% of the total were mainly hospital costs. The total economic burden of BPH treatment in Sweden was estimated as 305-390 million SEK, equivalent to 49-62 million US$ in 1988 prices. Because of the impending changes in management of BPH, follow-up of the financial consequences of these changes is important in order to secure effective use of health care resources.

Ambulatory Care↗

Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending.

The forkhead domain is a monomeric DNA binding motif that defines a rapidly growing family of eukaryotic transcriptional regulators. Genetic and biochemical data suggest a central role in embryonic development for genes encoding forkhead proteins. We have used PCR and low stringency hybridization to isolate clones from human cDNA and genomic libraries that represent seven novel forkhead genes, freac-1 to freac-7. The spatial patterns of expression for the seven freac genes range from specific for a single tissue to nearly ubiquitous. The DNA binding specificities of four of the FREAC proteins were determined by selection of binding sites from random sequence oligonucleotides. The binding sites for all four FREAC proteins share a core sequence, RTAAAYA, but differ in the positions flanking the core. Domain swaps between two FREAC proteins identified two subregions within the forkhead domain as responsible for creating differences in DNA binding specificity. Applying a circular permutation assay, we show that binding of FREAC proteins to their cognate sites results in bending of the DNA at an angle of 80-90 degrees.

Amino Acid Sequence↗

The role of national quality registers in the Swedish health service.

This article reports on a quality movement in Sweden that has gone largely unnoticed, namely the national quality control registers. These registers represent a potentially important primary data source for comparative studies and can play an important role in a national strategy for control and improvement of health care quality. First, we review the recent health care quality initiatives in Sweden and the background of national quality control registers. Secondly, we discuss our findings from a study on the purpose, content, value and problems associated with the registers. Our findings are based on (a) interviews with physician managers of the registers, (b) questionnaires to selected hospital departments participating in the registers and (c) questionnaires to elected officials and administrators representing the local health care providers. Finally, we discuss several crucial issues related to the registers. Although some have existed for several years, the registers are still defining their roles. Traditionally, this activity has been managed by the medical profession. However, interest in register information is increasing among health care policy makers and administrators at all levels in the system. Two key issues concern register ownership and finance, but the most sensitive issue concerns the right of policy makers and the public to access register information. The registers and the information they contain illustrate the ongoing conflict between openness and consumer sovereignty in health care on the one hand and professional autonomy on the other.

Cost-Benefit Analysis↗

Immediate and prolonged effects of pre- versus postoperative epidural analgesia with bupivacaine and morphine on pain at rest and during mobilisation after total knee arthroplasty.

Thirty-two patients scheduled for total knee arthroplasty were randomized to receive an identical epidural blockade initiated 30 min before surgical incision (N = 16), or at closure of the surgical wound (N = 16). Before induction of general anaesthesia the epidural catheter was tested with bupivacaine 7.5 mg.ml-1, 2 ml. General anaesthesia was induced with thiopentone, pancuronium or atracurium, and fentanyl 0.1-0.3 mg, and maintained with N2O/O2 and enflurane. The epidural regimen consisted of a bolus of 16 ml of bupivacaine 7.5 mg.ml-1 plus morphine 2 mg, and continuous infusion of bupivacaine 1.25 mg.ml-1 plus morphine 0.05 mg.ml-1, 4 ml.h-1 for the first 24 h, and bupivacaine 0.625 mg.ml-1 plus morphine 0.05 mg.ml-1, 4 ml.h-1, for the next 24 h after operation. Additional morphine 2.5-5 mg was administered i.v. or i.m. for the first 24 h postoperatively, and ketobemidone or morphine 5-10 mg orally or rectally from 24 h to 7 d postoperatively, on request. Paracetamol 1000 mg every 8 h was administered from 48 h to 7 days postoperatively. No significant differences were observed in request for additional opioids, or in pain scores at rest or during mobilisation of the operated limb, during or after cessation of the epidural regimen. These results do not suggest timing of analgesia with a conventional, continuous epidural regimen to be of major clinical importance in patients undergoing total knee arthroplasty.

Aged↗