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Biomedical subjects

P Carlsson

Publications and source records attributed to P Carlsson.

At least 91 records · Page 5Linked to original sources

Resonance frequencies of the human skull in vivo.

Patients with skin penetrating titanium implants in the temporal bone, for attachment of bone-anchored hearing aids, have made it possible to investigate the free-damped natural frequencies (resonance frequencies) of the human skull in vivo. The resonance frequencies of the skull of six subjects were investigated. Teh resonance frequencies were extracted from two frequency response functions (acceleration/force) measured on each subject: One point measurement where the force and acceleration were both measured at the same point, and one transcranial measurement where the acceleration was measured contralaterally. Between 14 and 19 resonance frequencies were identified for each subject in the frequency range 500 Hz to 7.5 kHz. The two lowest resonance frequencies were found to be on the average 972 (range 828-1164) and 1230 (range 981-1417) Hz. The relative damping coefficients of all resonances were found to be between 2.6 and 8.9%. Due to the relatively high damping coefficients, it is assumed that the resonance frequencies do not significantly affect bone conducted sound. In the transcranial measurements, however, a few large antiresonances were found which may affect bone-conducted sound. Intersubject variations were large, probably due to individual variations in skull geometry and in mechanical parameters. The results were shown to be consistent with previous results obtained on dry skulls. No obvious correlation between lowest resonance frequency and skull size was found.

Adult↗

Clinical and economic considerations in the treatment of prostate cancer.

Prostate cancer is a growing health problem with considerable economic consequences. Despite progress in the management of this disease, few areas in medicine generate greater disagreement. The larger part of healthcare resources are allocated to 'halfway technologies' aimed at palliative intervention to prolong life, while a relatively small part goes to measures aimed at preventing or curing the disease. The aetiology of this cancer is multifactorial and no practical measures for primary prevention are known. The number of patients diagnosed with prostate cancer is increasing steadily. The age-adjusted mortality, however, has increased only slightly. In its early stages, prostate cancer is often asymptomatic and is usually not diagnosed until it has advanced. Programmes for the early detection of prostate cancer (screening) claimed to reduce morbidity and mortality are a matter of controversy. Furthermore, there has been much debate regarding optimal treatment in the early stages of the disease. Economic considerations have not as yet been integrated into studies concerning localised prostate cancer. The routine first-line treatment of advanced prostate cancer usually involves some type of endocrine treatment. The most straightforward technique is surgical castration. Oral estrogens are as effective as castration, but have significant cardiovascular adverse effects. These may possibly be prevented if estrogens are given parenterally. A third principal endocrine treatment is the administration of antiandrogens. Medical castration can be attained by the administration of recently developed synthetic peptides, gonadotrophin-releasing hormone {luteinising hormone-releasing hormone (LHRH)} (GnRH) analogue agonists which are given parenterally. The advantage of this type of medical castration is that the trauma of surgical castration and the adverse effects of oral estrogens are avoided. In an attempt to improve the results obtained with endocrine treatment, the concept of combining surgical or medical castration with antiandrogens was introduced. This combination could offer improved response rates and survival in a significant number of patients. However, this advantage must be weighed against the tolerability profiles and the high costs of antiandrogens and GnRH analogues. When using expensive drugs, the duration of treatment is a crucial factor in the total cost. As the length of treatment varies greatly between patients it is difficult to decide the most cost-effective alternative for a single individual. The patient's preference is an important factor when selecting treatment. When there is little or no difference in the effect of different regimens the total lifetime cost is important.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Antagonists↗

The hLEF/TCF-1 alpha HMG protein contains a context-dependent transcriptional activation domain that induces the TCR alpha enhancer in T cells.

hLEF/TCF-1 alpha is a lymphoid cell-specific HMG protein that activates the distal enhancer of the gene encoding the alpha-subunit of the T-cell receptor (TCR alpha). We have shown previously that transcriptional activation by hLEF is highly dependent on the context of its binding site within the TCR alpha enhancer. Here, we demonstrate that hLEF contains a potent transcriptional activation domain that is separate from the HMG motif and is preferentially active in T cells. We find that hLEF/GAL4 fusion proteins can activate a GAL4-substituted TCR alpha enhancer up to 50-fold in T-cell lines and are as active as GAL4/VP16 in this context. Unlike GAL4/VP16, however, hLEF/GAL4 could not activate heterologous promoters bearing only GAL4 DNA-binding sites. Thus, activation by hLEF/GAL4, like that noted previously for the native hLEF activator, was strongly influenced by the context of its DNA-binding site within the TCR alpha enhancer. Inspection of enhancer mutants suggests that trans-activation by hLEF/GAL4 is especially dependent on TCF-2, a distinct T-cell-enriched protein that binds to sequences flanking the hLEF-binding site in the enhancer. Analysis of small deletion or clustered amino acid substitution mutants in the hLEF-coding sequences identified a minimal activation region between amino acids 80 and 256 that appears to be bipartite in structure. The hLEF activation domain is not notably acid or glutamine-rich but is proline-rich and includes a motif rich in tyrosine and serine residues. We conclude that sequences outside of the hLEF HMG box mediate cell- and context-specific activation of the TCR alpha enhancer and may facilitate interactions between hLEF and other T-cell-specific factors recruited to the enhancer.

Amino Acid Sequence↗

Quality of life after radical retropubic prostatectomy for carcinoma of the prostate.

131 patients treated by radical prostatectomy for localized prostatic cancer were studied with regard to quality of life. The patient's perception of his state of health before operation and 3, 6, 12 and 18 months later was assessed by questionnaires on 272 occasions. In the short term the patients complained of anxiety, voiding disorders, and loss of potency. In the long term only distress due to lack of erection persisted, but the overall well-being after 18 months was nevertheless better than before treatment.

Aged↗

Organization and regulation of the Bacillus subtilis odhAB operon, which encodes two of the subenzymes of the 2-oxoglutarate dehydrogenase complex.

The primary structure of Bacillus subtilis 105 kDa 2-oxoglutarate dehydrogenase (E10) was deduced from the nucleotide sequence of the odhA gene and confirmed by N-terminal sequence analysis. The protein is highly homologous to E1o of Azotobacter vinelandii and Escherichia coli and of bakers' yeast cells. The 5' end of the odhAB mRNA was determined and the promoter region for the odhAB operon was localized to a 375 bp DNA fragment. The cellular concentration of the 4.5 kb odhAB transcript was found to be growth stage dependent; its concentration during growth in nutrient sporulation medium decreased abruptly at the end of the exponential growth phase and it was not detectable in early stationary phase. This decrease in the cellular concentration of the transcript is not the result of an increased rate of decay of the full-length odhAB mRNA, suggesting that transcription is down-regulated at the end of the exponential growth phase. The cellular concentration of the odhA and odhB gene products, E1o and dihydrolipoamide transsuccinylase (E2o), remains essentially constant throughout the growth curve in nutrient sporulation medium, indicating that both are rather stable proteins. In exponentially growing cells, glucose in nutrient sporulation medium repressed the cellular concentration of the odhAB mRNA, as well as that of E1o and E2o, about four-fold. This effect is most likely the result of a decreased rate of transcription from the odhAB promoter, since neither the stability nor the 5'-end of the transcript were affected by glucose in the medium. It is concluded that the cellular concentration of the 2-oxoglutarate dehydrogenase multienzyme complex (E1o and E2o) is regulated mainly at the transcriptional level.

Amino Acid Sequence↗

Cost-benefit analysis of an educational program for general practitioners by the Swedish Committee for the Prevention and Treatment of Depression.

In 1983-1984 the Swedish Committee for the Prevention and Treatment of Depression launched an educational program on the diagnosis and treatment of depressive disorders for all general practitioners on the island of Gotland. The baseline year chosen was 1982 and the immediate effects were evaluated in 1985. In 1988 the long-term effects were evaluated. These two evaluations indicated strictly time-related beneficial effects on the frequency of sick leave and inpatient care for depressive disorders, the pattern of prescription of psychopharmacologic drugs and the frequency of suicide. This article describes a cost-benefit analysis of the program. The cost of the educational program, changes in drug prescription and inpatient care were calculated as well as indirect costs concerning changes in morbidity and mortality. The calculation of the savings to society was subject to a sensitivity analysis. This shows that the educational program resulted in savings to society on the order of about SEK 155 million (USD 26 million). It is concluded that educational programs of this kind should be repeated every second to third year.

Absenteeism↗

Cost effectiveness of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for medium-sized kidney stones. A randomised clinical trial.

To evaluate percutaneous nephrolithotomy (PNL) and extracorporeal shock wave lithotripsy (ESWL) for their clinical effects, their cost effectiveness, their complication rates, and the patients' experiences, 55 consecutive patients were randomised to have one or other operation between October 1986 and October 1988. Six patients were excluded, 21 were treated with PNL and 28 with ESWL as primary treatment. Mean hospital stay and length of treatment were longer for PNL than for ESWL. Since 1 July 1987 all patients having ESWL have been treated without anaesthesia (n = 15), whereas epidural anaesthesia was used for all PNL. Slightly more of the ESWL patients experienced some pain during treatment. Minor complications or pain were more common after ESWL during the first 10 days after discharge from hospital. If patients with stone fragments of 4 mm or less were regarded as having a successful outcome, the success rates after one year were 94% for PNL and 77% for ESWL. The overall total cost was lower for ESWL than for PNL, the cost per successfully treated patient being 2172 pounds for PNL and 1810 pounds for ESWL. Medium sized kidney stones (6-30 mm, or 2-3 stones of 20 mm or less) can be efficiently and cheaply treated by both PNL and ESWL, though the cost of ESWL is lower. Even if effects other than cost (such as complications and patients' experience) are borne in mind, ESWL was superior to PNL for this group of patients.

Cost-Benefit Analysis↗

Repeated screening for carcinoma of the prostate by digital rectal examination in a randomly selected population.

Of 9,026 males aged 50-69 years, 1,494 were randomly selected and invited to participate in a programme including two screenings for carcinoma of the prostate by digital rectal examination performed in 1987 and 1990. The remaining 7,532 served as a control group. Of the selected persons, 78% accepted the invitation to the first screening round and 70% to the second one. Carcinoma of the prostate was suspected in 45 of 1,163 men examined at the first screening round and in 42 of 953 at the second round. Carcinoma was confirmed by fine-needle aspiration biopsy in 13 cases from the first and in 7 from the second round. In the study group, 17.4 carcinomas were diagnosed per 1,000 men and in the control group 8.6 per 1,000 men. The screening cost was 1,640 pounds per detected cancer and 2,343 pounds per detected and potentially cured cancer. Screening for carcinoma of the prostate by digital rectal examination can be organised with a high population acceptance, and at a reasonable cost. The impact of screening on mortality in prostatic cancer remains uncertain.

Aged↗

The effects of cimetidine on the cost of ulcer disease in Sweden.

The economic impact of the drug cimetidine on the direct and indirect costs of ulcer disease was studied. Cimetidine appeared on the Swedish market in 1978. Unlike other innovations, whose spread is normally slow during the initial period, cimetidine was introduced very swiftly and its use quickly expanded. It was expected that it would reduce the number of elective ulcer operations, with resulting savings in medical care resources exceeding the cost of the new drug. The use of cimetidine was also expected to reduce the indirect costs related to short- and long-term illness. The aims of the study were: (1) to describe and calculate the economic impact of the introduction of cimetidine; (2) to compare the retrospective calculations with the prospective calculations; and (3) to investigate how routinely collected data could serve as a complement to studies of efficacy, effectiveness, and cost-effectiveness. Retrospective calculation of the economic effects shows that cimetidine has in fact increased the direct costs of medical care. On the other hand, the drop in indirect costs due to reduced long-term absence (disability) from work, and reduced short-term absence from work, exceeded the increase in the cost of medical care. Thus, the total economic cost of peptic ulcer disease was reduced.

Absenteeism↗

Screening for carcinoma of the prostate in a randomly selected population using duplicate digital rectal examination.

Of 9,026 males, aged 50-69 years, 1,494 were randomly selected and invited to participate in a screening programme for carcinoma of the prostate. Of these 1,163 (78%) accepted. Rectal examination was performed independently by a general practitioner (GP) and by a urologist at the GP's surgery. Carcinoma of the prostate was suspected by one or both physicians in 45 cases, and subsequently confirmed by cytological investigation in 13 cases. Ten patients underwent radical prostatectomy, one received radiation treatment, one case was too advanced for curative treatment, and one was scheduled for subsequent reassessment. Screening, as a means of early diagnosis of carcinoma of the prostate by either a urologist or a GP, using digital rectal examination, thus appears to be a cost-effective procedure, though the question still remains whether this will lead to prolongation of survival or not.

Aged↗

Two nuclear proteins bind to the major positive element of the apolipoprotein B gene promoter.

The promoter of the apolipoprotein B-encoding gene (apoB) contains a number of regulatory elements, which together produce a high level of expression that is restricted to two tissues: liver and intestine. In this paper we have used the gel retardation and methylation interference assays to identify two nuclear proteins, LIT1 and LIT2, which bind to the major positive element (MPE) of the apoB promoter. LIT1 is large protein, estimated to be approx. 200 kDa by gel filtration, which binds to the apoB promoter between positions of -79 and -65 bp in relation to the transcription start point. Its binding site is identical to the region responsible for cell-specific transcriptional activation. However, whereas the MPE has no influence on expression from a heterologous promoter in the non-apoB-expressing HeLa cells, these cells still contain a DNA-binding activity indistinguishable from LIT1. LIT2 binds to the apoB promoter immediately downstream from the LIT1 site. It is present in nuclear extracts from the apoB-expressing cell lines of hepatic (HepG2) and intestinal (CaCo-2) origin, but absent from HeLa cells. CCAAT/enhancer binding protein (C/EBP), expressed in bacteria, binds to the LIT2 site and produces a methylation interference pattern indistinguishable from that of LIT2. That C/EBP binds to and activates the apoB promoter in vivo, is shown by the increased chloramphenicol acetyltransferase activity observed when HepG2 cells, transfected with apoB-promoter-cat constructs, are cotransfected with a plasmid expressing c/ebp; an effect that depends on the presence in the apoB promoter of the LIT2 site.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗