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Biomedical subjects

L J Hansen

Publications and source records attributed to L J Hansen.

At least 19 recordsLinked to original sources
PubMed2001

[Screening for alcohol overconsumption in general practice. Experiences of general practitioners with a patient questionnaire].

INTRODUCTION: We investigated to which degree a sample of 143 general practitioners in the County of Copenhagen would screen their patients for problem drinking by using The Alcohol Use Disorders Identification Test (AUDIT). Furthermore, among users of AUDIT, we aimed to describe the doctors' perception of using it. METHODS: Eighty-one out of the 143 doctors requested AUDIT. However, after they had had the possibility of using AUDIT, only 38 had handed an AUDIT to at least one patient. These 38 doctors were asked to answer a questionnaire on which this study is based. RESULTS: Thirty-two percent (12/38) of the doctors handed out an AUDIT in more than 14 days, and 21% (8/38) gave at least 100 patients an AUDIT. The general practitioners worked a median of 20 days in their practice during the study period. Only 14% (5/36) would screen all their patients in the future, and 42% (15/36) only when they suspected problem drinking. Sixty-four percent (22/34) of the doctors stated that handing all patients an AUDIT was much too time-consuming, 50% (17/34) stated that financial incentives are necessary, and 53% (18/34) questioned whether the patients wanted an AUDIT. Sixty-six percent (23/35) of the doctors judged that they had improved in detecting patients with alcohol related problems. CONCLUSION: The participating general practitioners were not interested in handing all patients an AUDIT. Major barriers were lack of time and financial incentives and furthermore the doctors questioned whether the patients wanted an AUDIT. However, half of the doctors would use AUDIT for certain patients, especially when they suspected problem drinking.

Adult↗
PubMed1999

Encouraging GPs to undertake screening and a brief intervention in order to reduce problem drinking: a randomized controlled trial.

BACKGROUND: GPs are in a key position to screen the population for problem drinking. However, so far this has not been extensively undertaken in general practice. Thus, studies relating to encouraging the undertaking in general practice of screening and initiating a brief intervention for problem drinking are needed. OBJECTIVES: We aimed to compare three approaches direct mail, telephone contact and academic detailing to encourage GPs to undertake screening and a brief intervention (SBI) for problem drinking. METHODS: A total of 143 GPs in Copenhagen County were randomly assigned to the three approaches. The outcome measures were the proportion of GPs who requested the SBI package (uptake rate) and the fraction of GPs who started using the package (utilization rate). The costs of each approach were calculated. RESULTS: Compared with the direct mailing approach, uptake rates were significantly higher among GPs approached by telephone (30 versus 72%; P = 0.0001) and in the academic detailing approach (30 versus 67%; P = 0.0006). There was no significant difference between telephone contact and academic detailing (72 versus 67%; P = 0.75). There was a higher utilization rate in the academic detailing approach than in telephone contact (61 versus 31%; P = 0.023). There was no significant difference between direct mail and telephone contact (57 versus 31%; P = 0.16) or between direct mail and academic detailing (57 versus 61%; P = 0.95). The respective costs of the telephone and academic detailing approaches were 10 and 16 times that of the direct mailing approach. CONCLUSION: Telephone contact and academic detailing are more effective than direct mail in encouraging GPs to request an SBI package, but GPs who were approached by academic detailing were more likely to have utilized the package than GPs who were approached by telephone. The relatively high uptake and utilization rates obtained in the academic detailing approach suggest that this approach is to be preferred in encouraging a rapid uptake of SBI among GPs. However, the high costs associated with this approach need to be taken into consideration.

Adult↗
PubMed1999

Prospectively detected cancer in familial breast/ovarian cancer screening.

BACKGROUND: Early diagnosis and treatment are shown to improve survival of breast and ovarian cancer. Identification and medical follow-up of high-risk groups may be important for early diagnosis. METHODS: A prospective study of 845 women from breast/ovarian- and ovarian cancer kindreds who were classified according to pre-set inclusion criteria (Table I), were offered genetic counseling and annual medical examinations of breasts and ovaries. The material consisted of three series: 1) 754 unaffected women, 2) 49 women with breast cancer, and 3) 42 women with ovarian cancer. RESULTS: In series 1) nine ovarian cancers and 20 breast cancers, in series 2) seven ovarian cancers, and in series 3) three breast cancers were found. All but one of the ovarian cancers were 40 years or older, and 4/16 (25%) were Borderline cancer. All breast cancers were 30 years or older, and 89% were detected before spread. CONCLUSIONS: This is to our knowledge the first prospective report of the combined breast/ovarian cancer findings in breast/ovarian cancer kindreds. A woman with both breast and ovarian cancer is the hallmark of inherited breast/ovarian cancer, and 50% of the ovarian cancers were detected in these families. Borderline ovarian cancer may represent a manifestation of this syndrome. If prophylactic oophorectomy prevents ovarian cancer, oophorectomy at age 45 would have prevented 75% of such cancers. Based on these results we revised our protocol for annual follow-up in these kindreds: 1) clinical breast examination and mammography (ultrasound/cytology if indicated) from 30 years of age, 2) gynecologic examination (including vaginal ultrasound, serum-CA125) from 35 years of age, and 3) discuss oophorectomy at 45 years of age.

Adolescent↗
PubMed1994

Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) inhibits the replication of human herpes viruses.

The creatine kinase/creatine phosphate (CK/CrP) system plays an important role in cellular energy homeostasis. CK isoenzymes, which reversibly generate ATP from CrP, are compartmentalized at cellular sites where energy is produced or utilized. It has been noted that the expression of CK is induced in cells infected by several DNA viruses, implicating a role for cellular energy modulation as an important step for efficient viral replication. A CK substrate analog, 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine; CCr), was tested in vitro for antiviral activity against a variety of herpes viruses and RNA viruses. Several members of the human herpes virus family were found to be sensitive to CCr, including herpes simplex types 1 and 2 (HSV-1 and HSV-2). varicella-zoster virus, and cytomegalovirus. When administered to mice infected vaginally with HSV-2, CCr significantly reduced mortality, reduced vaginal lesion scores, and lowered the titers of recoverable virus. This treatment combined with acyclovir appeared to enhance the antiviral effects of acyclovir. In a second model, mice infected intraperitoneally with HSV-2 and treated with CCr showed a significant increase in survival compared to placebo. We conclude that CCr is the first example of a new class of antiviral compounds that target the CK/CrP system.

Acyclovir↗
PubMed1993

[Benign enlargement of the thymus after chemotherapy of metastasizing testicular cancer].

A young male with retroperitoneal recurrence of a germ cell tumour was successfully treated with chemotherapy. Four months after the last treatment a CT scan revealed hyperplasia of the thymus. A year after the last treatment the CT scan shows regression. A review of the literature demonstrates that 10% of patients treated for germ cell tumours develop a benign, reversible hyperplasia of the thymus within two years after treatment. Thus, benign hyperplasia of the thymus should be considered if a patient treated for germ cell tumour develops a tumour in the anterior mediastinum within two years.

Adult↗
PubMed1993

Neuroleptic drug utilization in out-patients--a prescription database study.

1 A prescription database study was conducted to describe the out-patient utilization of neuroleptics in the Odense area (207,000 inhabitants) during a period of 1 year. 2 Neuroleptic drug use is widespread, the period prevalence being 2.45% of the population. 3 The prevalence increases with increasing age. Fifteen percent of the population aged 90 years or more received neuroleptic drugs in spite of the many warnings against side effects in the elderly. 4 Estimated daily doses of neuroleptics were considerably lower than the Defined Daily Dose, probably as a reflection of many neuroleptics being prescribed to non-psychotic patients, in whom lower doses are used. 5 For perphenazine, a comparison of estimated daily doses from this study with doses from patients whose treatment had been adjusted by plasma concentration monitoring showed that generally much lower doses were used by patients included in this study.

Adult↗
PubMed1993

Differential activation of myc gene family members in hepatic carcinogenesis by closely related hepatitis B viruses.

Woodchucks infected with woodchuck hepatitis virus (WHV) and ground squirrels infected with ground squirrel hepatitis virus (GSHV) both develop hepatocellular carcinoma (HCC), but WHV-associated tumors arise more frequently and much earlier in life. These differences are preserved when the oncogenic potentials of the two viruses are examined in the same host (woodchucks). We examined RNA and genomic DNA from tumors arising from WHV- and GSHV-infected woodchucks to determine whether these viruses use the same oncogenic pathway. N-myc RNA was not expressed in normal liver but was expressed in 10 of 13 WHV-associated HCCs examined. Southern blot analysis showed that 7 of 17 WHV-induced tumors (41%) contained rearrangements at N-myc loci due to viral genomic integration. Six of these seven inserts affected N-myc2, and most of these were at the 5' end of the gene. In contrast, only two of seven GSHV-induced woodchuck HCCs expressed N-myc RNA, and only 1 of the 16 tumors (6%) contained a rearranged N-myc allele. The GSHV-associated HCCs all contained numerous viral insertions, so the low frequency of integration into N-myc loci by GSHV was not due to a general block to integration. Four of sixteen GSHV-induced tumors harbored amplified c-myc alleles, and five of seven GSHV tumors tested contained elevated c-myc RNA levels. By contrast, enhanced c-myc RNA levels were observed in only 2 of 13 WHV-induced HCC. We conclude that N-myc overexpression is a regular feature of WHV- but not GSHV-associated hepatocarcinogenesis in a common host. In contrast, c-myc transcriptional deregulation is rarely encountered in WHV-induced HCC but is frequent in GSHV-induced HCC.

Animals↗
PubMed1992

Changes in rates of protein synthesis and eukaryotic initiation factor-4 inhibitory activity in cell-free translation systems of sea urchin eggs and early cleavage stage embryos.

The characteristics of cell-free translation systems prepared from unfertilized eggs and early cleavage stage embryos of the sea urchin, Strongylocentrotus purpuratus, closely reflect the developmentally regulated changes in protein synthesis initiation observed in vivo. Cell-free translation systems prepared over the first 0-6 h following fertilization show gradually increasing activities, mimicking the changes observed in vivo. The mechanisms underlying these increases are complex and occur at several levels. One factor contributing to the rise in protein synthetic rate is the gradual increase in eukaryotic initiation factor (eIF)-4 activity. This is correlated with the progressive inactivation of an inhibitor of eIF-4 function, which can be reactivated by in vitro manipulations. The relatively slow activation of eIF-4 follows similar kinetics to the increased utilization of maternal mRNA and ribosomes, in contrast to the rapid rise in maternal mRNA activation, and the increase in eIF-2B activity. This slow release from eIF-4 inhibition following a rapid release from eIF-2B inhibition and increased mRNA availability is reflected in the pattern of initiator tRNA binding to the small ribosomal subunit observed in cell-free translation systems. In translation systems from unfertilized eggs, initiator tRNA is unable to interact with the small ribosomal subunit, consistent with an initial block in both eIF-2B and eIF-4 activity. In translation systems from 30-min embryos, 48 S preinitiation complexes accumulate, reflecting the release from inhibition of mRNA availability and eIF-2B activity, but continued low activity of eIF-4. The accumulation of initiator tRNA in 48 S preinitiation complexes disappears gradually in translation systems from later embryos, as eIF-4 is slowly released from inhibition.

Animals↗
PubMed1992

Ty3 GAG3 and POL3 genes encode the components of intracellular particles.

Ty3 is a Saccharomyces cerevisiae retrotransposon that integrates near the transcription initiation sites of polymerase III-transcribed genes. It is distinct from the copialike Ty1 and Ty2 retrotransposons of S. cerevisiae in both the sequences of encoded proteins and gene order. It is a member of the gypsylike family of retrotransposons which resemble animal retroviruses. This study was undertaken to investigate the nucleocapsid particle of a transpositionally active gypsylike retrotransposon. Characterization of extracts from cells in which Ty3 expression was induced showed the presence of Ty3 nucleoprotein complexes, or viruslike particles, that migrated on linear sucrose gradients with a size of 156S. These particles are composed of Ty3 RNA, full-length, linear DNA, and proteins. In this study, antibodies raised against peptides predicted from the Ty3 sequence were used to identify Ty3-encoded proteins. These include the capsid (26 kDa), nucleocapsid (9 kDa), and reverse transcriptase (55 kDa) proteins. Ty3 integrase proteins of 61 and 58 kDa were identified previously (L. J. Hansen and S. B. Sandmeyer, J. Virol. 64:2599-2607, 1990). Reverse transcriptase activity associated with the particles was measured by using exogenous and endogenous primer-templates. Immunofluorescence studies of cells overexpressing Ty3 revealed cytoplasmic clusters of immunoreactive proteins. Transmission electron microscopy showed that Ty3 viruslike particles are about 50 nm in diameter. Thus, despite the unusual position specificity of Ty3 upstream of tRNA-coding regions, aspects of the Ty3 life cycle are fundamentally similar to those of retroviruses.

Amino Acid Sequence↗
PubMed1991

Increase in eukaryotic initiation factor 2B activity following fertilization reflects changes in redox potential.

One of the factors involved in the postfertilization activation of protein synthesis in the sea urchin, Strongylocentrotus purpuratus, is the activation of eIF-2B, the initiation factor responsible for guanine nucleotide exchange on eIF-2. Cell-free translation systems from unfertilized eggs are stimulated by added eIF-2B, although this dependency is rapidly lost in translation systems prepared at various times following fertilization. Cell-free translation systems prepared from unfertilized eggs show significantly lower eIF-2B activities than those prepared from 2-h embryos. However, the provision of an NADPH regeneration system significantly stimulates eIF-2B activity in egg extracts and, in addition, stimulates both binding of initiator tRNA to the small ribosomal subunit and protein synthetic activity. These data suggest that the activation of eIF-2B following fertilization reflects the fertilization-induced increase in NADPH levels.

Animals↗
PubMed1991

Significance of IgM anti-hepatitis D virus (HDV) in chronic HDV infection.

Intrahepatic hepatitis D virus (HDV) antigen (HDAg) and serum HDV RNA are excellent markers of active HDV replication but the relation of IgM anti-HDV to HDV replication and histological activity is less certain. To further elucidate the significance of serum IgM anti-HDV, 90 paired sera and liver biopsies from 64 patients seropositive for total antibody to HDV were analysed for IgM anti-HDV, intrahepatic HDAg expression, and histological inflammatory activity. IgM anti-HDV was strongly associated with intrahepatic HDAg expression with a sensitivity of 94.1% but the assay lacked specificity since 14 out of 22 cases negative for intrahepatic HDAg were also positive for IgM anti-HDV. In 20 patients in whom follow-up biopsies and paired sera were available, two patients lost intrahepatic HDAg but paired serum remained IgM anti-HDV positive. Although the presence of serum IgM anti-HDV correlated significantly with a higher histological inflammatory activity (P = 0.001), there was a considerable overlap with the group seronegative for IgM anti-HDV, again indicating a poor specificity. This lack of specificity of IgM anti-HDV for both HDV replication and histological activity indicates that this assay provides no additional information over and above assay for total antibody to HDV.

Antigens, Viral↗
PubMed1991

Handling of tubal infertility after introduction of in vitro fertilization: changes and consequences.

This study aimed at quantifying some important social and economic consequences of the altered handling of tubal infertility after the establishment of IVF treatment. The number of tubal operations was reduced by 50%. This had most important and positive implications on the availability of the operating theater for other elective operations, on the availability of hospital beds for other patient groups, and on the total duration of the certificate of illness. The calculated costs per live birth were $17,000 after tubal surgery, compared with $12,000 after IVF treatment. Life table analyses demonstrated a highly significant increased rate of deliveries after a complete IVF treatment (72.3% per patient) compared with tubal surgery (23.7%, P less than 0.001).

Adult↗
PubMed1991

Alpha 1-antitrypsin deficiency, complement activation, and chronic liver disease.

Activation of the complement system, the main humoral mediator of inflammation, is restrained by the action of enzyme inhibitors including alpha 1-antitrypsin. Deficiency leads to chronic liver disease in about one in five children with this genetic defect. Complement activation was investigated in 34 children with alpha 1 AT deficiency (12 with minimal, 10 with moderate, and 12 with severe liver disease) and in 38 sex and age matched normal children by measuring the complement parent molecules C3, C4, the C3d fragment and by calculating the C3d:C3 ratio. C3 and C4 were lower in children with severe liver disease compared with controls, indicating impairment of hepatic protein synthesis or complement consumption. The C3d activation fragment was higher in all the patient groups when compared with controls while the C3d:C3 ratio, a measure of activation independent of the concentrations of the parent molecule, was higher in patients than in controls and increased with the degree of disease severity. These results suggest that complement may have a role in the pathogenesis of the chronic liver disease associated with alpha 1AT deficiency.

Adolescent↗
PubMed1991

Expression of intrahepatic hepatitis D viral antigen in chronic hepatitis D virus infection.

To elucidate the biological importance of intrahepatic hepatitis D virus antigen, its expression was correlated with biochemical and histological inflammatory activity in 98 biopsy specimens from 68 patients seropositive for total antibody to the virus. Seventy five specimens were positive for intrahepatic nuclear antigen for HDV antigen accompanied by cytoplasmic HDV antigen in only one biopsy specimen. This group had significantly higher serum transaminase activities and inflammatory activity than the remaining cases that were negative for HDV antigen. Among the group positive for HDV antigen, there was no correlation between the proportion of hepatocytes containing HDV antigen and either serum transaminase activity or histological inflammatory indices. In 22 HDV antigen positive patients who had follow up biopsy specimens taken at a median of two years, the proportion with cirrhosis increased from 36% to 73%. Serum transaminase activities remained the same during this period, but the proportion of HDV antigen positive cells dropped. Follow up of 51 patients showed that 21 died or underwent liver transplantation within three years. The absence of an association between intrahepatic HDV antigen expression and progression of histological liver damage does not support the view that HDV is directly cytopathic to hepatocytes. Immune mediated mechanisms may have a role in the pathogenesis of chronic liver disease related to HDV infection.

Adult↗
PubMed1991

Experience with GnRH agonists in an in vitro fertilization (IVF) program.

The experience using pre-treatment with GnRH-agonists in an IVF-program are reported. 55 patients having a 'poor response', premature LH surge, or follicular luteinization in previous treatment cycles were treated for a total of 68 cycles. Therapy with GnRH agonists was initiated in the midluteal phase, and given by self-administration subcutaneously. Stimulation started with exogenous gonadotropins on a fixed day (Saturday) after pituitary desensitization had first been obtained, and resulted in all follicular punctures being performed on weekdays. Five treatment cycles (7.4%) were cancelled because of 'poor response'. Where the indication for GnRH-agonist therapy was previous 'poor response', a cancellation rate of 36.4% was observed, whereas a cancellation rate of only 1.8% was found in the other indication groups (p less than 0.001). Altogether 26 clinical pregnancies were achieved, five of these ending in a spontaneous abortion. The rate of deliveries was 33% per oocyte retrieval, and 40% per pre-embryo replacement.

Buserelin↗
PubMed1990

Optimization and simplification of culture conditions in human in vitro fertilization (IVF) and preembryo replacement by serum-free media.

The results of 220 consecutive IVF treatments are presented, comparing the use of culture media supplemented with either patient serum (Group 1; n = 110), or Medi-Cult SSR 2 synthetic serum replacement with pyruvate, and human serum albumin (HSA) (GEA BioTech, Hvidovre, Denmark) (Group 2; n = 110). In both groups the Medi-Cult Hybritest was used for routine quality testing. A significantly (P less than 0.05) increased rate of deliveries/ongoing pregnancies was observed with the Group 2 medium. However, no significant differences in fertilization rate, cleavage rate, or implantation rate were observed. It is concluded that the serum-free culture medium described and the testing for absence of cytotoxicity in a sensitive bioassay (Hybritest) have yielded culture conditions capable of sustaining the development in vitro of human preembryos without impairing the fertilization process or the implantation rate, ultimately resulting in a significantly increased rate of deliveries/ongoing pregnancies and an apparently decreased abortion rate. The potential harmful effects of serum and the need for blood sampling and preparation further increase the advantages of replacing serum with the synthetic serum replacement SSR 2 in an IVF program.

Culture Media↗
PubMed1990

Characterization of a transpositionally active Ty3 element and identification of the Ty3 integrase protein.

Ty3 is a Saccharomyces cerevisiae retrotransposon associated with tRNA genes. Two Ty3 elements have been cloned and characterized. The complete nucleotide sequence for one element, Ty3-2, was reported previously (L. J. Hansen, D. L. Chalker, and S. B. Sandmeyer, Mol. Cell. Biol. 9:5245-5256, 1988). However, this element is incapable of autonomous transposition. The complete DNA sequence of a transpositionally competent Ty3 element, Ty3-1, is presented here. Its sequence translates into two overlapping open reading frames, TYA3-1 and TYB3-1, which encode proteins with homology to the proteins specified by the retroviral gag and pol genes, respectively. Comparison of the Ty3-1 nucleotide sequence to Ty3-2 suggests that the TYB3-2 open reading frame of Ty3-2 is truncated by the deletion of a single nucleotide, which causes a frameshift mutation. Restoration of the reading frame with insertion of a single adenine by site-directed mutagenesis converted Ty3-2 into a transpositionally active element, Ty3-2(+ A). Western blot analysis with antibodies made against synthetic peptides identified integrase (IN) proteins in viruslike particle preparations from cells expressing Ty3 elements. Cells expressing Ty3-1 and Ty3-2 (+A) produce antibody-reactive proteins with approximate molecular masses of 61 and 58 kilodaltons (kDa), while cells expressing Ty3-2 produce reactive proteins of approximately 52 and 49 kDa. Together, these data show that the 61- or 58-kDa protein, or both, provides the integrase function of Ty3.

Amino Acid Sequence↗