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Biomedical subjects

M Hansen

Publications and source records attributed to M Hansen.

At least 235 records · Page 13Linked to original sources

Assembly of gag-beta-galactosidase proteins into retrovirus particles.

We studied the expression of beta-galactosidase (beta-gal) and 15 gag-beta-gal fusion proteins in the presence of Moloney murine leukemia virus wild-type core (gag) proteins. Analysis indicated that proteins retaining the amino-terminal portion of gag through the capsid protein-coding region were incorporated into retrovirus particles. Proteins which deleted portions of the capsid protein were assembled into virions at low efficiency, indicating the importance of capsid protein interactions in retrovirus assembly. Fusion proteins which retained the amino-terminal matrix protein of the gag polyprotein but which lacked the capsid protein were released efficiently from cells in a nonviral form. The nonviral form was characterized by a high sedimentation coefficient and a low density, suggestive of membrane vesicles. While beta-gal was present in the cytoplasm of expressing cells, all fusion constructs were associated with cellular membranes. gag-beta-gal proteins which were capable of release from cells demonstrated a two-component immunofluorescence staining pattern consisting of a circle of fluorescence around the nucleus and a punctate pattern of staining throughout the remainder of the cell. Interestingly, fusions within the matrix protein were trapped intracellularly and yielded distinct perinuclear staining patterns, possibly localizing to the rough endoplasmic reticulum and/or Golgi. This observation suggests that Moloney murine leukemia virus gag proteins travel to the plasma membrane by vesicular transport associated with the cytoplasmic face of intracellular vesicles.

Animals↗

Problems in cerebral blood flow calculation using xenon-133 in patients with pulmonary diseases.

We used the end-tidal concentration of xenon-133 (air curve) to estimate the profile of its arterial concentration in calculating cerebral blood flow. We examined the effects of pulmonary disease and artificial ventilation on the air curve and the calculated cerebral blood flow. We studied the relation between arterial and end-tidal xenon activities in 19 subjects, of whom 15 had pulmonary dysfunction. The t 1/2 of the declining phases of the arterial and air curves were used to express their shapes. The mean +/- SD reference t 1/2 from 15 normal volunteers was 26.8 +/- 8.4 seconds. The mean +/- SD t 1/2 s of the air and arterial curves from the 15 patients with pulmonary dysfunction were 10.4 +/- 2.9 and 33.8 +/- 10.9 seconds. The degree of pulmonary dysfunction (expressed as the pulmonary shunt percentage) correlated with distortion of the air curve. Substituting the arterial for the air curve, mean calculated cerebral blood flow (as the initial slope index) increased from 40 to 61 for the 12 patients with chronic obstructive pulmonary disease. The degree of underestimation of cerebral blood flow using the air curve correlated with the pulmonary shunt percentage. Our work confirms the problems of estimating cerebral blood flow in subjects with pulmonary dysfunction.

Adult↗

Epirubicin cardiotoxicity: a study of 135 patients with advanced breast cancer.

The cardiotoxicity of epirubicin (EPI) was evaluated clinically, radiologically, with ECG, and with multiple ECG-gated radionuclide determination of the left ventricular ejection fraction (LVEF) during rest in 135 patients with advanced breast cancer. The EPI doses were 60 mg/m2 on days 1 and 8 every 4 weeks or 45 mg/m2 plus vindesine 3 mg/m2 on the same schedule. The median cumulative dose of EPI was 500 mg/m2 (range, 47 to 1,563). Eight of the 135 patients developed congestive heart failure (CHF). Of 67 patients treated with EPI less than 500 mg/m2, none developed CHF. Among 48 patients treated with doses between 500 and 1,000 mg/m2, one had CHF (2%; 95% confidence limits, 0.1 to 11.1). Among 20 patients who received EPI from 1,000 to 1,563 mg/m2, seven developed CHF (35%; 95% confidence limits, 15.4 to 59.2). Four patients died due to cardiotoxicity. The risk of EPI cardiotoxicity at the present schedule is considerable at doses above 1,000 mg/m2. At doses between 500 and 1,000 mg/m2 the risk of CHF decreases, and at doses below 500 mg/m2, it is negligible. For all patients, the prevalence of CHF was 6% and the sensitivity of LVEF high (95%), mainly due to the low incidence of CHF. Among the 20 patients who received EPI at more than 1,000 mg/m2, the prevalence of CHF was 35% and the sensitivity only 64%. The specificity was maximally 62%. Our results suggest that LVEF is of no value as a predictor for CHF.

Adult↗

Combined high-dose carboplatin and cisplatin, and ifosfamide in previously untreated ovarian cancer patients with residual disease.

Carboplatin 200 mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3, ifosfamide 1,500 mg/m2 days 1 to 3, and mesna 900 mg/m2 days 1 to 3 every 4 weeks for six cycles were given to 37 previously untreated ovarian cancer patients with residual disease after the primary laparotomy. The median observation time was 17+ months (range, 9+ to 24+ months). Of all the patients, 81% had primary residual disease larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 36 assessable patients was 58%, PCR was 42%. Of the PCR patients, 53% had primary residual tumor larger than 5 cm. The substantial hematologic toxicity was manageable, but also the main reason for dose modifications. During treatment, 92% and 100% of the patients developed WBC and platelet nadir values corresponding to World Health Organization (WHO) grades 3 to 4. Dose-limiting encephalopathy, nephro- and neurotoxicity each occurred in 6% of the patients. The high PCR rate warrants further investigations of combined high-dose platinum and ifosfamide.

Adult↗

Gynecological abnormalities following allogeneic bone marrow transplantation.

Forty-four post-pubertal women were studied 261-4628 days after allogeneic transplantation to determine the nature and degree of gynecological abnormalities following bone marrow transplantation. Evaluations included pelvic examinations, exfoliative cytology, serum gonadotropin levels, direct preparations for micro-organisms, and microbial cultures. Pelvic abnormalities were detected in 35 of 44 (80%) women and resembled atrophic changes known to occur after ovarian failure. Findings included reduced vaginal elasticity and rugal folds, pale tissues, small vaginal, uterine and cervical size, atrophic vulvovaginitis, introital stenosis, and loss of pubic hair. Atrophic abnormalities were noted in 33 of 36 recipients of total body irradiation (TBI) compared to two of eight women not prepared with TBI (p = 0.02). Vasomotor symptoms were reported in 67% of TBI recipients compared to 38% of those not given TBI. Elevated serum gonadotropin levels suggested that TBI had caused the ovarian failure. Recognition of these gynecological abnormalities can lead to earlier hormone replacement, alleviating unnecessary discomfort and improving the well-being of the marrow transplant recipient.

Adolescent↗

[Steroid response after long-term treatment with oral N-acetylcysteine in patients with chronic obstructive bronchitis].

The significance of long-term treatment with N-acetylcystein (NAC) for the steroid response on pulmonary function and general symptoms was investigated in patients with chronic bronchitis and moderate respiratory obstruction. All of the patients had received preliminary treatment with oral NAC in a dosage of 1,200 mg daily (Mucomyst Retard) or a placebo for 22 weeks in a double-blind design. After the conclusion of the long-term treatment but before the code was revealed, 37 non-allergic patients with irreversible respiratory obstruction participated in a follow-up investigation with 30 mg prednisone daily for 14 days. The peak flow was measured twice daily and the symptoms of bronchitis were registered by completion of 13 visual analogue scales. Pulmonary function was measured by means of spirometry on days 0, 7 and 14, respectively. In both of the treated groups, slight increase in the daily registered peak flow was found but no changes in the results of spirometry or the symptoms. Comparison between the groups revealed a significantly greater increase in the evening peak flow in the group which had received preliminary treatment with NAC. It is concluded that, in this investigation, no clinically relevant effect of long-term preliminary treatment with NAC on the results of a steroid test was observed in patients with chronic bronchitis and moderate respiratory obstruction.

Acetylcysteine↗

Isoelectric focusing of apo- and holo-transcobalamin present in human blood. Identification of a protein complexing with transcobalamin.

By means of isoelectric focusing we studied the factors influencing the isoelectric point of transcobalamin. Upon binding of cobalamin, the transcobalamin isopeptides M, X and S increase their isoelectric points by 0.4 pH units. Serum protein different from gammaglobulin changes the isoelectric point of transcobalamin, but the attachment of the transcobalamin-cobalamin complex to its acceptor is unchanged. Transcobalamin bound to auto-antibodies shows a characteristic pattern upon isoelectric focusing.

Agammaglobulinemia↗

[Use of the APACHE II scoring method for registering patients receiving intensive care at a central hospital].

The APACHE II scoring method was employed prospectively for registration of patients in intensive care in a central hospital. Scoring was performed in a total of 390 patients. Seventy-three patients (20.2%) of the patients died in hospital. A significant difference in the APACHE II score was found in the surviving patients (9 points) as compared with those who died (19 points). A significant linear connection was found between the frequency of death observed and the estimated risk of death in hospital. The APACHE II score could not be correlated to the number of bed-days in the intensive care unit but to the resources employed measured as the number of therapeutic procedures carried out. The APACHE II scoring method was found to be employable in the prognosis for survival as a control of quality, as a tool for description of the degree of severity of illness and as an indirect measurement of the resources required.

Adult↗

[Secondary multiple resistance during treatment of tuberculosis].

A case of severe bilateral pulmonary tuberculosis is presented. During treatment, the patient developed resistance to a total of six drugs. The reasons were poor patient compliance and incorrect treatment. In order to avoid problems with resistant strains, it is important that the departments undertaking treatment have experience with the medicinal treatment and understanding of the problem of compliance. If it is not possible to carry out satisfactory treatment, the patient must be referred to a county hospital.

Antitubercular Agents↗

Induction and recovery characteristics of propofol, thiopental and etomidate.

Propofol, thiopental and etomidate, with 20 patients in each group, were compared for anesthesia of short duration in women undergoing termination of pregnancy, with respect to: 1: pain on injection (equally often after propofol and etomidate, but more rarely after thiopental); 2: apnea following induction (no difference); 3: involuntary muscular movements more frequent after etomidate); 4: blood pressure (larger drop after propofol); 5: heart rate (greater increase after thiopental); 6: time to eye opening on command (longer after propofol); 7: Steward score on eye opening (no difference); 8: coin counting after 15, 30 and 60 min (performance better after propofol at 15 and 30 min, producing even shorter times than preoperatively at 60 min); 9: reaction time after 15, 30 and 60 min (performance better after propofol, producing even shorter times than preoperatively at 60 min. It is concluded that the faster recovery gives propofol an advantage over thiopental and etomidate in outpatient anesthesia.

Abortion, Induced↗

Passive transfer of antiviral antibodies restricts replication of Aleutian mink disease parvovirus in vivo.

When mink kits were infected neonatally with a highly virulent strain of Aleutian disease virus (ADV), 100% of both Aleutian and non-Aleutian genotype mink died of interstitial pneumonia characterized by permissive ADV infection of alveolar type II cells. Treatment of infected kits with either mink anti-ADV gamma globulin or mouse monoclonal antibodies against ADV structural proteins reduced mortality by 50 to 75% and drastically reduced the severity of clinical signs. Interestingly, mink kits that survived the acute pulmonary disease all developed the chronic form of immune complex-mediated Aleutian disease. Thus, the antibodies directed against ADV structural proteins were capable of modulating the in vivo pathogenicity from an acute fulminant disease to a chronic immune complex-mediated disorder. The mechanism of this modulation was examined by strand-specific in situ hybridization. We found that the number of ADV-infected type II cells was the same in both untreated and antibody-treated kits. However, in the treated kits, viral replication and transcription were restricted at the cellular level. These data suggested that antibodies prevented acute viral pneumonia by restricting the intracellular level of viral replication and that the relevant antigenic determinants were contained within the viral structural proteins. The restricted levels of viral replication and transcription seen in antibody-treated mink kits resembled the levels observed in infected adult mink and suggested a role of antiviral antibodies in development of persistent infection and chronic immune complex disease.

Acute Disease↗

High-dose platinum consisting of combined carboplatin and cisplatin in previously untreated ovarian cancer patients with residual disease.

A phase II trial of carboplatin, 300 mg/m2 day 1, and cisplatin, 50 mg/m2 days 2 and 3 every 4 weeks for six cycles, was performed in 42 previously untreated patients with residual disease after primary laparotomy. Overall, 79% of patients had primary residual tumor larger than 2 cm. The overall pathologic response rate (pathologic complete response [PCR] plus partial response [PPR]) in 37 evaluable patients was 62%, and in PCRs was 22%. Of the responding patients, 78% had primary residual tumor larger than 2 cm. The toxicity was cumulative but manageable, with thrombocytopenia being the main reason for dose reduction. Dose-limiting nephrotoxicity and neurotoxicity occurred in 22% and 7% of the patients, respectively. Combined high-dose platinum as a "single agent" appears to be as active as combination chemotherapy containing cisplatin, and the treatment is feasible. Further clinical trials of this combination alone or combined with other drugs are warranted.

Adult↗

Elevated plasma concentrations of C-flanking gastrin-releasing peptide in small-cell lung cancer.

Many small-cell lung cancers (SCLCs) produce gastrin-releasing peptides (GRPs) (mammalian bombesin) but the plasma concentration of GRP is rarely elevated, possibly because of its rapid elimination. We developed a radioimmunoassay for the C-terminal flanking peptide of proGRP and measured its concentration in plasma from 71 patients with SCLC, in 27 healthy subjects and in 49 patients with other diseases including lung carcinomas. In addition, we studied the molecular size of immunoreactive C-flanking peptide in two SCLC cell lines and in plasma from SCLC patients. The concentration of immunoreactive C-flanking peptide in normal subjects and in control patients did not exceed 10 pmol/L and 26 pmol/L, whereas 72% of the SCLC patients had C-flanking peptide concentrations above 10 pmol/L. In patients with extensive disease (n = 35) the median concentration was 71 pmol/L (range, 10 to 940). ProGRP C-flanking peptide levels paralleled the clinical course in 12 patients. The molecule(s) responsible for the immunoreactivity had a molecular size of about 8 to 10 kd in both patient plasma and tumor cell lines, suggesting that the measured peptide(s) represented major fragment(s) if not the entire C-flanking peptide of proGRP. Thus this peptide(s) seems to be a useful marker for SCLC.

Biomarkers, Tumor↗

Intestinal obstruction in patients with advanced carcinoma of the ovaries treated with combination chemotherapy.

An analysis of incidence, risk factors and treatment results of intestinal obstruction caused by carcinoma of the ovaries was performed in 310 consecutive patients with carcinoma of the ovaries, The International Federation of Gynecology and Obstetrics stage IIB to IV, treated with combination chemotherapy. With a median observation time of 46 months, the incidence was 14 per cent and the cumulated risk was estimated to be 26 per cent at five years after treatment was begun. Risk factors were stages IIIB and IV, residual primary tumor size greater than 2 centimeters and presence of intestinal carcinomatosis at primary laparotomy. There was no difference in the survival time between 16 conservatively treated patients and 25 surgically treated patients (a median of 30 and 68 days, respectively, p greater than 0.30). The complication risk of surgical treatment was high (64 per cent), and surgical benefit--defined as survival greater than 60 days with total palliation of intestinal symptoms--was achieved in only 32 per cent.

Adult↗

Clonidine-induced immune complex disease.

We report upon a 46-year-old woman, who developed immune complex disease after treatment with clonidine for one year. The diagnosis was verified with histological demonstration of IgG and IgM complexes as well as complement C1q, C3c and C4 between muscle fibres and at the dermo-epidermal junctions. The patient's symptoms abated and the abnormal results of blood tests reverted to normal following cessation of clonidine therapy.

Clonidine↗

Improving your written communications.

Writing letters and memos is a required task--welcome or not--of any administrator, and competition is fierce for an audience's attention and time. The authors offer a guide for improving organization of written messages through a time-saving technique called mapping and improving the message's style and tone through application of advice from the experts on writing clearly and concisely.

Correspondence as Topic↗