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Biomedical subjects

M Hansen

Publications and source records attributed to M Hansen.

At least 181 records · Page 10Linked to original sources

The insulin-like growth factor axis and collagen turnover during prednisolone treatment.

Serum concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), the carboxyterminal propeptide of type I collagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied in 10 prepubertal children with asthma (mean age 9.0 years). The children were treated with 2.5 and 5.0 mg/day prednisolone in a randomised double blind crossover trial with run in, treatment, and washout periods of two weeks. No statistically significant effects on serum concentrations of IGF-I and IGFBP-3 were found. Dose related reductions of PICP, ICTP, and PIIINP were observed: the mean (SEM) reduction in PICP was 33.4 (26.3) and 68.4 (20.6) micrograms/l, in ICTP 2.5 (0.5) and 2.9 (0.6) micrograms/l, and in PIIINP 2.1 (0.7) and 3.1 (1.8) micrograms/l during the 2.5 and 5.0 mg prednisolone periods respectively. Short term treatment with low daily doses of prednisolone is associated with suppression of serum markers of type I and III collagen turnover in children with asthma. Intermediate and long term effects remain to be studied.

Asthma↗

Acute interstitial pneumonia in mink kits inoculated with defined isolates of Aleutian mink disease parvovirus.

The present study addressed the causal role of Aleutian mink disease parvovirus (ADV) in acute interstitial pneumonia in mink kits. All the examined isolates of ADV caused interstitial pneumonia in newborn kits, although the severity of disease and the mortality varied. These findings indicate that ADV is the direct causal agent of this disease in mink kits and that cofactors, which could have been present in the original ADV-K isolate, do not play a role. Acute interstitial pneumonia characterized by hypertrophy and hyperplasia of alveolar type II cells, intranuclear viral inclusions, interstitial edema, and hyaline membrane formation was experimentally reproduced in mink kits infected as newborns with five different isolates of ADV. Four hundred forty-nine newborn mink kits were included in the study, of which 247 were necropsied. The lesions caused by the different isolates were indistinguishable by histopathologic examination, but the incidence (50-100%) and severity (mortality of 30-100%, n = 218) of disease among the mink kits varied. Also, the content of ADV antigens in the lungs of infected kits varied among the groups. According to these features, the examined isolates could be placed in groups of high and low virulence. ADV-K, ADV-Utah I, and ADV-DK were in a highly virulent group producing a mortality of 90-100% (n = 110) in mink inoculated as newborns. ADV-GL and ADV-Pullman belonged to a group of low virulence, with an incidence of clinical disease of 50-70% and a mortality of approximately 30-50% (n = 118) in kits inoculated as newborns. The mortality in the control group receiving a mock inoculum was around 12% (n = 34). The period from infection to development of fatal disease varied from approximately 12 days for the highly virulent isolates up to around 20 days for the isolates of low virulence. The 107 mink kits that survived inoculation with ADV as newborns developed lesions typical of classical Aleutian disease irrespective of the ADV isolate used. The lesions consisted of chronic immune complex-mediated glomerulonephritis and infiltrations with mononuclear cells, including plasma cells in lung, liver, spleen, kidney, mesenteric lymph node, and intestine. Surviving kits also had hypertrophy of the bronchus-associated lymphoid tissue and focal subpleural, intraalveolar accumulations of large cells with foamy cytoplasm, so-called lipid pneumonia.

Acute Disease↗

A sensitive immunoblotting technique for the serodiagnosis of Brucella ovis infections.

A simplified electrophoretic immunoblotting technique based on antigen extracted from Brucella ovis cells with sodium dodecyl sulfate/mercaptoethanol was compared with the complement fixation test (CFT), the enzyme-linked immunosorbent assay, and the gel diffusion test. Sera from 89 chronically infected, semen culture-positive rams, 378 sera from B. ovis-infected flocks, 300 sera from accredited disease-free flocks, and 29 sera from specific-pathogen-free sheep were used. The immunoblotting technique had sensitivity and specificity comparable to those of the standard tests and was able to identify several CFT-negative or -borderline sera as positive. The major immunoreactive antigens of B. ovis had molecular masses of 63, 29, 19 kD (proteins) and 8-12 kD (rough lipopolysaccharide). Antibodies against these antigens were present in 96% of CFT-positive sera from infected flocks and in 100% of sera from semen culture-positive rams. However, immunoblotting also identified antibodies to components other than the major antigens in 1% of CFT-negative sera from infected flocks and in 7.7% of the sera from flocks with a history of freedom from the disease. These reactions probably represent cross-reactivities with other microorganisms and were distinguishable from truly positive reactions.

Animals↗

How to diagnose cobalamin deficiency.

Cobalamin deficiency must be suspected in all patients with unexplained neuropsychiatric symptoms or unexplained anemia. Special attention should be paid to patients at risk of developing cobalamin deficiency such as elderly people, vegetarians, HIV-infected patients, patients with gastrointestinal diseases and patients with autoimmunity or a family history of pernicious anemia. The assays aimed to answer the question: does this patient suffer from cobalamin deficiency, include analysis of P--cobalamins and analyses of the metabolites that accumulate upon cellular cobalamin deficiency, P--methylmalonate and P--homocysteine. P--cobalamins or especially a fraction of P--cobalamins, P--TC cobalamins are markers for latent cobalamin deficiency. An increased concentration of P--methylmalonate that decreases upon injection of cobalamin indicates overt metabolic cobalamin deficiency. The same holds for P--homocysteine but this analysis is less specific than P--methylmalonate. We suggest that either assay of P--cobalamins or P--methylmalonate is employed as screening test for cobalamin deficiency, and that further tests are performed only if the initial test in combination with the clinical picture gives an unclear answer. Once cobalamin deficiency has been diagnosed, the cause for the deficiency should be sought and the patient should be treated for life. Cobalamin absorption tests such as the Schilling test are considered of limited use. Gastric atrophy is likely to be present in patients with increased P--gastrin or decreased P--pepsinogen A. However, this condition can be diagnosed also by upper gastrointestinal endoscopy.

Gastrins↗

Frontal plagiocephaly. Diagnosis and treatment.

Plagiocephaly is the term loosely applied to frontal or posterior cranial asymmetry. Deformational plagiocephaly is the most common form. Synostotic frontal plagiocephaly is usually sporadic, but can be syndromic or familial. These two major categories of plagiocephaly are distinguishable by physical findings. Deformational plagiocephaly tends to self-correct during infancy; this process can be ameliorated by conservative measures. Synostotic frontal plagiocephaly requires surgical correction during infancy.

Congenital Abnormalities↗

[Computerized tomography in diagnosis of lung metastases: improvement with the spiral technique].

Computed tomography is the imaging modality of choice for detection or exclusion of pulmonary metastases. In most cases these are spheric, multiple, bilateral, and located in the peripheral areas of the middle and lower fields of the lungs. Differential diagnosis of solitary pulmonary nodules is difficult. Evaluating whether they are malignant or benign is insufficient despite the application of multiple CT criteria. Spiral computed tomography acquiring an imaging volume in a breathhold has led to significant improvement in the sensitivity of detecting pulmonary nodules. Imaging protocols are presented, and the influence of the different parameters is discussed. Although not all pulmonary metastases may be detected with spiral computed tomography, it is the most important examination when considering pulmonary metastasectomy. Computed tomography is the imaging modality of choice when monitoring pulmonary metastases during systemic therapeutic regimens by measuring all nodules or "indicator lesions."

Diagnosis, Differential↗

Concordance between parental origin of chromosome 13q loss and chromosome 6p duplication in sporadic retinoblastoma.

Two hypotheses are capable of explaining nonrandom loss of one parent's alleles at tumor suppressor loci in sporadic cases of several pediatric cancers, including retinoblastoma--namely, preferential germ-line mutation or chromosome imprinting. We have examined 74 cases of sporadic retinoblastoma for tumors in which at least two genetic events--loss of heterozygosity for chromosome 13q markers and formation of an isochromosome 6p--have occurred. Sixteen cases were found to contain both events. In 13 of 16 such tumors, the chromosomes 13q that were lost and chromosomes 6p that were duplicated are derived from the same parent. These data may be explained within the framework of the genome imprinting model but are not predicted by preferential germ-line mutation.

Chromosome Deletion↗

[Purulent meningitis among adults in the county of Frederiksborg. Therapeutic results in the period 1 January 1980--31 December 1990].

A review of 158 cases of bacterial meningitis and meningococcal sepsis in adults is presented. The patients were admitted during a 11-year period, from 1980-1990. The incidence was 5.5/100,000 adults per year, which is high. The area had epidemics of meningococcal disease in the years 1987 and 1989. The bacterial agent was meningococci in 40.5%, pneumococci in 21.5% and unknown in 27.2%. The overall lethality was 13.9%, highest (26%) in patients who were infected by pneumococci. The meningococcal relative lethality was 14%. In the period of high meningococcal incidence 1986-1989, we found a relative lethality of 17%. The overall local hospital lethality was 18.3%, which has to be compared with 11.2% among patients primarily admitted to the County hospital. The lethality among patients who underwent emergency transfer from one of the local hospitals to the County hospital was 20%, which is as high as in the group of patients treated locally. Neither of these trends lethality are statistically significant at the level of 5%, tested by chi square tests.

Adolescent↗

Structure of the altromycin B (N7-guanine)-DNA adduct. A proposed prototypic DNA adduct structure for the pluramycin antitumor antibiotics.

Altromycin B belongs to the pluramycin family of antitumor antibiotics, which also includes kidamycin, hedamycin, pluramycin, neopluramycin, DC92-B, and rubiflavin A. These potent antitumor compounds react with DNA in as yet imprecisely determined ways. In the present investigation, we have used gel electrophoresis methods in combination with nuclear magnetic resonance and mass spectrometry to determine the structure of the altromycin B-DNA adduct. High-resolution gel electrophoresis demonstrated that guanine was the reactive base, and N7 was implicated from experiments in which N7-deazaguanine was used in place of guanine in a strand breakage assay. Experiments using supercoiled DNA demonstrated that altromycin B and related drugs intercalated into DNA, which implicated this as a common mechanism for binding of the pluramycin antibiotics to DNA. The altromycin B-guanine adduct was isolated from calf thymus DNA after thermal depurination of the alkylated DNA. Mass spectrometry confirmed that altromycin alkylated DNA through guanine, and 1H- and 13C-NMR was used to confirm the covalent linkage sites between altromycin B and guanine. On the basis of these results, we propose that altromycin B first intercalates into DNA via a threading mechanism, reminiscent of nogalamycin, to insert the disaccharide into the minor groove and position the epoxide in the major groove in proximity to N7 of guanine. Nucleophilic attack from N7 of guanine leads to an acid-catalyzed opening of the epoxide, resulting in the altromycin B-DNA adduct. On the basis of these results, a general mechanism for the interaction of the pluramycin family of antibiotics with DNA is proposed.

Alkylation↗

New cytostatic drugs in ovarian cancer.

BACKGROUND: Many ovarian cancer patients will after treatment of the recurrence with cisplatin based therapy enter phase I or II studies with new drugs. Lately, some new agents have shown activity. MATERIALS AND METHODS: The review is based on phase II studies mainly and focuses on paclitaxel (taxol). RESULTS: A Canadian/European study of high (175 mg/m2) versus low dose (135 mg/m2), and short (3 hours) versus long (24 hours) infusion confirms the reported activity of paclitaxel in previously treated patients. The preliminary overall response rate in 286 evaluable patients is 18.5%. A dose effect exists regarding neuropathy and neutropenia, and a longer infusion duration results in a higher frequency of grade 4 neutropenia. In a phase III study comparing cisplatin 75 mg/m2 plus cyclophosphamide (750 mg/m2) or plus paclitaxel 135 mg/m2 over 24 hours, the paclitaxel-based combination gave a superior response rate (54% versus 33%) and statistically significant longer progression-free interval. The semisynthetic docetaxel (taxotere) gives an overall response rate of 32% (95% confidence interval 23%-43%). Skin toxicity and edema are dose-limiting factors. Gemcitabine has also shown activity in platinum-resistant patients with an overall response rate of 23% (95% CI 10%-40%). CONCLUSIONS: The role of new drugs in first-line therapy remains to be seen. Further development of experimental work for screening and evaluation of new agents is needed.

Antimetabolites, Antineoplastic↗

Second-look laparotomy in the management of patients after radical surgery for ovarian cancer.

BACKGROUND: Radically excised ovarian cancers present an unsolved problem with regard to the value of routine second-look operation. This study presents the outcome of second-look operations in an effort to help elucidate this problem. PATIENTS AND METHODS: Twenty-eight patients who underwent radical surgery for ovarian cancer stage IC-IIIA were given adjuvant chemotherapy with cyclophosphamide 500 mg/m2 i.v., adriamycin 40 mg/m2 i.v. and 5-fluorouracil 500 mg/m2 i.v., all administered on days 1 and 8 every 4 weeks until achievement of a cumulative adriamycin dose of 400 mg/m2. It was planned that second-look laparotomy would be performed 10-12 months after the primary operation. RESULTS: Four of 28 patients (14.3%) had positive findings at second-look laparotomy. Two of these 4 patients had only microscopic disease, and after second-line chemotherapy including cisplatin one of them is clinically free of tumor 50 months after the primary operation. Two of 28 patients had clinical recurrences before the planned second-look operation. Four of the 22 patients (18.2%) with negative second-look operations developed recurrent disease within a median time of 12 months later. The 5-year survival rate for all 28 patients was 67%. CONCLUSION: Although a small group of patients may benefit from a strategy that includes delayed second-look operation, we conclude that this should not be a routine procedure in the management of patients who undergo radical surgery for ovarian cancer.

Adult↗

Saccadic eye movements as a measure of the effect of low vision rehabilitation on reading rate.

We assessed saccadic eye movements and reading capabilities in individuals with macular disease by a masked clinical study to determine whether changes in saccadic frequency were correlated to changes in reading rates or number of errors for a reading task. We used a measure of eye movement characteristics in the form of a saccadic frequency score (SFS). Twelve subjects with macular disease were tested before and after an intense 6-week inpatient vision rehabilitation program. The mean age was 70.9 years (63 to 77 years). Mean visual acuity was 10/100 (10/40 to 10/200). Mean reading rates at entry and discharge were 8.5 words/min and 20.9 words/min, respectively (p = 0.02). SFS improved from 2.709 to 2.022 (p = 0.07). Reading errors improved from 5.60 to 4.00 (p = 0.03). Reading rates and SFS's were highly inversely correlated both pre- and post-treatment (Pearson r = -0.892 and -0.896, respectively). SFS and the number of reading errors were highly correlated with both pre- and post-treatment as well (Pearson r = 0.782 and 0.601, respectively). Interestingly the data appeared to cluster into two groups, one showing improvement and the other showing none. Cluster analysis revealed a strong association among reading rate, saccade scores, and reading errors. Membership in the two clusters is consistent pre- and post-rehabilitation in all but one case. Clustering is most evident for reading rate and reading errors and less so for saccade scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Assembly and composition of intracellular particles formed by Moloney murine leukemia virus.

Assembly of type C retroviruses such as Moloney murine leukemia virus (M-MuLV) ordinarily occurs at the plasma membranes of infected cells and absolutely requires the particle core precursor protein, Pr65gag. Previously we have shown that Pr65gag is membrane associated and that at least a portion of intracellular Pr65gag protein appears to be routed to the plasma membrane by a vesicular transport pathway. Here we show that intracellular particle formation can occur in M-MuLV-infected cells. M-MuLV immature particles were observed by electron microscopy budding into and within rough endoplasmic reticulum, Golgi, and vacuolar compartments. Biochemical fractionation studies indicated that intracellular Pr65gag was present in nonionic detergent-resistant complexes of greater than 150S. Additionally, viral RNA and polymerase functions appeared to be associated with intracellular particles, as were Gag-beta-galactosidase fusion proteins which have the capacity to be incorporated into virions. Immature intracellular particles in postnuclear lysates could be proteolytically processed in vitro to mature forms, while extracellular immature M-MuLV particles remained immature as long as 10 h during incubations. The occurrence of M-MuLV-derived intracellular particles demonstrates that Pr65gag can associate with intracellular membranes and indicates that if a plasma membrane Pr65gag receptor exists, it also can be found in other membrane compartments. These results support the hypothesis that intracellular particles may serve as a virus reservoir during in vivo infections.

3T3 Cells↗

Effect of 8 wk of bicycle training on the immune system of patients with rheumatoid arthritis.

The effect of 8 wk of progressive bicycle training on the immune system was evaluated in a controlled study on 18 patients with rheumatoid arthritis and moderate disease activity. Maximal O2 uptake increased significantly, whereas heart rate at stage 2 and rate of perceived exertion decreased significantly, in the training group compared with the controls. Resting levels of a number of immune parameters were measured before and after 4 and 8 wk of training. Training did not induce changes in blood mononuclear cell subpopulations, proliferative response, or natural killer cell activity. Furthermore the plasma concentrations of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 did not change in response to training. It is concluded that 8 wk of bicycle training does not influence the immune system of patients with rheumatoid arthritis.

Aged↗