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Biomedical subjects

H Hansen

Publications and source records attributed to H Hansen.

At least 109 records · Page 6Linked to original sources
PubMed1993

Phase I and pharmacokinetics study of topotecan, a new topoisomerase I inhibitor.

PURPOSE: A phase I study with topotecan (SKF 104864-A, NSC 609699), a semisynthetic analog of camptothecin, was performed using a daily-times-5 regimen, given i.v. q 3 weeks, to evaluate the pharmacokinetics and toxicities of the compound. PATIENTS AND METHODS: Patients with a histologically confirmed diagnosis of a solid tumor no longer amenable to established forms of treatment were eligible for the study. Topotecan was given as a 30 min. infusion daily on 5 successive days, repeated every three weeks. In subsequent patient cohorts the dose was escalated from 0.5 to 1.5 mg/m2/day. Weekly evaluations included hematology and biochemistry. Response to treatment was assessed every 2 cycles. Pharmacokinetics were performed using a HPLC method. RESULTS: Forty-eight patients were entered. The maximal tolerated dose was 1.5 mg/m2/day. The dose limiting toxicity was leucocytopenia. Other major toxicities were alopecia and moderate nausea/vomiting. Partial remissions were observed in one patient with pretreated small-cell lung cancer, one with non-small-cell lung cancer and one with no-pretreated pancreatic cancer, lasting 130-240 days. Pharmacokinetics showed a t 1/2 (alpha) of 8.1 +/- 7.6 min., t 1/2 (beta) of 132 +/- 48 min., Vd,ss 72.7 +/- 26.9 L/m2 and Cltot of 0.57 +/- 0.16 L/min/m2. CONCLUSION: Topotecan is an interesting new topoisomerase I inhibitor exerting antitumor activity in this phase I trial. Leucocytopenia is dose-limiting. The recommended dose for phase II studies is 1.5 mg/m2/day for 5 consecutive days every 3 weeks.

Adult↗
PubMed1993

The increase of yellow skin colour beyond that of serum bilirubin: a proposed indicator of risk for bilirubin encephalopathy in the newborn.

Forty-seven newborn infants with 1 min Apgar score < 7 were studied. On the third postnatal day the following measurements were made: yellow skin colour, serum bilirubin concentration, reserve albumin concentration and plasma pH. Given the bilirubin concentration and the regression curve between the yellow skin colour and the bilirubin concentration, delta-TcB was calculated as the difference between measured yellow skin colour and the expected yellow skin colour. There was a negative correlation between delta-TcB and Apgar score (P = 0.003), pH (P = 0.026) and reserve albumin concentration (P = 0.045). Fourteen of the included newborns had central nervous system symptoms in the days just following birth. A tendency towards higher delta-TcB was noted in this group (P = 0.08). The results suggest that further study of delta-TcB determination as a tool in the assessment of the icteric newborn infant is justified.

Apgar Score↗
PubMed1993

Yeast phenotype classifies mammalian protein kinase C cDNA mutants.

The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of eukaryotic cellular signals. Molecular dissection of their mechanisms of action has been limited in part by the lack of random mutagenesis approaches and by the complexity of signaling pathways in mammalian cells which involve multiple PKC isoforms. Here we present a rapid screen which permits the quantification of mammalian PKC activity phenotypically in the yeast Saccharomyces cerevisiae. Bovine PKC alpha cDNA is functionally expressed in S. cerevisiae. This results in a phorbol ester response: a fourfold increase in the cell doubling time and a substantial decrease in yeast colony size on agar plates. We have expressed pools of bovine PKC alpha cDNAs mutagenized by Bal 31 deletion of internal, amino-terminal, or carboxyl-terminal sequences and have identified three classes of mutants on the basis of their distinct yeast phenotypes. Representatives of each class were analyzed. An internal deletion of amino acids (aa) 172 to 225 displayed ligand-dependent but reduced catalytic activity, an amino-terminal truncation of aa 1 to 153 displayed elevated and ligand-independent activity, and a carboxyl-terminal 26-aa truncation (aa 647 to 672) lacked activity under any conditions. Additional mutations confirmed the distinct functional characteristics of these classes. Our data show that deletion of the V1 and C1 regions results in elevated basal catalytic activity which is still Ca2+ responsive. Internal deletions in the V2 and C2 regions do not abolish phorbol ester or Ca2+ regulation of PKC activity, suggesting that most of the C2 domain is not essential for phorbol ester stimulation and most of the regulatory domain is dispensable for Ca2+ regulation of PKC activity. These distinct activities od the PKC mutants correlate with a specific and proportional yeast phenotype and are quantified on agar plates by yeast colony size. This provides a phenotypic screen which is suitable to identity rare, randomly altered but active mammalian PKC mutants. It quantifies their catalytic and biological activities in response to PKC activators or inhibitors for a systematic mapping of PKC structure and function or PKC-drug interaction.

Animals↗
PubMed1992

[Ondine's syndrome (alveolar hypoventilation)].

Ondine's syndrome is a rare condition characterised by alveolar hypoventilation during sleep on account of an abnormality in the automatic control of respiration. The respiration centre does not react adequately to the carbon dioxide tension in the blood required to maintain normal ventilation. We present a description of the course in an infant with congenital Ondine's syndrome because a therapeutic possibility is now available, viz, implantation of a phrenic nerve pacemaker. The infants showed respiratory insufficiency shortly after delivery. This disappeared on tactile stimulation. The infant had generalised hypotonia with absent patellar reflexes and weak sucking reflexes and, at the age of one week, seizures developed. The infant was treated with assisted ventilation but this could be reduced to use only during the period when the infant slept. The infant was in good health with normal psychomotor development until the age of two years. Plans had been made to implant a phrenic nerve pacemaker. Unfortunately, the infant developed Syncytial-virus pneumonia complicated by bacterial superinfection and developed severe anoxic brain damage which subsequently proved fatal.

Child, Preschool↗
PubMed1992

Stomach cancer patterns in European immigrants to Connecticut, United States.

Age-adjusted annual incidence rates of stomach cancer (ICD-9 code #151) were examined for the period 1973-88 among Connecticut residents who were born in the United States or who emigrated from one of five European nations (Italy, Poland, the United Kingdom, Germany, Portugal). Risk of stomach cancer among each of the five immigrant groups was elevated significantly above that of US-born residents. The magnitude of difference ranged from a 1.62-fold excess among persons born in Italy to a 4.27-fold increase in risk among persons born in Portugal. Cancer risk to foreign-born residents was less than that observed in their native countries, with decreases of 25-64 percent found here. Several differences in patient and disease characteristics were observed according to country of birth. Compared with US-born residents, there was a lesser predominance of males among patients born in Italy, Poland, and the UK. Among all foreign-born groups, the gastric cardia was involved less frequently, and the pyloric region more frequently, than in US-born patients. Adenocarcinomas were significantly less common among Polish-born cases. The findings suggest different etiologies in foreign and US-born patients.

Adolescent↗
PubMed1992

Targeting sequences of the two major peroxisomal proteins in the methylotrophic yeast Hansenula polymorpha.

Dihydroxyacetone synthase (DAS) and methanol oxidase (MOX) are the major enzyme constituents of the peroxisomal matrix in the methylotrophic yeast Hansenula polymorpha when grown on methanol as a sole carbon source. In order to characterize their topogenic signals the localization of truncated polypeptides and hybrid proteins was analysed in transformed yeast cells by subcellular fractionation and electron microscopy. The C-terminal part of DAS, when fused to the bacterial beta-lactamase or mouse dihydrofolate reductase, directed these hybrid polypeptides to the peroxisome compartment. The targeting signal was further delimited to the extreme C-terminus, comprising the sequence N-K-L-COOH, similar to the recently identified and widely distributed peroxisomal targeting signal (PTS) S-K-L-COOH in firefly luciferase. By an identical approach, the extreme C-terminus of MOX, comprising the tripeptide A-R-F-COOH, was shown to be the PTS of this protein. Furthermore, on fusion of a C-terminal sequence from firefly luciferase including the PTS, beta-lactamase was also imported into the peroxisomes of H. polymorpha. We conclude that, besides the conserved PTS (or described variants), other amino acid sequences with this function have evolved in nature.

Alcohol Oxidoreductases↗
PubMed1992

Chemical and radiological risk factors associated with waste from energy production.

We have tried to estimate the toxic potential of waste from nuclear power plants and from power plants burning fossil fuels. The potential risks have been expressed as 'risk potentials' or 'person equivalents.' These are purely theoretical units and represent only an attempt to quantify the potential impact of different sources and substances on human health. Existing concentration limits for effects on human health are used. The philosophy behind establishing limits for several carcinogenic chemicals is based on a linear dose-effect curve. That is, no lower concentration of no effect exists and one has to accept a certain small risk by accepting the concentration limit. This is in line with the establishment of limits for radiation. Waste products from coal combustion have the highest potential risk among the fossil fuel alternatives. The highest risk is caused by metals, and the fly ash represents the effluent stream giving the largest contribution to the potential risk. The waste from nuclear power production has a lower potential risk than coal if today's limit values re used. If one adjusts the limits for radiation dose and the concentration limit values so that a similar risk is accepted by the limits, nuclear waste seems to have a much higher potential risk than waste from fossil fuel. The possibility that such risk estimates may be used as arguments for safe storage of the different types of waste is discussed. In order to obtain the actual risk from the potential risk, the dispersion of the waste in the environment and its uptake and effects in man have to be taken into account.

Environmental Pollution↗
PubMed1992

Natural radiation--a perspective to radiological risk factors of nuclear energy production.

Radiation doses from natural radiation and from man-made modifications on natural radiation, and different natural radiological environments in the Nodic countries are summarized and used as a perspective for the radiological consequences of nuclear energy production. The significance of different radiation sources can be judged against the total collective effective dose equivalent from natural radiation in the Nordic countries, 92,000 manSv per year. The collective dose from nuclear energy production during normal operation is estimated to 20 manSv per year and from non-nuclear energy production to 80 manSv per year. The increase in collective dose due to the conservation of heating energy in Nordic dwellings is estimated to 23,000 manSv per year, from 1973 to 1984. An indirect radiological danger index is defined in order to be able to compare the significance of estimated future releases of radionuclides from a final repository of spent nuclear fuel to the consequences of natural radionuclides in different environments. The danger index of natural radiological environments will not be significantly increased by future releases of nuclear fuel radionuclides.

Hot Temperature↗
PubMed1992

Diagnostic problems with meningococcal disease in general practice.

Based on general practitioners' referral letters and hospital records, we made a retrospective analysis of a cohort of 177 consecutive cases of meningococcal disease that occurred during a period of 10 years in the County of North Jutland, Denmark. The analysis concerned diagnostic problems in general practice, prognosis, pre-hospital antibiotic treatment and its effect on subsequent cultures, and degree of obligatory notification. The referring doctor suspected meningococcal disease/central nervous infection in 123 patients (69.5%). Neck stiffness and petechiae were related to a correct referral diagnosis, in contrast to the occurrence of a non-petechial rash. The presence of disseminated intravascular coagulation was associated with the mortality rate, which was 0.062. The therapeutic recommendations of the Danish Health Authorities were followed in only 25 of the 98 patients who fulfilled the criteria for pre-hospital parenteral antibiotic treatment. Pre-hospital antibiotic treatment was related to negative culture of spinal fluid or blood. Seven of the 177 patients were not notified according to the rules. Difficulties in pre-hospital diagnosis seem not to influence the lethal course of the disease.

Adolescent↗
PubMed1992

Importance of the first day death rate in infant mortality.

The conventional partition of infant mortality into neonatal and postneonatal deaths, with the 28th day postpartum as the dividing line, has lost much of its epidemiological rationale in countries with low infant death rates. Infant deaths are concentrated increasingly at the start of the neonatal period: one out of three infant deaths in the United States occurs during the first 24 hours. Circumstances of early neonatal deaths differ considerably from those of later neonatal deaths. Failure to monitor separately early and late neonatal mortality can compromise the recognition of distinct epidemiological patterns. Racial disparities in the US tend to be larger for first day deaths than for any other infant deaths. Total US infant mortality declined rapidly in the 1950s and 1960s but first day deaths rose at a steady pace. Surveillance of infant mortality, whether on the national or the community level, should encompass first day, first month and first year death rates.

Ethnicity↗
PubMed1992

The Nordic concept of reactive psychosis--a multicenter reliability study.

Reactive psychosis is a common diagnosis in the Nordic countries (Norway, Sweden, Denmark, Finland and Iceland) and in several other parts of the world. In ICD-9 and DSM-III-R, the concept is defined more narrowly than in the Nordic tradition. In this study we examined the interrater reliability of the Nordic concept by the case-summary method between clinicians from 9 university departments in the Nordic countries. The results show that Nordic psychiatrists have a reasonably reliable concept of reactive psychosis, and that this psychosis can be diagnosed as reliably as schizophrenia and affective psychosis.

Affective Disorders, Psychotic↗
PubMed1992

Low-dose aspirin in primigravidae with positive roll-over test.

In a prospective, randomized, double-blind study for the prevention of pregnancy-induced hypertension and preeclampsia, 41 primigravidae with positive roll-over test (28th-32nd week of pregnancy) received 80 mg aspirin/day or placebo until the end of the 37th week. In the patients treated with acetylsalicylic acid (n = 22), 3 cases of proteinuria occurred, but no hypertensive pregnancy complication. In the placebo group (n = 19), 10 patients developed pregnancy-induced hypertension (6 of them preeclampsia). Group-specific differences concerning the occurrence of hypertension were statistically highly significant (p = 0.0004). No relevant differences were observed with regard to pregnancy duration, birth weight and umbilical artery pH value. The placebo group included 1 intrauterine death. No increased tendency to maternal or fetal bleeding was noticed.

Aspirin↗
PubMed1992

Quantification of regional myocardial blood flow using 13N-ammonia and reoriented dynamic positron emission tomographic imaging.

BACKGROUND: Regional myocardial blood flow has been quantified using transaxial positron emission tomographic (PET) imaging and tracer kinetic modeling. However, the use of transaxial images limits the accuracy of regional partial volume corrections and the localization of the quantified regional flow values. The purpose of the present study was to overcome both problems by calculating regional flows from reoriented short-axis PET images. METHODS AND RESULTS: Twelve experiments were performed in four dogs. 13N-ammonia was injected intravenously while microspheres were administered into the left atrium during baseline, hyperemic, and low-flow conditions. Serial transaxial frames were acquired with a 15-plane PET scanner and reoriented into short-axis frames. The arterial input function and eight regional myocardial tissue activity curves were derived from the reoriented frames. The arterial input functions were corrected for ammonia metabolites, and the myocardial tissue curves were corrected for spillover of activity, partial volume effects, and heterogeneities in the image's spatial resolution introduced during reorientation. Corrections for regional partial volume were based on estimates of the regional myocardial activity thickness derived from reoriented diastolic images of the heart. The myocardial 13N-ammonia kinetics were described with a two-pool compartmental model. Values of regional myocardial blood flow by PET correlated linearly with those by microspheres (slope, 0.94; y intercept, 0.06 ml/min/g; r = 0.93) over a wide range of flows. CONCLUSIONS: Regional myocardial blood flow can be measured accurately and noninvasively from serially acquired and reoriented short-axis 13N-ammonia images, thus overcoming limitations inherent to the use of transaxially acquired images and permitting a more complete evaluation of regional blood flows throughout the left ventricular myocardium.

Ammonia↗