Matrix Metalloproteinase Mediated Type I Collagen Degradation - An Independent Risk Factor for Mortality in Women.

Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major role in this matter. C1M is a biomarker measuring type I collagen degradation fragments in blood. The aim of the current study was to investigate whether MMP mediated type I collagen degradation (C1M) was predictive of mortality in a large prospective cohort of Danish women aged 48-89 (n = 5855). Subjects with high serum C1M showed significant increased mortality. The adjusted three year HR was 2.02 [95% CI: 1.48-2.76] for all-cause mortality, 2.32 [95% CI: 1.51-3.56] for cancer and 1.77 [95% CI: 0.98-3.17] for cardiovascular diseases. The adjusted nine year HR was 1.50 [95% CI: 1.28-1.75] for all-cause mortality, 1.49 [95% CI: 1.16-1.90] for cancer and 1.69 [95% CI: 1.27-2.24] for cardiovascular diseases. High MMP-mediated type I collagen degradation was associated with increased mortality. Subjects with high C1M had a 2-fold increase in mortality compared to subjects with low levels of this collagen degradation product.

Effect of free plant sterols in low-fat milk on serum lipid profile in hypercholesterolemic subjects.

OBJECTIVE: To determine the effect of nonesterified, nonhydrogenated plant sterols solubilized in a partly vegetable oil-filled low-fat milk on serum low-density lipoprotein cholesterol (LDL) in mildly hypercholesterolemic patients. DESIGN: Double-blind, randomized, placebo-controlled three-arm crossover study. SETTING: Outpatient clinical trial. SUBJECTS: A total of 138 patients were screened, providing 81 patients for randomization; 71 patients completed the study. INTERVENTIONS: The study product was a 500 ml milk blend with or without nonesterified, nonhydrogenated sterols. The daily consumption of sterols in the three groups was 0 g/day, control group (C); 1.2 g/day, (Lo); or 1.6 g/day, (Hi), respectively. The patients were randomly assigned to one of three different treatment sequences. Each intervention period was 4 weeks. The total study duration was 12 weeks. RESULTS: The milk product was well tolerated. The placebo-adjusted mean reduction in LDL was 7.13+/-12.31 and 9.59+/-12.44% (mean+/-s.d.) for Lo and Hi groups, respectively (P<0.0001); there was no statistically significant difference in LDL lowering for the Lo and Hi groups. There were no significant changes in serum vitamin E or carotenoid concentrations after standardization with LDL cholesterol during the study period. CONCLUSION: The present study shows for the first time a substantial reduction in LDL cholesterol with a new, partly vegetable oil-filled 1.2% low-fat milk product, containing nonesterified plant sterols from soybean oil, in a randomized, placebo-controlled trial. This result encourages further development of novel low-fat dairy products containing free plant sterols for future use in cholesterol-lowering initiatives.

Epiperikaryal synaptophysin reactivity in the normal human central nervous system.

An epiperikaryal synaptophysin immunoreactivity has been regarded as an indicator of neoplastic or otherwise abnormal neurons and this staining property serves as an important criterion to distinguish between normal and abnormal neurons. In the present study we have investigated the epiperikaryal synaptophysin reactivity in various regions of the normal human central nervous system by using autopsy materials from 11 subjects aged 3 months-86 years. We found a definite but variable staining of the brainstem and spinal cord motor neurons as well as the cerebellar Purkinje cells. A particular strong and consistent reactivity was seen in neurons of the cerebellar nuclei in which also axons and dendrites were labelled to a variable extent. This type of neuronal staining was never observed in the cerebrum. We therefore conclude that the employment of this staining property as a criterion for abnormal neurons should be used with caution in the cerebellum, brainstem, and spinal cord whereas it may be used more safely in the cerebrum.

[Scientific activities in departments of clinical physiology/nuclear medicine in Denmark during the period 1989-1994. A bibliometric analysis of the "impact" and citation frequency]. / Videnskabelig aktivitet på klinisk fysiologisk/nuklearmedicinske afdelinger i Danmark i perioden 1989-1994.En bibliometrisk analyse af "impact" og citeringsfrekvens.

This study reports a bibliometric analysis of 860 scientific publications of which 763 are papers in scientific journals emanating from departments of clinical physiology and nuclear medicine in Denmark in the years 1989-1994. The number of publications decreased significantly over time. The 763 papers were published in 239 different scientific journals, 80% in journals with an official "impact factor". The average impact per paper remained almost constant over time and was significantly above the national average. A close relationship was found between the number of papers from a department and its cumulated impact. In an analysis of 217 papers a direct relation was found between the journal impact factor and the citation factor. A linear relation was found between cumulated citations and time, and the number of citations per year reached a maximum 3-7 years after publication, whereas the general maximum for all medical specialties is 2-3 years. It is concluded that the total number of scientific papers from Danish departments of clinical physiology & nuclear medicine fell in the years 1989-1991, but the impact per paper was almost constant and above the national average. There seems to be a good agreement between journal impact factor and overall citation frequency in papers from clinical physiology & nuclear medicine.

The frequency of Lewy bodies in a consecutive autopsy series.

In a consecutive autopsy series comprising 284 subjects > or = 50 years, 22 cases (7.7%) revealed Lewy bodies (LBs) of whom 21 had LBs in substantia nigra and/or locus ceruleus and 9 (3.2%) in the cerebral cortex. Only one case had cortical LBs without concomitant inclusions in the brain stem. The mean age of subjects with LBs was significantly higher than in those without (78.0 vs. 72.3 years). Cortical LBs had not been demonstrated in routine HE stains in any case and their identification necessitated the use of staining for ubiquitin. Although great care was taken not to interpret globose neurofibrillary tangles (NFTs) as LBs, anti-tau staining revealed that many of the suspected LBs were in fact NFTs. Thus, we recommend to apply both anti-ubiquitin and anti-tau staining for the demonstration of cortical LBs. In this material 21 of the 22 cases with LBs (95.5%) also revealed Alzheimer type of pathology as compared with 187 of 262 cases without LBs (71.4%). This difference may be explained by the higher age of subjects with LBs. Altogether 96 of the 284 cases (33.8%) had cerebrovascular lesions. None of the 9 cases with cortical LBs were clinically demented, and our results do not support the assertion that Lewy body-associated dementias should outnumber those of vascular origins.

How well does journal 'impact' work in the assessment of papers on clinical physiology and nuclear medicine?

This study reports a citation analysis of 217 scientific papers on clinical physiology and nuclear medicine published in 69 different journals during the years 1985-92. The actual citation frequency was compared with the journal 'impact factor' (i.e. the average number of times a paper is cited in a particular journal in the year of publication and the subsequent year). The average impact factor per paper was 1.96 and per journal 1.92 (range 0.0-22.8). A direct relation was found between the journal impact factor and the citation factor (i.e. the actual citations in the year of publication and the subsequent year) (journals with five or more papers R = 0.69, P < 0.01; all journals R = 0.40, P < 0.001). However, the citation factor was significantly below the journal impact factor (P < 0.0001). An almost linear relation was found between cumulated citations and time (R = 0.99, P < 0.02.-0.0001), but an initial phase of no citation was identified, and the number of citations per year reached a maximum or plateau 3-7 years after publication, which was later than the general maximum of 2-3 years for all medical specialities. In a sample of 200 known autocitations, 75% of the papers had full recovery, 3% mixed recovery and 22% no recovery, giving an overall recovery of 70%. In conclusion, although a phase of no citation was identified, which gave a lower citation factor than the journal impact factor, the citation frequency increased over time, and altogether there seems to be a good agreement between journal impact factor and overall citation frequency of papers on clinical physiology and nuclear medicine.

Scientific publications from departments of clinical physiology and nuclear medicine in Denmark. A bibliometric analysis of "impact' in the years 1989-1994.

This study reports a bibliometric analysis of scientific publications emanating from departments of clinical physiology and nuclear medicine, Denmark, during the years 1989-1994. The total number of publications during this period was 860 (763 scientific journal papers, 71 book/book chapters and 26 theses). Whereas the number of publications per year (188-113) decreased significantly with time (r = -0.94, P < 0.02), the number of authors (mean 4.1) was almost constant over time. University/ university-related departments accounted for 96% of the papers. Only 8% of the papers resulted from a collaboration between two or more departments of clinical physiology and nuclear medicine, but the collaboration with other medical specialities and institutions was much greater (85%). The 763 papers were published in 239 different scientific journals, 80% in journals with an official 'impact factor', a bibliometric measure of quality (the average number of times a paper is cited in a journal in the publishing year and the subsequent year). Twenty per cent (20%) and 8.4% were printed in journals with an impact factor, respectively, of above 2.1 (the 500 journals most cited) and 3.7 (the 200 most cited), which is significantly above the national average 16.6% and 6.0%, P < 0.001). The "cumulated impact' (i.e. the impact of all papers) showed a borderline significant decrease over time (r = -0.77, P = 0.1), whereas the average impact per paper (1.53) remained almost constant and was significantly above the national average (1.10, P < 0.001). A close relationship was found between the number of papers from a department and its cumulated impact (r = -0.97, P < 0.001). It is concluded that the total number of scientific papers from Danish departments of clinical physiology and nuclear medicine fell in the period, whereas the volume of quality, as assessed on the cumulated impact, only fell with borderline significance, and the impact per paper was almost constant from 1989 to 1994, and was above the national average.

Pregnancies, calves and calf viability after transfer of in vitro produced bovine embryos.

Pregnancy, parturition and calf survival following the transfer of embryos produced in vitro were monitored. A total of 44 blastocysts was transferred in pairs to 1 uterine horn ipsilateral to the corpus luteum (CL) of 22 synchronized heifers. At Day 42 of development 14 recipients (64%) were pregnant; the calving rate was also 64%. The twinning rate was 9/14 at Day 42 and 7/14 at birth, for an overall fetal mortality rate of 9%. The average gestation length was 281 and 275 d for single and twin pregnancies, respectively. Blood samples from recipients were collected for determination of bovine pregnancy associated glycoprotein (bPAG) from 2 wk after transfer and throughout the pregnancy. During the first trimester of pregnancy, the bPAG concentration was significantly higher in twin than in single bearing heifers, and the perinatal increase in bPAG was correlated positively with the total weight of the fetus(es). The percentage of male calves was 43%. The birth weight of twin individuals was 25 +/- 1 kg, which was 78% of the birthweight of the singletons (32 +/- 2 kg). One singleton calf was oversized, weighing 58 kg (80% more than the median weight of the other singletons). Stillbirths occurred in 21% of the twins, butin none of the singletons. Calf mortality during the first 14 d was higher for twins (4/11) than for singletons (1/7) due to infections and cerebellar hypoplasia. Karyotyping the calves detected no cytogenetically recognizable abnormalities. All calves were negative for BVD virus and IBR antibodies. The results of this study showed that although the incidence of fetal loss was low, there was an unacceptable high perinatal mortality of the calves. Thus it is likely that the blood supply through the placenta of animals pregnant with twins was impaired or it is possible that these fetuses and calves had increased stress susceptibility caused by the in vitro conditions. Furthermore, the birth of 1 oversized calf, 2 calves with cerebellar hypoplasia and 5 calves succumbing to infections seems to indicate that a proportion of in vitro produced calves may suffer from factors inherent in the in vitro production system.

The characterization of Danish isolates of Salmonella enterica serovar Enteritidis by phage typing and plasmid profiling: 1980-1990.

Plasmid profiling, phage typing and antimicrobial resistance typing have been carried out on 736 isolates of Salmonella enterica serovar Enteritidis collected in Denmark during the period 1980 to 1990. Strains originated from cases of human salmonellosis, broiler poultry flocks, layer poultry flocks, quarantined imported poultry, environmental samples from hatchery units, and from bovines. Phage type (PT) 1 was found to be the most common type among isolates of poultry origin (57.6%) followed by PT4 (28.8%). Isolates belonging to PT8 were found exclusively in imported birds. Phage typing of a representative sample of human isolates revealed the predominance, as in most other Western European countries, of PT4 (61.8%). PT1, however, was found in 17.0% of human strains, a much higher incidence than expected. Antibiotic resistance was observed in 4 out of 107 human isolates (3.7%) and 2 out of 205 non-human isolates (1%) tested.

Synthesis of pyranoid analogues of the anti-HIV active 3'-deoxy-2',3'-didehydrothymidine (D4T).

The primary hydroxy group of ethyl 2,3-dideoxy-alpha-D-erythro-hex-2-enopyranoside (1) was selectively protected and the secondary hydroxy group was deoxygenated via the dithiocarbonate 3 from which ethyl 6-O-(4-methoxybenzoyl)-2,3,4-trideoxy-alpha-D-glycero-hex-2-eno pyranoside (4) and its regioisomer (5) were produced. These were converted into didehydro nucleosides by glycosylation of silylated heterocyclic bases in the presence of trimethylsilyl trifluoromethanesulfonate as catalyst. The configurations of the anomeric products were assigned by 1H-NMR analysis of the corresponding saturated compounds which were obtained by hydrogenation of the double bond in the carbohydrate moiety. The compounds 9a,b,d, 10a,b, 14a,b,e,f, and 15a,b,e,f did not show any significant activity against HIV or HSV-1.

A new simplified dietary history method for measuring intake of energy and macronutrients.

In this dietary history method, which preserves the characteristic features of the full dietary history, the principle of simplification is to group several food items into common codes. This enables us to complete both an interview and all nutrient calculations within 35-45 min. In this study we investigated whether the method could replace a 4-day food record for assessing individual intakes of energy and macronutrients. Dietary data were collected from 75 individuals (57 males and 18 females). Protein intake was validated by comparison with 24 h urinary nitrogen excretion (33 subjects), and energy intake was compared to weight maintenance energy intake from a later controlled diet study (19 subjects). When average intakes according to the two methods were compared, dietary history intakes were slightly higher than food record results (0-13%) except for alcohol. Comparison with urinary nitrogen excretion and energy intake data indicate that this is due to an overestimation by the dietary history method, rather than an underestimation by the food record. For individuals most of the correlations between the two methods were in the range 0.5-0.7, but alcohol correlation was down to 0.2. About 75% (53-93%) of the individuals at the extremes of the intake distribution were classified similarly by both methods. Although the ability of the dietary history to predict the individual food record results was unreliable the two methods agreed better when classifying individuals relative to certain cut-off points (sensitivity and specificity values of 0.7-0.9, relative to the food records).(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar rhabdomyosarcoma with cerebral and cerebellar metastases and subarachnoidal bleeding: a case report.

A 19-year-old male was hospitalized with a swelling tumor in his left foot. Bone marrow analysis showed marrow carcinosis. Blood investigations, x-rays, radioisotopic scanning and computer tomography did not show any signs of a tumor. The patient died 6 months after the first admission to hospital. Autopsy showed alveolar rhabdomyosarcoma (ARMS) in planta pedis. Besides metastasis in the columna and thoracal lymph nodes, there was tumor tissue in the arachnoidea and subarachnoidal bleeding, a combination not earlier described. ARMS is highly malignant and most of the patients are young.