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Biomedical subjects

H P Hougen

Publications and source records attributed to H P Hougen.

At least 19 recordsLinked to original sources

Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response to Pseudomonas aeruginosa lung infection.

Polymorphonuclear neutrophils (PMNs) are crucial for the outcome of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis. We compared PMNs and inflammatory cytokines in the lungs and blood from susceptible BALB/c and resistant C3H/HeN mice 1 and 2 days after intratracheal challenge with alginate embedded P. aeruginosa. These parameters were correlated with the quantitative bacteriology and histopathology of the lungs. After challenge, the content of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein-2 (MIP-2) was increased in the lungs and the sera and the percentage of PMNs was increased in the blood. However, 2 days after challenge the concentration of G-CSF and MIP-2 was higher in the lungs and sera of BALB/c mice. CD11b expression was higher on the PMNs of the C3H/HeN mice. The expression of CD62L on PMNs of both strains of mice was decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow and the persistent chemotactic gradient provided by MIP-2 in the lungs.

Animals↗

Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response.

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.

Agar↗

Asphyxial homicide in two Scandinavian capitals.

In the Oslo and Copenhagen capital areas, 94 asphyxial homicides were committed in the 10-year period 1985-1994, accounting for 22% of all homicides in that period. Sixty-nine (73%) of the asphyxia victims were female. The most common method of asphyxiation was manual strangulation. Seventeen (18%) of the victims were below the age of 10, accounting for 59% of all homicides in that age group. Whereas 38% of the female victims were killed by their spouse, this was the case for only one male victim. The motive was not known in a great proportion of cases. Fifty-seven percent of the victims had been subjected to additional violence, and in this respect there was no difference between the sexes. In 12 of the cases the offender was female; in 9 such cases the victim was her offspring. More than half of the victims had no blood alcohol. When disregarding the victims less than 10 years of age, 33% of the male and 49% of the female victims had no blood alcohol. The crime scene was the victim's domicile among 72% of female and 52% of male victims. Forty-two percent of the female and 11% of the male victims above the age of 10 years were married or cohabitant.

Adolescent↗

Mobile autopsy teams in the investigation of war crimes in Kosovo 1999.

On request of the International Criminal Tribunal for the former Yugoslavia (ICTY), the Danish-Swedish forensic teams worked in Kosovo during the summer and the fall of 1999. The teams worked mainly as "mobile teams" at sites with few graves. Only two larger sites were examined. Most of the bodies were buried separately. A few "multiple burial" graves were examined, but no mass graves were encountered. The main purpose of the autopsies was to establish the cause and manner of death. Identification was of less importance, but a majority of the bodies had been identified prior to the autopsy. A total of 308 bodies, mainly males, were examined. The age varied greatly with a mean age of 47 years. The most common cause of death was gun shot wounds and the most common manner of death was homicide.

Adolescent↗

Homicide by sharp force in two Scandinavian capitals.

In the Oslo and Copenhagen capital areas, 141 homicides by sharp force were committed in the ten-year period 1985-1994. This method accounted for 33% of the homicides in this period. Thirty-five percent of the victims were female, and most of the victims were between 20 and 50 years of age. The majority of the male victims were killed by an acquaintance, the females by their spouse. Sixty-five percent of the male and 37% of the female victims had alcohol in their blood. The majority of the female victims had lesions in 3-4 anatomical regions, while the males most often had lesions in only one anatomical region. Seventy-nine percent of the females and 36% of the males had self-defence injuries in the upper extremities. In 21 cases (15%) the offender was a woman, 19 of their victims being male; the weapon in these cases was most often a kitchen knife. Seventy-eight percent of the females and 49% of the males were killed in their own home. The most common circumstance was family row when the victim was female, while a fight was the most common circumstance when the victim was male. Three offenders committed suicide after having committed homicide(s) (seven victims; three offenders).

Adolescent↗

Homicide by firearms in two Scandinavian capitals.

In the Oslo and Copenhagen areas, 83 homicides by firearms were registered in the 10-year period 1985 to 1994, accounting for 19.3% of all homicides in that period. The majority of the victims were between 20 and 50 years old, and 58% were male, 42% female. The yearly number of firearm homicides varied between 4 and 15, with neither an increase nor decrease throughout the period. Most of the victims had no detectable blood alcohol at autopsy. Female victims were typically shot in their own domicile with a shotgun by their spouse, mostly because of jealousy or in a family argument, whereas male victims were shot on different locations, predominantly with a handgun, for many different reasons. Most victims were shot in the head, and few had entrance wounds in more than one anatomic region.

Adolescent↗

Histologic, cytologic, and bacteriologic examinations of experimentally induced Salmonella typhimurium infection in Lewis rats.

BACKGROUND AND PURPOSE: Histopathologic changes, cellular composition, and bacterial spreading were studied in rat spleen after experimentally induced infection with Salmonella typhimurium. METHODS: Lewis rats were inoculated intraperitoneally with 10(6) bacteria. Spleen weight, cell numbers, and cell surface markers were studied together with histopathologic changes, and expression of inducible nitric oxide synthase (iNOS). The spread of bacteria to blood, spleen, liver, mesenteric lymph nodes, lung, and kidney was studied at 12 hours, and 1, 3, 7, 14, and 28 days after inoculation. RESULTS: Experimentally induced infection caused an increase in spleen weight and leukocyte numbers, and a decrease in CD49d, on postinoculation days (PID) 3 through 7. Numerous granulomas were disseminated throughout the splenic red pulp also on PID 3 through 7. From PID 14 on, clearance of cellular exudate and regeneration of tissue structure were observed. Massive expression of iNOS was seen on PID 3. Bacterial growth was observed in liver and spleen from 12 hours to 14 days after inoculation. Bacteria were detected in blood on PID 3 and mesenteric lymph nodes were infected from PID 3 through 14. CONCLUSIONS: Salmonella typhimurium was rapidly taken up by the reticuloendothelial system. The infection induced weight increase and reversible changes in the spleen, peaking on PID 3 with granuloma formation and infiltration with macrophages. On PID 3, extensive production of iNOS within the granulomas was observed, suggesting initial killing of phagocytosed bacteria, followed by bacterial clearance and tissue regeneration. Cell surface marker expression on CD4+ T cells indicated no change in their numbers; however, there was a time-dependent change in expression of CD49d.

Animals↗

Entrance, exit, and reentrance of one shot with a shotgun.

The case being reported is one of a homicidal shotgun fatality with an unusual wound pattern. A 34-year-old man was shot at close range with a 12-gauge shotgun armed with No. 5 birdshot ammunition. The shot entered the left axillary region, exited through the left infraclavicular region, and thereafter penetrated the left side of the neck, causing tearing of the left common carotid artery and the right internal carotid artery. The entrance wound in the axilla was larger than the other wounds, and before autopsy it was believed that the shotgun had been fired twice, causing one wound in the neck and one wound perforating the infraclavicular region and exiting through the left axillary region. Thus, this case shows that unusual wound patterns in shotgun fatalities can easily lead to incorrect assumptions with regard to number and direction of shots fired unless thorough investigation is carried out postmortem.

Adult↗

Homicides in two Scandinavian capitals.

In this study we investigated homicides in the two Scandinavian capitals, Copenhagen, Denmark and Oslo, Norway, for the 10-year period from 1985 to 1994. The total number of homicides was 431; 63.8% occurred in Copenhagen and 36.2% in Oslo. The average homicide rate was 1.6/100,000 in Copenhagen and 1.8/100,000 in Oslo. Blunt force, sharp force, and strangulation were the most common methods. Firearms were also used but did not account for >20% in either of the two cities. This is probably due to strict gun laws in both countries. There was no clear difference between the homicide victim populations in the two cities with regard to age, gender, or social and marital status. The proportion of alcoholics and unemployed persons was much higher than in the background population and to a similar extent in both cities, indicating that the homicide victim populations differ from the background populations. The perpetrator knew the victim in the majority of the cases. The most frequent motives or circumstances in both cities were fights, family rows, financial controversies, or jealousy.

Adolescent↗

Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response.

Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates with a poor prognosis. We speculated that a change from this Th2-like response to a Th1-like response might decrease the lung inflammation and thus improve the prognosis in CF patients. To investigate this, we infected C3H/HeN and BALB/c mice intratracheally with P. aeruginosa. In addition, we studied the early immune response leading to different Th responses. Mortality was lower in the C3H/HeN mice (p<0.005), they cleared the bacteria faster (day 3 p<0.01, day 7 p<0.02), had a milder lung inflammation (day 7 p<0.01, day 14 p< or =0.0005) and had a Th1-like IgG subclass switch. At day 3, the C3H/HeN mice produced less NO and TNF-alpha, (p<0.01 and p<0.03) and had the lowest IL-10/IL-12 ratio (p< or =0.05). At day 7, the C3H/HeN mice had the highest IFN-gamma (p<0.02), and the lowest IL-4 (p<0.02) production in the lungs. In conclusion, these results show that the Th1-reacting C3H/HeN mice with chronic P. aeruginosa lung infection have a better disease outcome compared to the Th2-reacting BALB/c mice, indicating that a Th1 response might be beneficial in CF patients with chronic P. aeruginosa lung infection.

Animals↗

A histomorphometric and scanning electron microscopy study of human condylar cartilage and bone tissue changes in relation to age.

OBJECTIVES: To determine the possibility for adaptive growth in human condyles, quantifying the thickness of fibrocartilage and the constitution of cells with potential activity, the trabecular bone volume, and the structural parameter: marrow space star volume in a larger sample of human autopsy condyles. EXPERIMENTAL SETTING AND DESIGN: A histomorphometric and scanning electron microscopic analysis of cartilage characteristics and bone remodelling activity. The Departments of Orthodontics and Cell Biology at Aarhus University, Denmark. An autopsy sample of condyles from 20 individuals, 18-31 years of age. Correlation analyses between ages and all parameters were conducted. RESULTS: There was a statistically significant correlation between age and the fibrocartilage thickness (r = -0.48, p < 0.05) and age and the trabecular bone volume (r = -0.52, p < 0.05). There was a statistically significant correlation between age and the hypertrophic chondrocytes (r = -0.50, p < 0.05) and age and the hypertrophic chondrocytes in bone (r = -0.48, p < 0.05). There was no significant correlation between age and the two other zones in the fibrocartilage. No statistical analyses were carried out concerning gender differences, as the sample consisted of very few females. Individual morphological description was performed, and is described in the article. Only slight age-related differences were found concerning the quantitative measurements for the fibrocartilage and the underlying bone tissue. CONCLUSIONS: Quantitative and qualitative investigations of the turnover activity in the fibrocartilage and the bone tissue, describing activity of hypertrophic chondrocytes and the trabecular bone tissue, indicated condylar growth potential in the age group until 30 years of age. The growth activity seemed to decline with age.

Adaptation, Physiological↗

Results of medical examination of refugees from Burma.

OBJECTIVES: To describe exposure to human rights violations among refugees from rural Burma; to compare exposure experienced by an ethnic Burmese minority group, the Shans, with that of the rest of the study population; and to compare exposure of those who had fled Burma recently with that of refugees who had arrived in Thailand earlier. DESIGN: Cross-sectional interview and clinical examination. SETTING: Refugee settlements and refugee camps in Northern Thailand near the border to Burma in November 1997. SUBJECTS: 92 persons (group A) were examined according to the program. Fourty-six were Shans; 34 had migrated within the past five months. A further 96 person (group B), more randomly selected, were interviewed according to an abbreviated interview program; of these, 38 had fled recently. MAIN OUTCOME MEASURES: A score was used to quantify the exposure. Testimonies of exposure to physical violence were validated, assessing the consistency between the reported exposure, reported ensuing symptoms and the result of the clinical examination. RESULTS: Both groups reported massive exposure to the following human rights violations: forced labour (group A: 66%, group B: 35%), porter service (65%, 44%), forced relocation (51%, 51%), killing of family members (36%, 29%). In group A, there were twelve cases of self-reported torture. Moreover, there were reports of rape, disappearances and land mine accidents. In all cases of exposure to physical violence the testimonies were appraised to be valid. CONCLUSION: The violations of human rights in Burma were massive. The Shans were exposed as heavily as the others. Those who had arrived recently were as heavily exposed as the other groups. Apart from the land mine problem, the Burmese army was held responsible for all the reported and documented human rights violations.

Adolescent↗

Serological diagnosis of experimental Enterococcus faecalis endocarditis.

A modified rat model of endocarditis with catheterization for 2 days was established in female Lewis rats using different inocula of Enterococcus faecalis (strain no. EF 19) in order to measure IgG antibodies in serum during the course of infection. Increasing the inocula intravenously resulted in an increase in the CFU/g vegetation and the CFU/g spleen, the ID50 being about 10 CFU/ml and the ID90 about 1x10(2) CFU/ml. The lowest bacterial inoculum infecting 100% of the rats was 3x10(3) CFU/ml, and for further investigations we used this inoculum size. Rats were sacrificed on day 2, 5, 7, 9, 11 and 28 after infection. The CFU/g vegetation and the CFU/g spleen increased until day 7 and then decreased. Serum samples were collected from 129 rats at different times after challenge. Three different ELISA systems were established to measure the IgG antibody responses: E. faecalis sonicate ELISA (a pool of four sonicates of strain no. EF 10, EF 11, EF 19 and EF 48), E. faecalis whole cell ELISA (strain no. EF 19) and E. faecalis purified cell wall ELISA (strain no. EF 19). An IgG antibody response was detected already on day 2, and except for a minor decrease on day 6/7 the antibody response continued to increase until day 14 (whole cell ELISA and sonicate ELISA) and day 21 (purified cell wall ELISA) when a plateau was reached. Significant increases in IgG antibody responses (p<0.05) were found between groups of rats from days 0-2, 2-8/9 and 8/9-14 in the E. faecalis whole cell and sonicate ELISAs and from days 0-2, 2-10/11 and 10/11-21 in the E. faecalis purified cell wall ELISA. In conclusion, we established a model of endocarditis in rats with catheterization for 2 days and were able to demonstrate an increase in IgG antibodies during the course of infection.

Animals↗

Transfer of primed CD4+OX40- T lymphocytes induces increased immunity to experimental Salmonella typhimurium infections in rats.

The protective effect of primed CD4 T cells against a lethal dose of Salmonella typhimurium was studied in Lewis rats. Primed CD4 T cells were obtained by inoculating Lewis rats with a non-lethal dose of S. typhimurium. Four weeks after the infection, spleen non-adherent mononuclear cells were isolated. The cells were separated according to their expression of CD4 and the OX40 antigen by FACS. OX40+ and OX40- CD4+ T-cell subpopulations were together with unsorted CD4+ T cells transferred to untreated rats 24 h prior to infection with S. typhimurium. Transfer of either unsorted CD4+ T cells or CD4+ T cells sorted into OX40- or OX40- subpopulations significantly increased animal survival compared to controls. Animals receiving OX40+CD4+ T cells did not differ significantly in survival probability from those receiving unsorted CD+ T cells. However, animals receiving OX40-CD4+ T cells had a significantly better survival compared to animals given unsorted CD4+ T cells. It is concluded that OX40-CD4+ T cells can induce significant protection against S. typhimurium infections in rats. This is most likely due to the fact that the OX40-CD4+ T-cell population contains a significant number of antigen-specific memory T cells that have returned to a resting state.

Animals↗

Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle.

The ongoing lung tissue damage in chronically Pseudomonas aeruginosa infected cystic fibrosis (CF) patients has been shown to be caused by elastase liberated from polymorphonuclear leukocytes (PMN), which dominate the chronic inflammation in these patients. Most CF patients, however, contract the chronic lung infection with P. aeruginosa after a one-year period (median) of intermittent colonization. Therefore, prevention of the onset of the chronic infection or prevention of the dominance of the inflammation by PMNs would be important goals for a vaccine strategy against P. aeruginosa in CF. In a rat model of acute P. aeruginosa pneumonia we studied whether it was possible to improve the initial bacterial clearance and diminish the inflammatory response by vaccination prior to challenge with free, live P. aeruginosa. The vaccines studied were PAO 579 sonicate, O-polysaccharide toxin A (TA) conjugate, depolymerized alginate (3064) TA conjugate (D-ALG TA), or P. aeruginosa alginate (6680 + 8839). The vaccines could, however, not improve the very efficient natural clearance of P. aeruginosa from the lungs of the rats. In a rat model of chronic P. aeruginosa lung infection we found that none of the vaccines could prevent chronic lung inflammation. After challenge, however, none of the rats immunized with D-ALG TA died in contrast to the other vaccine groups combined (p = 0.03). In addition, the inflammatory response changed from an acute type inflammation dominated by PMNs as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes. This response was achieved within the first week after challenge in D-ALG TA immunized rats; in the controls, the inflammation was still acute 4 weeks after challenge. Rats immunized with D-ALG TA had a significantly reduced severity of the macroscopic lung inflammation compared to the other vaccination groups (p = 0.009). The same effect could be obtained by IFN-gamma treatment (p = 0.004). The chronic P. aeruginosa lung infection was established in two inbred mice strains C3H/HeN, known as TH1 responders, and Balb/c, known as TH2 responders. The mortality due to the infection was significantly lower in C3H/HeN mice compared to Balb/c mice (p < 0.0003). P. aerurinosa was cleared more efficiently by C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology than Balb/c mice (p < 0.025). Supernatants from Concanavalin A stimulated spleen cells from C3H/HeN mice contained three times higher IFN-gamma concentration but only half as high interleukin-4 concentration than those of Balb/c mice. These findings suggest that change from the TH2-like response seen in CF patients towards a TH1 response might improve their prognosis.

Animals↗

Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice.

The chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) is characterized by a pronounced antibody response and microcolonies surrounded by numerous polymorphonuclear neutrophils (PMN). Poor prognosis is correlated with a high antibody response to P. aeruginosa antigens. An animal model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p < 0.025). P. aeruginosa was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p < 0.02), and we found significantly fewer microabscesses in C3H/HeN mice than in BALB/c mice (p < 0.005). In supernatants from P. aeruginosa antigen and concanavalin A-stimulated spleen cells from the two strains of mice, the interferon-(IFN-) gamma levels were higher, whereas IL-4 levels were lower in C3H/HeN mice than in BALB/c mice. The implications of these findings for CF patients with chronic P. aeruginosa lung infection are discussed.

Animals↗