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Biomedical subjects

J Søndergaard

Publications and source records attributed to J Søndergaard.

At least 19 recordsLinked to original sources

Histamine release in immediate-type hypersensitivity reactions in intact human skin measured by microdialysis. A preliminary study.

The purpose of this study was to evaluate the application of a microdialysis technique for measurement of interstitial histamine levels in intact human skin. Three allergic subjects were investigated. Single dialysis fibers were glued to nylon tubings and inserted in forearm skin by means of a fine cannula. Dialysis fibers were inserted in triplicate and perfused with isotonic saline at a rate of 3 microliters/min. After a period of 2 h a 60-microliters base-line period was established. Then the patients were skin prick tested (SPT) with allergen in duplicate and a single saline control. Dialysate was collected in consecutive 30 microliters fractions. Histamine concentration in the dialysate was analyzed with a glass fiber fluorescence assay. Median base-line histamine level was 4 (range 4-7) ng/ml. Following allergen SPT, dialysate histamine concentration increased to 81 ng/ml (74-128), with maximum values 10-20 min after SPT. Intraindividual coefficient of variation on peak histamine levels was 18.9%. No histamine increase was seen following saline SPT. We consider microdialysis to be a valuable method for assessment of allergic mechanisms in intact human skin.

Adult

Ceftriaxone vs. ampicillin + metronidazole as prophylaxis against infections after clean-contaminated abdominal surgery.

In a prospective, controlled, double-blind study, 496 patients undergoing abdominal surgery were given antibiotic prophylaxis with a single dose of either ceftriaxone or ampicillin + metronidazole. No significant intergroup difference was found between the respective overall rates of infectious complications (3.2% and 4.9%). Analysis of the microbiologic findings showed incisional wound infections, mainly caused by gram-negative rods, to be more common in the ampicillin-metronidazole group, whereas deep wound infections were more frequent in the ceftriaxone group. It is concluded that ceftriaxone seems to be more efficient than ampicillin-metronidazole as prophylaxis against incisional wound infection, but should preferably be supplemented with an antianaerobic agent to prevent deep wound infections.

Abdomen

Leukotriene B4 in atopic dermatitis: increased skin levels and altered sensitivity of peripheral blood T-cells.

Employing a radioimmunoassay, de-proteinated suction blister fluid from 12 patients with active atopic dermatitis appeared to contain higher levels of the pro-inflammatory and immunomodulatory mediator leukotriene B4 (LTB4) than suction blister fluid from 12 non-atopic individuals. Indirect support for the identity of the mediator was obtained by HPLC of pooled samples. Nylon wool enriched T cells from six patients with atopic dermatitis and six non-atopic people preincubated with LTB4 (10(-10) M - 10(-8) M) expressed no statistically significant suppression in co-culture with mitogen stimulated autologous mononuclear cells, and there was no difference between atopic and non-atopic T cells in this respect. In contrast, LTB4 induced a dose-dependent reduction in the percentage of phenotypic Leu 2a (suppressor) cells leading to an increased helper/suppressor ratio in five atopic patients that was not observed in five non-atopics. Elevated skin levels of LTB4 may initiate or amplify dermal inflammation, and abnormal T cell response to the mediator may account for the increased helper/suppressor ratio characteristic of patients with atopic dermatitis.

Adult

Reduced neutrophil production of leukotriene B4 associated with AIDS.

Neutrophils from 10 homosexual men with evidence of HIV infection and 10 healthy controls were tested for their capacity to generate leukotriene B4. Neutrophils from patients with AIDS produced less leukotriene immunoreactivity when appropriately stimulated than neutrophils from healthy controls, whereas no significant difference could be detected between HIV-antibody-positive individuals without AIDS and healthy controls. This observation may be pertinent to the recurrence of some of the opportunistic infections associated with AIDS but more importantly, if reflecting a general defect in leukotriene production, it may provide further understanding of the mechanism which leads to reduced natural killer-cell activity, interleukin-2 and interferon-gamma production in AIDS.

Acquired Immunodeficiency Syndrome

Prostaglandin E1 and prostaglandin F2 alpha in exudate in nickel allergy.

Ten nickel-allergic patients and 5 healthy control subjects participated in a study of the kinetics of the flux and concentration of migrated leukocytes and extracellular PGE1 and PGF2 alpha during a 48 h period, using a skin chamber technique. The patients were provided with two skin chambers, one with and one without nickel challenge. A higher flux of leukocytes, PGE1 and PGF2 alpha was observed during the second day of allergen exposure, while the concentrations probably due to dilution were unchanged or diminished, indicating an unspecific role of the prostaglandins during the contact allergic reaction. No correlations were found within the groups between the migration of leukocytes and the prostaglandin content.

Adult

Cervical signs of HPV infection in PAP-smear negative women with external genital warts.

Forty-eight women with external genital warts, all with normal cervical cytological PAP smears, were examined by means of colposcopy. One cervical biopsy for histological evaluation was taken from each woman, irrespective of the colposcopic findings. Koilocytosis was detected in 18/48 (38%) and dysplasia (CIN-1) in 3/48 (6%) of the patients. The presence of aceto-white lesions on the cervix was significantly associated with abnormal histology; 12 of 17 (71%) aceto-white lesions and 8 to 31 (26%) normal-appearing cervices showed histological changes indicating HPV infection (p less than 0.01). Women with koilocytosis and dysplasia had genital warts for a mean of 201 days compared with 79 days in women with normal cervical histology (p less than 0.01). It is concluded that even the clinically normal appearing cervix frequently is a reservoir for HPV and that colposcopy should be a routine procedure in women with external genital warts, irrespective of the result of the PAP smear, to provide a basis for proper counselling and individual therapy.

Adult

Lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate in delayed type hypersensitivity.

A skin window technique was used to study the morphology of leucocytes in upper dermis and exudate during nickel challenge in patients with contact allergy to nickel. Contact allergic patients and healthy volunteers tested with a skin widow without addition of nickel to the chamber medium served as controls. The morphology of the leucocytes in dermis was studied in biopsies taken 8, 24, or 48 h after skin window application, and in a parallel test the morphology of the exudate was examined by sequential collection of the chamber medium during a 48 h period. The infiltrate in dermis of contact allergic patients with nickel challenge in the chamber medium showed a time-dependent increase of mononuclear cells, eosinophils and basophils and a concomitant decrease of polymorphonuclear granulocytes, characteristic of a combined specific and unspecific inflammation. The morphology of the exudate in contact allergic patients exposed to nickel showed a dominance of polymorphonuclear granulocytes throughout the study period, while mononuclear cells, eosinophils and basophils were detected at a much lower quantity and with a considerable delay. Further, we studied the kinetics of the leucocyte granule proteins: lactoferrin, myeloperoxidase, lysozyme and eosinophil cationic protein in exudate fluid in a parallel test. A significant higher flux was found for all during the second day of allergen exposure compared to contact allergic patients without allergen challenge as well as normal volunteers. The increased protein fluxes were not accompanied by an increased flux of polymorphonuclear granulocytes in the exudate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

AIDS related changes in pattern of sexually transmitted disease (STD) in an STD clinic in Copenhagen.

Testing for antibodies against human immunodeficiency virus (HIV) was introduced in 1984 in this major sexually transmitted disease (STD) clinic in Copenhagen, which is attended by about 10,000 new patients each year. From 1984 to 1987 the proportion of patients examined for antibodies to HIV rose from 6% to 32%. The overall incidence of HIV antibody positivity decreased from 30% in 1984 to 3% in 1987, the combined result of decreased positivity in high risk patients tested and increased screening in low risk patients. HIV antibody positivity has been confined largely to homosexual men and drug addicts. Since 1985, however, 21 out of 2623 (0.8%) heterosexuals who were not drug addicts were found to be HIV antibody positive. During 1984-6 the incidence of STDs most often encountered in high risk groups (syphilis and gonorrhoea) decreased by 64% and 41% respectively, whereas the incidence of diseases most often diagnosed in low risk groups (condylomata acuminata and genital herpes) increased by 70% and 34% respectively in the same period. The addition of HIV infection to the list of STDs requires the allocation of more resources to the STD clinics to enable these clinics to handle this new problem. Screening for all patients attending an STD clinic for antibodies to HIV must be considered, and in our area it would be cost effective.

Acquired Immunodeficiency Syndrome

Skin and oral mucosal changes in patients infected with human immunodeficiency virus.

During a 6-month-period, 150 patients infected with Human Immunodeficiency Virus (HIV) were repeatedly examined by dermatologists and dentists for lesions of skin and oral mucosa. The most frequently encountered diseases were: oral hairy leukoplakia (21%), dermatophytosis (including tinea unguium/tinea pedis et inguinalis) (20%), seborrheic dermatitis (19%), viral infections (10%), oral candidiasis (7%), acne vulgaris (6%), and folliculitis (5%). A variety of other manifestations were seen, with frequencies less than 5%. Herpes zoster was seen in 3% of the patients, indicating a rate of 60/1,000 per annum. The presence of seborrheic dermatitis was statistically associated with low T-helper lymphocyte count. Patients with low T-helper lymphocyte count had on average twice as many mucocutaneous lesions as patients with a normal or moderately decreased count. Any one of the manifestations seborrheic dermatitis, oral candidiasis or oral hairy leukoplakia was associated with a greater average number of additional mucocutaneous changes than seen in patients exhibiting none of these three conditions. The high proportion of HIV-infected patients with cutaneous and oral lesions underlines the importance of referring the patients to dermatologists and dentists for examination. Prospective examinations of the study population remain to elucidate the prognostic significance of mucocutaneous manifestations of HIV-infected patients.

Acquired Immunodeficiency Syndrome

Chemotactic activity of LTB4 in man.

An improved skin window chamber technique has been developed and used for a quantitative study of the chemotactic effect of leukotriene B4 (LTB4). LTB4 (0.5 microM) was exposed to a skin window on the forearm of eight healthy volunteers, while phosphate buffered saline served as control in a skin window on the other forearm. Skin window exudates and samples of blood draining the skin window areas were collected after 1, 2, 4, 8, and 24 h. The samples were quantitated for the different types of leukocytes as well as the intra- and extracellular concentration of the eosinophilic cationic protein and lactoferrin as markers of eosinophil and neutrophil granulocytes. A significantly increased migration of neutrophil granulocytes into the skin window chamber containing LTB4 was found from the 2nd to the 8th hour after the initial LTB4 exposure. The eosinophils reached a significant peak at the 4th hour. The rise in the actual number of eosinophil cells did not reach significance, whereas measurements of the eosinophilic cationic protein in the cellular fraction of the exudate exhibited a significant increase as a reflection of the number of eosinophils. This highlights the potential clinical value of eosinophilic cationic protein measurements to reveal eosinophilia instead of the traditional eosinophil counts. Extracellular eosinophilic cationic protein and lactoferrin did not change significantly in the LTB4-exposed skin window, implying that LTB4 does not activate the eosinophils and neutrophils to exocytosis of their enzymes. The present in vivo results support the concept of LTB4 being a potent chemoattractant to neutrophil and less so to eosinophil granulocytes in humans, a chemoattractant that recruits the leukocytes but does not seem to activate them.

Adult

New parameters for evaluation of blood flow in patients with leg ulcers.

Three new parameters have been introduced to provide data for quantitative evaluation of peripheral cutaneous blood flow in patients with leg ulcers. Reactive hyperemia was induced by occlusion of the blood flow for four minutes at the thigh-level. Blood flow was subsequently measured by laser-Doppler velocimetry in an unselected group of 14 patients with leg ulcers and a matched control group. The parameters used for evaluation was: 1) "peak flow" f(p), 2) divided by time to "peak flow" t(p), rendering a rate constant k (k = f(p)/t(p)) expressing the ability to increase blood flow abruptly in case of need. These parameters were all significantly reduced in the patients with leg ulcers, indicating that this simple and atraumatic technique was useful for discriminating blood flow values that may be relevant for healing time and with a sensitivity comparable to the measurements of distal systolic blood pressure. Distal systolic blood pressure measurements can still be considered to be of value when screening for arterial insufficiency in patients with leg ulcers. The values obtained were significantly lower in 36 patients with leg ulcers compared with 9 age-matched control persons.

Adult

DNA interstrand crosslinks visualized by electron microscopy in PUVA-treated psoriasis.

An electron microscopic method has been used to visualize crosslinks after total denaturation of DNA isolated from epidermis and dermis in patients with psoriasis treated with 8-methoxypsoralen (8-MOP) and irradiation with ultraviolet light at 360 nm (PUVA treatment). This technique enabled accurate measurement of the number and density of DNA interstrand crosslinks. 30 biopsies were studied and a total of 9503 DNA molecules were scored in the electron microscope. 6 patients were treated topically with 8-MOP and 10 were on systemic treatment and biopsies were obtained immediately after irradiation. 1% of the total DNA molecules examined contained 3 or more crosslinks. The overall frequency of crosslinks was almost identical in the epidermis (1.1%) and in the dermis (0.9%) and, furthermore, virtually the same in patients on topical and systemic PUVA treatment. The total number of crosslinks was of the same magnitude as those previously found by us in normal human skin. Thus, though the formation of interstrand DNA crosslinks can be considered as an indicator of damage of the genetic material, we were unable to demonstrate this as being a consequence of PUVA treatment using 8-MOP.

Adult

Fibrinogen/fibrin degradation products in exudates from bullous dematoses.

Inflammatory exudates from 10 patients with bullous skin diseases were analysed by immunochemical techniques including crossed immunoelectrophoresis. The results were compared with those obtained in fluid from suction bullae obtained in normal skin in 13 control subjects and synovial fluid from 20 patients with rheumatoid arthritis. Abnormal fibrinogen degradation products identical with those found in synovial fluid from patients with rheumatoid arthritis were detected in exudates from each of the patients with bullous dermatoses, whereas significantly smaller amounts of fibrinogen antigenic material were detected in fluid obtained by suction. The fibrinogen antigenic material demonstrated in exudates from pathological bullae, immunochemically similar to that found in rheumatoid synovial fluid, indicates that the presence of these products reflects the more general features of an inflammatory exudate.

Aged

Cyclic AMP and psoriasis once more.

Imbalanced cyclic nucleotides are implicated as an underlying pathogenetic mechanism in psoriasis, but conflicting data on the levels of cAMP in psoriatic tissue have been obtained by different laboratories. Using heat separation and a competitive protein binding cAMP assay, a noticeably decreased epidermal level of cAMP was detected in newly formed guttate lesions in 10 patients with psoriasis (involved: 4.32 +/- 1.06 pmol/mg dry weight mean +/- S.E.M.). uninvolved: 7.97 +/- 1.63 pmol/mg dry weight mean +/- S.E.M.). In proliferative rat skin, bidirectional alterations in cAMP levels are known to occur. On the basis of present observation, we assume that the conflicting data hitherto obtained in psoriatic tissue similarly may merely reflect the various levels of cAMP at different developmental stages.

Adolescent