Biomedical subjects
Publications and source records attributed to M Pedersen.
A synergistic effect of clotrimazole and certain anionic surfactants against a strain of Candida albicans was confirmed. Measurement of apparent partition coefficients indicated that lipophilic ion pairs between clotrimazole and anionic surfactants were formed. It is suggested that the synergistic effect of the drugs may be due to ion pair formation.
A prospective investigation of 188 patients with cancer of the rectum and rectosigmoid colon with synchronous liver metastases is described. The mean survival time for 183 patients who did not receive any treatment for the liver metastases was six months and only one survived for longer than 37 months. After extirpation of the primary tumour, the most significant prognostic factors were etrahepatic metastases, enlarged liver on account of metastases and more than three liver metastases. Serum basic phosphatases had the greatest significance among a series of laboratory tests. In the sub-groups with the best possible prognoses, the mean survival time was 12 months. 25% five-year survival has been described in the literature following resection of the liver in patients with a maximum of three metastases, no other metastases and age under 70 years. Provided this holds true, liver surgery will be a therapeutic possibility in at least 100 patients per annum in Denmark with synchronous liver metastases and 25 of these will be cured. This figure requires an improved programme for the diagnosis of synchronous liver metastases than at present and the same high frequency of extirpation of the primary colorectal cancer on a national basis which was achieved in the present material.
Ninety-three patients with small cell carcinoma of the lung (SCLC) treated with chemotherapy or chemotherapy plus radiotherapy in the department for oncology and radiotherapy in Aalborg Hospital are reviewed in view of the response and survival. The relevant literature is mentioned.
HIV antigen-induced histamine release was examined in leukocyte suspensions from 12 patients with AIDS and 10 healthy controls. Nine of the twelve patients released histamine, while no release was obtained in cells from the control group. The mechanism was examined by removal of immunoglobulins (Ig) from the patient cells before stimulation with HIV antigen, which resulted in an abolition of the histamine release. Transfer of the Ig to cells from normal individuals rendered these cells able to respond to HIV. The removal and fixation of Ig were followed by disappearance and reappearance of the response to anti-IgE. These findings indicate that the histamine release by HIV is caused by a type I (IgE-mediated) reaction.
Mediator release was examined from superficially lying cells in the airway epithelium obtained by bronchoalveolar lavage (BAL) in 13 non-atopic individuals. The BAL-cells were incubated (20 min, 37 degrees C) with Staphylococcus (Staph.) aureus or with human influenza A virus Staph. aureus was found to release histamine from cells from 7 of the 13 individuals and influenza A virus in 3 of 5 persons. Furthermore, Staph, aureus stimulated the BAL-cells to release leukotriene B4 in 7 of 11 subjects, whereas no release was found by influenza A virus in 7 examined persons. When cells from 4 persons were stimulated with Staph. aureus no release of leukotriene C4 was found. The mediator release caused by bacteria and virus might be of importance for the exacerbation of bronchial asthma in upper respiratory tract infections, since histamine is assumed to increase the epithelial permeability with entrance of allergens and other insulting particles, and leukotriene B4 facilitates airway inflammation.
Infection following emergency Caesarean section was reduced significantly by changing certain hygienic procedures, i.e. cutting instead of shaving abdominal hair, reducing vaginal examinations prior to operation, swabbing the external genitalia with aqueous chlorhexidine gluconate, minimizing the traffic in the operating theatre and abandoning peroperative dilatation of the cervix. Wound infection was reduced from 5.6% to 5.1% and endometritis from 14.3% to 4.4%.
Between October 1979 and May 1985, 626 patients with pharynx and larynx carcinoma were randomized to two different split-course radiation regimens and given either misonidazole (MISO; 11 g/m2) or placebo during the initial 4 weeks of treatment. Patients in the different treatment groups were evenly distributed among stages. The small number of females (136) gave an uneven distribution, thus making analysis difficult. The results show that females had a statistically better loco-regional control (45 vs. 33%; 5-year actuarial value). Overall, the MISO treated group did not have a significantly better control rate than the placebo groups (37 vs. 34%). However, a difference was found in patients with pharynx carcinomas (38 vs. 27%; p less than 0.05). The pre-irradiation hemoglobin (Hb) concentration was found to be a prognostic parameter. In females, loco-regional control for IIb values below or above 8 mmol/l were 37 and 47%, respectively. In males, the same values were below or above 9 mmol/l 26 and 38%. Hb influence on local control was only seen in supraglottic and pharynx tumors. This effect was independent of tumor size, which also was of prognostic value. In addition Hb concentration and MISO had an apparent additive effect. Thus in the male pharynx group, placebo patients with low Hb had a 14% disease rate compared to 40% in MISO treated patients with Hb above 9 mmol/l. MISO induced significant peripheral neuropathy in 26% of the treated patients, whereas other drug related side effects were minimal and tolerable.
AIDS patients in contrast to healthy individuals show basophil histamine release by stimulation in vitro of their blood leukocytes with Candida albicans (CA) and Herpes simplex virus Type I (HSV-I). Passive sensitization of cells from healthy individuals with the patient serum or surface immunoglobulins (Ig) derived from leukocytes of AIDS patients caused histamine release by the following stimulation of the cells with CA or HSV-I. When IgE was removed from the surface Ig no response was obtained, whereas a removal of IgG did not diminish the response. In contrast, no passive sensitization was obtained by serum derived from healthy individuals. The results show that IgE is responsible for the histamine release caused by CA and HSV-I in AIDS patients.
Type I allergy directed against Pneumocystis carinii (PC) has been investigated in 14 patients with AIDS. The Pneumocystis carinii pneumonia often shows a rapid and severe course, and type I allergy against the parasite might be a pathogenic co-factor in the interstitial lung inflammation. In twelve of the AIDS patients the clinical symptoms and course of illness indicated a PC pneumonia. The basophil histamine release test was used as a sensitive test to detect type I allergy against PC. Eight of the patients showed significant histamine release when stimulated with PC. In contrast, only two patients in the group of 12 HIV antibody-positive homosexual men and none in the control group of 13 heterosexual men released histamine. The histamine release was mediated by an immunological reaction, since the release was abolished and regained by removal from and refixation to the cell surface of the cell-bound immunoglobulins before the antigen challenge. The results suggest an involvement of type I allergy as a pathogenic co-factor in Pneumocystis carinii pneumonia.
Pulmonary clearance (Pcl) of aerosolized 99mTc-DTPA was studied in fourteen patients with primary ciliary dyskinesia (PCD), (median age 23.5 yrs, range 12-44 yrs) and nine normal individuals (median age 23 yrs, range 18-27 yrs). All had never smoked. Regional Pcl was studied for arbitrarily defined central and peripheral regions of the lung using a gamma camera method, whilst total Pcl was studied by a plasma sample method. The patients with PCD had significantly reduced total Pcl compared to the normal individuals (p less than 0.05) and also significantly lower total lung capacity (TLC), vital capacity (VC), forced expiratory volume in one second (FEV1), and FEV1/VC values (p less than 0.05). There was no correlation between Pcl and FEV1/VC. It is concluded that the reduced Pcl in the PCD patients may be associated with their small lung volumes. In addition, reduced bronchial clearance of surfactant in PCD may be associated with an increased alveolar lining fluid volume and/or an impaired movement of 99mTc-DTPA along the alveolar septa to the bronchoalveolar junction, where the epithelium may be more specialized for absorption.
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We have characterized the beta-adrenergic receptor binding site and the beta-adrenergic cAMP response of the HL-60 cell. The hydrophilic ligand [3H]-(-)-CGP-12177 was specifically and reversibly bound to one single class of binding sites (Kd 220 pM and Bmax 1,970 sites/cell). The adrenergic agonists inhibited the specific radioligand binding. The order of potency was isoproterenol greater than epinephrine greater than norepinephrine. The beta-2 selective antagonist ICI 118551 had a binding affinity 3 orders of potency higher than the beta-1 selective antagonist, atenolol. The adrenergic agonists elevated the cAMP accumulation in a concentration-dependent mode. The order of potency was isoproterenol greater than epinephrine greater than norepinephrine. Both the binding and the functional studies revealed stereospecificity and reversibility. The present data show that HL-60 cells possess beta-2 adrenergic receptors functionally coupled to adenylate cyclase.
The effect of inhaled beclomethasone dipropionate and budesonide on the adrenal function was studied in 30 children (aged 7 to 15 years) with mild bronchial asthma. The trial was designed as a prospective double-blind parallel study of the effect of stepwise increase of either beclomethasone dipropionate or budesonide from 200 micrograms through 400 micrograms, to 800 micrograms daily in three consecutive periods of 4 weeks. At the end of each period, the adrenal stress response was evaluated by measurements of serum cortisol and androstenedione during a short adrenocorticotropic hormone test. The unstimulated diurnal production of glucocorticosteroids was assessed by measurements of free cortisol in 24-hour urine samples. Free cortisol in urine was found a valid measure of the total diurnal excretion of cortisol metabolites, since it exhibited a good correlation to the fractional cortisol metabolites measured by gas chromatography. The adrenal response to adrenocorticotropic hormone stimulation was unaffected by treatment or dose. The unstimulated diurnal production of glucocorticosteroids demonstrated a highly significant dose-related suppression in response to the inhaled steroids. No significant difference was found between the two topical steroids (probability value 5.3%), and yet the suppression was apparent in the group of children treated with beclomethasone dipropionate but not in the group of children treated with budesonide. Further studies are desirable in order to ascertain whether budesonide offers an improved ratio between beneficial anti-inflammatory effect and unwanted systemic activity.
The prognostic value of several clinical and histopathological characteristics has been evaluated in patients with Dukes' B and C carcinoma of the rectum and the rectosigmoid. Data on 260 Dukes' B and 208 Dukes' C tumours entered into a prospective, randomized clinical trial of post-operative radiotherapy (50 Gy given with 2 Gy/fraction in an overall time of 7 weeks) were analyzed by means of the Cox proportional hazards model. The Dukes' stages B and C were analyzed in two separate multivariate analyses. In patients with Dukes' B tumours, a poor prognosis was associated with age above 60, perineural and venous invasion, tumour located less than 10 cm from the anal verge and elevated pre-operative carcinoembryonic antigen (CEA) (greater than 3.2 ng ml-1). In patients with Dukes' C tumours, perineural and venous invasion, tumour located less than 10 cm from the anal verge, and elevated pre-operative CEA were associated with a poor prognosis. In addition, a large tumour diameter had a strong, negative influence on the prognosis. Males seemed to have a poorer prognosis than females among the Dukes' C patients. Resection of neighbouring organs was also associated with a poor prognosis in this stage. Post-operative radiotherapy as administered in the present series had no significant influence on prognosis. Based on the derived prognostic models patients with a hazard of death above the median in each stage were selected. A separate analysis of the survival in these high risk patients showed no survival benefit from radiotherapy. The proportional hazards model may be a useful tool in selecting patients for more aggressive adjuvant treatment.
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A double-antibody sandwich ELISA was developed for the detection of antigenic differences between wild and vaccine-derived strains of poliovirus type 2 and poliovirus type 3. Antibodies were prepared in rabbits by immunization with purified antigens of vaccine strains (type 2: Sabin P712, and type 3: Sabin Leon) and wild type strains (type 2: MEF, and type 3: Pool 30). Immunoblotting analysis of all antisera demonstrated that the IgG antibodies raised in rabbits have specificity towards the main structural proteins (Vp1, Vp2 and Vp3) of poliovirus. IgG fractions were purified from antisera by affinity chromatography, on a protein A-activated Sepharose 4B column. Purified IgG antibodies were used for coating of microtest plates (catching antibodies). The same reagents labelled with horseradish peroxidase were used as conjugates, after cross-adsorption with antigens of the same type heterologous virus strains (strain-specific conjugates). 29 poliovirus type 2 strains and 73 poliovirus type 3 strains isolated from clinical samples, were differentiated intratypically, as vaccine-derived or wild types, no intermediate strains were found and all samples tested fell in two distinct (vaccine/wild) categories. As little as 40 ng of poliovirus antigens was detected in stool samples from healthy children or from polio patients cultivated in monkey kidney tissue cultures. Preparation of strain specific conjugates did not require large amounts of poliovirus antigens. The developed ELISA, which is economic and capable of (1) detection of low amounts of poliovirus antigens in cultivated clinical samples, and (2) intratypic differentiation of poliovirus antigens as either vaccine-derived or wild type, is therefore well suited for large scale screening of poliovirus isolates.
We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured in a blind design by a microphoto-oscillographic technique. A total of 740 ciliated cells from seventy-four cell scrapings were studied. Mean baseline of ciliary beat frequency was 10.2 Hz. The ciliary beat frequency exhibited a pronounced variability in the spontaneous changes between the cell scrapings, yet less so within cell samples from the cell scrapings. We, therefore, evaluated the effect of the test solutions relative to the spontaneous decrease found during simultaneous perfusion with control solution of samples from the same cell scrapings. LTC4, 3-300 nmol/l, caused a highly significantly dose-related decrease in the ciliary beat frequency by up to approximately 20% as compared to the corresponding control solution. The effect of LTC4 was significantly inhibited by the SRS-A receptor antagonist FPL 55712 (10 mumol/l), but not by indomethacin (10 mumol/l). LTD4, 300 nmol/l, also decreased the ciliary beat frequency. LTB4, which is a leukotriene, although without the sulphidopeptide side chain of the SRS-A leukotrienes, did not affect the ciliary beat frequency in a concentration of 100 nmol/l. This would seem to confirm the structure specificity of the elucidated effect of the SRS-A leukotrienes. Histamine (100 mumol/l) did not affect the ciliary beat frequency.(ABSTRACT TRUNCATED AT 250 WORDS)