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Biomedical subjects

K Holmberg

Publications and source records attributed to K Holmberg.

At least 109 records · Page 6Linked to original sources

Intranasally administered budesonide, a glucocorticoid, does not exert its clinical effect through vasoconstriction.

Dermally applied topical glucocorticoids induce a pallor of the skin. 'vasoconstriction', which has been used to grade the anti-inflammatory potency of such preparations. This study was performed in order to explore the possibility of a similar 'vasoconstrictor' phenomenon existing in the upper airway mucosa, which might thus offer one explanation for the clinically beneficial effect of topical glucocorticosteroid preparations in the treatment of allergic and non-allergic rhinitis. The possibility of a changed sensitivity to alpha and/or beta-adrenergic stimulation was also evaluated. Ten normal subjects participated in the present double-blind, randomized, crossover, placebo-controlled study. After establishing a baseline in nasal peak flow and nasal mucociliary clearance, the patients were treated for 8 days with either budesonide 100 micrograms/nasal cavity morning and evening, or a matching placebo. After a wash-out period of 2 weeks the treatment was repeated using the other treatment alternative. Nasal peak flow measurements were taken immediately before and 1 h after each application of treatment. After 1 week of treatment the nasal mucociliary transport was determined and the subjects were subjected to an intranasal challenge with 0.05 mg of oxymetazoline and 5.2 mg terbutaline on 2 different days in order to test for alpha and beta-adrenoceptor sensitivity. The response to these challenges was monitored by symptom scores and nasal peak flow measurements. Neither active treatment with budesonide aqueous suspension nor the placebo treatment induced any change in the mucociliary transport time nor in nasal airway as measured with the peak flow meters.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Candida albicans: mannan and protein activation of cells from various human lymphoid organs.

Challenging human lymphocytes with soluble cytoplasmic Candida albicans protein antigen (CP) and cell-wall-derived C. albicans mannan (CM) induced DNA synthesis and antibody secretion measured as plaque-forming cells (PFC) in an indirect haemolytic assay. Enriched T and B lymphocytes responded poorly to CP and CM. However, when adherent cells were added, T and B cells responded well to CM, but not to CP. Peripheral blood lymphocytes responded more strongly to CP than to CM, with peak stimulation on day 7. Bone marrow cells displayed similar DNA synthetic responses as blood lymphocytes, but peak stimulation occurred on days 4 and 5 for CP and CM, respectively. Cells from the various parenchymal organs, including adenoid, tonsil, and spleen, showed peak DNA synthesis ranging from days 3 to 5 with a tendency for CM to produce an earlier response than CP. In contrast to that observed in blood and bone marrow cells, CM induced a higher DNA synthesis in cells from parenchymal organs than CP, which gave low stimulations. PFC, like DNA synthesis, in blood and bone marrow cells responded best to CP, whereas spleen cells showed the highest response to CM. In blood and bone marrow cells, only IgG PFC were induced, but in spleen cells IgA and IgM PFC were also stimulated by CM. Fetal liver cells responded poorly to these two Candida preparations. CM but not CP stimulated DNA synthesis in umbilical cord blood lymphocytes and IgG, IgA, and IgM in spleen cells, suggesting that CM is a polyclonal activator and that CP acts as an antigen.

Antibodies, Fungal↗

Mucosal blood flow in the human nose following local challenge with histamine.

Nasal blood flow was measured using the 133Xe wash-out method in 10 non-allergic subjects and 13 asymptomatic hay fever patients. Determinations were made before and 15 min after challenge with diluent, 0.13 mg, 1.3 mg and 13 mg of histamine/nasal cavity. Nasal symptom scores were recorded. The nasal inspiratory peak flow was determined simultaneously in the hay fever patients. No differences in blood flow or symptom score recordings were found between the normal subjects and allergic patients under basal conditions or after histamine challenge. The nasal blood flow increased after challenge with the highest histamine dose. The increase was 34% (P less than 0.05) from baseline in normals and 47% (P less than 0.05) in allergics. There was a dose-dependent increase in nasal symptom scores following histamine challenge, again with no difference between normal and allergic subjects. The nasal peak flow decreased in a similar manner with a maximum decrease of 74% (P less than 0.001). The present study gives further support to the notion that histamine is not the only mediator involved in vascular reactions during allergic rhinitis.

Adult↗

Effects of topical treatment with H1 and H2 antagonists on clinical symptoms and nasal vascular reactions in patients with allergic rhinitis.

Fifteen asymptomatic subjects with allergic rhinitis participated in a double-blind, randomized, crossover, placebo-controlled study. The subjects were pretreated intranasally with a single dose of a selective H1 receptor antagonist, levocabastine, and/or selective H2 receptor antagonist, ranitidine, prior to a nasal allergen challenge. The nasal symptoms obtained at the challenge were assessed using a scoring technique 15 min after the allergen exposure. The nasal airway resistance was determined twice prior to and once after the allergen challenge using anterior rhinomanometry. The nasal mucosal blood flow was determined before and 15 min after allergen challenge using the 133Xe wash-out technique. After pretreatment with the H1 antagonist there was a statistically significant reduction in the number of sneezes and rhinorrhea compared to pretreatment with placebo. Pretreatment with the H2 receptor significantly decreased the rhinorrhea but not the sneeze. The nasal blockage was unaffected by both the H1 and the H2 antagonists. Pretreatment with the H1 and/or the H2 antagonists inhibited the reduction in the nasal mucosal blood flow induced by the allergen challenge to a significant degree. The present findings suggest that topical treatment with the highly selective histamine antagonist, levocabastine, inhibits allergen-induced reflex-mediated symptoms. H1 and H2 receptors do not appear to be involved in the regulation of the tone of the capacitance vessels. This indicates that a more complex mechanism participates in the induction of nasal blockage than the direct effect of histamine on H1 and H2 receptors on the capacitance vessels of the nasal mucosa alone. Both H1 and H2 receptors are of importance for the regulation of nasal mucosal blood flow during the allergic reaction.

Administration, Topical↗

Surveillance tests for the diagnosis of invasive fungal infections in bone marrow transplant recipients.

A system for serial surveillance cultures and serological tests for diagnosis of disseminated fungal infections (FI) was evaluated retrospectively in 14 bone marrow transplantation (BMT) patients with autopsy proven FI (11 with Candida albicans and 3 with Aspergillus fumigatus) and 14 control BMT patients without FI. The 2 groups did not differ with regard to clinical features. Serial cultures for candida from various sites were more often positive in the FI group than in the controls (p less than 0.001). Consistently negative cultures were never seen in the FI patients (p less than 0.05). Positive conventional blood cultures or cultures of specimens from bronchoscopy were suggestive of FI before death in 6/14 of the patients with FI. No blood cultures were positive among the controls. Sequential serum samples taken before death in 7 patients with systemic candidiasis, 3 with invasive aspergillosis, and 12 control patients, were tested retrospectively for diagnostic candida and aspergillus antibody titers and free circulating candida mannan. The serological tests gave evidence of FI in 9/10 patients with FI and in half of the controls (p less than 0.05). In 8/10 cases with FI, serological tests became positive before a positive blood culture or a clinical suspicion of FI. With a prevalence of 7.5% of FI at our clinic, the predictive values for positive and negative was 100% and 97% for the antigenemia test and 14% and 100% for the ELISA test for IgA antibody against C. albicans mannan. Our data suggest that a rational use of surveillance cultures and serological tests may aid in an earlier diagnosis of FI in BMT patients.

Adolescent↗

Influence of topical phenylpropanolamine on tachyphylaxis and mucociliary clearance in the human nose.

Topical nasal phenylpropanolamine in a 2.5 per cent solution (PPA) was used in an evaluation of the possible development of tachyphylaxis and of possible effects on the mucociliary system after one week of treatment in healthy humans. The tendency of PPA to produce tachyphylaxis was evaluated by rhinomanometrie measurements of nasal airway resistance after repeated dose-response provocations. The mucociliary transport time was tested with the saccharine-dye test. No reduced dose-response effect or change in mucociliary transport time was found with PPA, thus indicating that one week of treatment does not contribute to such adverse effects.

Adolescent↗

Karyotypes of human T-lymphocyte clones.

T-Lymphocyte clones from healthy males and females and from melphalan-treated ovarian carcinoma patients were studied with regard to sporadic chromosomal aberrations and clonal karyotype: 85% of the clones showed a normal, diploid karyotype, and sporadic aberrations were found to occur at about the same low frequency as in short-term lymphocyte cultures. An abnormal karyotype was found in 11 of the 72 clones studied. Loss of an X chromosome, which was the most frequent abnormality in female clones, was verified by densitometry of Southern blots of clonal DNA hybridized with a probe for the X-linked hprt locus. Abnormal karyotype due to chromosomal rearrangement was found in nine clones, and, in five of these, chromosome 12 was involved in the aberration. About 33% of the clones from melphalan-treated patients had an abnormal karyotype, in comparison with about 10% of clones from healthy control subjects. This difference indicated that melphalan treatment may induce stable chromosomal rearrangements that are compatible with cellular proliferation and clonal expansion.

Cells, Cultured↗

Nasal mucosal blood flow after intranasal allergen challenge.

The nasal mucosal blood flow in patients with allergic rhinitis was determined at nasal allergen challenges with the 133Xenon washout method. Determinations were made in 12 subjects before and 15 minutes after challenge with diluent and increasing doses of allergen. The time course was followed in eight subjects by means of repeated measurements during 1 hour after a single allergen dose. Finally, the blood flow was measured after unilateral allergen challenge in the contralateral nasal cavity. A dose-dependent decrease in blood flow was found after nasal challenge with increasing doses of allergens, whereas challenge with diluent alone did not induce any changes. The highest allergen dose, which also induced pronounced nasal symptoms, resulted in a decrease in blood flow of 25% (p less than 0.001). The time-course study demonstrated a maximum decrease in blood flow 10 to 20 minutes after challenge and then a gradual return to baseline. Unilateral allergen challenge resulted in a decrease in blood flow in the contralateral, unchallenged nasal cavity, suggesting that part of the allergen-induced changes in blood flow were reflex mediated.

Adult↗

Diagnostic methods for human actinomycosis.

Human actinomycosis is caused by Actinomyces israellii and other Actinomyces spp. together with Arachnia spp. These are common commensal bacteria which colonize many body surfaces. Infection of damaged tissues follows trauma, surgery and so on. This article outlines the techniques available for detecting these organisms and actinomycosis infection.

Actinomyces↗

Influence of topical beclomethasone dipropionate suspension on human nasal mucociliary activity.

The local effect of an aqueous suspension of beclomethasone dipropionate on human nasal mucociliary clearance was studied in 14 healthy volunteers. A triple blind, randomized, placebo controlled, cross-over design was utilised. Measurements of mucociliary clearance were made before treatment, after a single dose and after one week of continuous treatment either with placebo or active substance, utilising the saccharine-dye test. No change in mucociliary clearance was found after treatment with beclomethasone dipropionate or placebo suspension.

Administration, Topical↗

Comparison of tympanometry and otomicroscopy during healing of otitis media.

One hundred ears in 50 children with acute otitis media during healing were examined with tympanometry and the objective measures were compared with the subjective evaluation of otomicroscopy by four otolaryngologists independently. Tympanometric findings could more often correctly suggest reduced tympanic membrane mobility than did otomicroscopy, but both methods gave an equally good indication of middle ear effusion. However, otomicroscopy was necessary when evaluating the colour and the appearance of the tympanic membrane and revealed middle ear effusion in a few cases with 'normal' tympanometry. As a rule: normal tympanometry (Jerger type A) was closely correlated with a normal tympanic membrane and a normal middle ear without effusion; pathological tympanometry (Jerger type B) was accompanied by middle ear effusion and needed follow-up; ears with tympanometric pressure more negative than -150 mmH2O but more positive than a flat curve needed otomicroscopy to identify middle ear effusion.

Acoustic Impedance Tests↗

In vitro assessment of antifungal drug resistance.

Several studies have documented the variability in the susceptibility pattern of fungi to antifungal drugs, and fungi possess resistance determinants to negate the effects of antifungal agents. In vitro assessment of both resistance and susceptibility are measured by suitable concentration endpoints of the antifungal drug, the minimal inhibitory concentration (MIC). MICs serve as the main parameter to define the fungistatic action on fungi growing in culture. For the antifungals used for treatment of local mycoses, the limit between a MIC value indicating susceptibility and one indicating resistance is usually determined empirically on the basis of the correlation between MIC values, and either positive or negative response to chemotherapy. The principles of susceptibility testing of fungi are essentially the same as those for bacteria. However, testing with fungi must deal with the fact that interpretation of the results is complicated by inherent differences in fungal morphology, growth rate, and optimal culture conditions. Several factors could adversely affect the test results and must be considered in the design of susceptibility testing of fungi. It is obvious when the present data on fungal susceptibility testing are reviewed that much more work on standardization of techniques and interpretation of results is necessary. This presentation will focus on the in vitro susceptibility testing for determining primary and secondary drug resistance of griseofulvin and azole antifungal agents, and the correlation between the activities of these antifungals in vitro and in vivo.

Antifungal Agents↗

New diagnostic methods in dermatological mycology.

In dermatological mycology, direct microscopy and culture are the main diagnostic procedures. Microscopic examination of a wet KOH preparation is usually satisfactory for the detection of the infecting organism based on the morphological characteristics of the fungal elements. However, examination of the KOH mount requires skill and experience. In order to help the unskilled personnel to recognize fungal elements by microscopic examination, a number of differential strains have been described. Great strides have been made to improve the sensitivity and specificity of direct microscopy for the detection of fungi also on chemical properties of the fungal cell wall. Thus fluorescence microscopy using fluorescent brighteners, e.g. Blancophor BA holds great promise for its wide application in dermatologic mycology. Culture media enjoy considerable application in the isolation and identification of dermatophytes and Candida species from clinical specimens. Some novel media have been formulated recently to assist in the early detection and identification of some fastidious dermatophytes e.g. Trichophyton verrucosum. In dermatological mycology the predictive diagnostic value of the diagnostic tests has to be delineated for each disease state. As an example, direct microscopy is a useful diagnostic procedure for the detection of dermatophytes and Pityrosporum-yeasts in clinical materials, but less valuable for the detection of Candida. Furthermore, considerable attention needs to be focused on the utilization of new and old diagnostic tests from a series of viewpoints including necessity, usefulness, clinical relevance and cost-benefit analysis.

Candida↗