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Biomedical subjects

J Dolovich

Publications and source records attributed to J Dolovich.

At least 145 records · Page 8Linked to original sources

Occupational asthma in nurses handling psyllium.

Five nurses aged 31-55 years old had a history of asthmatic symptoms after being exposed to psyllium that they prepared and distributed to patients. They had been nurses for 9-20 years and had reported asthmatic symptoms related to work in the past 3-12 months. They reported symptoms of rhinoconjunctivitis and all were atopic but only one had a previous history of asthma. Four of the five tested subjects had an immediate skin reaction to a commercial psyllium extract. All had IgE antibodies to psyllium. At the time that they were investigated, four out of the five had a significant increase in bronchial responsiveness to methacholine (PC 20 less than 8 mg/ml). Inhalation challenges with psyllium caused isolated immediate (one subject) and dual reactions (three subjects). One subject exposed for only 1 min to the psyllium powder experienced a severe immediate bronchospastic reaction, which required intubation for 3 h with complete functional recovery thereafter. This experience illustrates the precautions necessary, with the inclusion of a cautious dose-response approach, even with an 'occupation-type' challenge in the laboratory.

Adult↗

Antibody responses to hemodialysis-related antigens in chronic hemodialysis patients.

Allergic-type reactions during hemodialysis are sometimes due to sensitization to ethylene oxide. To examine the possibility that additional antigens might be a basis for unexplained reactions, antibodies to formaldehyde and phthalate-related antigens and to dialyzer extracts were measured. Unselected sera from 113 chronic hemodialysis patients (CHP) and 200 control subjects were tested for IgG antibodies to formaldehyde-treated human serum albumin (HSA). The IgG antibody activity was confirmed in sera of five CHP who had used formaldehyde-treated dialyzers. These antibodies also reacted with formaldehyde-treated red blood cells. Sera from 71 CHP and 80 controls were tested for IgE antibodies to diethylphthalate-treated HSA; antibody was detected in two CHP sera. With extracts from hollow-fiber dialyzers, IgG antibody was detected in approximately 1/3 and IgM antibodies in approximately 1/2 of CHP sera. This antibody was found in comparable numbers of control sera. It was concluded that these additional substances are immunogenic and could be involved in allergic-type reactions.

Anaphylaxis↗

Ethylene oxide sensitivity in hemodialysis patients.

Sera from 138 patients who had experienced hypersensitivity-type reactions while on hemodialysis (reactors) were examined retrospectively by the radioallergosorbent test (RAST) for specific IgE antibody to ethylene oxide (ETO). Seventy-eight hemodialysis patients without a history of reaction were also evaluated as controls. Elevated serum RAST values (greater than 2.0) were more common in reactors (63%) than in controls (11%, p less than 0.001). In a second study, RAST assays were performed using human serum albumin conjugated to ETO (HSA-ETO) as antigen and also using a concentrate of fluid used to rinse ETO-sterilized dialyzers ("dialyzer extract") as antigen. The RAST ratios obtained with HSA-ETO were similar to those obtained using the dialyzer extract (rank order correlation coefficient = 0.829, p less than 0.001). In a third study, RAST inhibition was demonstrated both by HSA-ETO and dialyzer extract. Our results, extending previously published reports, suggest that hypersensitivity to ETO might play an important role in hemodialysis-associated hypersensitivity-type reactions.

Antigens↗

Contribution of basophil/mast cell and eosinophil growth and differentiation to the allergic tissue inflammatory response.

The mechanisms underlying allergic tissue basophil/mast cell (BMC) or eosinophil (Eo) accumulation are unclear, especially since chemotaxis or IgE levels do not offer a sufficient explanation. We have found that a formaldehyde-blockable, steroid-responsive nasal metachromatic cell (NMC) population predominates in epithelium and correlates well with symptoms and signs in patients with allergic rhinitis. Circulating BMC and Eo progenitors (colony-forming cells in culture; CFU-c) are increased in atopic patients, inversely related to NMC counts, and fall as NMC numbers rise during seasonal allergen (ragweed pollen) stimulation. The metachromatic cell progeny of these CFU-c are also formaldehyde-blockable in their staining reaction and thus may correspond to NMC. Human nasal polyps yield BMC CFU-c. Nasal polyp epithelial scrapings or mononuclear cells, T lymphocytes or keratinocytes in vitro all produce potent BMC or Eo colony-stimulating activities (CSA) as well as an interleukin-3-like activity, each of which is partially separable from the others. Nasal epithelial cells cultured from scrapings of atopic, as opposed to nonatopic, patients also produce BMC or Eo CSA with an enhanced effect of the former on atopic peripheral blood CFU-c growth. These studies support the hypothesis that BMC and Eo accumulate in allergic inflammation as a result of in situ growth and differentiation of progenitors stimulated by soluble hemopoietic factors derived from mucosal cell populations.

Basophils↗

Toluene diisocyanate respiratory reactions. I. Reassessment of the problem.

A series of workers with exposure to and respiratory symptoms from toluene diisocyanate (TDI) was compared with a group of exposed, asymptomatic workers and with normal controls using immunologic and clinical evaluations. Improved understanding of TDI-induced respiratory disease may best be achieved by categorizing the symptomatic workers into at least 3 and possibly 4 groups: immunologic TDI asthma; pre-existing chronic respiratory disease exacerbated or unaffected by TDI; asthma coincidental with TDI exposure, and possibly TDI respiratory disease secondary to toxic or inflammatory mechanisms.

Adult↗

Metachromatic cell progenitors and specific growth and differentiation factors in human nasal mucosa and polyps.

We previously demonstrated that fluctuations in circulating metachromatic cell progenitors were inversely related to nasal metachromatic cell (NMC) counts and nasal symptoms in allergic rhinitis. Now, we have quantitated NMC progenitors and lineage-specific growth factors using a hemopoietic colony assay. Cell suspensions from excised collagenase-treated nasal polyps (n = 7) contained 3.8 +/- 1.1 granulocyte colony-forming cells per 10(6) cells plated, compared to less than or equal to 0.5 in human tonsil suspensions, less than or equal to 0.5 in nasal mucosal epithelial scrapings, and 33 +/- 8 in peripheral blood of patients with ragweed allergic rhinitis (p less than 0.01). The percentage of metachromatic cells in nasal-polyp-derived colonies was 47 +/- 10 compared with 3.0 +/- 0.7 in peripheral blood colonies (p less than 0.005). Highly potent metachromatic cell colony-stimulating activity (CSA) was detected in supernatants from cultured human nasal epithelial scrapings from both polyps and atopic nasal mucosa, but not from nonatopic nasal mucosa. Supernatants from polyp mononuclear cells stimulated with phytohemagglutinin also contained metachromatic cell-CSA, which had an approximate molecular size of 25 to 70,000 daltons on column chromatography. An IL-3-like activity was also detected in these supernatants. These observations provide further evidence for in situ hemopoietic mechanisms in human nasal mucosa, involving epithelium-derived stimulation of local metachromatic cell progenitor growth and differentiation in allergic rhinitis.

Basophils↗

Occupational asthma and IgE sensitization in a pharmaceutical company processing psyllium.

We assessed the prevalence of occupational asthma and IgE sensitization to psyllium in a pharmaceutical company producing psyllium hydrophilic mucilloid, which is used as a laxative. Workers were intermittently exposed, approximately 5 times/yr, for periods of less than 10 days. Of the 140 employees, 130 (93%) were studied before a processing period via a questionnaire spirometry (n = 125), blood sampling (n = 118), and skin prick tests (n = 120) with 7 common inhaled allergens as well as plantain and psyllium. Thirty-nine workers had a history suggestive of occupational asthma. Twenty-three of 120 (19%) showed a skin wheal diameter greater than or equal to 3 mm to psyllium and 31 of 118 (26%) had increased specific IgE antibodies; 39 (32%) workers had at least 1 of these 2 features. Subjects with a questionnaire suggestive of asthma or occupational asthma were further investigated by serial monitoring of peak expiratory flow rates and PC20 methacholine before and during the psyllium processing period. All workers had spirometry repeated during the processing period. Twenty-one subjects who had a PC20 less than or equal to 16 mg/ml (n = 10) and/or decreased their PC20 by a greater than or equal to 3.2-fold difference (n = 4) and/or changed their FEV1 by greater than or equal to 10% (n = 13) during the processing period were referred for inhalation challenges to psyllium in the laboratory. Five of the 18 workers for whom these tests were feasible gave an immediate bronchoconstrictive reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mast cell involvement in various inflammatory processes.

Mast cells from different tissue sites may have different histochemical, chemical, and functional properties. Whatever the basis for these differences, they must be important in terms of their biologic significance. Through their mediators, mast cells are involved in many different acute and chronic inflammatory processes. They act in delayed hypersensitivity, immediate hypersensitivity, and in granulomatous reactions. They can influence phagocytosis, chemokinesis, and many aspects of immune activity in several different T and B cell pathways, to mention only a few effects. Mast cells are involved in repair processes including fibroblast function and fibrosis. Their growth may be influenced by T cell-derived factors as well as factors derived from the epithelium. They appear to be intimately involved with nerves and can form apparent communications with neurones, especially those containing Substance P, which causes all types of mast cells to degranulate. Mast cells may therefore act as central switchboards between the central nervous system and migrating and sessile cell types in inflammatory processes.

Animals↗

Prevention of chymopapain anaphylaxis by screening chemonucleolysis candidates with cutaneous chymopapain testing. A preliminary report.

The risk of anaphylaxis in candidates for chemonucleolysis for herniated lumbar discs is approximately 1%. An investigation was designed to eliminate or reduce the incidence of chymopapain anaphylaxis. The procedure was to restrict chemonucleolysis to patients who are prick test-negative to chymopapain at a concentration of 10 mg/ml. The authors skin-tested 292 chemonucleolysis candidates; five were positive and 287 were negative. None of the positive patients were injected with chymopapain. There were no instances of unequivocal chymopapain anaphylaxis in the skin test-negative group. This 0% incidence of anaphylaxis in skin test-negative patients was compared with a population estimate of 1%, based on historical data. The resulting value of p = 0.08 value fell short of the conventional level of significance of 0.05. The p value will reach 0.05 when the series of skin test-negative patients without anaphylaxis reaches 360. It is important that this information is readily available to physicians concerned about anaphylactic reactions to chymopapain.

Adult↗

Human asthma due to a dog's drugs.

A woman had a recurrence of asthma due to sensitization to her dog's pancreatic enzyme powder. The cause of her asthma was confirmed by bronchial inhalation challenge, and specific IgE antibodies against the enzymes were found in her serum but not in that of control subjects.

Animals↗

The origin of airway hyperresponsiveness.

Consideration of the origin of airway hyperresponsiveness appears central to understanding the origin of asthma. Subjects with and without asthma differ both in the ease with which airway narrowing is produced by inhalation of histamine or methacholine and in the ability to demonstrate a maximal response to these agents. The latter appears, on present evidence, to be due to an added mechanism in asthma rather than the absence of a potent inhibitory process. Airway hyperresponsiveness is probably acquired during life as a result of airway reactions to various stimuli, although genetic factors such as atopy are likely to predispose the person to develop hyperresponsiveness. Environmental stimuli include inhaled allergens, chemical sensitizers, airway infections, immunization, and ozone. Allergen-induced airway hyperresponsiveness occurs in association with late-phase asthmatic responses. This and ozone-induced hyperresponsiveness have been demonstrated to be associated with release of chemical mediators and the cellular phase of inflammation. Their effect does not appear to be accounted for by increase in airway epithelial permeability, decrease in airway caliber, reflex bronchoconstriction, or beta-adrenoceptor blockade. The mechanism(s) responsible for the induced hyperresponsiveness are unknown but may involve airway epithelial damage, edema in and around the airway walls, stimulation of the noncholinergic excitatory or inhibition of the nonadrenergic inhibitory systems, or a change in function of airway smooth muscle. Airway hyperresponsiveness can be transient or persistent. Transient increases in responsiveness are almost certainly associated with mediator release and inflammation. It is not known whether persistent hyperresponsiveness is due to the same process, fired, for example, by leaky mediator-releasing cells and/or to some persisting change in neurogenic or smooth muscle function.

Allergens↗

Polyethylene glycol-modified ragweed extract: comparison of two treatment regimens.

Fifty ragweed-sensitive subjects were each administered a course of 12 injections of polyethylene glycol-modified ragweed extract. To investigate the effect of two treatment regimens, subjects were paired according to their skin sensitivity to ragweed extract and the severity of their rhinoconjunctivitis the previous year. One of each pair was randomly allocated to receive injections at weekly intervals, and the other subject was to receive injections daily until a local or systemic adverse reaction occurred and then to switch to a weekly schedule for the rest of the course. Blood was obtained immediately before each injection and at the end of the study to examine the rates of change of ragweed-specific IgE and IgG antibody levels and to evaluate whether these or other variables could be used to predict the occurrence of adverse reactions. Immediate reactions were minimal in both groups, but more late reactions occurred in subjects receiving the modified rush regimen; therefore, although the total number of injections received by the two groups was similar, the total dose of protein injected in the rush group was only half that achieved in the weekly group. Treatment induced increases in ragweed-specific IgE and IgG antibodies in both groups; the increase in IgE was similar in the two groups, but the increase in IgG was higher in the weekly group. There was a marked decrease in skin sensitivity to ragweed extract after treatment that was directly related to the IgG antibody response, and therefore, these changes were greater in the weekly group.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Basophilic cell progenitors, nasal metachromatic cells, and peripheral blood basophils in ragweed-allergic patients.

Circulating hematopoietic progenitor cells giving rise to colonies containing basophilic cells (basophilic cell colony-forming units in culture [CFU-c]), nasal epithelial metachromatic cells (basophils and/or mast cells) (NMC), and blood basophils were enumerated before, during, and after a ragweed-pollen season in patients with ragweed hayfever and patients with perennial allergic rhinitis who were not ragweed allergic. In the patients with seasonal hay fever, the following was observed: basophilic cell CFU-c, measured as basophilic cell or histamine-containing colonies, were significantly reduced during the ragweed season compared to before (p less than 0.005) or after (p less than 0.025) the season in the ragweed-allergic group only. Conversely, peripheral blood basophils were higher during the ragweed season than before or after (p less than 0.001) in the ragweed-allergic group, whereas the number of NMC was higher during the season than before the season in this group (p less than 0.05). There were no such changes during the season in the group of patients with perennial allergic rhinitis. The observed seasonal changes in both NMC and circulating basophilic cell CFU-c are discussed in the context of lineage relationships among metachromatic cell types.

Basophils↗

Effect of beclomethasone dipropionate on nasal metachromatic cell sub-populations.

The effect has been investigated of local administration of beclomethasone dipropionate (BDP) on cell numbers of nasal epithelial metachromatic cell (NMC) sub-populations. Twenty-one patients with perennial allergic rhinitis were studied in four groups according to the duration of treatment or after treatment with BDP. Nasal scrapings were taken after 1 week (Group 1) or 2 weeks (Group 2) of BDP treatment, or after discontinuing BDP for 1 week (Group 3) or 2 weeks (Group 4). Cells were fixed with Mota's lead acetate or 10% buffered formalin followed by toluidine blue staining to count the number of NMC and to classify these according to morphological sub-types (basophils or mast cells). Formalin-sensitive mast cells and basophils in nasal scrapings were reduced more than formalin-resistant mast cells with BDP treatment. Formalin-sensitive mast cells were also more prompt to recover from BDP than formalin-resistant mast cells. The results suggest that the formalin-sensitive NMC is a sub-population of cells which responds to BDP treatment in allergic rhinitis.

Administration, Topical↗

Peripheral blood basophils, basophil progenitors, and nasal metachromatic cells in allergic rhinitis.

Relationships among mature blood basophils, blood basophil colony-forming units in culture (CFU-c), and nasal metachromatic cells (NMC) were investigated using hemopoietic and histochemical techniques in 29 patients with allergic rhinitis and in 7 nonatopic control subjects. Total blood granulocyte and basophil CFU-c were significantly elevated in atopy; the highest levels of basophil CFU-c were found in patients with low total NMC counts in nasal scrapings (Group I), compared with those with intermediate (Group II) or high (Group III) counts: 10 +/- 3 basophil CFU-c per 10(6) cells in 10 Group I patients, 4 +/- 2 in 10 Group II patients, 3 +/- 1 in 9 Group III patients, and 0.1 +/- 0.1 in nonatopic control subjects (p less than 0.05). Mean histamine content and frequency of histamine-positive granulocyte colonies correlated with counts of basophils in colonies (r = 0.864, p less than 0.001). Peripheral blood basophils, which stained metachromatically with toluidine blue at pH 0.5 after Mota's lead acetate but not after formalin fixation, were highest in atopic Group III and lowest in Group I; a similar relationship was observed only for NMC, which also failed to stain after formalin fixation. Metachromatic cells in colonies were similar to formalin-sensitive NMC and to peripheral blood basophils in their sensitivity to different fixatives. Nasal symptoms correlated inversely with the number of basophil CFU and directly with the number of either formalin-sensitive NMC or peripheral blood basophils. These findings confirm and extend evidence for increased nasal metachromatic cells, basophilia, and alterations in basophilopoiesis in atopy.

Adolescent↗