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Biomedical subjects

J S Gallagher

Publications and source records attributed to J S Gallagher.

At least 19 recordsLinked to original sources

The trials, tribulations, and relative success of the ongoing clinical merger of two large academic hospital systems.

The North Shore Health System and the Long Island Jewish Medical Center merged in 1997 and now form the third largest not-for-profit academic health care system in the United States. The authors analyze the specific factors responsible for the relative success of the clinical merger, review their merger's initial failures and how they crafted a more pragmatic and appropriate set of guiding principles to continue the merger, and discuss the future of their institution's clinical integration strategy. In 2000, clinical integration of the 19 clinical departments at the two merged institutions was surveyed across five broad areas: conferences, residency programs, common faculty and support staff, finances, and research. Extents of clinical integration ranged from 20% to 72%. Six departments had more than 50% clinical integration, and overall clinical integration was 42%. Not surprisingly, clinical integration had occurred most frequently with conferences (50%) and least with finances (25%). The single-chairperson model for department leadership has been most successful in achieving significant clinical integration of the formerly separate departments. The relative success of the clinical merger has been guided by the principle that no clinical service should be integrated simply for the sake of merging, but rather that integration should be encouraged where and when it makes sense to achieve specific program goals. In addition, the merger would not have proceeded without constant communication among the leadership and staff, flexibility in building leadership models, patience in having events progress over a time course that developed trust among the senior leaders, and the presence of a senior executive structure whose authority to make decisions is accepted. The most important factor for achieving a reasonable level of clinical integration is the ability of the clinical leaders to collaborate and lead the change process.

Academic Medical Centers↗

Indirect assessment of 4,4'-diphenylmethane diisocyanate (MDI) exposure by evaluation of specific humoral immune responses to MDI conjugated to human serum albumin.

BACKGROUND: A study of occupational asthma among workers exposed to 4,4'-Diphenylmethane Diisocyanate (MDI). OBJECTIVE: To demonstrate if serum concentrations of MDI-specific IgG or IgE are sensitive biological markers of disease or of MDI exposure. METHODS: The study group consisted of nine MDI-exposed workers and nine nonexposed workers. Air sampling for MDI and polymethylene polyphenyl isocyanate, occupational and medical histories, respiratory physical exams, pre- and postshift spirometry, and self-administered peak expiratory flow rates were performed. Serum specific IgE and IgG antibodies to an MDI-human serum albumin (HSA) conjugate were assayed by the radioallergosorbent test and the enzyme-linked immunosorbent assay, respectively, and compared to nine nonexposed laboratory controls. RESULTS: No definitive cases of occupational asthma were documented. The mean level of MDI-specific IgG was significantly greater among exposed workers compared to nonexposed workers and laboratory controls (p = 0.04). Mean levels of TDI and HDI-specific IgG were also increased. CONCLUSION: This study demonstrates that serum concentrations of MDI-specific IgG appear to be a moderately sensitive biological marker of MDI exposure, but not an indicator of occupational asthma. Workers with IgG antibodies specific for one diisocyanate-HSA conjugate exhibit cross-reactivity to antigens prepared with other diisocyanates.

Adult↗

Isolation and characterization of high endothelial cell lines derived from mouse lymph nodes.

Two long-term cultured cell lines were established from BALB/c mouse axillary and cervical lymph nodes that exhibited a combination of functional, morphological, and phenotypic characteristics consistent only with high endothelial venule cells. Spleen lymphocytes selectively bound and migrated across the cell lines. On Matrigel, these cell lines formed tubules with lumens, a characteristic unique to endothelial cells. Morphologically the cells were 20-30 microns in diameter and exhibited contact inhibition. The cells were not myeloid in origin because they lacked sodium fluoride-inhibitable nonspecific esterase activity, myeloperoxidase activity, and F4/80 antigen. The cell line phenotypes were compared to high endothelial venule (HEV) cells in tissue sections. HEV cells in lymph node tissue sections expressed endoglin, PECAM-1, ICAM-1, VCAM-1, laminin, fibronectin, collagen IV, H2Kd, MECA 79, MECA 325, and vWF. The cell lines expressed endoglin, VCAM-1, fibronectin, and H2Kd. The cell line derived from cervical lymph nodes also expressed laminin and H2Dd. Neither cell line expressed collagen IV, IAd, ICAM-1, ICAM-2, dendritic cell antigen, or PECAM-1. They also did not express MECA antigens or intracellular vWF, consistent with reports of many cultured endothelial cells. To further substantiate cell ine identification, antiserum generated against the cell lines bound specifically to HEV cells in frozen lymph node tissue sections and to both of the lymph node-derived cell lines but not control cell lines. Thus, the lymph node derived-cell lines expressed molecules found on HEV cells in vivo and most importantly retained the functions of tubule formation, lymphocyte adhesion, and promotion of lymphocyte migration.

Animals↗

Antibodies to morphine in workers exposed to opiates at a narcotics manufacturing facility and evidence for similar antibodies in heroin abusers.

According to the International Narcotics Control Board, over 45,000 kg of morphine and 54,000 kg of codeine were ethically manufactured in 1986 at three facilities in the United States. Little information exists about possible adverse health effects associated with workplace exposure to opiate compounds in this industry. Because there are no specific federal standards for workplace exposure to narcotic dusts, exposure-control defaults to the nuisance dust standard (10 mg/m3, as an 8 hr time-weighted average). Narcotics manufacturing workers were evaluated for anti-morphine IgG before and 10 mo. after the implementation of an improved respiratory protection program (RPP). Significantly elevated IgG levels were measured before the improved RPP (P less than 0.005). After the improved RPP, a significant reduction was observed (P less than 0.001), suggesting that specific antibody levels could be used as biomarkers of exposure. Inhibition studies showed that the antibodies were specifically directed against morphine with some cross reactivity with morphine derivatives. Preliminary results are also shown which indicate that similar anti-morphine antibodies are present in the sera of intravenous heroin abusers. Elevated levels (P less than 0.05) of anti-morphine antibodies were detected in sera from heroin abusers, providing evidence that similar antibodies may be produced from non-occupational exposure to opiates. These finding have potentially far-reaching implications for addiction research and drug testing.

Air Pollution↗

Selective desensitization to seminal plasma protein fractions after immunotherapy for postcoital anaphylaxis.

A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation. Systemic reactions (SRs) were prevented by use of condoms. Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma. The intradermal end point threshold concentrations (ETC) were 10(-4) and 10(-1) micrograms of protein per milliliter to fractions 2 and 3, respectively. Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3. A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3. The patient experienced an SR after receiving a cumulative dose of 38.55 micrograms of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms. There was a one-log10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2. IT was continued three times weekly for 4 months until the patient tolerated 100 micrograms doses of both fractions 2 and 3. At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped. The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2. Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions. Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neonatal exposure to methyl chloroform in tape remover.

Methyl chloroform (MC) is commonly used solvent found in some adhesive tape remover products used in intensive care nurseries. Since volatile substances can accumulate inside an infant incubator, we measured levels of MC following simulated use of 2 commercially available adhesive tape remover pads. Readily detectable levels of MC could be found in incubator air for several minutes. Although adult occupational neurotoxic thresholds are higher, increased toxic susceptibility of the neonate CNS indicates caution should be observed.

Air↗

Immune responses of cynomolgus monkeys to phthalic anhydride.

Four groups of four Macaca fascicularis monkeys were administered 10 consecutive weekly subcutaneous injections of 2 mg aluminum hydroxide plus one of the following: 200 micrograms of phthalic anhydride (PA)-monkey serum albumin (PA-MSA, group 1); 200 micrograms of PA dissolved in ethanol-saline (EtOH-sal, group 2); 200 micrograms of MSA (group 3); or EtOH-sal alone (group 4). Direct intracutaneous tests to PA-MSA, PA-EtOH-sal, MSA, and EtOH-sal were applied at biweekly intervals throughout the course of the immunization. Serum-specific IgG to PA-MSA and specific IgE to PA-MSA were determined at 2-week intervals according to the ELISA and RAST methods, respectively. The prevalence of cutaneous sensitivity to PA-MSA in the PA-MSA-immunized group (group 1) was significantly greater after 4 and 6 (p less than 0.01) and 8 and 10 (p less than 0.05) weeks, compared with the other treatment groups. Significantly elevated (p less than 0.01) PA-MSA-specific IgG was also observed in monkeys in group 1 compared with the other treatment groups. No significant changes in PA-MSA RAST or total IgE were observed in any group during the study. These results indicate that parenteral sensitization to PA in subhuman primates requires the presence of new antigenic determinants formed by PA on protein carriers.

Animals↗

Pulmonary and immunologic evaluation of foundry workers exposed to methylene diphenyldiisocyanate (MDI).

A cross-sectional evaluation was performed of workers in a steel foundry in which methylene diphenyldiisocyanate (MDI) was used as a component of a binder system used to make cores and molds. Preshift and postshift spirometry and clinical evaluations were performed on 26 currently exposed (group I), on six formerly exposed (group II), and on 14 nonexposed workers to MDI (group III). Serum samples were assayed for total antibody binding, specific IgG by ELISA, and specific IgE by the RAST method to MDI-human serum albumin (HSA). Symptoms compatible with occupational asthma were elicited from seven (27%) of 26 group I workers and from three of six group II workers. No symptoms were reported by group III workers. Intrashift change in FEV1 (a mean decrease of 0.049 L) in group I workers was significantly decreased compared to that in unexposed group III workers (a mean increase of 65 ml; p = 0.043). Specific IgG and total antibody responses to MDI-HSA were detected only in workers with current or former exposure to MDI. Only one worker was identified with IgE-mediated occupational asthma exhibiting a positive prick test and elevated RAST to MDI-HSA of 25.5% bound. In this occupational setting, polyclonal immune responses to MDI-HSA and clinical sensitization to MDI were demonstrated to occur.

Adult↗

Anaphylaxis in pregnancy.

Anaphylaxis is a relatively uncommon event in pregnancy that can have serious implications for both mother and fetus. A case is presented of anaphylaxis to intravenous (IV) ampicillin given during labor, and the pertinent literature is reviewed. Maternal morbidity occurred after the use of IV epinephrine. Fetal outcome was good, presumably as a result of prompt delivery near term. The management of anaphylaxis in pregnancy is reviewed.

Adult↗

Occupational asthma from inhaled egg protein.

We evaluated workers and performed an industrial hygiene assessment at a plant where raw eggs are processed into powdered egg yolk and whole egg. Egg dust levels in the packaging room straddled the American Conference of Governmental Industrial Hygienists' (ACGIH) exposure guideline of 10 mg/m3 for nuisance dust. We obtained medical histories from 25 workers, and performed physical examinations, spirometry, and serial determinations of peak expiratory flow rate (PEFR) by portable meter every 3 hrs (while awake) for 7 days. We defined symptomatic bronchial lability to be a decrement in PEFR on any one day of 20% or more of the day's maximum, with concurrent symptoms. Skin-prick tests and serum assays for specific IgE by the radioallergosorbent (RAST) method were performed to assess sensitivity to commercial egg proteins, egg protein fractions, and freshly prepared extracts of whole egg powder and yolk. We classified participants as definite cases of asthma if both the examining physician diagnosed asthma and symptomatic bronchial lability was demonstrated by serial PEFR determinations. Definite noncases of asthma were those participants in whom the physician did not diagnose asthma and in whom symptomatic bronchial lability was not demonstrated by PEFR. All five definite cases, compared to three of 16 definite noncases of asthma, had one or more positive skin-prick tests to egg proteins. Four of five cases, compared to 0 of 14 noncases, who had serum determinations, had an elevated RAST to one or more of the egg proteins. This study demonstrates that occupational asthma associated with IgE-mediated allergy to egg proteins occurs among workers exposed to inhaled egg proteins.

Air Pollutants, Occupational↗

Cockroach sensitization in laboratory workers.

Six laboratory workers who were exposed to American cockroaches (AC) and German cockroaches (GC) while they were performing immunologic experiments were evaluated for cockroach hypersensitivity. Prick skin testing and RAST were performed with whole body extracts (1:20 wt/vol) of AC, brown-banded (BB), and GC species as well as hemolymph and fecal (F) extracts of AC. Three of six workers reported work-related nasal and ocular symptoms associated with xenografting and bleeding of cockroaches. All three symptomatic workers exhibited cutaneous reactivity to at least one cockroach antigen. Elevated RAST binding was observed in one of the three symptomatic workers. A nasal provocation to AC was positive in the most symptomatic worker at a provocative dose of 3.2 X 10(-3) mg causing a 50% decrease of nasal flow rate from baseline. After pretreatment with nasal cromolyn, the provocative dose causing a 50% decrease from baseline increased to 2.6 X 10(-1) mg. Nasal provocation with the same concentrations of AC were negative in two skin test negative subjects. RAST-inhibition studies demonstrated cross inhibition of the serum-specific IgE binding to AC-hemolymph by AC, GC, and BB whole body extracts. However, specific IgE binding to AC-F was inhibited by AC-F and AC but not by GC or BB whole body extracts, suggesting there was greater specificity of the F allergens. This study demonstrated that cockroach allergens elicit IgE-dependent upper respiratory sensitization in the workplace.

Adult↗

Investigations of culture medium-free house dust mites. III. Antigens and allergens of body and fecal extract of Dermatophagoides farinae.

Crossed immunoelectrophoresis (CIE) and crossed radioimmunoelectrophoresis (CRIE) were used to characterize antigens (Ags) and allergens derived from Dermatophagoides farinae (DF) culture media-free mite body and mite fecal matter extracts. CIE of DF body and DF feces extracts revealed the presence of 35 and 20 Ags, respectively. CRIE experiments demonstrated IgE binding by 14 and seven DF body and DF feces Ags, respectively, when CIE gels were incubated with reference sera from clinically mite-sensitive patients. Binding of specific IgE to the various Ags in the two extracts varied significantly both in frequency and in strength from patient to patient and within the same patient's serum. Sera from some patients demonstrated IgE binding predilection for specific DF body Ags, whereas other sera exhibited greater binding preference for DF feces Ags. Homologous, heterologous, and intermediate gel CIE and CRIE clearly demonstrated that DF bodies and DF feces share some common Ags or epitopes, but the two different extracts also were quantitatively different. Some Ags and allergens originate from mite body material and are not present in mite feces. These results indicate that only extracts containing high concentrations of both body and fecal allergens should be used in clinical testing and therapy.

Allergens↗

Investigations of culture medium-free house dust mites. IV. Cross antigenicity and allergenicity between the house dust mites, Dermatophagoides farinae and D. pteronyssinus.

Heterologous crossed immunoelectrophoresis (CIE) analysis demonstrated that Dermatophagoides pteronyssinus body and D. farinae body extracts contained up to 21 cross-reacting antigens (Ags). Incubation of CIE gels with two mite-sensitive individual sera and a serum pool of mite-sensitive patients indicated that up to nine cross-reacting Ags bound mite-specific IgE on crossed radioimmunoelectrophoresis and were common allergens. Likewise, heterologous CIE analysis of D. pteronyssinus feces and D. farinae feces extracts demonstrated approximately 13 cross-reacting Ags. Up to eight of these cross-reacting fecal Ags bound mite feces-specific human IgE. Additional cross antigenicity and allergenicity was evident between body extract of one species and feces extract of the other species. The amount of specific IgE binding to cross-reacting Ags in interspecific extracts varied both between and within individual sera. Different cross-reacting Ags contained potent allergens, and these varied from patient to patient. Also of major significance was the fact that body and fecal extracts of each species contained Ags and allergens that were unique and species specific.

Allergens↗

Clinical and immunologic studies among egg-processing workers with occupational asthma.

Twenty-five workers in an egg-processing factory were evaluated for respiratory sensitization to inhaled egg proteins by a physician evaluation, serial peak expiratory flow rate (PEFR) measurements for a 1-week period, and immunologic tests. Immunologic studies included skin prick tests, serum-specific IgE (RAST), and specific IgG (ELISA) to solutions prepared from commercial food allergens: factory-powdered egg white and yolk products and purified egg white fractions, including ovalbumin, ovomucoid, lysozyme, and conalbumin. Six workers had significant daily PEFR lability (greater than 20%) of whom five had associated cutaneous reactivity to at least one egg allergen. A diagnosis of "definite asthma" was established in five workers suspected by the physician of having asthma. These five workers exhibited significant decrements in daily PEFR that were accompanied by bronchial symptoms. Occupational asthma was diagnosed by the physician in four of the five latter workers. Definite asthma was significantly associated with both cutaneous reactivity to egg allergens (p less than 0.01) and RAST binding (p less than 0.01). Of eight workers with cutaneous reactivity to at least one egg reagent, four workers (50%) were positive to only purified egg white fractions. The highest levels of RAST binding were detected in four workers, and the best binding activity was to ovomucoid and ovalbumin fractions. Elevated specific IgG responses were significantly higher in egg-factory workers to whole egg (p less than 0.005), lysozyme (p less than 0.002), and conalbumin (p less than 0.002) allergens compared to responses of nonexposed control subjects. However, no differences in specific IgG were detected between symptomatic and asymptomatic workers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Occupational asthma caused by himic anhydride.

Acid anhydride compounds are reactive chemicals that have been previously associated with immunoglobulin E (IgE) mediated occupational asthma. Twenty workers with exposure to himic anhydride powder used for the manufacture of a synthetic flame retardant were questioned about respiratory symptoms. The study was initiated after one individual from the plant developed asthma. A test for serum-specific IgE to human serum albumin conjugates of himic anhydride, phthalic anhydride, hexahydrophthalic anhydride and trimellitic anhydride was performed for seven workers with respiratory symptoms associated with himic anhydride exposure. Three of the seven symptomatic workers who reported wheezing at work exhibited elevated specific IgE to two or more acid anhydride-human serum albumin conjugates. Radioallergosorbent inhibition studies performed with sera containing high levels of himic anhydride-human serum albumin specific IgE from a symptomatic worker demonstrated cross-allergenicity between himic anhydride-human serum albumin and hexahydrophthalic anhydride-human serum albumin allergenic determinants. This study demonstrated that himic anhydride can elicit IgE-mediated sensitization in the workplace.

Adult↗

Prevalence of house dust mites in nursing homes in southwest Ohio.

Dermatophagoides spp house dust mites were found to be prevalent in geriatric nursing homes in southwestern Ohio. Mite density was lower in nursing homes than in private homes in comparable dust-sampling areas and at similar times of the year. Generally, fewer mattresses, floors, and articles of furniture were mite positive in nursing homes by comparison to private homes. Lower institutional mite levels were attributed to frequent linen and mattress cover changes and rigorous cleaning practices, coupled with the lack of a favorable mite environment provided by high ambient temperatures, low relative humidity, tiled or vinyl-covered floors and furniture, and covered or encased mattresses.

Aged↗