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Biomedical subjects

G Sussman

Publications and source records attributed to G Sussman.

At least 19 recordsLinked to original sources

Substance abuse policy and peace in the Middle East: a Palestinian and Israeli partnership.

This paper describes the working exchange between Israelis, Palestinians and international experts who engaged in a process to promote communications, cooperation and coordination of efforts directed toward peace as well as the prevention and treatment of drug abuse in the region. From 1997 to 1999, a program of training workshops and courses, drug prevention and treatment skills development and collaborative research was conducted on the basis of mutual respect and cooperation among Palestinians and Israelis. By tapping into the issue of substance abuse and by focusing on its professional and academic dimensions, this initiative engaged representative delegations of the police force, academia, treatment centers and various government ministries. While events of this period underscored the dependence of "bottom-up" peace initiatives on the prevailing political situation, the experience revealed the vital role of NGO frameworks in providing a safety net for promoting and sustaining relations as well as addressing an issue of common concern. This case study shows that addiction professionals, both clinicians and researchers, can be instrumental in conflict resolution as well as the prevention and treatment of drug abuse.

Health Policy↗

Latex allergy in the workplace.

While less than 1% of the general population is sensitized to latex, the U.S. Occupational Safety and Health Administration estimates that 8-12% of health-care workers are sensitized. The major source of workplace exposure is powdered natural rubber latex (NRL) gloves. NRL is harvested from HEVEA: brasiliensis trees and ammoniated to prevent coagulation resulting in the hydrolysis of the latex proteins. Prior to use in manufacturing, the latex is formulated by the addition of multiple chemicals. Thus, human exposure is to a mixture of residual chemicals and hydrolyzed latex peptides. Clinical manifestations include irritant contact dermatitis, allergic contact dermatitis (type IV), and type I immediate hypersensitivity response. Type I (IgE-mediated) NRL allergy includes contact urticaria, systemic urticaria, angioedema, rhinitis, conjunctivitis, bronchospasm, and anaphylaxis. Taking an accurate history, including questions on atopic status, food allergy, and possible reactions to latex devices makes diagnosis of type-I latex allergy possible. To confirm a diagnosis, either in vivo skin prick testing (SPT) or in vitro assays for latex-specific IgE are performed. While the SPT is regarded as a primary confirmatory test for IgE-mediated disease, the absence of a U.S. Food and Drug Administration-licensed HEVEA: brasiliensis latex extract has restricted its use in diagnosis. Serological tests have, therefore, become critically important as alternative diagnostic tests. Three manufacturers currently have FDA clearance for in vitro tests, to detect NRL-specific IgE. The commercially available assays may disagree on the antibody status of an individual serum, which may be due to the assay's detecting anti-NRL IgEs to different allergenic NRL proteins. Sensitized individuals produce specific IgE antibody to at least 10 potent HEVEA: allergens, Hev b 1-Hev b 10, each of which differs in its structure, size, and net charge. The relative content and ratios of Hevs in the final allergen preparation most probably could effect diagnostic accuracy. The Hev proteins have been cloned and expressed as recombinant proteins. Sequencing demonstrates both unique epitopes and sequences commonly found in other plant proteins. Sequence homology helps to explain the cross reactivity to a variety of foods experienced by latex allergic individuals. The development of recombinant allergens provides reagents that should improve the diagnostic accuracy of tests for latex allergy. Although clinical and exposure data have been gathered on the factors affecting response in latex-allergic individuals, less is known regarding the development of sensitization. Coupled with in vitro dermal penetration studies, murine models have been established to investigate the route of exposure in the development of latex sensitization. Time-course and dose-response studies have shown subcutaneous, intratracheal, or topical administrations of non-ammoniated latex proteins to induce IgE production. Both in vitro penetration and in vivo studies highlight the importance of skin condition in the development of latex allergy, with enhanced penetration and earlier onset of IgE production seen with experimentally abraded skin. The diagnosis of latex allergy is complicated by these variables, which in turn hinder the development of intervention strategies. Further epidemiological assessment is needed to more explicitly define the scope, trends, and demographics of latex allergy. Diagnostic accuracy can be improved through greater knowledge of proteins involved in the development of latex allergy, and better documentation of the presently available diagnostic tests. In vivo and in vitro models can elucidate mechanisms of sensitization and provide an understanding of the role of the exposure route in latex allergy-associated diseases. Together, these efforts can lead to intervention strategies for reducing latex allergy in the workplace.

Dermatitis, Allergic Contact↗

Skin prick test reactivity to recombinant latex allergens.

BACKGROUND: Allergy to latex has become a serious and increasingly common health problem, particularly for healthcare workers and patients who undergo frequent surgical procedures. Testing for latex allergy currently involves in vitro tests and skin prick testing using crude preparations of natural rubber latex (NRL). To date, 10 latex proteins have received designation as allergens (Hev b 1 to Hev b 10) and, except for Hev b 4, have been cloned as recombinant proteins. Our aim was to compare the skin prick test (SPT) reactivity of six recombinant latex allergens with SPT reactivity to natural rubber latex proteins in known latex-allergic individuals. METHODS: Six recombinant proteins were expressed in Escherichia coli, and tested as the intact fusion proteins (Hev b 2, 5, 6, 8) or as purified proteins (Hev b 3 and 7). SPT with the six recombinant latex allergens was performed using 10-fold serial dilutions on 31 latex-allergic subjects to determine the level of reactivity to each recombinant allergen. Latex-specific IgE was determined using the AlaSTAT assay. RESULTS: All six recombinant allergens were reactive by SPT in at least 1 latex-allergic patient but not in any of the control patients. The frequency of sensitization to the various recombinant allergens was similar to previous studies using the native proteins isolated from NRL. The minimal level of protein for a positive skin test was 70 pg/ml for NRL and 1 ng/ml for one recombinant allergen (Hev b 7). In our patients, the use of a combination of recombinant latex allergens Hev b 5, 6 and 7 diagnosed latex allergy with 93% sensitivity and 100% specificity. CONCLUSION: Recombinant latex allergens are clinically reactive, can be produced in a standardized manner, and could potentially provide safe, sensitive and specific reagents for the diagnosis of latex allergy.

Adult↗

Intravenous ondansetron for the control of opioid-induced nausea and vomiting. International S3AA3013 Study Group.

This randomized, double-masked, placebo-controlled, multicenter trial was conducted in 9 countries to assess the safety and efficacy of 2 doses of intravenous ondansetron (8 and 16 mg) for the control of opioid-induced nausea and vomiting. A total of 2574 nonsurgical patients who presented with pain requiring treatment with an opioid analgesic agent participated in this trial. The most common presenting painful condition was back or neck pain, reported by approximately one third of patients. A total of 520 patients (317 females, 203 males) developed nausea or vomiting after opioid administration and were randomly assigned to receive a single dose of 1 of 3 study treatments: placebo (n = 94), ondansetron 8 mg (n = 215), or ondansetron 16 mg (n = 211). Ondansetron 8 and 16 mg led to complete control of emesis in 134 of 215 patients (62.3%) and 145 of 211 patients (68.7%), respectively. Results with both doses were significantly better than those seen with placebo (43 of 94 patients [45.7%]). Complete control of nausea was achieved in 6.8% of placebo patients, 14.8% of ondansetron 8-mg-treated patients, and 19.4% of ondansetron 16-mg treated patients; only ondansetron 16 mg was significantly better than placebo (P = 0.007). Significantly more patients who received ondansetron 8 mg than patients who received placebo were satisfied/very satisfied with their antiemetic treatment, as assessed by 4 patient-satisfaction questions. Significantly more patients who received ondansetron 16 mg compared with placebo were satisfied/very satisfied on 2 of 4 satisfaction questions. In conclusion, based on the observed incidence of opioid-induced nausea and vomiting in this study, it may be more appropriate to treat symptoms on occurrence rather than administering antiemetic agents prophylactically. The results of this study demonstrate that intravenous ondansetron in doses of 8 or 16 mg is an effective antiemetic agent for the control of opioid-induced nausea and vomiting in nonsurgical patients requiring opioid analgesia for pain.

Adult↗

Relationship of the dose of intravenous gammaglobulin to the prevention of infections in adults with common variable immunodeficiency.

The objective was to assess clinical efficacy of 3 dosages of intravenous gammaglobulins to prevent infectious episodes in adult common variable immunodeficiency. We designed a randomized, double blind, dose-assessing study. The setting was at University Hospital, Out-patient Clinic. Our patients were twenty-one adult patients with common variable immunodeficiency. The measurements were comparative study of the number and severity of infections using 3 various dosages of intravenous gammaglobulins, each given monthly for M least 6 months. Results indicated four hundred and eighty-four infectious episodes occurred while giving 305 infusions of IVIG 200 mg/kg; 205 infectious episodes while giving 170 infusions of 400 mg/kg and 436 infectious episodes while giving 247 infusions of 600 mg/kg. The morbidity scores (infection/infusion) were 1.59, 1.21 and 1.77 respectively (p - N/S). There was no significant difference in the severity of infections on the above 3 dosages, and no difference in the duration of infection-free intervals. The conclusions resulted in no significant differences in morbidity in adult patients with common variable immunodeficiency treated in cross-over pattern with IVIG 200 mg/kg, 400 mg/kg and 600 mg/kg. Thus, high dosages of IVIG are not conferring better protection against infections in such patients.

Adult↗

Correlation of protein levels with skin prick test reactions in patients allergic to latex.

BACKGROUND: Natural rubber latex (NRL) gloves are the major source of proteins that cause latex allergic reactions in sensitized health care workers and patients. OBJECTIVE: This study evaluated the effect of manufacturing changes on reducing protein, antigen, and allergen levels of latex medical gloves. METHODS: Three types of NRL gloves were manufactured with a common batch of compounded latex. The NRL gloves were analyzed for total protein by using the American Society for Testing and Materials D5712-95 Lowry method, and specifically for latex proteins by immunoassay. Allergen levels in the extracts were determined by end-point titration skin prick tests (SPTs) on patients allergic to NRL. RESULTS: Extracts from regular powdered gloves had detectable levels of latex proteins and allergens (62% SPT positive), whereas the powder-free gloves were low in protein content and allergenicity (5% to 8% SPT positive). No significant difference in SPT reactivity was observed between the chlorinated powder-free gloves and the polymer-coated gloves. Although the protein levels determined by the Lowry assay correlated with SPT reactivity (r = 0.95), the test was restricted by a high detection limit (9.3 micrograms/ml). Fifty-eight percent of patients allergic to latex reacted at the 50 micrograms/gm detection limit allowed by the Food and Drug Administration. The ELISA had a good correlation with SPT reactivity (r = 0.93), and because of the greater sensitivity, gloves testing below the ELISA reporting limit (0.06 microgram/ml) have a significantly lower potential for eliciting reactions in patients allergic to latex. CONCLUSIONS: Results of protein assays are acceptable criteria with which to rate the potential allergenicity of gloves; however, the American Society for Testing and Materials D5712-95 assay may lack the sensitivity to provide clinically relevant data.

Biomarkers↗

Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients.

BACKGROUND: Perennial allergic rhinitis is chronic and persistent, may lead to a constellation of secondary complaints including sinusitis, mouth-breathing, and some symptoms resembling a permanent cold, and often requires constant medical intervention. Well-tolerated nasal corticosteroids, alone or in combination with antihistamines, have been found to be very effective in treating this condition. OBJECTIVE: To compare the effectiveness and tolerability of mometasone furoate aqueous suspension, a new once daily nasal spray, to placebo vehicle and to beclomethasone dipropionate, administered twice daily, in patients with perennial allergic rhinitis. METHODS: This was a randomized, double-blind, placebo-controlled, double-dummy, parallel group study, in 427 patients age 12 years and older at 24 centers in Canada and Europe. Patients allergic to at least one perennial allergen, confirmed by medical history, skin testing, and adequate symptomatology were eligible to receive one of the following regimens for 3 months: mometasone furoate, 200 micrograms only daily; beclomethasone dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo vehicle control. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS: Three hundred eighty-seven patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < or = .01) more effective than placebo and was indistinguishable from beclomethasone dipropionate. Similar trends were seen among individual symptoms, physician symptom evaluations, and therapeutic response. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSIONS: Mometasone furoate nasal spray adequately controls symptoms of perennial allergic rhinitis, offers the advantage of once daily treatment, and is well tolerated.

Administration, Intranasal↗

Configuration of the interferon-alpha/beta receptor complex determines the context of the biological response.

Constituents of the Type 1 interferon (IFN) receptor (IFNABR) identified to date include the alpha and beta transmembrane subunits and the associated intracellular kinases, Jak 1 and Tyk 2. In this report, we demonstrate that a human cell type that expresses both subunits of IFNABR, together with Jak 1 and Tyk 2, exhibits a limited binding capacity for and is only partially sensitive to the effects of IFN-alpha/beta, despite adequate levels of the cytoplasmic transcription factors Stat1, Stat2, and Stat3. Specifically, a low affinity interaction between IFN-alpha/beta and cell surface receptors results in ISGF3 (Stat1:2) activation and an antiviral response, yet no IFN-inducible growth inhibition. Using a panel of murine cells that are variably configured with respect to the human IFNABR-alpha/beta subunits, we provide evidence that an additional component(s) encoded on human chromosome 21 is required to confer high affinity binding and IFN-inducible growth inhibition to cells that express the alpha and beta subunits of the IFNABR. The data indicate that transcriptional activation that leads to an antiviral response is mediated by IFN-alpha/beta activation of IFNABR-alpha and IFNABR-beta in the context of a low affinity interaction, yet a high affinity interaction is necessary for signal transducing events that mediate growth inhibition. We provide evidence that the extent of ISGF3 activation correlates directly with the magnitude of an antiviral but not a growth inhibitory response.

2',5'-Oligoadenylate Synthetase↗

Exposure characteristics and cutaneous problems in operating room staff.

Health care personnel have exposure to a variety of cutaneous irritants and allergens and a high prevalence of cutaneous problems. The objectives of this exploratory study were to characterize the exposures and determine the prevalence of cutaneous symptoms and findings in operating room personnel, and to examine relationships between exposure characteristics and cutaneous outcomes. A questionnaire and standardized hand examination were used to assess the exposures and cutaneous status of operating room personnel. 184 operating room staff (90% of the eligible population) were assessed. Current skin problems were reported by 26%. Hand examination revealed that 9% had findings consistent with eczema and 10% changes of moderate dryness. A variety of preventive practices were being used by those with symptoms or findings. Cutaneous problems are common in operating room personnel. The use of preventive strategies (changing the type of gloves worn or the type of soap used for scrubbing, the use of glove liners and emollients) varied between different groups. These workers might benefit from more education regarding cutaneous hazards, preventive stategies and the importance of appropriate investigation of these problems.

Adult↗

Impact of intravenous infusions of low and high doses of gamma globulins (IVIG) on phagocytic functions in adults with primary humoral immunodeficiency.

Twelve adult patients with primary humoral immunodeficiency were treated for at least six months with IVIG 200 mg/kg/mo and then crossed over to a high dose of 600 mg/kg/mo. Polymorphonuclear and mononuclear cells of these patients were tested after the third infusion in the low-dose cycle and then after the third infusion in the high-dose cycle, each time a day before, four days after, and 14 days after intravenous infusion. Each time, patients' cells and normal cells were tested using normal sera and patients' sera. IVIG infusions led to a significant increase in the level of circulating IgG, which was much more prominent in the high-dose group. Phagocytosis, phagocytic index, intracellular bactericidal activity and chemotaxis of polymorphonuclear cells (PMNs) were at least as active as in healthy controls. Actually in both cycles patients' PMN's had slightly higher phagocytic activity than normal cells. Patients' serum in the high dose cycle supported chemotaxis better than normal serum. Efficient phagocytic activity was maintained throughout the cycle; however, it was more active (P < 0.0125) in the midcycle in the high-dose cycle. Superoxide generation was normal in all conditions. Monocytic function was also normal in all conditions tested. It may be concluded that as far as cellular phagocytic functions are concerned, the high dose of IVIG does not protect the host more efficiently than the low dose.

Adult↗

Control of airborne latex by use of powder-free latex gloves.

OBJECTIVE: Our objective was to assess airborne latex allergen exposure in the workplace of a hospital laboratory technician with occupational latex sensitization and repeated anaphylactic episodes from this. Her allergic manifestations had cleared only when coworkers changed to powder-free latex gloves. Therefore a laboratory still using powdered latex gloves was selected for comparative airborne latex sampling. DESIGN: The design was a survey. SETTING: We used a hospital hematology laboratory, and a biochemistry laboratory was used for comparison. PARTICIPANTS: The index case with latex allergy is described. An average of 10 employees worked on the day shift in the same laboratory, and 10 employees worked in the biochemistry laboratory studied. MAIN OUTCOME MEASURE: Airborne latex allergen levels obtained by high airflow area sampling were compared in the laboratory using powder-free latex gloves and in the laboratory using powdered latex gloves. RESULTS: Levels were below the level of detection (< 0.02 ng/m3 of latex allergen) in the laboratory using powder-free latex gloves but ranged from 39 to 311 ng/m3 in the laboratory using powdered gloves. CONCLUSIONS: Airborne latex allergen is produced with use of powdered latex gloves. Such usage by coworkers may provoke respiratory and anaphylactic response to latex in sensitized subjects. Use of powder-free gloves by coworkers may enable such patients to continue work in their trained profession and may prevent measurable airborne latex exposure. Affected patients, however, still need to avoid direct latex contact.

Adult↗

A study of immunoglobulin G subclass levels in black and white patients with various forms of obstructive lung disease.

The association of various respiratory disorders with disturbances in immunoglobulin G (IgG) subclass levels is increasingly being recognised. This was a prospective study of the IgG subclass levels in 71 patients (37 white, 34 black) with various respiratory disorders associated with obstructive airways disease. Ten white patients with adult cystic fibrosis were studied, 4 of whom were colonised with Pseudomonas aeruginosa. Alterations in individual subclass levels were seen in these patients and abnormalities noted included a decrease in IgG3 and/or an increase in IgG1 and/or IgG2 levels. Of the 17 black and 16 white patients with asthma, 2 had absent IgG4 levels associated with severe and recurrent respiratory infections, 2 had deficient IgG3 and 1 decreased IgG1 levels. Several patients had increased levels of several IgG subclasses, of which IgG1 was the most commonly affected. Both atopy and recurrent chest infections occurred most often in the latter group of patients. In the studies of 17 black and 11 white patients with bronchiectasis, all but 3 white patients were shown to have some alteration in IgG subclass levels. The commonest deficiencies were an absence of IgG4 (3 cases), and an absence of all subclasses (2 cases). One of the latter patients had an associated deficiency of total IgG and IgM, and the other demonstrated pan-hypogammaglobulinaemia. Abnormalities of IgG subclass levels appear to be commonly associated with several respiratory disorders including recurrent infections, atopy and bronchiectasis.

Adolescent↗

Supernatants derived from CD8+ lymphocytes activated by mycobacterial fractions inhibit cytokine production. The role of interleukin-6.

Our study examined the effects of supernatants derived from CD8+ lymphocytes treated with high molecular weight components of Mycobacterium tuberculosis on cytokine production. Such suppressor but not control supernatants increased the production of IL-4 and IL-6 whilst suppressing IL-1 beta, TNF-alpha, IL-2 and IFN-gamma production by monocytes and lymphocytes. The effects on cytokine production were time dependent being observed as early as 4 hours with peak activity observed at 24 hours. The inhibition of IL-1 beta and TNF-alpha by monocytes appeared to be related to increases in IL-6 levels present in supernatants of non-adherent lymphocytes incubated with mycobacterial components. This was confirmed by studies demonstrating that the addition of recombinant IL-6 to cultures depressed the production of these cytokines. Furthermore the addition of monoclonal anti-IL6 to such cultures restored the production of IL-1 beta and TNF-alpha. The results suggest that mycobacterial components inhibit host cellular functions by manipulating the host's cytokine network.

Antigens, Bacterial↗

Generalized allergic reactions during anesthesia.

Twenty-eight adults with a history of a generalized allergic reaction during anesthesia were investigated. The reactions were systemic in 23 adults, urticaria/angioedema in four, and bronchial obstruction in one adult. The study population and an additional 35 subjects with a history of use of thiopental during anesthesia but without reactions were investigated by methods including thiopental skin test, succinylcholine skin test, and IgE RAST for antibodies to thiopental, succinylcholine, or latex. Among the 28 patients with reactions, 17 had positive thiopental skin tests; 14/28 reactors and 1/35 of the control group had an IgE thiopental RAST value greater than 2 SD above the mean for control sera from ragweed-allergic subjects. The one control subject with a positive thiopental RAST also was the only control subject with a positive thiopental skin test. IgE succinylcholine RAST was negative in all 23 reactor sera tested. The IgE latex RAST was strongly positive in one reactor. In conclusion, evidence of allergy, particularly allergy to thiopental as a possible basis for the reactions, was obtained in greater than 50% of the patients who were investigated. No allergy to succinylcholine was found.

Adolescent↗

Prevalence of latex sensitization among hospital physicians occupationally exposed to latex gloves.

Patients undergoing surgery who have a history of occupational exposure to latex gloves may be predisposed to intraoperative anaphylaxis caused by latex allergy. Thus, medical personnel who routinely wear latex gloves may be at higher risk than the general population. The prevalence of latex sensitization has not been reported previously among physicians using latex gloves in a North American hospital setting. Using a latex skin prick test (SPT), we determined the prevalence of latex sensitization among 101 staff anesthesiologists, radiologists, and surgeons who regularly use latex gloves and among 100 atopic controls who were not occupationally exposed to latex gloves. Latex SPT was positive in 10 of 101 physicians (rho = 0.099; 95% confidence interval [CI] 0.041, 0.157) and 3 of 100 controls. Subgroup analysis showed that 9 of 38 atopic physicians were SPT-positive (rho = 0.237; 95% CI 0.102, 0.372). Atopic physicians were more likely to be latex SPT-positive than either nonatopic physicians or atopic controls (atopic vs. nonatopic physicians: P = 0.0006, odds ratio = 19.2, 95% CI 15.4, 23.1; atopic physicians vs. atopic controls: P = 0.0005, odds ratio = 9.1, 95% CI 7.5, 11.6). We conclude that compared to nonatopic physicians exposed to latex, or nonexposed atopic controls, atopic physicians who wear latex gloves are at increased risk of latex allergy.

Adult↗

Ocular and systemic determination of IL-1 beta and tumour necrosis factor in a patient with ocular inflammation.

Cytokines such as interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) may play an important role in ocular inflammation. We studied a patient with clinical features of sympathetic ophthalmia secondary to previous penetrating ocular injuries, and compared the ocular and systemic levels of IL-1 beta and TNF to control serum, and correlated these findings to histopathological sections of the patient's eye. Histology showed the presence of a diffuse chronic inflammatory infiltrate within the choroid and in a perivascular distribution in the retina. The significantly elevated ocular and systemic levels of IL-1 beta and TNF suggest that there is not only a localized ocular response but a systemic response as well. The presence of IL-1 beta TNF may play a role in the pathogenesis of ocular inflammation once the blood ocular barrier has been breached and ocular antigens have been exposed to the systemic immune system.

Endophthalmitis↗