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Biomedical subjects

G Sussman

Publications and source records attributed to G Sussman.

18 recordsLinked to original sources

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

Production of a suppressor factor by CD8+ lymphocytes activated by mycobacterial components.

The lipid component present in high-molecular-mass fractions with molecular masses of greater than 200 kDa derived from Mycobacterium tuberculosis extracts passaged through Sephacryl S.200 columns activate CD8+ lymphocytes to suppress lymphocyte blastogenesis. Suppression is mediated by the release of suppressor molecules by these CD8+ lymphocytes. Release of suppressor molecules occurs as early as 2 h following pulsing with the high-molecular-mass mycobacterial components and is maximal at 24 h, after which their release declines rapidly. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting indicates that the active components are carbohydrate moieties with approximate molecular masses of 122 to 148 kDa. Our results suggest a mechanism of interaction between mycobacteria and host mononuclear cells such that mycobacterial lipids, once exposed, activate CD8+ suppressor lymphocytes. Activation of these lymphocytes results in the release of carbohydrate-containing molecules that ultimately inhibit the blastogenesis of other lymphocytes.

Antigens, Differentiation, T-Lymphocyte

Controlled trial of H1 antagonists in the treatment of chronic idiopathic urticaria.

The efficacy of astemizole, diphenhydramine, and hydroxyzine hydrochloride in the treatment of chronic idiopathic urticaria was evaluated in this 3-month double-blind, randomized, parallel group study. Thirty-six adult patients were randomly assigned, 13 to the astemizole group (10 mg daily), 12 to the diphenhydramine group (25 mg t.i.d.), and 11 to the hydroxyzine hydrochloride group (25 mg t.i.d.). Demographic data were statistically similar for all variables assessed in the three treatment groups. Seven (58%) of the diphenhydramine patients withdrew before the end of the study, six because of lack of efficacy and one because of drowsiness. Two (18%) of the hydroxyzine hydrochloride patients withdrew, one because of lack of efficacy and one because of drowsiness. Two patients (15%) in the astemizole group withdrew, one because of adverse reaction, and the other because of lack of efficacy. Mean total symptom scores and mean individual symptom scores were lower in the astemizole group than in the other two groups. Wheal area measurements (0.1 mg/mL histamine challenge) decreased more in the astemizole and hydroxyzine hydrochloride groups than in the diphenhydramie group (P = .02). With regard to symptoms, 12/13 patients in the astemizole group improved clinically during their treatment period, versus 8/11 in the hydroxyzine hydrochloride group and 5/12 in the diphenhydramine group. The mean time to first observed therapeutic effect (maintained for three consecutive days) was 5.5 days in the astemizole group, 10.9 days in the hydroxyzine hydrochloride group, and 7.2 days in the diphenhydramine group. In this study, astemizole was as effective as hydroxyzine in patients treated for chronic idiopathic urticaria.

Adult

Hypersensitivity to natural latex.

Rubber hypersensitivity is well described but usually as a contact dermatitis caused by chemicals added during the process of making natural latex or synthetic rubber. IgE-mediated reactions, mainly contact urticaria, have rarely been reported in Europe. We report a case of immediate hypersensitivity to latex. A 34-year-old female operating room nurse developed hand eczema to natural latex. On two occasions, while she was gloving for surgery, she had the following reactions: flushing, tachycardia, urticaria, angioedema, wheezing, and light-headedness. Prick and patch testing to thiuram mix, mercaptobenzothiazole, phenylenediamine mix, and carbamate mix (common rubber additives) were negative. Prick tests to natural latex elicited a 4+ reaction associated with immediate flushing, tachycardia, urticaria, and light-headedness. Five control subjects did not react. IgE antibodies to latex by RAST demonstrated 17.7% binding (control, 4%). This case demonstrates that natural latex can cause IgE-mediated symptoms. The route of exposure was cutaneous absorption of relevant latex allergens. As the use of latex rubber products continues to escalate, more cases are likely to occur.

Adult

Considerations of hospital viability in rural Texas.

The rural hospitals in Texas face the same situation as rural hospitals throughout the country. Unfortunately, little data are available to define the scope or possible duration of the problem. However, rural hospital administrators currently believe that their facilities are being hurt by increased government regulation and that today's figures on average daily census indicate that the problem could threaten their hospital's long-term viability. Initial investigations have shown that the problem of casualty is a complex one; multiple factors interact to exacerbate the situation, such as more stringent enforcement of Medicare certification standards, review of claims and quality of care by PROs, and the use of PPS. Other factors cited include the economic recession, the exodus of young people from rural areas to urban areas, the high cost of technology, and the preadmission review by insurance companies. A study that will both sample and survey rural hospital viability using financial ratio analysis and service utilization data is presently being undertaken to provide some responses to these concerns. Further, it will later examine how rural hospital administrators are responding to the problem of decreased hospital viability. It is possible that new coping strategies may be developed from the study results that will change present modes of health care delivery and result in regional networks and more diversified health care services.

Cost Control

Suppression of cytokine production by supernatants from CD8+ lymphocytes activated by mycobacterial fractions: the role of interleukins 4 and 6.

Supernatants derived from CD8+ lymphocytes treated with mycobacterial components, or the partially purified carbohydrates from these supernatants, increased the production of IL-4 and IL-6 by mononuclear cells. The addition of anti-IL4 or anti-IL6 antibodies to LPS stimulated MN cells incubated with supernatants from CD8+ lymphocytes or carbohydrates resulted in the restoration of other cytokine production by these MN cells. Recombinant IL-4 and IL-6 on their own suppressed the production of IL-1 beta, TNF-alpha, IL-2 and IFN-gamma by mononuclear cells. Such suppression could be reversed with antibodies to IL-4 and IL-6. The addition of rIL-4 and rIL-6 did not increase the suppression of cytokine production induced by suppressor supernatants or carbohydrates. Interleukin 4 decreased the production of IL-6 by MN cells; whilst IL-6 suppressed IL-4 production in a dose dependent manner. Both effects could be reversed with the appropriate antisera. Our results suggest that mycobacteria could evade host immunity by inducing the production of IL-4 and IL-6 by host mononuclear cells. These cytokines, in turn, would suppress the production of other cytokines necessary for effective cellular immunity.

CD8-Positive T-Lymphocytes