Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles.

OBJECTIVE: Metabolic dysfunction characterized by insulin resistance (IR) is an important risk factor for type-2 diabetes and coronary artery disease (CAD). The aim of this study was to determine if clinical lifestyle interventions differing in scope and intensity improve IR, defined by the lipoprotein IR (LPIR) score, in individuals differing in the severity of metabolic dysfunction. METHODS: Subjects with diagnosed type-2 diabetes, CAD or significant risk factors participated in one of two clinical lifestyle modification interventions: (i) intensive non-randomized programme with a strict vegetarian diet (n = 90 participants, 90 matched controls) or (ii) moderate randomized trial following a Mediterranean-style diet (n = 89 subjects, 58 controls). On-treatment and intention-to-treat analyses assessed changes over 1 year in LPIR, lipoprotein profiles and metabolic risk factors in intervention participants and controls in both programmes. RESULTS: In the on-treatment analysis, both interventions led to weight loss: [-8.9% (95% CI, -10.3 to -7.4), intensive programme; -2.8% (95% CI, -3.8 to -1.9), moderate programme; adjusted P < 0.001] and a decrease in the LPIR score [-13.3% (95% CI, -18.2 to -8.3), intensive; -8.8% (95% CI, -12.9 to -4.7), moderate; adjusted P < 0.01] compared with respective controls. Of the six lipoprotein parameters comprising LPIR, only large very-low-density lipoprotein particle concentrations decreased significantly in participants compared with controls in both programmes [-26.3% (95% CI, -43.0 to -9.6), intensive; -14.2% (95% CI, -27.4 to -1.0), moderate; P < 0.05]. Intention-to-treat analysis confirmed and strengthened the primary results. CONCLUSION: A stringent lifestyle modification intervention with a vegetarian diet and a moderate lifestyle modification intervention following a Mediterranean diet were both effective for improving IR defined by the LPIR score.

Cell-mediated immune response to tuberculosis antigens: comparison of skin testing and measurement of in vitro gamma interferon production in whole-blood culture.

Although delayed-type hypersensitivity skin testing with tuberculin purified protein derivative (PPD) is the standard for tuberculosis screening, its variability suggests the need for a more sensitive, noninvasive test. An in vitro whole-blood assay has been proposed as an alternative. Using health care worker volunteers, we confirmed the correlation between PPD skin test (PPD-ST) results (positive, induration of >15 mm) and a standardized gamma interferon (IFN-gamma) assay, QuantiFERON-TB (Q-IFN), manufactured by CSL Biosciences in Australia, and we evaluated Mycobacterium tuberculosis culture subfractions as potential substitutes for PPD. Twenty healthy volunteers with positive PPD-ST results and 20 PPD-ST-negative controls were enrolled. Whole blood was cultured with human PPD antigens (HuPPD), Mycobacterium avium complex (MAC) PPD, phytohemagglutinin (PHA), and four M. tuberculosis culture subfractions: low-molecular-weight culture, filtrate, culture filtrate without lipoarabinomannan, soluble cell wall proteins, and cytosolic proteins, all developed from M. tuberculosis strain H(37)RV. Secretion of IFN-gamma (expressed as international units per milliliter) was measured by an enzyme immunoassay. The PPD or subculture fraction response as a percentage of the PHA response was used to determine positivity. Sixteen of 20 PPD-ST-positive individuals were classified as M. tuberculosis positive by Q-IFN, and 1 was classified as MAC positive. Sixteen of 20 PPD-ST-negative individuals were M. tuberculosis negative by Q-IFN, 2 were MAC positive, and 2 were M. tuberculosis positive. The tuberculosis culture subfractions stimulated IFN-gamma production in PPD-ST-positive volunteers, and significant differences could be seen between the two PPD-ST groups with all subfractions except soluble cell wall protein; however, the response was variable and no better than the Q-IFN PPD. The agreement between the Q-IFN test and the PPD-ST was good (Cohen's kappa = 0.73). The Q-IFN assay can be a useful tool in further studies of immune responses to M. tuberculosis antigens.

Mosquito bite pathogenesis in necrotic skin reactors.

Mosquito bite exposure results in a variety of reactions and secondary complications. Clinical hypersensitivity manifests primarily as local reactions with anaphylaxis being a very rare event. Risk factors for more severe local reactions include immunodeficiency, young children and visitors to an area with new exposure to indigenous mosquitoes. Necrotic skin reactions to mosquito bites have been associated with a newly recognized hemophagocytic syndrome in predominantly oriental populations. Diagnostic and therapeutic agents in the clinical management of mosquito hypersensitivity remain limited, but recent discovery of 3 recombinant proteins (rAed a 1, rAed a 2, rAed a 3) shared by several mosquito species promise to be more specific skin test antigens for the future.

Induction and measurement of in vivo antibody responses.

The capacity of the human immune system to mount an antibody response following in vivo immunization with a protein or polysaccharide antigen is a revealing indication of the overall integrity of both the B and T cell arms of the immune system. As such, in vivo immunization followed by measurement of the antibody response is an appropriate test of immune function in the various acquired and congenital immunodeficiencies and in a host of other conditions affecting the immune system. This unit describes procedures for in vivo immunization and for the measurement of the subsequent immune response using an ELISA technique.

Varicella immunity: persistent serologic non-response to immunization.

OBJECTIVE: Varicella-zoster (VZV) infection is an occupational hazard for health care workers. The "gold standard" for assessing protection is a positive antibody titer. We present a case of persistent serologic non-responsiveness following VZV immunization and discuss a management strategy. METHODS: A 29-year-old woman, immunocompetent pediatric resident was repeatedly removed from her clinical duties because of a negative history of chicken pox and the absence of a VZV antibody titer. She received a total of three doses of the VZV vaccine and continued to have a negative antibody titer as measured by a commercial ELISA assay (Wampole). Subsequently, she had three direct contacts with infectious children and did not develop clinical chicken pox. RESULTS: A lymphocyte proliferation assay was performed using inactivated varicella vaccine and tetanus antigens. The patient's varicella and tetanus stimulation index (SI) were 46.5 and 42, respectively. The SI for the positive control (a patient recently recovered from a wild type infection) were 144 (varicella specific), and 114 (tetanus). The SI secondary to VZV antigens reported in the literature is 30.5 +/- 9.1. We reassessed the varicella antibody titer using more sensitive assays: fluorescent antibody to membrane antigen and latex agglutination. Both tests verified the presence of VZV specific IgG at a titer of 1:8 in our patient. CONCLUSION: This case illustrates that in a subgroup of individuals the antibody response to VZV vaccine may be low despite an adequate cell-mediated response. Commercial VZV ELISA assays were designed to measure higher titers associated with natural infection rather than the lower titer induced by the vaccine. Repeated immunizations plus more sensitive measures of VZV-specific IgG should be used to validate protection rather than the current commonly utilized ELISA screening. Clinicians should be aware of the variability in VZV-specific antibody assays when assessing post VZV vaccine titers prior to determining protection in health care workers.

Probenecid hypersensitivity in AIDS: a case report.

BACKGROUND: Cidofovir plus probenecid is a new therapeutic alternative for refractory cytomegalovirus and acyclovir-resistant herpes infections in AIDS patients. Probenecid is used in conjunction with the antiherpetic medication (cidofovir) in order to reduce the incidence of nephrotoxicity by cidofovir. OBJECTIVE: To present therapeutic alternatives for successful administration of probenecid to AIDS patients who develop a hypersensitivity reaction to the medication. METHODS AND RESULTS: We describe a patient with AIDS who was being treated with the cidofovir/probenecid combination for a peri-anal acyclovir-resistant herpetic infection. The patient subsequently developed a cutaneous hypersensitivity reaction to probenecid alone. A pretreatment regimen consisting of prednisone, H1 and H2 blockers was administered before the dosing of probenecid in order for the patient to continue with the antiviral therapy. CONCLUSION: Cutaneous hypersensitivity reactions to probenecid may be seen more frequently with the increasing use of cidofovir in AIDS patients. Our pre-treatment protocol is one therapeutic alternative to be considered in order to continue with probenecid.

Immediate hypersensitivity to human recombinant granulocyte-macrophage colony-stimulating factor associated with a positive prick skin test reaction.

BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF), also known as sargramostim, is used to accelerate myeloid recovery following bone marrow transplantation or cytotoxic chemotherapy. "Anaphylactic" reactions to sargramostim have been reported on a limited basis and are poorly characterized. OBJECTIVE: It is the purpose of this report to describe an adverse reaction to sargramostim treatment involving palmar itching, urticaria, angioedema, and throat tightness and to demonstrate the utility of prick skin testing to determine type I sensitization. METHODS: Prick skin testing with 100 and 250 micrograms/mL sargramostim and 300 micrograms/mL rhu G-CSF (filgrastim) was performed in the patient and four control subjects. RESULTS: The patient experienced an immediate wheal and flare reaction with both concentrations of sargramostim while the control subjects demonstrated no reaction. There was also no reaction with filgrastim (rhu G-CSF) in either group and the patient subsequently tolerated filgrastim therapy. CONCLUSION: Prick skin testing with rhu GM-CSF and rhu G-CSF may be useful to demonstrate type I sensitization. Additional studies are needed to determine the incidence and prevalence of skin test reactions in larger numbers of patients with cytokine therapy exposure.

Practice parameters for the diagnosis and management of immunodeficiency. The Clinical and Laboratory Immunology Committee of the American Academy of Allergy, Asthma, and Immunology (CLIC-AAAAI)

In this brief review, only the most useful immunologic tests available for defining host defects that lead to susceptibility to infection have been emphasized. It should be pointed out that those evaluations and tests ordered by the physician will rule out the vast majority of the currently recognized defects. Finally, it is important that any patients identified as abnormal by these screening tests be characterized as fully as possible in centers specializing in these diseases before therapy is initiated, since what may appear to be a simple diagnosis on the surface may be an indicator of more complex underlying problems.

Tannic acid's effect on bird antigen.

BACKGROUND: Birds have been associated with many diseases including hypersensitivity pneumonitis and allergic diseases such as asthma and rhinitis. Bird antigen from homes of patients with hypersensitivity pneumonitis persists long after the bird is removed from the home. This may account for the persistence of symptoms, signs, and bird-specific IgG in patients with hypersensitivity pneumonitis. Tannic acid application has been effective in decreasing cat and mite allergen levels. No data have been available on tannic acid's effect on bird antigen. OBJECTIVE: It is the purpose of this study to determine whether tannic acid reduces bird antigen in the home. METHOD: Dust samples were collected from homes with bird antigen before and after application of tannic acid. Samples were assayed for bird antigen levels using a competitive inhibition ELISA. Pre- and post-bird antigen levels were compared using a paired t test to determine whether antigen was reduced significantly. RESULTS: There was not a statistical difference between bird antigen levels before and after application of tannic acid as compared by paired t test (P = .09). CONCLUSION: Tannic acid is not effective in decreasing bird antigen levels. In patients with hypersensitivity pneumonitis or allergic disease to birds, the bird should be removed from the home and environmental cleanup should be undertaken, but tannic acid application is not indicated.

Chronic sulfasalazine therapy in the treatment of delayed pressure urticaria and angioedema.

BACKGROUND: Delayed pressure urticaria/angioedema can be profoundly disabling with painful and prolonged swelling of feet and hands as well as systemic symptoms of malaise and flu-like illness. Occupations requiring prolonged standing and forceful use of hands may be seriously compromised by this condition. The severe forms of the disease are usually unresponsive to antihistamines and nonsteroidal anti-inflammatory drugs, and patients frequently require corticosteroids for control of symptoms. OBJECTIVE: It was the purpose of this report to evaluate the clinical utility of sulfasalazine for two patients with refractory delayed pressure urticaria. METHODS: Sulfasalazine, starting at 500 mg/day (with weekly incremental dosing to a total of 4 g), was administered to two patients with disabling pressure urticaria and angioedema (symptomatic daily with normal activities) who had failed all other reported therapeutic options except corticosteroids. RESULTS: Patient A required daily prednisone in excess of 30 mg (for more than 6 months) to control his painful angioedema sufficiently in order to continue working as a colorectal surgeon. Patient B also experienced daily symptoms for more than 1 year. Both patients tolerated sulfasalazine to a dose of 4 g/day without adverse reactions and achieved complete resolution of symptoms. Patient A continued to be well controlled 1 year after starting but must maintain a dose of 2 g or greater per day. Patient B reported excellent control 6 months after starting but was subsequently lost to follow-up. CONCLUSION: Sulfasalazine, in doses used for inflammatory bowel disease, appears to be an effective alternative therapy for delayed pressure urticaria and angioedema in patients poorly controlled by traditional treatment and may act as a corticosteroid-sparing agent.

Mosquito bite anaphylaxis: immunotherapy with whole body extracts.

BACKGROUND: Adverse reactions to mosquito bites have been recognized for some time. These usually consist of large local swellings and redness, generalized urticaria, angioedema and less easily definable responses such as nausea, dizziness, headaches, and lethargy. METHODS: We report two patients who experienced systemic anaphylaxis from mosquito bites. Both were skin tested and given immunotherapy using whole body mosquito extracts. RESULTS: Skin testing using whole body mosquito extracts was positive to Aedes aegypti at 1/1,000 weight/volume (wt/vol) in one patient and to Aedes aegypti at 1/100,000 wt/vol, and Culex pipiens at 1/10,000 wt/vol in the other. Skin testing of ten volunteers without a history of adverse reactions to mosquito bites was negative. Immunotherapy using these extracts resulted in resolution of adverse reactions to mosquito bites in one patient and a decrease in reactions in the other. CONCLUSIONS: Immunotherapy with whole body mosquito extracts is a viable treatment option that can play a role in patients with mosquito bite-induced anaphylaxis. It may also result in severe side effects and one must determine the benefit versus risks for each individual patient.

Wheezing, hypoxia, and dyspnea in a 62-year-old woman.

This patient presented with dyspnea, hypoxia, and generalized wheezing; however, her pulmonary function testing did not suggest asthma. Subsequent evaluations for conditions that may mimic asthma were not helpful. An invasive procedure (pulmonary angiogram) was required to diagnose pulmonary embolism, a potentially life threatening but treatable condition. The angiogram was performed despite nondiagnostic ventilation and perfusion scans because of a high index of suspicion for pulmonary embolism. In our patient, observation revealed episodes of sudden tachycardia, dyspnea, and increased wheezing which further raised our suspicion. Because pulmonary emboli can have such protean manifestations, it would be wise to consider pulmonary emboli in any patient with presumed asthma who has symptoms out of proportion to his or her pulmonary function testing and/or is not responding to treatment.