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Biomedical subjects

J A Bernstein

Publications and source records attributed to J A Bernstein.

At least 37 records · Page 2Linked to original sources
PubMed1995

Nonimmunologic adverse drug reactions. How to recognize and categorize some common reactions.

When a patient experiences an adverse drug reaction, the history is in most instances the only clinical tool available for establishing a diagnosis. Thus, when taking a history, physicians should always inquire about drugs the patient has been taking and prior reactions to drugs. Clinicians should characterize every adverse drug reaction according to an accepted classification system. Familiarity with the types of reactions discussed here is therefore essential. The majority of adverse drug reactions are nonimmunologic in origin, and the most common reactions occur in response to relatively few classes of drugs. It is important not to incorrectly label a reaction as allergic, since this implies an immune-mediated response, which often precludes future use of the drug. On the other hand, if there is any concern that a reaction may be allergic, it is best to err on the side of caution by using an alternative, non-cross-reacting drug for treatment.

Drug Hypersensitivity↗
PubMed1995

Allergic drug reactions. How to minimize the risks.

Assessment of patients in whom an allergic drug reaction is suspected should include a carefully taken drug history. This should be followed by diagnostic testing if it is available for the drug in question. If neither an alternative therapeutic agent nor a diagnostic test is available, then a provocation challenge or desensitization may be necessary. Increased understanding of allergic drug reactions requires the following: better pharmacoepidemiologic studies, improved in vitro and in vivo methods of studying the immune responses involved, and expanded comparisons between the pharmacokinetics and pharmacodynamic effects of drugs and their metabolites. Until improvements are made in these areas, the appropriate approach is to avoid the unnecessary use of drugs. When a drug is required, patient risk factors for an allergic reaction must always be weighed against the benefits of treatment.

Algorithms↗
PubMed1994

A combined respiratory and cutaneous hypersensitivity syndrome induced by work exposure to quaternary amines.

The quaternary amine, benzalkonium chloride, has been associated with cutaneous and mucosal delayed hypersensitivity reactions and with paradoxical bronchoconstriction after use of aerosolized asthma medications. Until now, quaternary amines have not been reported to cause occupational asthma. We describe a case of occupational asthma caused by prolonged exposure to a cleaning solution containing benzalkonium chloride in the workplace. Single-blind, placebo-controlled, open-room challenges were performed to determine the specific agent responsible for the patient's symptoms. Pulmonary function and epicutaneous challenge tests were also performed. The patient had positive responses to challenges with a liquid toilet bowl cleaner containing benzalkonium chloride but was unreactive to other agents tested. Removal from the workplace resulted in complete resolution of symptoms. The exact mechanisms responsible for occupational asthma induced by quaternary amines remain unknown; however, this case emphasizes the importance of recognizing reactive chemicals as possible causes.

Adult↗
PubMed1994

Rapid venom immunotherapy is safe for routine use in the treatment of patients with Hymenoptera anaphylaxis.

BACKGROUND: Rapid venom immunotherapy regimens have been developed to provide safe protection to individuals who have experienced Hymenoptera anaphylaxis by administering greater than 50 micrograms of venom over two to three hours on treatment day 1. A rapid venom immunotherapy protocol which consisted of administration of a cumulative dose of 58.55 micrograms of each venom on treatment day 1 followed by an accelerated build-up over 3 weeks to a final maintenance dose of 100 micrograms per venom was developed by our group in 1984. OBJECTIVE: We report our 10-year cumulative experience with this rapid venom immunotherapy regimen. METHODS: Seventy-seven venom-allergic patients received a cumulative dose of 58.55 micrograms per venom on treatment day 1 in an ambulatory care setting. Rapid venom immunotherapy was assessed for safety. A cost analysis was performed to compare rapid venom immunotherapy to a modified rush immunotherapy regimen. RESULTS: Four patients (5.2%), experienced mild systemic reactions consisting of diffuse urticaria on day 1. Treatment was otherwise well tolerated. Resting events occurred in 21 patients, a mean number of 12 months (range: 3 days to 48 months) after treatment, without systemic reactions. CONCLUSIONS: This experience confirms that rapid venom immunotherapy is safe to administer in an ambulatory setting and should be considered especially for patients during the stinging insect season when rapid protection is required.

Adult↗
PubMed1993

Allergic rhinitis. Helping patients lead an unrestricted life.

Allergic rhinitis is a common, chronic disorder that responds well to treatment. Evaluation should begin with thorough history taking and be followed by a comprehensive treatment plan that includes avoidance measures, combination medical therapy, and allergen immunotherapy, when appropriate. The management objective should be to alleviate symptoms so that the patient can lead a normal, unrestricted life.

Adult↗
PubMed1993

The low prevalence of occupational asthma and antibody-dependent sensitization to diphenylmethane diisocyanate in a plant engineered for minimal exposure to diisocyanates.

BACKGROUND: Diisocyanate chemicals are leading causes of occupational asthma (OA). METHODS: We conducted a cross-sectional study of 243 workers exposed to diphenylmethane diisocyanate (MDI) in a urethane mold plant that had been designed to minimize MDI exposure (levels were maintained below 0.005 ppm and were continuously monitored). All participants were screened by questionnaire and tests for serum antibodies to MDI-human serum albumin (HSA). On the basis of questionnaire responses, diagnoses were derived that included OA; non-OA; work-related and non-work-related rhinitis; and lower respiratory irritant responses. Serial peak expiratory flow rate studies were performed for 2 weeks in 43 workers with and in 23 workers without lower respiratory symptoms. RESULTS: Results of serial peak expiratory flow rate studies were abnormal in 3 (33%) of 9 workers with OA, in 2 (50%) of 4 with non-OA, and in 2 (9%) of 23 case control subjects. A significant association was found between peak flow rate variability and a questionnaire asthma diagnosis (chi 2 p < 0.002). Physicians confirmed three cases of OA, one of which occurred in a control worker who was free of symptoms. In all three cases asthma symptoms remitted after the worker left the workplace. Serum specific IgE and IgG levels were elevated in 2 of 243 workers, one of whom was prick test positive to MDI-HSA and had had cutaneous anaphylaxis after MDI exposure. CONCLUSIONS: On the basis of these cases, specific work activities associated with exposure to MDI were identified and corrective measures were instituted. Strict control and monitoring of ambient MDI exposure was associated with a low prevalence of specific sensitization to MDI and a lower than expected prevalence of OA.

Air Pollutants, Occupational↗
PubMed1993

Occupational asthma induced by inhaled egg lysozyme.

A 26-year-old man employed in a company which manufactured hen egg white derived lysozyme for use in the pharmaceutical industry was evaluated for occupational asthma. The worker began to experience immediate-onset asthmatic symptoms two months after starting to work with egg lysozyme powder. The work process involved the production of approximately 1,000 kg of purified dried lysozyme powder per week. Prick skin testing was positive to egg lysozyme (50 mg/ml) and other egg protein components, but negative to whole egg white and egg yolk reagents. Serum specific IgE to egg lysozyme was documented. Decrements in serial peak expiratory flow rates were associated with lysozyme exposure at work. A specific bronchoprovocation challenge to lysozyme powder was positive demonstrating an isolated immediate asthmatic response (48 percent decrease from baseline FEV1). This is the first reported case of lysozyme-induced asthma specifically caused by inhalational exposure to egg lysozyme.

Adult↗
PubMed1993

Evaluation and treatment of localized vaginal immunoglobulin E-mediated hypersensitivity to human seminal plasma.

BACKGROUND: Localized vaginal inflammation after contact with seminal plasma has been previously described but without a clear understanding of the underlying immunopathogenesis. The purpose of this report is to describe three women who presented with localized postcoital vaginal reactions that were successfully treated with rapid immunotherapy using human seminal plasma proteins. CASES: One atopic and two nonatopic women with histories of immediate onset of localized postcoital vaginal symptoms and immediate skin test reactions to human seminal plasma were treated with rapid immunotherapy using their spouse's purified seminal plasma protein fractions. One of the women had decreased cutaneous reactivity post-therapy and detectable circulating specific immunoglobulin (Ig) G and IgE antibodies to her spouse's fractionated seminal plasma proteins. Increased IgG, IgE, and IgA antibodies were found in these patients' sera to whole seminal plasma of a normal male control and to fractionated proteins of different men, indicating that one or more homologous seminal plasma proteins may be responsible for these reactions. Their localized vaginal symptoms resolved completely after rapid immunotherapy treatment. Two of the women have remained symptom-free, whereas the third woman had recurrent localized vaginal symptoms after failing to maintain frequent sexual intercourse after treatment. CONCLUSIONS: Rapid immunotherapy immediately alleviated vaginal reactions to seminal plasma in all patients. These cases indicate that the pathogenesis of some localized vaginal inflammatory reactions may involve IgE-mediated or other immune responses to human seminal plasma proteins.

Adult↗
PubMed1992

Occupational asthma. 'My job is making me sick!'.

Future well-organized epidemiologic studies may enhance our understanding of the risk factors, prognosis, and natural course of asthma caused by a variety of inciting agents found in the workplace. Until such studies are completed, employees should be educated regarding exposure to hazardous chemicals, and strict safety measures should be enforced to prevent large spills of chemicals and other unnecessary risks.

Asthma↗
PubMed1991

The effect of the oral leukotriene antagonist, ICI 204,219, on leukotriene D4 and histamine-induced cutaneous vascular reactions in man.

Eighteen normal male subjects were recruited for a double-blind, placebo-controlled, randomized, two-period crossover study to determine the effects of a new, potent, highly selective, oral peptide leukotriene antagonist (ICI 204,219) on cutaneous vasculature. Skin testing for leukotriene D4 (LTD4) and histamine was performed at three different time intervals after receiving ICI 204,219 or placebo. The LTD4 threshold dose responses were recorded in duplicate to verify reproducibility. These data confirm known remarkable dose-response variation of cutaneous vascular reactions to LTD4 since some subjects reacted to a dose as low as 0.001 fmol. Twelve subjects (67%) demonstrated a more than one-half log increase in their threshold response after receiving ICI 204,219. Five of these 12 subjects (28%) had greater than 1 log-dose response after ICI 204,219. Two of these subjects (11.1%) had a 5 or 10 log increase in their threshold response after receiving ICI 204,219. Given the role of leukotrienes as potentially important mediators in immediate-type reactions, our results raise the possibility for additional investigation of the antagonistic effect of ICI 204,219 in nonallergic and allergic cutaneous diseases.

Adolescent↗
PubMed1991

Potentially fatal asthma and syncope. A new variant of Munchausen's syndrome in sports medicine.

We report a case of Munchausen's syndrome in a 19-year-old female college athlete who presented with potentially fatal asthma and recurrent syncopal episodes. Failure to control her asthma with the appropriate medications and the lack of objective findings on both physical examination and diagnostic testing raised the possibility of factitious disease. Munchausen's syndrome, although not described with any frequency in asthmatic patients, should be considered in the differential diagnosis of those patients refractory to aggressive medical management.

Adult↗
PubMed1991

Asthmatic patients with panic disorders: report of three cases with management and outcome.

Panic disorders, a subgroup of the primary anxiety disorders, have an estimated worldwide prevalence of 2.5% to 5%. Although the causes of these disorders have not been completely elucidated, it seems that environmental and genetic factors in addition to central nervous system biochemical abnormalities play important roles. Mild to moderate anxiety levels may prove advantageous in the management of asthmatics but when their anxiety level becomes maladaptive, as in the case of panic attacks, their medical care is placed in jeopardy. Herein are three case reports of asthmatics who also exhibited panic disorders and their clinical outcome. It is concluded that a team approach, involving the primary physician and psychologist or psychiatrist, is beneficial in the long-term management of these patients.

Adult↗
PubMed1990

Immunoblot analysis of sera from patients with allergic bronchopulmonary aspergillosis: correlation with disease activity.

Immunoblot analysis was used to evaluate the IgG, IgE, and IgA responses to Aspergillus fumigatus antigen with the sera of five patients with allergic bronchopulmonary aspergillosis (ABPA) before, during, and after suspected exacerbation of their disease. The results revealed a heterogenous antibody response, unique for each patient, to specific Aspergillus fumigatus antigens that correlated with the molecular weights of previously well-characterized antigens of importance in the immunopathogenesis of ABPA. A rating scale was devised for measuring band intensity that allowed the patient's antibody responses to be reproducibly semiquantitated. Immunoblot analysis demonstrated qualitative and semiquantitative information that is not available with other in vitro assays used in the study of patients with ABPA, such as ELISA. These initial results emphasize the need for additional evaluation of this technique to assess its potential clinical application in this disease.

Antigens, Fungal↗
PubMed1989

Characterization of the helicase and primase activities of the 63-kDa component of the bacteriophage T7 gene 4 protein.

Leading and lagging strand DNA synthesis at the replication fork of bacteriophage T7 DNA requires the helicase and primase activities of the gene 4 protein. Gene 4 protein consists of two colinear polypeptides of 56- and 63-kDa molecular mass. We have demonstrated previously that the 56-kDa protein possesses helicase but lacks primase activity (Bernstein, J. A., and Richardson, C. C. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 396-400). The 63-kDa gene 4 protein has now been purified from extracts of T7-infected cells. The preparation contains 5-10% contaminating 56-kDa protein, as shown by Western analysis using polyclonal antibodies to the purified 56-kDa protein. The 63-kDa protein catalyzes DNA-dependent dTTP hydrolysis and has helicase activity; both specific activities are similar to those determined for the 56-kDa protein. The 63-kDa protein efficiently synthesizes sequence-specific di-, tri-, and tetraribonucleotides and stimulates the elongation of tetraribonucleotides by T7 DNA polymerase. Although the 56-kDa protein alone lacks primase activity, it enhances the primase activity of the 63-kDa protein 4-fold. This stimulation can be accounted for by a similar increase in the amount of primers synthesized by the 63-kDa protein in the presence of the 56-kDa protein.

Blotting, Western↗
PubMed1988

Purification of the 56-kDa component of the bacteriophage T7 primase/helicase and characterization of its nucleoside 5'-triphosphatase activity.

Bacteriophage T7 gene 4 protein, purified from phage-infected cells, consists of a mixture of a 56- and a 63-kDa species that provides primase and helicase activities for T7 DNA replication. The 56-kDa species has been purified 1800-fold from Escherichia coli cells containing a plasmid that encodes this gene 4 protein. The purified 56-kDa protein is homogeneous, as determined by denaturing gel electrophoresis, and is monomeric in its native form, as indicated by gel filtration. The binding of the 56-kDa protein to single-stranded DNA is stimulated by nucleoside 5'-triphosphates, as is the case for a mixture of the two molecular weight species. In the presence of DNA, the 56-kDa protein preferentially hydrolyzes dTTP (Bernstein, J. A., and Richardson, C. C. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 396-400). Since nucleoside 5'-triphosphatase activity is necessary for both helicase activity and for translocation of gene 4 protein to primase recognition sites, we have characterized this activity using the 56-kDa protein alone. In the DNA-dependent hydrolysis reaction, the enzyme displays a Km of 10 mM for dTTP, and a Vmax of 2.9 x 10(-5) M/min/mg of protein (at 2.5 micrograms/ml). There is little cooperativity with respect to dTTP binding (Hill coefficient = 1.1) except in the presence of ribonucleoside 5'-triphosphate, an inhibitor of dTTP hydrolysis (Hill coefficient greater than 1.5). The apparent KD for single-stranded circular DNA is 0.2 microM. The active species in dTTP hydrolysis is an oligomer of at least two subunits, as indicated by the effect of enzyme concentration upon the rate of DNA-dependent hydrolysis. The 56-kDa protein also catalyzes DNA-independent hydrolysis of dTTP with a Km of 0.11 mM and a Vmax of 1.3 x 10(-7) M/min/mg of protein (at 8 micrograms/ml). The active species in DNA-independent dTTP hydrolysis is also an oligomer.

Chromatography↗
PubMed1988

A 7-kDa region of the bacteriophage T7 gene 4 protein is required for primase but not for helicase activity.

Bacteriophage T7 gene 4 protein, purified from phage-infected cells, consists of a mixture of 56- and 63-kDa species that provides helicase and primase activities required for T7 DNA replication. The 56-kDa species has been purified independently of the colinear 63-kDa species. Like a mixture of the two proteins, the 56-kDa protein binds single-stranded DNA in the presence of dTTP, catalyzes DNA-dependent hydrolysis of dTTP, and has helicase activity. In contrast to the mixture, the 56-kDa protein cannot catalyze template-dependent RNA primer synthesis. In the absence of a DNA template, both the 56-kDa protein and the mixture of the two species synthesize low levels of diribonucleotide. A putative "zinc finger" present near the amino terminus of the 63-kDa protein but absent from the 56-kDa protein may play a major role in the recognition of primase sites in the template.

DNA Helicases↗
PubMed1986

Template requirements for in vivo replication of adenovirus DNA.

The adenovirus (Ad) DNA origin of replication was defined through an analysis of the DNA sequences necessary for the replication of plasmid DNAs with purified viral and cellular proteins. Results from several laboratories have shown that the origin consists of two functionally distinct domains: a 10-base-pair sequence present in the inverted terminal repetition (ITR) of all human serotypes and an adjacent sequence constituting the binding site for a cellular protein, nuclear factor I. To determine whether the same nucleotide sequences are necessary for origin function in vivo, we developed an assay for the replication of plasmid DNAs transfected into Ad5-infected cells. The assay is similar to that described by Hay et al. (J. Mol. Biol. 175:493-510, 1984). With this assay, plasmid DNA replication is dependent upon prior infection of cells with virus and only occurs with linear DNA molecules containing viral terminal sequences at each end. Replicated DNA is resistant to digestion with lambda-exonuclease, suggesting that a protein is covalently bound at both termini. A plasmid containing only the first 67 base pairs of the Ad2 ITR replicates as well as plasmids containing the entire ITR. Deletions or point mutations which reduce the binding of nuclear factor I to DNA in vitro reduce the efficiency of plasmid replication in vivo. A point mutation within the 10-base-pair conserved sequence has a similar effect upon replication. These results suggest that the two sequence domains of the Ad origin identified by in vitro studies are in fact important for viral DNA replication in infected cells. In addition, we found that two separate point mutations which lie outside these two sequence domains, and which have little or no effect upon DNA replication in vitro, also reduce the apparent efficiency of plasmid replication in vivo. Thus, there may be elements of the Ad DNA origin of replication which have not yet been identified by in vitro studies.

Adenoviruses, Human↗