DISSIMILAR ALLERGIC DISEASE IN IDENTICAL TWINS—A Study of Psychosomatic Aspects

Identical twins with bronchial asthma were studied. One had the first attack of the disease in late adolescence, the other not until he was adult.Both were demonstrated by immunologic means to be sensitive to house dust and certain foods. Yet, of itself, the factor of exposure to a known allergen seemed not enough to precipitate clinical allergic reaction in either of them.It is believed that emotional stress is accompanied by physiologic changes which facilitate increased reactions to antigenic agents that in normal circumstances would not cause clinical disease.The twins were widely different with regard to emotional development and in their reaction to situations of stress. In both of them allergic manifestations were associated with periods of emotional conflict.The dissimilar clinical manifestations of allergy in these identical twins may be explained by differences in personality and therefore in reactions to stress situations.     

Spectrum of Asthma in Children—II,Allergic Components

The incidence of a variety of clinical and immunological features of an allergic state was studied at 7, 10, and 14 years of age in a group of children suffering from one of four grades of asthma, ranging from mild subclinical to severe unremitting, and compared with the incidence in a control group of non-asthmatic children. The incidence of all features of allergy was significantly higher in the asthmatics but no one feature unequivocally distinguished the asthmatics from the controls. Almost all the asthmatics showed several features of the allergic state at 14 years of age. A cluster of allergic features was a differentiating characteristic of the asthmatics, and the children with the most allergic manifestations were usually the children with the most severe and persistent asthma. The first appearance of and subsequent variation in some of the allergic manifestations often did not correspond to the clinical course of the asthma.Though many manifestations of asthma can be understood on an allergic basis the mechanism by which emotional disturbance, exercise, viral infections, and non-allergenic stimuli precipitate attacks of asthma and the relation of these factors to allergy are unknown.     

Antioxidant activity levels and oxidative stress as blood markers of allergic response to drugs.

Antioxidant enzymes work together in human blood cells against toxic reactive oxygen species. Although their relationship with several pathophysiologic processes has been stated, not much is known about the connection between antioxidant defence and allergy. This study was designed to determine the enzymatic activities and the oxidative indices in the blood and serum proteins in patients suffering from allergy to drugs. We hypothesize that serum and blood reactions may serve as useful clinical marker for the allergic state. We used enzymatic antioxidant activities, thiobarbituric acid reactive substances, and carbonyl contents of proteins as suitable markers. We determined superoxide dismutases, glutathione peroxidase and catalase activities in each cell type. After antihistaminics plus steroids were given as part of a protocol treatment, enzymatic antioxidant activities, thiobarbituric acid reactive substance levels, and carbonyl contents were used as recovering markers for the disease. We found a relationship between antioxidant enzymatic activities, thiobarbituric acid reactive substance levels, and carbonyl contents for allergic reactions belonging to several type I and type IV allergies, as well as cross-reactive intolerance to nonsteroidal anti-inflammatory drugs and an anaphylactoid reaction to a radiocontrast media. A similar pattern also exists for analogous allergic manifestations and disease-like status.     

Emotional stress and diabetic control: a postulated model for the effect of emotional distress upon intermediary metabolism in the diabetic

The findings of a number of clinical investigators across a wide variety of situations and using a wide variety of observational procedures agree on the disruptive effects of emotional distress upon diabetic control. An integrative model of coordinated neural and hormonal reactions to emotional stress and their additive and potentiating effects on intermediary metabolism is proposed. The end result of these effects, as part of a general fight/flight or defense-alarm reaction, is a strong energy mobilization response (namely, a sharp rise in blood glucose and free fatty acid levels resulting in increased levels of serum cholesterol, triglycerides, and ketone bodies), which the diabetic cannot readily counterregulate. It is further proposed that increased diabetic control, together with lower insulin requirements, may result from the inclusion of stress management procedures as an adjunct to traditional medical treatment. The findings of a large number of investigators supporting these propositions are presented and discussed.     

Emotional stress during conditioned reflex transformation of heterogeneous instrumental reflexes

The factors leading to pronounced emotional stress accompanied by changes in electrical activity of hippocampus were studied in four dogs during elaboration of conditioned switching-over of heterogeneous instrumental reflexes. Objectively recorded signs of emotional stress were observed in two cases: when the animal was not accurate enough in discerning defensive and alimentary situations and throughout the improvement of instrumental defensive reflex. Pronouncement of hippocampal theta-rhythm increased at those stages of switching-over elaboration where the probability of successful avoiding pain stimulation was relatively low. The data obtained permit the conclussion that theta-rhythm is the correlate of the degree of the emotional stress and not only a manifestation of general arousal reaction depending on the level of sensory input.     

Anaphylactic shock and lethal anaphylaxis caused by compound amino acid solution, a nutritional treatment widely used in China

Compound amino acid solution (CAAS) is a large class of solution of amino acids’ mixture and was widely used in China. Its extensive nutritional treatment was accompanied by a substantial incidence of adverse reactions, especially life-threatening anaphylaxis. However, the adverse reactions were reported in isolated case reports only, and the reasons behind this needed further investigation. The Chinese language papers were searched from China National Knowledge Infrastructure and Wanfang database published in China from 1985 to 2010. The search terms “anaphylactic”, “anaphylaxis”, “allergic”, “allergy”, “shock”, and “adverse reaction” combined with the term “amino acid” were used. Totally 71 episodes of anaphylactic shock and seven deaths in 38 articles were analyzed. Chest distress and cool extremities were the most common clinical manifestations. Almost all patients suffered from significant hypotension. The vast majority of patients were not found to be allergic to certain substances. CAAS was inappropriately administrated in more than one-third of patients. The life-threatening anaphylaxis was prominently prevalent in pregnant women, the elderly and patients with hypersensitivity such as asthma, and patients without medicinal indication. Innovation of processing technique and establishment of more strict supervision system are an urgent need for CAAS to control its production quality and thus improve its safety in China.     

Peculiarities of the Effects of Stimulation of Emotiogenic Central Structures under Conditions of a Kindling Model of Epilepsy

In our study, we tried, first, to elucidate whether induction of emotional behavior resulting from stimulation of the dorsomedial hypothalamus (DMH) influences the development of seizure activity in the course of epileptogenesis within the framework of fast kindling (stimulation of the hippocampus) and, second, to estimate if such stimulation is capable of modulating manifestations of generalized seizures under conditions of the pre-formed “full” epileptic syndrome. Stimulation of the DMH in the above two experimental situations resulted in significant suppression of both electrographic and behavioral manifestations of seizure activity. We hypothesize that the respective emotional reactions can be interpreted as phenomena of instinctive behavior having an adaptive defensive significance. These reactions are related to inhibitory processes providing protection from the development of seizure activity.     

Investigating T cell activation and tolerance in vivo: peptide challenge in allergic asthmatics

In the atopic allergic individual, challenge with allergen elicits manifestations of both the humoral (IgE-mediated or early-phase reaction) and the cell-mediated immune response (late-phase reaction). Detailed study of late-phase cell-mediated events is confounded by the effects of the earlier IgE-mediated response which results in mast cell and basophil activation. Thus the relative contributions to allergic inflammation of individual cell types, such as T cells and eosinophils, are difficult to define. In this review we describe experiments, largely from our own group, in which we have attempted to dissociate early and late allergic reactions. To this end, cell-mediated responses were induced in the absence of preceding IgE-mediated events, by the delivery of synthetic peptides representing T cell epitopes of the allergen. Activation of T cells resulted in airway narrowing and an increase in airway reactivity to non-specific stimuli. Furthermore, we describe the induction of antigen-specific hyporesponsiveness or "tolerance" following intradermal, but not mucosal, peptide delivery. The induction of peptide-induced hyporesponsiveness could be temporally dissociated from the initial T cell activation resulting in bronchoconstriction and likely occurred through a different mechanism. Analysis of in vitro allergen responses of peripheral blood cells revealed that hyporesponsiveness was associated with reductions in both Th1 and Th2 cytokines, together with a concomitant increase in the regulatory cytokine IL-10. We conclude that activation of T cells in vivo may result in manifestations of chronic allergic inflammation including bronchoconstriction and hyperreactivity. Additionally, when administered systemically at low dose, peptides may induce long-lasting hyporesponsiveness in the T cell compartment, through a mechanism that is associated with induction of IL-10.     

Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations

Systemic Lupus Erythematosus (SLE) is one of the most relevant world-wide autoimmune disorders. The formation of autoantibodies and the deposition of antibody-containing immune complexes in blood vessels throughout the body is the main pathogenic mechanism of SLE leading to heterogeneous clinical manifestations and target tissue damage. The complexity of etiology and pathogenesis in SLE, enclosing genetic and environmental factors, apparently is one of the greatest challenges for both researchers and clinicians. Strong indications for a genetic background in SLE come from studies in families as well as in monozygotic and dizygotic twins, discovering several SLE-associated loci and genes (e.g. IRF5, PTPN22, CTLA4, STAT4 and BANK1). As SLE has a complex genetic background, none of these genes is likely to be entirely responsible for triggering autoimmune response in SLE even if they disclosure a potentially novel molecular mechanisms in the pathogenesis'' disease. The clinical manifestations and disease severity varies greatly among patients, thus several studies try to associate clinical heterogeneity and prognosis with specific genetic polymorphisms in SLE associated genes. The continue effort to describe new predisposing or modulating genes in SLE is justified by the limited knowledge about the pathogenesis, assorted clinical manifestation and the possible prevention strategies. In this review we describe newly discovered, as well as the most studied genes associated to SLE susceptibility, and relate them to clinical manifestations of the disease.     

Emotional stress and diabetic control: A postulated model for the effect of emotional distress upon intermediary metabolism in the diabetic

The findings of a number of clinical investigators across a wide variety of situations and using a wide variety of observational procedures agree on the disruptive effects of emotional distress upon diabetic control. An integrative model of coordinated neural and hormonal reactions to emotional stress and their additive and potentiating effects on intermediary metabolism in proposed. The end result of these effects, as part of a general fight/flight or defense-alarm reaction, is a strong energy mobilization response (namely, a sharp rise in blood glucose and free fatty acid levels resulting in increased levels of serum cholesterol, triglycerides, and ketone bodies), which the diabetic cannot readily counterregulate. It is further proposed that increased diabetic control, together with lower insulin requirements, may result from the inclusion of stress management procedures as an adjunct to traditional medical treatment. The findings of a large number of investigators supporting these propositions are presented and discussed.I am indebted to the following people for their extensive editorial comments and suggestions; G. Blakemore Evans, William Hay, and Theodore J. Lavaque. I am thankful to Roger Hatcher for his support and extensive input as well as his editorial comments.     

Predisposing Factors in Adverse Reactions to Drugs

Predisposing factors were sought in 118 patients who developed adverse drug reactions in hospital. Significantly more patients of 60 years and over, and more women than men, developed adverse drug reactions. Patients with reactions had more drugs before the development of the reaction than patients who did not develop reactions. A previous adverse drug reaction and a history of allergic disease were significant factors, while a history of jaundice or the presence of diabetes mellitus and renal disease was not.     

Nasal hyperreactivity and inflammation in allergic rhinitis

The history of allergic disease goes back to 1819, when Bostock described his own 'periodical affection of the eyes and chest', which he called 'summer catarrh'. Since they thought it was produced by the effluvium of new hay, this condition was also called hay fever. Later, in 1873, Blackley established that pollen played an important role in the causation of hay fever. Nowadays, the definition of allergy is 'An untoward physiologic event mediated by a variety of different immunologic reactions'. In this review, the term allergy will be restricted to the IgE-dependent reactions. The most important clinical manifestations of IgE-dependent reactions are allergic conjunctivitis, allergic rhinitis, allergic asthma and atopic dermatitis. However, this review will be restricted to allergic rhinitis. The histopathological features of allergic inflammation involve an increase in blood flow and vascular permeability, leading to plasma exudation and the formation of oedema. In addition, a cascade of events occurs which involves a variety of inflammatory cells. These inflammatory cells migrate under the influence of chemotactic agents to the site of injury and induce the process of repair. Several types of inflammatory cells have been implicated in the pathogenesis of allergic rhinitis. After specific or nonspecific stimuli, inflammatory mediators are generated from cells normally found in the nose, such as mast cells, antigen-presenting cells and epithelial cells (primary effector cells) and from cells recruited into the nose, such as basophils, eosinophils, lymphocytes, platelets and neutrophils (secondary effector cells). This review describes the identification of each of the inflammatory cells and their mediators which play a role in the perennial allergic processes in the nose of rhinitis patients.     

Canine atopic dermatitis: validation of recorded diagnosis against practice records in 335 insured Swedish dogs

A cross-sectional study of insured Swedish dogs with a recorded diagnosis of canine atopic dermatitis (CAD) was performed. In order to validate the correctness of this specific diagnosis in the insurance database, medical records were requested by mail from the attending veterinarians. All dogs with a reimbursed claim for the disease during 2002 were included in the original study sample (n = 373). Medical records were available for 335 individuals (response rate: 89.8%). By scrutinizing the submitted records it was determined that all dogs had been treated for dermatologic disease, and that 327 (97.6%) could be considered to have some allergic skin disease. However, as information regarding dietary trial testing was missing in many dogs the number that were truly atopic could not be determined. The clinical presentation and nature of test diet for dogs with or without response to dietary trial testing was compared for a subset of 109 individuals that had undergone such testing. The only significant difference between these two groups was that the proportion of dogs with reported gastrointestinal signs was higher in the group that subsequently responded to a diet trial. In conclusion, the agreement between the recorded diagnosis in the insurance database and the clinical manifestations recorded in the submitted medical records was considered acceptable. The concern was raised that many attending veterinarians did not exclude cutaneous adverse food reactions before making the diagnosis of CAD.     

Memory in the grip of emotions and stress: a necessarily harmful impact?

While intense negative events are vividly recalled, information learned during stressful situations is poorly remembered. These differential effects of emotions and stress on memory have been attributed to the physiological manifestations generated during those affective states. Intense emotional and stressful events trigger the secretion of catecholamines and of glucocorticoids, in particular. These hormones would be modulatory agents of memory functions. In the first part of this paper, we review the specific effects emotions and stress have on memory. We then summarize the psychological and biological determinants responsible for these effects. Finally, we discuss different methodological issues that could explain the discrepancy found between the impact of emotions and stress on memory. Defining more precisely the effects emotion and stress have on memory will lead to a better comprehension of the cognitive problems that characterize patients dealing with emotional turmoil, such as patients suffering from depression or post-traumatic stress disorder.     

Cardiac Responses to Thermal,Physical, and Emotional Stress

We have studied the effect of a short period of exposure to the intense heat of a sauna bath on the electrocardiogram and plasma catecholamine, free fatty acid, and triglyceride concentrations in 17 subjects with apparently normal hearts and 18 persons with coronary heart disease. Similar observations were made on 11 of the 17 normal subjects and on 7 of the persons with coronary heart disease in response to exercise.Exposure to heat was associated with an increase in plasma adrenaline with no change in noradrenaline, free fatty acid, or triglyceride concentrations. Exercise was associated with the expected increase in both plasma noradrenaline and adrenaline concentrations. A heart rate up to 180 beats/min was observed in response to both heat and exercise. Apart from the ST-T changes inherent to sinus tachycardia, ST-T segment abnormalities were frequent in response to heat in both the subjects with normal and abnormal hearts, but little change occurred in the ST-T configuration when the subjects were exercised to produce comparable heart rates. Ectopic beats, sometimes numerous and multifocal, were observed in some subjects of both groups in response to heat, but not to exercise. It seems likely that the net unbalanced adrenaline component of the increased plasma catecholamine concentrations (which is also seen in certain emotional stress situations) is predominantly responsible for ischaemic-like manifestations of the electrocardiogram in susceptible subjects. The observations provide further validation for previously reported studies that it is the increased plasma noradrenaline in response to emotional stress that is associated with the release of free fatty acids and ultimate hypertriglyceridaemia, of probable importance in the aetiology of atheroma.     

THE SIGNIFICANCE OF INFECTION IN ALLERGIC DISEASE—Its Influence on Diagnosis and Management

The presence of infection in allergic disease produces a confused picture in which two different causative factors must be clearly separated by the physician if he is to treat the patient successfully. The effects of infection are not consistent. There are situations, as seen in infectious diseases, where symptoms of allergic disease are temporarily relieved and others where the infection may intensify or precipitate the allergic condition. It is likewise important to recognize the complications superimposed upon allergic disease by infection. In such cases, control of the infection is as dependent upon control of the allergy as it is upon antibiotics.     

THE SIGNIFICANCE OF INFECTION IN ALLERGIC DISEASE-Its Influence on Diagnosis and Management

The presence of infection in allergic disease produces a confused picture in which two different causative factors must be clearly separated by the physician if he is to treat the patient successfully. The effects of infection are not consistent. There are situations, as seen in infectious diseases, where symptoms of allergic disease are temporarily relieved and others where the infection may intensify or precipitate the allergic condition. It is likewise important to recognize the complications superimposed upon allergic disease by infection. In such cases, control of the infection is as dependent upon control of the allergy as it is upon antibiotics.     

Comparative study of the psychotropic activity of tuftsin and its analogs

Tuftsin and its Leu1 and D-Arg4 analogs displayed stimulating activity in experimental behavioral despair in mice. In rats with different types of emotional reactions and with destroyed catecholamine terminals (6-OHDA treatment), tuftsin increased exploratory activity, with fear manifestations being decreased and avoidance behavior improved. This was shown while testing the rats in the "open field" and according to the ability to accomplish an extrapolation task of avoiding critical stress-situation. Leu1-tuftsin increased the emotional stress and sharply hindered the avoidance reaction, while D-Arg4-tuftsin modulated the behavior of the animals with increased emotional reactivity and made the avoidance behavior prompter. Pentapeptide, an inhibitor of tuftsin stimulation of phagocytosis, had no significant effect on the behavior. Modifications in the structure of tuftsin resulted both in the changes in phagocytosis-stimulating activity and the appearance of other psychotropic effects.     

Allergic rhinoconjunctivitis: the role of histamine

Allergic rhinoconjunctivitis is the most common atopic condition encountered in clinical practice. Analysis of the pathogenesis of this condition permits identification of optimal therapeutic targets. The increased knowledge of the underlying pathophysiology suggests that multiple inflammatory mediators are involved in the pathogenesis of the allergic reaction in the ocular and nasal mucosa. However, despite the presence of a wide range of different mediators, it would appear that histamine plays a key role. Experimental allergen challenge studies have demonstrated that histamine is the only mediator which produces the full spectrum of clinical manifestations of the acute allergic reaction when applied to the mucosal surface. While both H(1)- and H(2)-receptors are present in the nasal and ocular mucosa, only H(1)-receptor antagonists are capable of inhibiting histamine-induced symptoms of allergic rhinoconjunctivitis. Furthermore, although the exact role of histamine in the immediate and prolonged allergic reaction has not yet been fully elucidated, these findings do not exclude the possibility that histamine is involved in these processes. The available evidence therefore supports current clinical practice for use of H(1)-receptor antagonist as a first-line therapy in patients with this atopic condition.     

The development of experimental allergic encephalomyelitis with immunizing doses of myelin basic protein.

Rabbits immunized with low (11.25 mg) and high (57.50 mg) doses of myelin basic protein from several species develop antibasic protein antibodies, delayed type hypersensitivity, and clinical and pathological signs of experimental allergic encephalomyelitis. More than 55% of rabbits immunized with relatively high doses of basic protein develop disease. The absence of circulating antibasic protein antibodies in immunorespondent animals is associated with the appearance of clinical or histological signs of experimental allergic encephalomyelitis; however, the presence of humoral antibodies did not prevent completely the development of disease. Delayed-type hypersensitivity, specific for the basic protein, appears as early as 5 days after immunization and is maintained in nondiseased and surviving animals. Neither excess encephalitogen nor encephalitogen-induced antibody is sufficient to suppress completely the eventual development of clinical or histological manifestations of disease.