Selected developments in the understanding of diabetic ketoacidosis.

Advances in the understanding of diabetic ketoacidosis have contributed to the recent decrease in the morbidity and mortality associated with this condition. The role of counterregulatory hormones in its pathogenesis is considerable, but insulin deficiency is necessary for diabetic ketoacidosis to develop. Therapy begins with identification and treatment of the factors precipitating ketosis. Isotonic saline is the fluid of choice for initial intravenous therapy; subsequently 0.45% saline is appropriate. Sodium bicarbonate is necessary only if the arterial pH is less than 7.1, and phosphate should be given only when the serum phosphate level is below 0.5 mg/dl (0.16 mmol/l). Factors other than pH are important in causing the hyperkalemia so commonly seen at the time of presentation, but whether or not hyperkalemia is present potassium supplementation is almost always necessary and should be given as long as the urinary output is adequate. Intravenous doses of insulin as low as 5 to 15 U/h are sufficient in most cases, but the occasional patient will require larger amounts. Close clinical and biochemical monitoring is necessary for successful management.     

THE EFFECTS OF CORTISONE AND ADRENOCORTICOTROPIC HORMONE (ACTH) ON CERTAIN RHEUMATIC DISEASES

The adrenal cortical hormone, cortisone, and the pituitary adrenocorticotropic hormone (ACTH) possess potent antirheumatic properties. Their administration produces strikingly beneficial effects on a number of rheumatic diseases including rheumatoid arthritis, rheumatoid (ankylosing) spondylitis, acute rheumatic fever, disseminated lupus erythematosus, periarteritis nodosa, psoriatic arthritis, dermatomyositis, and gout. In general the effects of these substances are temporary and they cause suppression rather than cure of the disease processes. Improvement is maintained usually only by continuing administration, and on hormonal withdrawal prompt or fairly prompt relapse of the disease manifestations ensues. In addition to their antirheumatic effects cortisone and ACTH influence a wide variety of physiologic functions. Administration of them therefore may produce a number of metabolic and clinical changes, some of which are not advantageous from a therapeutic standpoint. Adverse side-reactions are more liable to occur when large doses of the hormones are given for prolonged periods; such reactions appear to be reversible and disappear when administration of the hormones is stopped. With cortisone, comparatively few untoward signs develop when smaller amounts are administered continuously even for periods of months.Greater clinical experience is needed before optimal doses and schedules of administration are finally determined. It appears that some severe cases, many moderately severe cases, and most moderate and mild cases of rheumatoid arthritis may be adequately controlled with smaller “maintenance” doses of cortisone ranging from 32 to 65 mg. a day, providing larger doses to suppress the disease manifestations are employed initially.Neither cortisone nor ACTH should be considered as a therapeutic agent for general use until more information regarding their physiologic activities and the consequences of prolonged or repeated administration of them are available. Until the potential dangers of these hormones can be determined precisely, the use of them should be considered as an investigative procedure.     

Allergic bronchial asthma and rhinitis; the importance of studies for sensitivity to foods

The authors consider sensitivity to foods and sensitivity to inhalants about equal in importance in bronchial asthma, allergic rhinitis and allergic bronchitis. Food allergens are the sole cause of bronchial and nasal allergic disease in 20 to 40 per cent of cases throughout life, including old age; inhalants are the sole cause in approximately an equal number; and sensitivity to foods and to inhalants are often associated. THEIR FREQUENT RECOGNITION OF SENSITIVITY TO FOODS AS A CAUSE OF DISEASE, THE AUTHORS BELIEVE, DEPENDS ON: (1) The recognition of the fallibility of skin testing and the usual negative skin reactions to allergenic foods in chronic and recurrent bronchial asthma and allergic rhinitis. (2) The adequate use of trial diets, especially cereal-free elimination diet. (3) The realization that ingested foods remain in the body usually for two to four weeks and that the diet must be continued until symptoms have been relieved for two to three times as long as preceding relief between attacks.     

ALLERGIC BRONCHIAL ASTHMA AND RHINITIS—The Importance of Studies for Sensitivity to Foods

The authors consider sensitivity to foods and sensitivity to inhalants about equal in importance in bronchial asthma, allergic rhinitis and allergic bronchitis. Food allergens are the sole cause of bronchial and nasal allergic disease in 20 to 40 per cent of cases throughout life, including old age; inhalants are the sole cause in approximately an equal number; and sensitivity to foods and to inhalants are often associated.Their frequent recognition of sensitivity to foods as a cause of disease, the authors believe, depends on: (1) The recognition of the fallibility of skin testing and the usual negative skin reactions to allergenic foods in chronic and recurrent bronchial asthma and allergic rhinitis. (2) The adequate use of trial diets, especially cereal-free elimination diet. (3) The realization that ingested foods remain in the body usually for two to four weeks and that the diet must be continued until symptoms have been relieved for two to three times as long as preceding relief between attacks.     

Theophylline in the management of airflow obstruction. 2. Difficult drugs to use,few clinical indications.

The narrow therapeutic index, potential toxicity, and need to monitor plasma concentrations make theophyllines difficult to use. Other drugs provide comparable or better bronchodilator and prophylactic efficacy. In asthma theophyllines should be considered for chronic stable asthma when treatment with optimal doses of inhaled steroids and bronchodilators fails to provide adequate control; for nocturnal asthma; and for prophylaxis and relief of symptoms in children and adults when inhaled treatment cannot be given. In general, theophyllines cannot be recommended for chronic airflow obstruction. A trial of theophylline is reasonable in individual patients whose symptoms remain troublesome despite a trial of steroids and optimal doses of inhaled bronchodilators.     

Illicit anabolic-androgenic steroid use

The anabolic-androgenic steroids (AAS) are a family of hormones that includes testosterone and its derivatives. These substances have been used by elite athletes since the 1950s, but they did not become widespread drugs of abuse in the general population until the 1980s. Thus, knowledge of the medical and behavioral effects of illicit AAS use is still evolving. Surveys suggest that many millions of boys and men, primarily in Western countries, have abused AAS to enhance athletic performance or personal appearance. AAS use among girls and women is much less common. Taken in supraphysiologic doses, AAS show various long-term adverse medical effects, especially cardiovascular toxicity. Behavioral effects of AAS include hypomanic or manic symptoms, sometimes accompanied by aggression or violence, which usually occur while taking AAS, and depressive symptoms occurring during AAS withdrawal. However, these symptoms are idiosyncratic and afflict only a minority of illicit users; the mechanism of these idiosyncratic responses remains unclear. AAS users may also ingest a range of other illicit drugs, including both “body image” drugs to enhance physical appearance or performance, and classical drugs of abuse. In particular, AAS users appear particularly prone to opioid use. There may well be a biological basis for this association, since both human and animal data suggest that AAS and opioids may share similar brain mechanisms. Finally, AAS may cause a dependence syndrome in a substantial minority of users. AAS dependence may pose a growing public health problem in future years but remains little studied.     

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.     

PAGET'S DISEASE—Changes Occurring Following Treatment with Newer Hormonal Agents

From experience in six cases the anabolic steroid hormones, especially long-acting testosterone and estrogen preparations, are the treatment of choice in Paget''s disease, as in postmenopausal osteoporosis. Details of the management of three patients over a period of four years are presented.Roughly 4 per cent of the population, mostly persons over 40, show some evidence of Paget''s disease. Only a small number of them, however, have severe manifestations requiring treatment, such as pain, howing or fracture of the bones, pressure on nerves or heart failure. In rare cases malignant changes occur in the involved bone.Since the cause of Paget''s disease is not known, treatment in the past has been largely empirical. Reifenstein and Albright had advocated the therapeutic use of calcium, vitamin D and ascorbic acid, and, in postmenopausal women, administration of estrogens; but with fractures or immobilization, intake of calcium-containing foods, such as milk, must be restricted to avoid dangerous piling up of calcium and kidney stones, and fluids must be forced. In recent years anabolic steroid hormones, principally oral androgens and estrogens, have been employed by Gordan and others to promote bone repair, lessen bone pain and decrease urinary excretion of calcium. While these hormones probably do not arrest the disease, they seem to stabilize it and bring relief of symptoms.More recently, Albright and Henneman demonstrated that very large doses of corticotropin (ACTH) or cortisone resulted in immediate cessation of bone pain, decrease in urinary excretion of calcium and histologic evidence of regression of the disease process. The large doses required, however, also produce dangerous side effects, such as psychosis and osteoporosis, indicating that such treatment probably should not be continued over long periods.     

Hormones of youth?

Ageing is doubtless complicated, lifelong process regarding many body systems, including endocrine system. Human hormonal system changes with age. Although these changes concern secretion of many hormones, they are not unidirectional, there are hormones secretion of which is diminished, whereas secretion of the others is augmented or not changed with age. A possible role of hormones which are often termed "hormones of youth"(growth hormone, melatonin, and dehydroepiandrosterone) in the ageing process is discussed in the present article. Although some experimental and clinical data indicate that these hormones may play some role in the human ageing process, it appears from presented data that we are still far away from conclusion that, indeed, one (or more) of the discussed hormones could be considered as "hormone of youth", which may slow down ageing process. However, some symptoms of the quality of life improvement following administration of dehydroepiandrosterone, melatonin, and growth hormone may suggest that they may promote so called "successful aging".     

Suppression and reversal of allergic encephalomyelitis in rhesus monkeys with basic protein and peptides

We have extended earlier studies on the suppression of clinically evident experimental allergic encephalomyelitis (EAE) in monkeys, using repeated injections of human basic protein. The results confirm that after suppressive treatment, recovered animals remain clinically normal and do not show spontaneous recurrence of symptoms. However, recovered animals are susceptible to EAE upon renewed challenge, and they develop the disease more rapidly and more severely than after the initial challenge; resuppression is also accomplished in these cases by the same methods used previously. The present results indicate further that the basic protein or peptide T administered without mycobacteria is effective in suppressing the development of basic protein-induced EAE regardless of the species from which it was derived.     

MEDICAL PROGRESS: Histamine and the Antihistaminic Drugs

The tissues affected by histamine and anaphylactic reactions are identical. Epinephrine antagonizes the action of histamine by acting on effector cells in a direction opposite to that of histamine. The so-called antihistaminic drugs block rather than antagonize the action of histamine. The injection into the human body of epinephrine or certain antihistaminic substances provokes the release of histamine and thereby produces a rise in the histamine blood level.There is a remarkable conformity of potency of antihistaminics as determined by Dale experiments and by histamine intoxication experiments in the intact guinea pig. Neoantergan, Pyribenzamine and Histadyl are usually superior to other compounds when potency is assayed by these methods.All antihistaminics provide similar protection again animal anaphylaxis. Larger doses are necessary to protect against anaphylaxis than against histamine intoxication.The differences in potency as determined by Dale experiments and histamine experiments in animals are not found in clinical use. One compound is not generally superior to all others in the treatment of any one or several allergic disorders.The antihistaminic drugs are beneficial in the symptomatic treatment of allergic rhinitis, acute urticaria and angioneurotic edema, and mild non-infective bronchial asthma. Their effectiveness in the management of moderately severe and severe non-infective bronchial bronchial asthma; infective bronchial asthma; migraine; atopic dermatitis (disseminated neurodermatitis), and pruritus of skin disorders other than acute urticaria and angioneurotic edema, is not worthy of particular commendation.The size of the dose of any antihistaminic substance influences the incidence of but not the type of side-effect that may accompany its usage. The quality of side effects varies according to the drug, although there is an individuality of response for each patient which must be reckoned with. In selecting an antihistaminic compound it is necessary to consider the percentage of cases in which side effects occur, as well as the percentage of good results. Optimal results are obtained by employing combinations of compounds and changing from one to the other as the case demands.     

Histamine and the antihistaminic drugs

The tissues affected by histamine and anaphylactic reactions are identical. Epinephrine antagonizes the action of histamine by acting on effector cells in a direction opposite to that of histamine. The so-called antihistaminic drugs block rather than antagonize the action of histamine. The injection into the human body of epinephrine or certain antihistaminic substances provokes the release of histamine and thereby produces a rise in the histamine blood level. There is a remarkable conformity of potency of antihistaminics as determined by Dale experiments and by histamine intoxication experiments in the intact guinea pig. Neoantergan, Pyribenzamine and Histadyl are usually superior to other compounds when potency is assayed by these methods. All antihistaminics provide similar protection again animal anaphylaxis. Larger doses are necessary to protect against anaphylaxis than against histamine intoxication. The differences in potency as determined by Dale experiments and histamine experiments in animals are not found in clinical use. One compound is not generally superior to all others in the treatment of any one or several allergic disorders. The antihistaminic drugs are beneficial in the symptomatic treatment of allergic rhinitis, acute urticaria and angioneurotic edema, and mild non-infective bronchial asthma. Their effectiveness in the management of moderately severe and severe non-infective bronchial bronchial asthma; infective bronchial asthma; migraine; atopic dermatitis (disseminated neurodermatitis), and pruritus of skin disorders other than acute urticaria and angioneurotic edema, is not worthy of particular commendation. The size of the dose of any antihistaminic substance influences the incidence of but not the type of side-effect that may accompany its usage. The quality of side effects varies according to the drug, although there is an individuality of response for each patient which must be reckoned with. In selecting an antihistaminic compound it is necessary to consider the percentage of cases in which side effects occur, as well as the percentage of good results. Optimal results are obtained by employing combinations of compounds and changing from one to the other as the case demands.     

Oligosaccharins, brassinolides, and jasmonates: nontraditional regulators of plant growth, development, and gene expression.

Each of the nontraditional plant hormones reviewed in this article, oligosaccharins, brassinolides, and JA, can exert major effects on plant growth and development. However, in many cases, the mechanisms by which these compounds are involved in the endogenous regulation of morphogenesis remain to be established. Nevertheless, the use of mutant or transgenic plants with altered levels or perception of these hormones is leading to phenomenal increases in our understanding of the roles they play in the life cycle of plants. It is likely that in the future, novel modulators of plant growth and development will be identified; some will perhaps be related to the peptide encoded by ENOD40 (Van de Sande et al., 1996), which modifies the action of auxin.     

Animal cell cultures as a source of hormones

Current methodology now makes it possible to establish in culture a variety of mammalian cells which perform organ-specific functions during serial propagation for periods of months or years. This report describes the results of experiments with animal and human cells that produce growth hormone, adrenocortical steroid hormones, thyrocalcitonin, and parathyroid hormone. Within the next decade it should be possible to use cell culture methods for manufacturing purposes to produce hormones and other valuable cellular products which are difficult to obtain in other ways. At first it may be necessary to use neoplastic cells for this purpose; but evidence is accumulating to suggest that it may eventually be possible to establish in culture normal, functional animal and human cells.     

Direct in vivo monitoring of acute allergic reactions in human conjunctiva

Immediate allergic reactions are initiated by allergen-induced, specific IgE-mediated mast cell degranulation and involve leukocyte recruitment into the inflamed site. We compared conjunctival signs, symptoms, and in vivo leukocyte rolling and extravasation into sites of inflammation in five patients allergic to birch pollen and in 10 nonallergic controls who received a challenge to birch allergen or histamine. Both the specific allergen in allergic patients and histamine, both in patients and in healthy controls, induced symptoms and signs of an immediate allergic reaction together with leukocyte rolling within the conjunctival blood vessels. However, only allergen, not histamine, caused leukocyte extravasation into the site of inflammation in the allergic patients. Allergen also increased expression of endothelial P-selectin in conjunctival vessels and slowed the rolling of leukocytes which is required for their extravasation from blood circulation into the target tissue. Finally, i.v. heparin strongly reduced the number of slowly rolling cells during allergen- or histamine-induced reactions and this can probably hinder the leukocyte extravasation after allergen exposure. These findings suggest that slow rolling is required for leukocyte extravasation in acute allergic reactions, and it can be inhibited by heparin in vivo in therapeutically relevant conditions.     

ANTIHISTAMINIC DRUGS IN DERMATOLOGY

From the results of treatment of 1,770 patients with dermatologic diseases (1,458 as reported in the literature and 312 observed by the author) it is concluded that antihistaminic preparations are of great value in allergic diseases where it is hypothecated that liberated histamine is the offender, as in acute edematous types of urticaria, erythema multiforme, and some cases of allergic pruritus.The indiscriminate use of these drugs is to be avoided. Antihistaminic drugs are palliative—they do not cure. They often prolong the disease. They give temporary relief from swelling and pruritus. They develop no specific immunity and do not replace immunizing efforts. They do not replace or interfere with epinephrine or ephedrine.     

Is There a Threshold Concentration of Cat Allergen Exposure on Respiratory Symptoms in Adults?

Background and Objective

Cat allergen concentrations higher than 8 μg/g in settled house dust, have been suggested to provoke exacerbation of allergic respiratory symptoms. However, whether the 8μg/g of indoor cat allergen concentration is indeed the minimal exposure required for triggering the asthma related respiratory symptoms or the development of sensitization has not yet been confirmed. We studied the associations between domestic cat allergen concentrations and allergic symptoms in the European Community Respiratory Health Survey II, with the aim of confirming this suggested threshold.

Methods

Cat allergen concentrations were measured in the mattress dust of 3003 participants from 22 study centres. Levels of specific immunoglobulin E to cat allergens were measured in serum samples using an immunoassay. Information on allergic symptoms, medication use, home environment and smoking was obtained from a face-to-face interview.

Results

Domestic cat allergen concentrations were not associated with allergic/ asthmatic symptoms in the entire study population, nor in the subset sensitized to cat allergen. We also found no association among individuals exposed to concentrations higher than 8 μg/g. However, exposure to medium cat allergen concentrations (0.24-0.63 μg/g) was positively associated with reported asthmatic respiratory symptoms in subjects who have experienced allergic symptoms when near animals.

Conclusions

The proposed 8 μg/g threshold of cat allergen concentrations for the exacerbation of allergic/ respiratory symptoms was not confirmed in a general European adult population. Potential biases attributable to avoidance behaviours and an imprecise exposure assessment cannot be excluded.     

Hormone treatments and preventive strategies in the aging male: whom and when to treat?

Sex hormones have a broad range of actions in regulating very diverse systems throughout life. Testosterone and other related hormones change with age to varying degrees and may induce pathophysiological changes and the clinical condition known as andropause. Androgen replacement is the accepted but not the only possible treatment for andropause. The presence of clinical symptoms, including a loss of sexual function, intellectual capacity, lean body mass, or bone mineral density; alterations in body hair, skin, or sleep pattern; or increases in visceral fat, together with low levels of serum testosterone characterize andropause. An appreciation of the potentially undesirable impact of androgens on the biology of prostate cancer, as well as possibly the cardiovascular system, is necessary. However, proper evaluation of aging men with symptoms of andropause will result in a decision to initiate androgen therapy in some aging men.     

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.