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Cases from the Osler Medical Service at Johns Hopkins University.

PRESENTING FEATURES: An 18-year-old white man was admitted to the Osler Medical Service with the chief complaint of back pain. Two weeks prior to admission, the patient developed diffuse and aching upper back pain. Over the next couple of days, he also developed severe anterior chest pain that was somewhat pleuritic in nature but diffuse and extending bilaterally into the shoulders. One week prior to admission, he developed intermittent fevers and night sweats. The patient denied any lymphadenopathy, pharyngitis, sick contacts, shortness of breath, rash, or bleeding. He was seen by a physician and told that he had thrombocytopenia. There was no history of recent or remote unusual bleeding episodes. His medical history was unremarkable except for a childhood diagnosis of attention deficit/hyperactivity disorder. He was not taking any medications and had no history of tobacco, alcohol, or illicit drug use. He had no risk factors for human immunodeficiency virus infection. Physical examination showed that he was afebrile and had normal vital signs. He was a well-appearing man who was lying still because of pain. HEENT examination was unremarkable. There was no pharyngeal erythema or exudates. His lungs were clear. His neck was supple and without lymphadenopathy. Examination of his back and chest revealed no focal tenderness. There was no hepatosplenomegaly, and his skin was without petechiae or rashes. Examination of the patient's joints showed pain on passive and active movement of his shoulders bilaterally, but no frank arthritis. There was no rash, petechiae, or echymoses. Chest radiograph and electrocardiogram were unremarkable. On admission, the laboratory examination was notable for a hematocrit level of 32.5%, with a mean corpuscular volume of 79 fL, and white blood cell count of 2.8 x 10(3)/microL. Platelet count was 75 x 10(3)/microL. A white blood cell differential revealed 7% bands, 53% polys, 34% lymphs, 5% atypical lymphocytes, 2% nucleated red cells, and a few young unidentified cells. His chemistry studies were unremarkable. What is the diagnosis?

Adolescent↗

Predicting development of anticipatory nausea in cancer patients: prospective examination of eight clinical characteristics.

An algorithm based on learning theory and previous research for predicting which cancer patients would develop nausea in anticipation of chemotherapy treatments was tested. Patients with four or more of the following eight characteristics after their first treatment were predicted to develop anticipatory nausea (AN) by their fourth chemotherapy treatment: experienced nausea and/or vomiting after first treatment; nausea after treatment described as "moderate, severe, or intolerable;" vomiting after treatment described as "moderate, severe, or intolerable;" less than 50 yr of age; a susceptibilty to motion sickness; feeling warm or hot all over after treatment; sweating following treatment; feelings of generalized weakness following treatment. The characteristics significantly predicted subsequent anticipatory nausea development (p less than .01) by their fourth treatment in 355 consecutive cancer patients. Results were independent of the type of cancer being treated. The accuracy of the prediction was less specific than prior research, 34% of patients predicted to develop AN did so, compared to 16% of the total sample. Results are consistent with a learned etiology for the development of anticipatory side effects and support the importance of predictive methodologies in investigating mechanisms of anticipatory nausea development.

Antineoplastic Agents↗

[Group sports as adjuvant therapy for patients with atopic eczema].

The therapeutic value of regular physical exercise for patients with atopic eczema (AE) and other chronic inflammatory dermatoses has not yet been investigated systematically. At our institution an adjuvant group sports programme for voluntary inpatients has been in place for 3 years. Using a standardized questionnaire we found positive psychological influences of this program on the patients' mood and psychosocial wellbeing. Since most dermatologists, however, regard sweating as detrimental for patients with AE, we studied the impact of regular sports activities on the skin condition of AE-patients otherwise subdued to usual dermatotherapy (yet without corticosteroids) by aid of a standardized symptomscore system. Thirty inpatients with AE participated regularly in the sports programme, another 30 inpatients with AE (the control group) did not. The skin condition improved similarly the two groups over the study period of about 3 weeks. Cutaneous thermoregulation (with one arm in a 41 degrees C water bath as thermic stimulus) was examined in patients with AE before and after the study period. While many AE patients initially showed paradoxical, i.e. decreasing, skin temperature in the contralateral arm, after 3 weeks of physical training most of the participants had normalized consensual, i.e. increased, temperature reaction to the same warmth exposure. The conclusion is drawn that regular sports may be of adjuvant therapeutic value in patients suffering from AE, except in the acute stages of the disease.

Adaptation, Psychological↗

The illness perceptions of women following symptoms of acute myocardial infarction: a self-regulatory approach.

BACKGROUND: Coronary Heart Disease (CHD) has been socially constructed as a gender-specific disease with women not seen to be at risk. Women tend to delay seeking help following the onset of symptoms of acute myocardial infarction (MI). An illness perceptions approach has been used to explain treatment-seeking behaviour. AIMS: The aim of this study was to explore the illness perceptions of a sample of women following acute MI using the self-regulatory model of illness behaviour as the theoretical framework. METHODS: Ten women, with a range of ages, took part in semi-structured interviews, 3 months following an acute infarct. Data were analysed thematically according to the theoretical framework. RESULTS: The development of a serious model of the illness and the decision to seek help was influenced by the experience of severe, unusual symptoms especially if of sudden onset; the absence of co-morbidities and similarities to the known experience of others. Perceived lack of susceptibility to the disease and a belief that symptoms were benign may have resulted in a delay in seeking help. Coping strategies were initially aimed at relieving symptoms before seeking help from families and friends. This resulted in a call for professional help. CONCLUSION: Health promotion strategies need to emphasis the uniqueness of the individual's experience. Interventions designed to alter illness perceptions may influence treatment-seeking behaviour.

Adaptation, Psychological↗

Susceptibility to motion sickness induced by optokinetic rotation and self-rotation by walking around a vertical pole.

31 subjects viewed an optokinetic rotating drum for 12 min. in one session and self-rotated by walking quickly around a vertical pole with eyes closed while alternately flexing and extending the neck in another session. The self-rotation session contained 6 trials (3 clockwise and 3 counterclockwise rotations). Each trial contained 20 cycles of self-rotations. Self-reported ratings of nausea and symptoms of motion sickness were obtained for each session. The subjects developed symptoms of nausea, sweating, dizziness, headache, drowsiness, and changes in salivation in both drum rotation and self-rotation sessions. However, the subjects reported higher ratings of nausea in the session of optokinetic rotation than in the session of self-rotation around a vertical pole. These results indicated that both optokinetic rotation and self-rotation with eyes closed while alternately flexing and extending the neck are effective means of inducing nausea and motion sickness.

Adolescent↗

[Mechanism of development of space motion sickness].

Astronauts and scientists are scheduled to stay aboard the International Space Station (ISS) for three-month periods, and various problems relating to the human ability to live in space for such long periods of time, as well as medical problems, are being studied. For the crews that have operated and worked on the US space shuttle, the longest time spent in the gravity-free (accurately speaking, microgravity) environment of space has been about two weeks. Even such short periods have generated reports of various physical changes and symptoms caused by the absence of gravity. Particularly striking effects are circulatory system changes, muscular atrophy and decalcification of bones. In addition, serious problems arise during the time in space due to the symptoms of space motion sickness, caused by neuro-otological changes. Space motion sickness is experienced by nearly 70% of the first-time astronauts, in the form of such symptoms as nausea, and vomiting. It is said that space motion sickness develops at the time of adaptation of the body to the gravity-free environment. Unlike motion sickness on Earth, space motion sickness is characterized by a feeling of fullness of the head, a hot face and reduced sweating. The provocative factors include movement of the head in the pitch and roll directions and the unusual visual field. This paper reviews the research that has been carried out to date on space motion sickness, and its counter measures comprehensively, in terms of the changes in the otolith organ as well as asynchronization of information between the movements of the head and eyeballs, the deep sensations and body fluid shifts. Other problems, which may be encountered as a result of yet longer stays in space, are also discussed.

Adaptation, Physiological↗

Scopolamine withdrawal syndrome.

As travel by air and ship becomes increasingly popular, more and more travelers are using transdermal scopolamine to avoid motion sickness. In fact, it has become almost fashionable for ocean travelers to sit on the sun deck with a patch behind the ear. This article describes withdrawal symptoms in a patient who used transdermal scopolamine beyond the recommended 3 days.

Administration, Cutaneous↗

Simulator induced syndrome in Coast Guard aviators.

The incidence of adverse symptoms in Coast Guard aviators undergoing flight simulator training was determined. A voluntary, multi-part questionnaire was completed by 238 pilots. During the first simulator flight 64.3% of pilots reported at least one adverse symptom, 39.4% during the last flight. Simulator induced syndrome (SIS) was present in 47.1% of subjects during the first simulator flight, 23.5% during their last flight. Most subjects reported their symptoms as mild, with some symptoms rated as moderate or severe in nature. There was no statistically significant association (p greater than 0.05) between the development of SIS and flight experience, simulator experience, length of simulator session, or self-determined motion sickness susceptibility. There was a significant association (p less than 0.05) between SIS development and the use of simulators with computer-generated imagery (CGI). Nine pilots experienced adverse symptoms at least 2 d after their last simulator flight. In conclusion, this study revealed that SIS occurs frequently, is more common when CGI is present, may recur, suggests an adaptative process, and may not be associated with some factors previously claimed.

Aerospace Medicine↗

Scopolamine for preventing and treating motion sickness.

BACKGROUND: Motion sickness - the discomfort experienced when perceived motion disturbs the organs of balance - may include symptoms such as nausea, vomiting, pallor, cold sweats, hypersalivation, hyperventilation and headaches. The control and prevention of these symptoms have included pharmacological, behavioural and complementary therapies. Although scopolamine has been used in the treatment and prevention of motion sickness for decades, there have been no systematic reviews of its effectiveness. OBJECTIVES: To assess the effectiveness of scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination for motion sickness in persons (both adults and children) without known vestibular, visual or central nervous system pathology. SEARCH STRATEGY: The Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (OVID, 1966 to March Week 1 2004), EMBASE (1974 to 2004) CINAHL (Ovid, 1982 to March Week 1 2004) and reference lists of retrieved studies were searched for relevant studies. No language restrictions were applied. SELECTION CRITERIA: All parallel-arm, randomised controlled trials (RCTs) focusing on scopolamine versus no therapy, placebo, other drugs, behavioural and complementary therapy or two or more of the above therapies in combination were included. Outcomes relating to the prevention of onset or treatment of clinically-defined motion sickness, task ability and psychological tests, changes in physiological parameters and adverse effects were considered. DATA COLLECTION AND ANALYSIS: Data from the studies were extracted independently by two authors using standardised forms. Study quality was assessed. Dichotomous data were expressed as odds ratio (OR) and a pooled OR was calculated using the random effects model. MAIN RESULTS: Of 27 studies considered potentially relevant, 12 studies enrolling 901 subjects met the entry criteria. Scopolamine was administered via transdermal patches, tablets or capsules, oral solutions or intravenously. Scopolamine was compared against placebo, calcium channel antagonists, antihistamine, meth-scopolamine or a combination of scopolamine and ephedrine. Studies were generally small in size and of varying quality. Scopolamine was more effective than placebo in the prevention of symptoms. Comparisons between scopolamine and other agents were few and suggested that scopolamine was superior (versus meth-scopolamine) or equivalent (versus antihistamines) as a preventative agent. Evidence comparing scopolamine to cinnarizine or combinations of scopolamine and ephedrine is equivocal or minimal. Although sample sizes were small, scopolamine was no more likely to induce drowsiness, blurring of vision or dizziness compared to other agents. Dry mouth was more likely with scopolamine than with meth-scopolamine or cinnarizine. No studies were available relating to the therapeutic effectiveness of scopolamine in the management of established symptoms of motion sickness. REVIEWERS' CONCLUSIONS: The use of scopolamine versus placebo in preventing motion sickness has been shown to be effective. No conclusions can be made on the comparative effectiveness of scopolamine and other agents such as antihistamines and calcium channel antagonists. In addition, no randomised controlled trials were identified that examined the effectiveness of scopolamine in the treatment of established symptoms of motion sickness.

Humans↗

Drug treatment of motion sickness: scopolamine alone and combined with ephedrine in real and simulated situations.

In two placebo-controlled, double-blind, randomized trials scopolamine (0.3 mg) alone or combined with ephedrine (25 mg) was tested for its effectiveness in the prevention of seasickness during 24 h at sea and of motion sickness in rotating chair tests in a laboratory. Scopolamine was effective both alone and in combination with ephedrine, which supports the hypothesis on central cholinergic overactivity in the pathogenesis of motion sickness. Ephedrine did not markedly increase the effectiveness of scopolamine. Side-effects were slight and did not disturb the operating ability of the volunteers.

Adult↗

Illusory self-motion and motion sickness: a model for brain-gut interactions and nausea.

Motion sickness provides a unique setting for the study of nausea. Studies of illusory self-motion have linked nausea and objective measures of gastric dysrhythmias and the stress hormones vasopressin and epinephrine. Electrogastrographic methods utilize Ag-AgCl electrodes placed on the abdominal surface in the epigastric region to record electrogastrograms (EGGs), a noninvasive measure of gastric myoelectrical activity. The EGG frequencies of interest are the normal range (2.4-3.6 cpm), tachygastrias (3.6-9.9 cpm), and bradygastrias (1.0-2.4 cpm), and duodenal respiratory frequencies (10.0-15.0 cpm). Illusory self-motion or vection is produced with a rotating drum. Minutes before vection-induced nausea is reported, the baseline EGG signal shifts into tachygastrias or mixed tachygastrias and bradygastrias. Quantitative analyses show that the percentage of power in the tachygastria range correlates with the intensity of nausea. Plasma vasopressin levels correlate positively with intensity of nausea. Asian subjects have higher intensity nausea and higher vasopressin levels compared with Caucasian subjects, indicating a potential genetic susceptibility to vection-induced motion sickness and nausea. Vection-induced motion sickness represents an experimental model of acute-onset nausea with accompanying symptoms such as headache, drowsiness, cold sweating, and fatigue. Illusory self-motion is a purely central nervous system (visual-vestibular) stimulation that evokes dramatic shifts in gastric electrical activity and significant release of the posterior pituitary hormone vasopressin. Central nervous systems pathways that evoke gastric dysrhythmias and release vasopressin may also have a pathophysiologic role in the cyclic vomiting syndrome.

Brain↗

[Motion sickness in the aerospace environment].

After a brief description of the newest and special form of motion sickness known as "space sickness" arising in space flight, and the various hypotheses on its aetiopathogenesis, motion sickness in general and the air or plane sickness deriving from atmospheric flying are discussed. The aetiopathogenesis of air sickness derives from abnormal stimulations that are primarily vestibular but also visual and somesthesic, and generated by irregular movements or variations in attitude of the plane. Reflex action than produces effects that are primarily neurovegetative (nausea, vomiting, pallor, scialorrhea, sweating, bradycardia) and neuropsychological (depression, drowsiness, headache, discomfort and general debility with altered cenesthesia). After a description of the symptoms, the prevention and treatment of air sickness are discussed.

Humans↗

A genetic polymorphism of the alpha2-adrenergic receptor increases autonomic responses to stress.

We hypothesized that individual differences in autonomic responses to psychological, physiological, or environmental stresses are inherited, and exaggerated autonomic responsiveness may represent an intermediate phenotype that can contribute to the development of essential hypertension in humans over time. alpha(2)-Adrenergic receptors (alpha(2)-ARs), encoded by a gene on chromosome 10, are found in the central nervous system and also mediate release of norepinephrine from the presynaptic nerve terminals of the peripheral sympathetic nervous system and the exocytosis of epinephrine from the adrenal medulla. We postulated that, because this receptor mediates central and peripheral autonomic responsiveness to stress, genetic mutations in the gene encoding this receptor may explain contrasting activity of the autonomic nervous system among individuals. The restriction enzyme Dra I identifies a polymorphic site in the 3'-transcribed, but not translated, portion of the gene encoding the chromosome 10 alpha(2)-AR. Southern blotting of genomic DNA with a cDNA probe after restriction enzyme digestion results in fragments that are either 6.7 kb or 6.3 kb in size. Transfection studies of these two genotypes resulted in contrasting expression of a reporter gene, and it is suggested from these findings that this is a functional polymorphism. In a study of 194 healthy subjects, we measured autonomic responses to provocative motion, a fall in blood pressure induced by decreasing venous return and cardiac output, or exercise. Specifically, we measured reactions to 1) Coriolis stress, a strong stimulus that induces motion sickness in man; 2) heart rate responses to the fall in blood pressure induced by the application of graded lower body negative pressure; and 3) exercise-induced sweat secretion. In all of these paradigms of stress, subjective and objective evidence of increased autonomic responsiveness was found in those individuals harboring the 6.3-kb allele. Specifically, volunteers with the 6.3-kb allele had greater signs and symptoms of motion sickness mediated by the autonomic nervous system after off-axis rotation at increasing velocity (number of head movements a subject could complete during rotation before emesis +/- SE: 295 +/- 18 vs. 365 +/- 11; P = 0.001). They also had greater increases in heart rate in responses to the lower body negative pressure-induced fall in blood pressure (increase in heart rate +/- SE: 3.0 +/- 0.4 vs. 1.8 +/- 0.3; P = 0.012), and the 6.3-kb group had higher sweat sodium concentrations during exercise (mean sweat sodium concentration in meq/l over 30 min of exercise +/- SE: 43.2 +/- 7.1 vs. 27.6 +/- 3.4; P < 0.05). This single-nucleotide polymorphism may contribute to contrasting individual differences in autonomic responsiveness among healthy individuals.

3' Untranslated Regions↗

Changes in nasal mucosal innervation in horses with grass sickness.

REASONS FOR PERFORMING STUDY: Equine grass sickness is a dysautonomia characterised by widespread destruction of autonomic ganglia, resulting in the clinical signs of dysphagia, constipation, profuse sweating, tachycardia, rhinitis sicca and high mortality rate. Rhinitis sicca is a common finding in horses with the chronic form and we have postulated that alterations in autonomic innervation of the nasal mucosa might underlie this clinical presentation. OBJECTIVES: In this study, the expression and distribution of nerve fibres immunoreactive for calcitonin gene-related peptide (CGRP), substance P (SP), the general neuronal marker protein gene-product 9.5 (PGP 9.5; ubiquitin) and the intermediate neurofilaments (PAN-N; neurorfilaments L, M and H) in the nasal mucosa of normal horses (n = 10) and horses with EGS (n = 18; acute n = 8, subacute n = 3, chronic n = 7) was assessed. METHODS: Innervation density and distribution was investigated in the different groups using standard immunohistochemical techniques. RESULTS: Significant differences were noted when comparing the density and distribution of nerve fibres immunoreactive for PGP 95 and PAN-N, with PGP 95 consistently giving better staining in all groups and at all sites in the nasal mucosa. An apparent increase in the density of innervation was noted for acute vs. normal cases. A significant reduction in the density of innervation was noted only with PAN-N when comparing normal horses and acute cases with the chronic group (P < 0.05). CGRP and SP immunoreactive nerve fibres were typically most abundant in the epithelial and subepithelial layers, but the quality of staining and nerve fibre density was greater for SP, achieving significant difference in several comparisons. The density of innervation for SP was significantly reduced in the chronic group compared to the normal and acute groups (P < 0.01). A significant decrease was noted for CGRP only for the acute and chronic groups (P<0.05). CONCLUSIONS: These results demonstrate a reduction in the expression of the sensory neuropeptides in nasal mucosal innervation as a consequence of equine dysautonomia, and may underlie the clinical presentation of rhinitis sicca noted with this disease. POTENTIAL RELEVANCE: Nasal biopsy may be of use in antemortem diagnosis of grass sickness and identification of mucosal denervation; and might also be useful in the treatment of rhinitis in EGS cases.

Acute Disease↗