Cytarabine-induced anaphylaxis. Demonstration of antibody and successful desensitization.

An anaphylactic episode occurred in a patient receiving cytarabine (Ara-C) for acute myeloid leukemia. Specific allergy of the patient to cytarabine was demonstrated in vivo by intradermal testing and in vitro by four-hour passive cutaneous anaphylaxis in guinea pigs. Desensitization to cytarabine was successfully performed. This case represents the first known report of both cytarabine anaphylaxis and densensitization, and provides immunologic evidence implicating an allergic reaction to cytarabine.

Occult sinus abnormalities in the asthmatic patient.

Unrecognized sinusitis has been cited by others as a significant unrecognized factor in patients with asthma, chronic rhinitis, and urticaria. The current study examines the utility of roentgenography of the paranasal sinuses in such patients. Forty-seven percent of patients with flare-ups of asthma had abnormal sinus roentgenograms, a highly significant difference from the 29% prevalence in patients presenting with complaints of rhinitis. The patient's clinical history was most often not helpful in predicting whether or not roentgenographic abnormalities of the sinuses would be detected. Since maxillary sinusitis is the most frequent finding, the erect Waters' view is the most useful single roentgenogram.

A randomized controlled trial comparing zileuton with theophylline in moderate asthma. The Zileuton Study Group.

BACKGROUND: Zileuton, a leukotriene pathway inhibitor, was compared with slowly absorbed theophylline in a randomized, double-blind study of patients with chronic asthma. The primary efficacy measure was improvement in forced expiratory volume in 1 second (FEV1). METHODS: Eligibility criteria included FEV1 of 40% to 80% of predicted, documented reversibility of airway disease, and age 18 to 60 years. Initially, the theophylline dosage was titrated to achieve trough concentrations of 8 to 15 micrograms/mL. After washout and 1-week placebo lead-in, patients were randomly assigned to 13 weeks of the appropriate theophylline dose or zileuton, 400 or 600 mg 4 times daily. The FEV1 was measured before the morning dose at 2-week intervals and serially after the dose on days 36 and 92. Patients kept daily diaries of asthma symptoms, beta-agonist usage, and peak expiratory flow rate; on days 36 and 92, they completed quality-of-life questionnaires. RESULTS: Of 471 eligible patients at 38 centers, 377 were randomly assigned to the study; 313 completed the study. On first-dose administration, all groups showed 11% to 13% improvement in FEV1 within 30 minutes. Patients who received zileuton, 400 mg, had significantly greater improvement at several points than did theophylline-treated patients. The range of long-term maximum improvement in FEV1 in the groups was 30% to 34% (P = .40 for zileuton 600 mg; P = .90 for zileuton 400 mg vs theophylline). Initially, the theophylline group improved significantly more in symptom scores, beta-agonist usage, and peak expiratory flow rate, but at maximal effect there was no significant difference. All groups showed significant improvement in quality of life. No overall differences were observed between the zileuton dosage groups. Adverse events were comparable in all groups. CONCLUSION: Zileuton appears as effective and safe as theophylline in patients with chronic asthma.

Bronchodilating effect of terbutaline aerosol.

We compared the efficacy of terbutaline with that of metaproterenol, isoproterenol, and placebo aerosols in 16 asthmatic patients. Terbutaline, metaproterenol, and isoproterenol produced equivalent improvements in flow rates. At 5 hr, the effect of terbutaline on tests of small airways, FEF25%--75%, and FEF50%, was greater (p less than 0.05) than that of metaproterenol and isoproterenol. Terbutaline produced no significant change of heart rate or blood pressure.

Anaphylaxis: issues in diagnosis.

Although anaphylaxis continues to be recognized as a life-threatening clinical problem, efforts to develop in-vitro methods for diagnosis and verification continue. The results have been interesting but not yet definitive, so that the necessity for clinical diagnosis remains pivotal.

Colorectal cancer and noncancer patients have similar labeling indices by microscopy and computed image analysis.

The labeling index (LI), a microscopic measurement of proliferative activity in colonic crypts, is proposed as an indicator of colonic cancer risk. Computed image analysis of proliferative regions is less labor intensive and more objective than is direct microscopy but has not been validated for labeling indices by direct comparison. The authors compared colonic crypt proliferation in 26 cancer and 13 noncancer patients by using Ki-67 monoclonal antibody (McAb) labeling of flat mucosa obtained from surgically removed, frozen specimens. In cancer patients, the mucosa specimen was excised 10 cm away from the tumor, and the LI was determined microscopically for the whole crypt, the upper two thirds, and the upper one third of 15 crypts. Nuclear antigen levels of 15 whole crypts were determined by using the CAS-200 computed image analyzer (Cell Analysis Systems, Elmhurst, IL). Cancer and noncancer specimens were compared as were microscopically determined LI and stained nuclei specimens by using image analysis. No statistically significant difference in proliferative activity of whole crypts, or the upper two thirds of crypts, was observed between cancer specimens and noncancer specimens from using either technique. However, a significant correlation existed between microscopic analysis and computed image analysis of labeled nuclei. Computed image analysis using Ki-67 McAb labeling can be used instead of microscopy to determine crypt LI, but neither method can be used to distinguish cancer specimens from noncancer specimens.

Phenelzine treatment of depression with chronic diarrhea.

The monoamine oxidase inhibitors (MAOIs) have been used increasingly in treating nonendogenous depressions. Patients with psychophysiologic disorders have many characteristics in common with known MAOI responders. The authors present the case of a man who had had diarrhea for 36 years, with an underlying chronic depression. The patient was unresponsive to ECT and tricyclic antidepressants. Phenelzine, 60 mg/day, produced dramatic improvement in the patient's diarrhea and his sense of well-being.

Adverse effect of propranolol on airway function in nonasthmatic chronic obstructive lung disease.

Bronchomotor tone is, in part, under beta-adrenergic control, and beta-adrenergic agonists are commonly used in the therapy for chronic obstructive pulmonary disease (COPD). Beta-adrenergic blockade with propranolol is contraindicated in asthmatic patients, yet little is known of its effect in patients with COPD. We studied 13 patients with COPD in a random-entry, double-blind crossover comparison of oral propranolol, 40 mg, and oral placebo on separate day. Pulmonary function worsened after administration of propranolol. Significant differences were present between the drugs' effect on heart rate, airway resistance, specific resistance, and flow rates at one hour, and persisting through four hours (p less than 0.01). Propranolol may have a deleterious effect on pulmonary function in nonasthmatic COPD. We conclude that when propranolol is to be used in patients with COPD, the short- and long-term effects on airway should be measured sequentially.

Beta-adrenergic blockade of the lung. Dose-dependent cardioselectivity of tolamolol in asthma.

Beta-adrenergic blocking agents are widely used to treat disorders of cardiac rhythm and rate, angina, and hypertension. Propranolol is the most widely used beta-adrenergic blocking agent in this country. Because of its nonselective beta-adrenergic blocking effect, propranolol may be associated with significant bronchoconstriction in asthmatic subjects and in some patients with chronic obstructive pulmonary disease. Since tolamolol, a new beta-adrenergic blocking agent, has cardioselectivity in animals, we studied asthmatic subjects for six hours on three separate days in a double-blind crossover comparison of oral therapy with 40 mg of propranolol, its beta-adrenergic blocking equivalent dose of tolamolol (50 mg), and a high dose of tolamolol (100 mg). All three dosages had equipotent effects on heart rate and systolic pressure. The 50-mg dose of tolamolol had no effect on pulmonary function over six hours; however, both propranolol (40 mg) and the 100-mg dose of tolamolol had equivalent deleterious effects on airway resistance and on rates of expiratory flow. We conclude that the cardioselectivity of tolamolol is dose-limited but is present at the dosage of 50 mg, which is equivalent to the usual antiarrhythmic beta-adrenergic blocking dose of propranolol (40 mg).

A comparative study of the clinical efficacy of nedocromil sodium and placebo. How does cromolyn sodium compare as an active control treatment?

Nedocromil sodium and cromolyn sodium are the only two currently available nonsteroid anti-inflammatory agents for treatment of asthma. Clinical differences between the two agents remain under continuous investigation with reports differentiating the two on the basis of atopy of the patient and reversibility of bronchoconstriction. This study investigated the efficacy of nedocromil sodium (4 mg, qid) for treatment of mild-to-moderate asthma in comparison to placebo using cromolyn sodium (2 mg, qid) as an active control treatment. Patients were primarily allergic asthmatics (with at least 15% reversibility) previously maintained on a regimen of regular bronchodilator therapy. During a 2-week run-in period, the patient's slow-release theophylline therapy was removed, and the patients were randomized to treatment after deterioration of asthma control (asthma symptom summary score of 3 for 7 of the 14 days). After 8 weeks of treatment, patients were returned to as occasion requires bronchodilator therapy, as per the 2-week baseline period. The results demonstrate that patients treated with nedocromil sodium showed statistically significant improvements during the primary time period (mean weeks 3 through 8) over placebo-treated patients as evidenced by all indexes of asthma symptoms, pulmonary function measures, and decreased bronchodilator reliance (p<0.05). Patients treated with cromolyn sodium demonstrated similar improvements over placebo-treated patients. Comparisons between nedocromil sodium and cromolyn sodium showed the two agents to be comparable in this group of primarily allergic patients with reversible disease. Between-group differences were noted for 3 of the 13 variables (nighttime asthma, FEV1, and forced expiratory flow rate between 25 % and 75% of the FVC) in favor of cromolyn sodium when the data were pooled during the primary time period. The number of patients missing 1 or more days from work/school/regular activity due to asthma was significantly fewer compared with placebo, and favoring nedocromil sodium over cromolyn sodium. No differences were observed among the three treatments for adverse events. This study demonstrated that in primarily allergic patients with reversible airways disease, nedocromil sodium and cromolyn sodium are both significantly more effective than placebo for treatment of mild-to-moderate asthma.

Serum trypsin inhibitory capacity and pi phenotypes. II. Prevalence of alpha1-antitrypsin deficiency in an allergy population.

A series of 138 patients seen consecutively in an adult allergy clinic were studied to determine serum alpha1-antitrypsin (alpha1-AT) levels and protease inhibitor (Pi) phenotypes. These were compared with a control group of 700 healthy young adult blood donors. Both total serum trypsin inhibitory capacity (STIC) and alpha1-AT levels as determined by immunoelectrophoresis (IEP) were measured. Phenotypes were determined by antigen-antibody-crossed IEP. Alpha1-AT levels in the allergy group were not significantly different from control values. STIC in the allergy group was 1.34 +/- 0.28 mg. trypsin inhibited per ml. serum and in the controls, 1.32 +/- 0.28 mg. IEP values were 205 +/- vs. 200 +/- 36 mg. per dl. Similarly, no increase in Pi phenotypes known to be related to any disease state was observed. Since Pi phenotypes other than the most common MM are rare in Negro populations, phenotype data were corrected to include only Caucasian subjects. In the allergy group adjusted for racial composition we found 2.86% MZ, 5.72% MS; no SZ, SS or ZZ was detected. A comparable control group contained 3.68% MZ, 6.23% MS, 0.71% SZ-SS, but no ZZ Pi phenotype.

Studies in stinging insect hypersensitivity: postmortem demonstration of antivenom IgE antibody in possible sting-related sudden death.

The purpose of this study was to extend previous findings of elevated antivenom IgE antibodies in sera from persons experiencing fatal insect sting reactions. Elevated IgE antibodies to at least one venom were measured in sera from four of six witnessed fatal cases of sting anaphylaxis; in one of two unwitnessed cases of sudden, unexpected death in which the circumstances suggested possible sting anaphylaxis; and in one unwitnessed death where autopsy findings of massive swelling of the pharynx and larynx suggested anaphylaxis. Conversely, no elevated IgE antibodies were measured in serum from a boy who received more than 40 yellow jacket stings with subsequent cardiopulmonary arrest, from which he was successfully resuscitated. Measurement of IgE antibodies in postmortem sera may not only provide confirmatory evidence of fatal anaphylaxis following witnessed insect stings, but also may provide useful additional data in unwitnessed deaths where the clinical history or autopsy findings suggest unexplained anaphylaxis.

Sudden death due to stinging insect hypersensitivity: postmortem demonstration of IgE antivenom antibodies in a fatal case.

This case report of a documented, witnessed death from an anaphylactic reaction to a single yellow jacket sting confirms the ability to demonstrate specific IgE antivenom antibodies in postmortem blood specimens. Implications and potential clinical impact are briefly discussed.

Tolerance and efficacy of polyethylene glycol 3350/electrolyte solution versus lactulose in relieving opiate induced constipation: a double-blinded placebo-controlled trial.

Chronicity and high therapeutic cost prompted this study to determine a cost-effective and efficacious regimen in treating narcotic-induced constipation. The efficacy of lactulose was compared with polyethylene glycol 3350/electrolyte solution for relief of methadone-induced constipation. This was a randomized, triple cross-over after control run-in (no treatment) study conducted at a methadone maintenance program in Baltimore, Maryland in 57 patients who are affected by opiate-induced constipation. The study was measured by self-reported frequencies, consistency, and ease of defecation during a 1 week run-in control period, followed by 3 treatment phases of 2 weeks each. Polyethylene glycol 3350/electrolyte solution and lactulose produced more "nonhard" stools than the placebo (P < 0.01) and control (P < 0.003). Polyethylene glycol 3350/electrolyte solution produced the loosest stool (P < 0.0001) compared with the control, whereas lactulose had the most adverse effects. There were no significant differences in reducing hard stool formation in either experimental group, but both were better than having nothing or just the placebo. Polyethylene glycol/electrolyte solution resulted in the loosest (diarrheal) stool. It is also likely that polyethylene glycol/electrolyte solution is the most cost effective.

A blitz of bends: decompression sickness in four students after hypobaric chamber training.

This paper reports three cases of type II and one case of type I decompression sickness occurring in a group of nine vigorously active US Army parachutists who took a hypobaric chamber HALO (high altitude-low opening) training flight to a maximum altitude of 9,908.5 m (32,500 ft). After the cases of decompression sickness were diagnosed and treated, the aviator mask regulators were checked and found to be functioning properly; the oxygen supply was analyzed and found to be pure. All cases fully recovered after treatment on US Navy Diving Table 6 and have returned to full military duty. This HALO training profile is not in use with either the US Navy or the US Air Force and should probably be considered unsafe for future use in training.

Bulimia: psychoanalytic perspectives.

Bulimia, the syndrome of food binging often followed by purging has been reported to be increasing in recent years. This communication reviews the psychoanalytic understanding of eating disorders, focusing on the pathology of early object relations and later intrapsychic conflicts over incestuous impregnation fantasies. Ancillary symptoms of kleptomania, laxative abuse, and vegetarianism are discussed, and associations with masturbatory conflicts and early adolescent phallic activity, i.e., horseback riding, are elaborated.

Illness in the doctor: implications for the psychoanalytic process.

The meaning and impact of serious illness in the therapist is described as it affects the doctor's intrapsychic analytic space, the analyzing field, and the fantasy life of patients. The brief literature on this topic is reviewed with particular reference to what patients should be told about one's illness. The author's experience of serious illness is described as it related to his reaction to his work with patients. Patient material is presented that demonstrates the utility of an abstinent stance even when encountering real and disturbing events. Freud's experience with long-term disability is recalled and the special circumstances posed by major illness for the analytic relationship are discussed. The unparalleled experience provided the patient by one's delicate neutrality at such times reveals to him the true depth of unconscious fantasy and its lasting influence on adult functioning.

Salmeterol compared with current therapies in chronic asthma.

BACKGROUND: Therapy with salmeterol, a long-acting, selective, inhaled beta 2-adrenergic agonist, is effective and safe for patients with persistent asthma; however, few long-term studies comparing salmeterol with current combination treatment regimens have been reported. METHODS: A multicenter, randomized, placebo-controlled, double-blind study was conducted in 386 patients over 41 to 46 weeks in 27 medical centers (two thirds of the investigators were primary care physicians). Patients were randomized to receive either salmeterol or placebo, and further randomized to weaning or nonweaning from current asthma therapies (except inhaled corticosteroids). Treatment groups were: salmeterol/weaning (S + W), placebo/weaning (P + W), salmeterol/no weaning (S + NW), and placebo/no weaning (P + NW). Attempts at active weaning were carried out at the discretion of the investigator for 2 to 6 weeks. Pulmonary function, albuterol use, and asthma symptoms were measured. RESULTS: The clinical benefits of salmeterol occurred despite weaning off existing nonsteroidal asthma medications. The mean morning peak expiratory flow rate was significantly increased in the S + W group (32.3 L/min) compared with both the P + W (4.9 L/min) and P + NW (6.8 L/min) groups (P < .001). Compared with the P + W and P + NW groups, the S + W group experienced significant (P < .05) improvements in overall mean asthma symptom scores, mean number of puffs of supplemental albuterol, the percentage of days with no supplemental albuterol use, and the mean number of awakenings caused by asthma (except for the P + NW comparison, P = .090). No significant differences were noted between treatment groups in any safety evaluation, including 12-lead electrocardiograms. CONCLUSIONS: The addition of salmeterol in the treatment of persistent asthma resulted in sustained improvement in pulmonary function and symptoms. The long-term use of salmeterol is safe and improves the clinical course and stability of asthma following reductions in nonsteroidal asthma therapy.

[Posterior infarction due to coronary embolism in a patient with valve prosthesis. A case report]. / Infarto posterior por embolia coronária em portador de prótese valvular. Relato de caso.

A female patient, 56, with mitral heart disease and chronic atrial fibrillation is presented. She underwent mitral valve replacement with bioprosthesis twice previously. Suffering from hypercholesterolemia and not in anticoagulant therapy, she was admitted in the emergency room with clinical history and electrocardiogram of a posterior infarction. Diagnosis was later assured by serum CK-MB and coronary arteriography. The electrovectocardiographic aspects of the case agree with those reported in the literature.