Hypersensitivity lung disease: Early diagnosis

The early diagnosis of hypersensitivity lung disease (HLD) is important because of its progressive morbidity. It is often difficult to establish the diagnosis in the early stages because of the absence of defined symptoms. Case histories of 2 patients with pigeon breeder's HLD are reported. Both patients presented with unusual manifestations of the disease: one patient was asymptomatic but had an abnormal chest radiograph; the other patient had a normal chest radiograph but experienced occasional symptoms of exertional dyspnea. Both patients had abnormal pulmonary function and precipitin bands against pigeon serum. Following inhalation challenge with pigeon serum both patients developed fever and leukocytosis, but no significant pulmonary function response was observed. In both patients pulmonary function tests returned to near normal levels after corticosteroid therapy. Early detection of HLD may prevent progressive irreversible pulmonary damage. This requires a high index of clinical suspicion and appropriate screening tests. Inhalation challenge procedures are useful in establishing the diagnosis.     

Serum IgE as an important aid in management of allergic bronchopulmonary aspergillosis

Differentiating patients with allergic bronchopulmonary aspergillosis (ABPA) from patients with asthma who have immediate skin reactivity to Aspergillus fumigatus may be difficult when the characteristic clinical and laboratory findings of ABPA are absent. This article describes the response of ABPA patients to corticosteroid therapy. After treatment of the acute stage of the disease with corticosteroid therapy, all ABPA patients had greater than or equal to 35% reduction of the total serum IgE within 2 mo. In 30 exacerbations of ABPA in 15 patients, there was greater than or equal to 35% reduction total serum IgE, in 24 exacerbations within 2 mo. Of the six exacerbations with less than 35% reduction of total serum IgE, noncompliance to medical therapy was clearly documented in three exacerbations. In one exacerbation with a slowly resolving pulmonary infiltrate, 6 mo of corticosteroid therapy was required before the total IgE decreased 35%. The total serum IgE and its response to corticosteroid therapy is a sensitive marker in ABPA and can be considered an important aid in management of ABPA. Failure to achieve greater than 35% reduction of total serum IgE by 2 mo with the administration of corticosteroid therapy in patients highly suspected of ABPA should make one either question the diagnosis of ABPA or consider noncompliance of the patient to medical management with corticosteroids.     

Studies of perennial ragweed immunotherapy.

Perennial ragweed immunotherapy was studied in 24 patients with ragweed pollenosis. Cellular responsiveness was determined by measuring the cellular reactivity and sensitivity to ragweed antigen E (RW-AgE) by RW-AgE-induced leukocyte histamine release. Serum blocking antibody content was determined by measuring the serum RW-AgE binding capacity by ammonium sulfate coprecipitation of bound RW-AgE. Specific IgE (anti-RW-AgE) concentration was determined by polystyrene tube radioimmunoassay. Cellular responsiveness decreased with continuing immunotherapy, as did the specific IgE concentrations. The serum RW-AgE binding capacity, in contrast, increased as treatment continued. The absence of demonstrable correlations between RW-AgE binding capacity and cellular reactivity, cellular sensitivity, and specific IgE concentrations contrasted impressively with the demonstration of multiple significant correlations between the change in the RW-AgE binding capacity and the other parameters studied. The degree of increase in RW-AgE binding capacity correlated significantly with the degree of decrease in both the specific IgE concentration (p is less than 0.04) and the cellular sensitivity to RW-AgE (p is less than 0.003). these findings suggest that the active process of blocking antibody production, rather than the passive presence of blocking antibody, is related to the process which decreases the specific IgE concentration and the degree of cellular responsiveness and therefore results in clinical improvement.     

The predictive value of initial cytogenetic studies in 148 adults with acute nonlymphocytic leukemia: a 12-year study (1970-1982)

When leukemic blood or marrow specimens from 148 adults with newly diagnosed acute nonlymphocytic leukemia (ANLL) were studied with chromosome banding techniques, 79 were found to have clonal abnormalities. Among 130 treated patients, the 53 with initially normal karyotypes had a significantly longer survival rate than the 16 in whom no normal metaphases were observed (p = 0.02). The 55 patients with both normal and abnormal metaphase cells had an intermediate survival. Once a complete remission had been attained, however, there was no significant difference in median survival between those patients with entirely normal karyotypes and those with abnormal karyotypes. Among the various FAB morphologic subsets of ANLL, the differences in complete remission rate and overall survival between the various cytogenetic subsets were greatest in acute myelogenous leukemia (AML, M1 + M2). The presence of an abnormal clone was a more important predictor of clinical outcome (p = 0.02) than the presence of normal stem cell clones. Aneuploidy alone (hyperdiploidy or hypodiploidy) was not of predictive value, indicating that the use of banding techniques to identify structural rearrangements in pseudodiploid cells was essential. Clonal chromosomal abnormalities were nonrandom and acquired, and specific abnormalities were closely associated with specific clinical-pathologic subsets of ANLL. All 13 patients with acute promyelocytic leukemia and adequate cytogenetic specimens had t(15;17); this translocation was not found in any other subset of ANLL. Six patients with AML (M2) had t(8;21) or a variant of this rearrangement. Seven patients had inv(16)(p13q22) associated with acute myelomonocytic leukemia (AMMoL, M4) and abnormal marrow eosinophils. Two patients had ins(3;3) and thrombocytosis. Four patients had a translocation involving 11q, but none of these had acute monocytic leukemia (AMoL, M5); no patient had del(11q).     

Serum IgE concentration in atopic dermatitis. Relationship to severity of disease and presence of atopic respiratory disease

A survey was conducted to evaluate the serum IgE concentrations of 58 patients with atopic dermatitis of varying severity and activity. The determination of serum IgE concentrations does not provide a diagnostic criterion for atopic dermatitis because 57% of the patients had levels of IgE considered to be within a normal range. When serum IgE concentrations are elevated in atopic dermatitis, this is associated with an increased severity of the disease, with coexistent atopic respiratory disease or with both. This association may have relevance to the pathogenesis of the respiratory disease, which is IgE-mediated, the severity of the dermatitis, or both. The manner in which this may occur, if there is more than a coincidental relationship, is uncertain.     

Immediate-type reactions in patients with allergic bronchopulmonary aspergillosis

Allergic features of 38 patients with allergic bronchopulmonary aspergillosis (ABPA) were reviewed. These features included skin reactivity to other inhalant antigens and to molds other than Aspergillus fumigatus (Af) plus clinical manifestations of rhinitis, conjunctivitis, asthma, eczema, urticaria, anaphylaxis, food allergy, and drug allergy. ABPA patients have a high degree of allergic reactivity in all these clinical features, in particular, clearly documented food allergy. These findings differ from those previously reported in ABPA patients in England, where it was noted that patients with ABPA whose asthma began after age 30 had few manifestations of other allergic diseases. By contrast, our patients in the same age group (onset of asthma after age 30) had the same multiple allergic manifestations as younger patients. These results show that ABPA patients are a subset of atopic individuals with a greater predisposition for the development of a wide spectrum of allergic diseases, despite the lack of manifestations of other major immunologic disease patterns.     

Alteration of T cell function in healthy persons with a history of thymic x-irradiation.

The possible late effects of x-irradiation to the infantile thymus were investigated by studying immune functions in 12 healthy persons with a history of thymic x-irradiation and healthy control subjects. No differences were found in serum immunoglobulin values, humoral antibody levels, lymphocyte counts, and lymphocyte reactivity to phytochemagglutinin, vaccinia virus, purified protein derivative (PPD), and allogeneic cells. The irradiation group exhibited cellular hyperresponsiveness to streptoskinase-streptodornase (SK-SD). In contrast, mean skin and in vitro lymphocyte responses to Candida albicans were depressed in the patients with thymic irradiation. A dissociation of these two Candida responses was found in only 1 of 14 healthy control subjects but in 7 of 12 irradiated individuals. While thymic irradiation did not result in impaired immunologic defenses leading to clinical disease, it caused alterations in T cell responses similar to those reported in patients with chronic mucocutaneous candidiasis.     

Polymerized whole ragweed: A two-year follow-up of patients treated with an improved method of immunotherapy

We have previously reported, in a 1-yr study, the effectiveness of polymerized ragweed (PRW) as an improved method of immunotherapy for patients suffering from ragweed hay fever. In that study, treatment with PRW was found to be superior to treatment with monomer ragweed extract (MRW) because of the reduced allergenicity of the PRW. The current study is a 2-yr follow-up of nine patients treated with PRW and nine patients treated with MRW. After 1 yr of immunotherapy, both MRW- and PRW-treated patients received 9,000 protein nitrogen units (PNU) and after a second year of maintenance therapy both groups received a cumulative dose of 15,000 PNU. Serum blocking antibody against ragweed antigen E (AgE) was measured periodically during the study. After 1 yr of immunotherapy, blocking antibody in the PRW- and MRW-treated groups was similar with respective means of 1,300 and 1,500 ng AgE bound per milliliter of serum. At the end of 2 yr of therapy, these serum AgE binding activities rose to 2,700 and 4,100, respectively. No significant local or systemic reactions occurred in the PRW-treated group during the year of maintenance therapy. However, large local reactions prevented three of the nine patients treated with MRW from achieving a monthly maintenance schedule. A significant decrease in rhinitis symptoms was noted in both treated groups as compared with the season before immunotherapy and also to a group of patients untreated with immunotherapy during the 1978 ragweed season.     

The effect of histamine-1 and histamine-2 antagonists on airway responses to histamine in the rhesus monkey.

This study used rhesus monkeys with consistent respiratory responses to aerosolized histamine. Two systems of histamine challenge were evolved to study the effects of histamine antagonists on the histamine-induced respiratory response. One system consisted of administering increasing subreactive concentrations of histamine until an airway response (H) occurred. This threshold histamine dose was repeated (H'). The pulmonary function changes occurring with the H' challenge were less intense than those with H. M, a histamine-2 receptor antagonist, when given before the H' dose was associated with a potentiated H' response compared with the threshold H response. This provides evidence for histamine-2 receptor sites in rhesus monkey airways. A second system used duplicate histamine challenges with a known reactive dose of histamine. In this system, the pulmonary function changes occurring with the repeated challenge (H') were greater than with the first reactive challenge dose (H). This H' response was inhibited partially with diphenhydramine, a histamine-1 receptor antagonist. These two systems of histamine challenge provide an experimental model for evaluating pharmacologic alteration of histamine-induced respiratory responses. There is evidence for the existence of histamine-1 and histamine-2 receptor sites in the airways of the rhesus monkey.     

The Corticosteroid Dose Graph : Use in determination of corticosteroid requirements, characterization of patients, and prevention of seasonal exacerbation in corticosteroid-dependent patients

Sixty-three corticosteroid(CS)-dependent asthmatics were evaluated by a method which records asthmatic exacerbations as a function of change in CS dosage. This method, the Corticosteroid Dose Graph (CSDG), is a graphic representation of the patients' narrative charts. It is useful in assessing and directing the care of these patients and in evaluating the efficacy of altered therapeutic regimens in asthmatics. The CSDG categorizes cooperative patients (CP) and distinguishes these patients from those who are less cooperative (LCP). Evaluation of the progress of CP by the graphic analysis system showed that CP have fewer severe exacerbations of asthma than LCPs. Evaluation of the 63 patients by this graphic method shows a significantly increased incidence of asthmatic exacerbations in the Chicago area in October as compared to other months. The CSDG also demonstrates that some individuals experienced significantly increased numbers of asthma exacerbations at certain times of the year unique to themselves. Because the, CSDG predicts exacerbations, it was shown to be applicable to prevent such exacerbations by prophylactic increase in CS dose during a high-risk season for selected CS-dependent asthmatics.     

Cytogenetic and ultrastructural features of de novo acute promyelocytic leukemia; The university of Chicago experience (1973–1978)

Of seven patients with de novo acute promyelocytic leukemia (APL) seen at the University of Chicago in a 6-year period, six had sufficient karyotypes to analyze. All six patients had the 15;17 translocation chromosome present in their leukemic cells. Four patients had typical hypergranular APL, but two patients required confirmation by transmission electron microscopy. In these two cases, the distribution of the granules was similar to the hypergranular type, but the granules were smaller than 250 nm, therefore below the limits of light microscopy resolution. Four of the six patients had clinical evidence of disseminated intravascular coagulation. It is important to make the diagnosis of APL initially as specific therapeutic choices exist.     

Persistence of efficacy after a brief course of polymerized ragweed allergen: a controlled study

Immunotherapy with PRW has been demonstrated to be safe and effective. To determine whether the efficacy would remain in successive ragweed seasons without further therapy, a trial was conducted comparing PRW to histamine placebo therapy in patients that had received courses of PRW previously. Those patients were also compared to previously untreated ragweed-sensitive patients. In a double-blind fashion, 21 previously treated patients were treated before the 1982 ragweed season with four injections of PRW therapy, whereas 21 previously treated patients were treated with four injections of placebo therapy. An additional control group of 21 previously untreated ragweed-sensitive patients received no injections. Daily symptom and medication score sheets were completed by patients each day of the ragweed season. Blocking antibody rose elevenfold with treatment (p less than 0.0001) in the PRW group. There was a statistically significant difference in symptom score mean between untreated patients (1007 +/- 174) and previously treated patients whether they received supplemental injections (554 +/- 180) (p less than 0.01) or whether they did not (650 +/- 168) (p less than 0.03). In summary the efficacy of 15 injections of PRW immunotherapy persists at least several years without need for supplemental immunotherapy.     

Long-term effects of beclomethasone dipropionate on prednisone dosage in the corticosteroid-dependent asthmatic

The average prednisone dosage of 54 corticosteroid-dependent asthmatics was computed for one year prior to initiation of beclomethasone dipropionate. This was compared to the average prednisone dosage after nine months on the beclomethasone with progressive tapering of prednisone to either dose compatible with control of asthma or discontinuation. Beclomethasone was found clinically useful in the great majority of these patients because it permitted a significant decrease in dosage of prednisone, a change from daily to alternate-day prednisone, or discontinuation of prednisone after cautious tapering. The first two advantages were most evident in those asthmatics who initially required higher doses of oral steroids while the latter was evident in those requiring lower doses. Those patients whose prednisone dosage does not appear to be beneficially affected by the use of beclomethasone should be suspect as to adherence to proper medical dosage schedule.     

Organicity and tardive dyskinesia

A review of clinical, epidemiologic, electroencephalographic, radiologic, and psychological studies leads to the suggestion that in patients with affective disorders, tardive dyskinesia (TD) may constitute a distinct disease entity. This possibility points to the importance of the primary psychiatric diagnosis in view of the association between brain damage and TD in patients with affective disorders. The question remains whether preexisting brain damage predisposes patients to TD or whether the latter leads to brain damage.     

Radiographic contrast media studies in high-risk patients

Patients with prior anaphylactoid reactions (AR) to radiographic contrast media (RCM) are at increased risk for another reaction upon repeat exposure to RCM. One hundred one patients, who had prior AR to RCM, who gave informed consent, and who had an essential need for a repeat RCM study, were pretreated with prednisone, 50 mg orally every 6 hours for 3 doses ending one hour prior to RCM study, and diphenhydramine, 50 mg intramuscularly, one hour prior to RCM study. The repeat RCM study was then carried out using standard procedures with resuscitation equipment readily available. Ninety-six patients had no reaction. Five of the 101 (4.95%) developed AR. These AR consisted only of mild urticaria or pruritus. No significant or life-threatening reactions occurred. Pretreatment decreases the risk in this population of patients and is recommended as standard prophylaxis for patients requiring RCM who have had a previous AR.     

Chromosomal banding patterns in patients with acute nonlymphocytic leukemia

Approximately 50% of acute nonlymphocytic leukemia (ANLL) patients studied with banding techniques have detectable clonal karyotypic abnormalities. Although there is considerable variability, certain nonrandom abnormalities are observed, including trisomy 8, monosomy 7, and the 8;21 translocation (frequently accompanied by loss of an X or Y). The 15; 17 translocation is highly specific for acute promyelocytic leukemia. Clonal evolution of the karyotype can be observed in a significant number of ANLL patients for whom serial cytogenetic analyses are obtained. Gain of a No. 8 is the most frequently observed evolutionary change. Bone marrow cells from patients who develop ANLL following treatment of a previous malignancy often have hypodiploid modal numbers and frequently show loss of all or part of a chromosome No. 5 or No. 7.     

Fluvoxamine and chlorimipramine in endogenous depression

Thirty patients were treated in a randomised double-blind efficacy study of fluvoxamine and chlorimipramine. The dose range for both drugs was 50-300 mg in divided daily doses. Mean daily doses were higher for fluvoxamine than chlorimipramine. Generally the baseline recordings were comparable for both drug groups. Fluvoxamine was superior to chlorimipramine in all the rating scales used without achieving statistical significance. Chlorimipramine, but not fluvoxamine, caused a significant decrease in blood pressure. There were no significant effects on ECG or laboratory variables. There was no significant relationship between plasma levels of either compound or metabolite and clinical response. Chlorimipramine exerted more unwanted effects than fluvoxamine. Autonomic effects of fluvoxamine were minimal in comparison with chlorimipramine. Chlorimipramine patients required more concurrent anxiolytic medication than fluvoxamine. Both drug groups required a significant amount of concurrent hypnotic medication.     

The immune response of patients with ragweed hay fever treated with polymerized ragweed antigens.

This report describes the immune response of patients with ragweed hay fever treated with polymerized ragweed antigens (PRW). Their IgG antibody responses to crude ragweed extract, antigen E, antigen K, and antigen Ra3 were determined by a solid-phase radioimmunoassay. The results indicate that PRW contains an array of clinically important antigens that are available for immunologic processing and result in an immune response in patients treated with this new form of immunotherapy for ragweed hay fever.     

Surgery in corticosteroid-dependent asthmatics

Seventeen patients with asthma of such severity that corticosteroids were required for maintenance therapy had 21 surgical procedures. These patients were managed by a single team of physicians, and complications of the surgical procedures in this group of patients are reviewed. There was one postoperative discoid atelectasia and a case of small suture abscess. There were no fatalities and no serious pulmonary or wound complications or significant evidence of adrenocortical insufficiency. It is concluded that severe corticosteroid-dependent asthmatics can tolerate surgical procedures well provided there is adequate preoperative preparation.     

Immunohistologic demonstration of abnormal colonic crypt cell kinetics in ulcerative colitis

A monoclonal antibody, Ki-67, that reacts with cells in the proliferative phases (G1, G2, S, and M) of the cell cycle was used in an immunohistochemical labeling reaction to examine the colonic crypt epithelium in active ulcerative colitis, inactive ulcerative colitis, and normal mucosa. The proportions of labeled cells in the lower two thirds (proliferative zone) and in the upper quarter of the crypt were determined. The proportions of Ki-67-positive crypt epithelial cells in both the proliferative zone and the upper crypt were higher in biopsy specimens from patients with active ulcerative colitis than from patients with normal mucosa or with inactive ulcerative colitis. In inactive ulcerative colitis the proportion of Ki-67-positive epithelial cells in the proliferative zone of the crypt was higher than in normal mucosa. These results are similar to those obtained in studies using tritiated thymidine to determine the proportion of cells in the DNA-synthesizing thymidine to determine the proportion of cells in the DNA-synthesizing phase of the cell cycle and suggest that immuno-histochemical staining with Ki-67 may be a practical method for measuring the proliferative activity of epithelial cells in patients with ulcerative colitis and other disorders of the gastrointestinal tract.