Endotracheal tuberculous stenosis: ventilation rescue and bronchography guided stenting.

We present the case of a 16-year-old female patient who presented with dyspnoea, cough and noisy breathing that progressed further in hospital with the development of stridor and severe respiratory compromise requiring mechanical ventilatory support. Investigations were consistent with a diagnosis of endotracheal tuberculosis with tracheal and bronchial stenosis. Despite adequate anti-tuberculous therapy and ventilation the patient had high airway pressures, low tidal volumes and hypercapnia, which prevented weaning from mechanical ventilation. Balloon dilatation and stenting of the 4.5cm long, 2.3mm diameter stenotic tracheal segment was performed under radiological guidance. The patient was weaned successfully from the ventilator post-procedure. This report illustrates the successful management of an uncommon presentation of a common disease with modern endoscopic therapy.

Multifocal idiopathic fibrosclerosis mimicking tuberculosis of the abdomen.

We present a 13 year old girl from Assam who had been treated as abdominal tuberculosis for 2 years due to the presence of refractory lymphocyte-predominant ascites and multiple small bowel strictures associated with significant anorexia and weight loss. On evaluation she was found to have retroperitoneal fibrosis with hydroureteronephrosis, mediastinal fibrosis and a retro-orbital pseudotumour. Based on these findings the diagnosis of Multifocal Idiopathic Fibrosclerosis (MIFS) was made. Ascites and multiple bowel strictures have been only rarely been described in association with MIFS. The other unique features in this patient were the early age of presentation, the presence of mediastinal fibrosis in association with retroperitoneal fibrosis, extensive soft tissue fibrosis of the neck, axillae and the presence of trismus. In a country like ours where Tuberculosis is commonplace, one would not think twice about treating such a case with antituberculous therapy. However, with a constellation of findings suggestive of a diffuse fibrotic process, MIFS should be an important consideration.

Acenocoumarol and phenytoin toxicity in the presence of CYP2C9 mutation.

This case report describes a rare interaction between therapeutic doses of phenytoin and acenocoumarol resulting in both acute phenytoin toxicity and increased international normalized ratio (INR). Interactions between these drugs are due to the pharmacokinetics and the common metabolising pathway by hepatic cytochrome P450 isoenzyme-CYP2C9. Our patient was detected to be homozygous for CYP2C9*3 by PCR-RFLP analysis resulting in markedly decreased metabolism of both the drugs. Given that these two drugs are often given concomitantly in the medical out patient department, and that CYP2C9 polymorphisms are not uncommon, clinicians should be aware of this interaction and suspect this in patients with toxicity to these drugs.

Peripheral CD4+/CD8+ T-lymphocyte counts estimated by an immunocapture method in the normal healthy south Indian adults and HIV seropositive individuals.

BACKGROUND: Flow cytometry is the standard method for the estimation of CD4/CD8 counts, but the high initial investment for this instrument and costly reagents make it unaffordable to most of the centers in a developing country like India. OBJECTIVES: To evaluate the feasibility of an alternate system for the estimation of CD4 and CD8 counts in normal south Indian adults and validate the usefulness of this assay to monitor the counts in HIV seropositive individuals. STUDY DESIGN: Forty-six normal healthy adults and 68 HIV seropositive individuals both belonging to south Indian linguistic groups were enrolled in this cross-sectional study. The HIV seropositive individuals included 54 HIV-1, 9 HIV-2 and 5 HIV 1&2 infected individuals serologically confirmed by one of the commercial Immunoblot kits. The Capcellia CD4/CD8 whole blood assay, an immuno-capture ELISA based kit from Sanofi DIAGNOSTICS Pasteur, (France) was used with a few modifications in the procedure to measure the CD4 and CD8 counts. RESULTS: The mean CD4 cell counts were 1048 (central 95 centile only), 746 and 424 for the normal healthy adults, asymptomatic HIV seropositives and symptomatic HIV patients, respectively, and the mean CD8 counts were 595, 889 and 732, respectively. Statistically significant differences were observed in the CD4 cell counts between HIV seronegative healthy adults and asymptomatic (P < 0.001) as well as asymptomatic and symptomatic (P < 0.05) HIV infected individuals. The mean CD4 counts of asymptomatic HIV-2 infected individuals was significantly higher than the counts of asymptomatic HIV-1 infected individuals (P < 0.05). CONCLUSIONS: This is an user friendly test and can be an alternate to flow cytometry for the estimation of peripheral T-lymphocyte subsets in developing countries. The assay system has certain limitations inherent to ELISA techniques.

Evaluation of a school-based asthma education program for inner-city children.

BACKGROUND: We have previously reported a high prevalence of current asthma-related symptoms affecting predominantly Hispanic, socioeconomically disadvantaged schoolchildren in Southeast San Diego. OBJECTIVE: We sought to assess the impact of a school-based education program on asthma outcomes. METHODS: In cooperation with the San Diego Unified Schools, we developed and implemented a school-based asthma education program. Based on the National Heart, Lung, and Blood Institute consensus guidelines for asthma, the five-session bilingual, interactive curriculum was conducted in 20-minute segments. Asthma knowledge was tested before and after the education program, and asthma severity was prospectively assessed at monthly intervals. Outcome parameters were compared in educated and control (noneducated) fourth grade students with asthma by using nonparametric techniques. RESULTS: After asthma education, students demonstrated improvement with increases in mean scores for: asthma knowledge quiz from 9.9 (SEM = 0.44, n = 34) to 13.7 (SEM = 0.30); peak flowmeter technique from 3.9 (SEM = 0.33, n = 32) to 6.4 (SEM = 0.29); and inhaler technique from 2.3 (SEM = 0.26, n = 32) to 4.3 (SEM = 0.26). All changes were highly significant (p < or = 0.00001 as determined by Wilcoxon matched-pairs signed-rank test). Mean score comparisons for asthmatic control students given paired examinations after a time interval matched with the educated students, did not reach statistical significance: quiz score of 11.3 (SEM = 0.80, n = 11) versus 10.9 (SEM = 0.68), peak flowmeter technique score of 2.6 (SEM = 0.50, n = 18) versus 3.1 (SEM = 0.37) , and inhaler technique score of 2.5 (SEM = 0.37, n = 18) versus 2.2 (SEM = 0.31). Prospective monthly data were collected on 27 educated and 15 control asthmatic subjects. Severity of asthma was not significantly different between groups at entry to the study. Symptom questionnaires, validated for functional asthma severity, revealed a significant reduction in mean symptom scores at 180 days for the educated (2.87, SEM = 0.447) versus the control (4.36, SEM = 0.573) groups (p = 0.0188 as determined by the Mann-Whitney U test). CONCLUSION: Child-centered asthma education can be successfully conducted in the school setting, resulting in increased asthma knowledge, improved skills for peak flowmeter and inhaler use, and a reduction in the severity of asthma symptoms.

Current prevalence of asthma-related symptoms in San Diego's predominantly Hispanic inner-city children.

Ethnic minorities of low socioeconomic status are disproportionately represented in the trends of increasing asthma prevalence, morbidity, and mortality. We surveyed a cohort of 998 fourth-grade students in an impoverished area of southeast San Diego with a high percentage of Hispanic Mexican-Americans. Of the 654 Hispanic 9-12-year-olds, 14.4% were categorized as probable current asthma (within the past year), based on symptom of wheezing or physician diagnosis of asthma [with respiratory symptom(s) or medication]. An additional 13.5% had respiratory symptoms indicating possible asthma. Differences by ethnic group in the percentage of probable asthma or related symptoms were highly significant (p < 0.0001). Among Hispanics with a category of probable asthma, only 57.4% had a physician diagnosis versus 80.6% of black and 85.7% of white students. The frequency of health insurance coverage differed significantly between ethnic groups (p < 0.0001), with Hispanics among the lowest (37.2%).

Evidence for IgG autoantibodies to galectin-3, a beta-galactoside-binding lectin (Mac-2, epsilon binding protein, or carbohydrate binding protein 35) in human serum.

Galectin-3 is a beta-galactoside-binding animal lectin formerly called epsilon protein, Mac-2, carbohydrate binding protein 35, CBH 30, L-29, or L34. The possible occurrence of autoantibodies to galectin-3 was investigated because crosslinking of galectins bound to IgE or Fc epsilon RI might produce mediator release from mast cells or basophils. Unexpectedly, a control serum from an individual free of current allergic symptoms was found to have a significantly elevated level of IgG anti-galectin-3 by ELISA employing galectin-3-coated wells incubated with test serum followed by HRPO-conjugated goat anti-human IgG. The reaction was not inhibitable by lactose, suggesting that it is not a result of binding of IgG by galectin-3 through lectin-carbohydrate interactions. The antibody activity was specifically adsorbed by galectin-3 and protein A-conjugated Sepharose and was associated primarily with subclass IgG1. The presence of the antibodies was confirmed by immunoblotting showing binding of IgG to the 30-kD galectin-3 band. The relevant epitopes were in the galectin-3 N-terminal domain. The propositus was subsequently found to have adenocarcinoma of the colon, and titers of IgG anti-galectin-3 were found to be sharply elevated after hemicolectomy. Similar antibody titers have not been found in family members, but small numbers of normal persons and patients with malignant neoplasms have been found to have evidence of IgG anti-galectin-3 antibodies at lower titers than the propositus. The pathogenesis of this autoimmune reaction is unclear, though there is a trend for it to occur in older persons.

Improved method for measuring C1-r-C1-s-(C1 inh)2 complexes by an enzyme-linked immunosorbent assay.

Measurement of C1-r-C1-s-(C1 inh)2 complexes in serum or plasma by enzyme-linked immunosorbent assay (ELISA) has been proposed as a relatively convenient and sensitive means for assessing C1 activation. However, interference by unactivated C1q (r-s)2 at low serum or plasma dilutions has resulted in estimates that vary widely with the degree of serum or plasma dilution. Precipitating the interfering C1q (r-s)2 with 6% polyethylene glycol has been proposed to resolve this problem, but here it is shown that this procedure also precipitates or coprecipitates some of the C1-r-C1-s-(C1 inh)2 complexes. Satisfactory results have been achieved without PEG precipitation by testing high plasma dilutions under conditions where there is a sufficient excess of anti-C1s coating the microtitration plate wells that removal of C1q (r-s)2 is not necessary. Optimizing conditions for quantitating these complexes at high dilution have been investigated. The mean normal EDTA plasma C1-r-C1-s-(C1 inh)2 complex measurement was 36.6 +/- 7.0 (S.D.) ELISA units with a 95% confidence interval of 19.5-47.6u. Besides providing a sensitive assay for C1 activation, measuring C1-r-C1-s-(C1 inh)2 complexes may help to clarify the pathophysiologic mechanisms resulting from C1 inh deficiency under various conditions.

Cold-dependent activation of complement: recognition, assessment, and mechanism.

Cold-dependent activation of complement (CDAC) is a phenomenon characterized by low hemolytic complement activity in chilled serum. Complement component levels are normal when measured immunologically, and there is normal hemolytic activity in EDTA plasma or serum maintained at 37 degrees C. Little attention has been paid to CDAC except in Japan, and current unfamiliarity with it, even by clinical immunologists, can lead to confusion and unnecessary laboratory tests. A 66-year-old patient with a complex medical history is described whose complement tests showed abnormalities characteristic of CDAC. Evidence for classical complement pathway activation in the cold was obtained by CH50 measurements, by hemolytic C4 determinations, by C4a, C3a, and C4d generation, and by quantitating C1s-C1r-(C1 inhibitor)2 complexes. A good correlation was observed among these parameters. Cryoprecipitates were absent. CDAC activity has persisted for over 5 years and is greater at 13 than at 4 degrees C. Activation is ablated by heating at 56 degrees C and restored by the addition of C1 to the heated serum. Adsorption by streptococcal protein G-Sepharose and precipitation by 2.5% polyethylene glycol support the hypothesis that CDAC is caused by aggregated IgG. The CDAC factor(s) also induces complement activation in normal serum but has not interfered with Raji cell or C1q binding tests or with FACS analysis. More limited studies of a second individual experiencing CDAC yielded similar results.

Controlled clinical assessment of astemizole in the treatment of chronic idiopathic urticaria and angioedema.

Astemizole, one of the newer generation of nonsedating antihistamines, was evaluated in a double-blind study of forty-six patients who had chronic idiopathic urticaria with or without angioedema; most had severe disease. Nineteen of twenty-three patients who were on placebo discontinued treatment because of lack of response compared to only five of twenty-three astemizole-treated patients (p less than 0.0001). Fourteen of twenty-two astemizole-treated patients and two of twenty-two placebo-treated patients considered the results to be good or excellent (p less than 0.0001). Blinded assessment by the investigators yielded similar results (p less than 0.0001). Therapeutic response was the same in patients with and without angioedema in addition to urticaria and in those requiring corticosteroids. Duration of urticaria also did not influence the results. Increased appetite and weight gain were the main side effects reported more frequently in the astemizole-treated than in the placebo-treated group, and no significant toxicity was noted. Follow-up after terminating the drug study indicated a high frequency of remissions during the subsequent year.

Generation of drug metabolite antigenicity in the intestinal mucosa.

Both nitroreductase and transglutaminase activities have been assayed in the 10,000 X g supernatant fluids of rat intestine homogenates after Triton X-100 treatment. Incubation of 14C-nitrofurantoin in the intestine extract yielded protein-bound 14C-labeled products. Injection into rabbits of the conjugated protein similarly prepared with unlabeled nitrofurantoin elicited formation of antibodies against nitrofurantoin. These results suggest that intestinal metabolism and conjugation to protein of orally administered drugs may serve as a probable mechanism of drug allergy, and this may be accomplished by enzymatic coupling of relatively stable drug metabolites to protein carriers.

Plasma protease inhibitor and anaphylatoxin inactivator levels in chronic urticaria/angioedema and in patients experiencing anaphylactoid reactions to radiographic contrast media.

Since a protease inhibitor or anaphylatoxin inactivator deficiency might explain why certain individuals are prone to develop chronic urticaria/angioedema or anaphylactoid reactions to radiographic contrast media, serum alpha 1-protease inhibitor, alpha 1-antichymotrypsin, alpha 2-macroglobulin, inter-alpha-inhibitor, antithrombin III, alpha 2-plasmin inhibitor, C1 inhibitor, and serum carboxypeptidase N were assessed by immunologic or functional methods. These values all were within normal limits in both groups of patients except for a low mean alpha 1-protease inhibitor level in chronic idiopathic urticaria/angioedema and cold urticaria patients and marginal decreases of alpha 1-protease and inter-alpha-inhibitor levels in radiographic contrast medium reactors. However, these abnormalities were not thought to be of pathogenetic significance.

Decreased synthesis of serum carboxypeptidase N (SCPN) in familial SCPN deficiency.

Serum carboxypeptidase N (SCPN) is the primary inactivator of the C3a, C4a, and C5a anaphylatoxins as well as an inactivator of bradykinin. Thus SCPN deficiency potentially could result in significant pathophysiologic consequences. Previous studies identified a deficient subject afflicted with frequent episodes of angioedema, and other family members also had SCPN deficiency. To delineate this abnormality further, the fractional catabolic rate (FRC) and enzyme synthesis were determined in three members of the afflicted kindred as well as in five normal persons following the infusion of homogeneous 125I-SCPN. The mean FCR and synthesis rates for SCPN in the normal subjects were 1.3%/hr and 20,793 U/kg/hr, respectively. Reduced synthesis was concluded to be primarily responsible for the low SCPN levels in the afflicted kindred. The high FRC of SCPN discourages attempted maintenance therapy with infusions of enriched SCPN preparations.

The urticarias. Current concepts in pathogenesis and treatment.

Urticaria is a very common disease which is often associated with angioedema. Release of histamine and perhaps other mediators from the cutaneous mast cells is believed to be the likeliest cause for the development of these wheals in most instances, but there may be both non-immunological as well as immunological inputs into this final common pathway. The former include trauma, cholinergic mechanisms and non-immunological histamine release by drugs. Immune mechanisms most commonly are of the IgE-mediated type, but occasionally the activation of complement or other mediators of hypersensitivity may be involved. Drug and food allergy are among the most common causes of acute urticaria, but there are numerous other possibilities which mandate a thorough general medical history and physical examination (including ruling out infection, connective tissue disease and neoplasms). In cases of chronic urticaria, when the lesions have persisted for longer than about 2 months, no cause for the disease is discernable in most instances. However, in these cases, as well as in acute urticaria, symptomatic treatment generally can provide substantial symptom relief, with emphasis on the astute use of various types of antihistamines.