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PubMed2002

Effects of nitric oxide inhalation on periodic breathing in awake patients with chronic heart disease.

BACKGROUND: Periodic breathing, an abnormal pattern of respiration consisting of alternating hyperpnea and hypopnea, has been recognized in patients with heart failure. Although fluctuations in pulmonary blood flow have been considered as a possible cause of this type of breathing, its patho-physiological mechanisms are not fully understood. In this study, we sought to determine whether inhaled nitric oxide (NO), a selective pulmonary vasodilator, attenuates periodic breathing. METHODS: Eight cardiac patients who exhibited clear oscillatory ventilation while awake (age: 62 +/- 16 years, left ventricular ejection fraction: 48 +/- 20%) were enrolled in the study. After breathing room air (RA) for 15 min, the subjects inhaled air containing 30 ppm of NO for 15 min. Respiratory gas variables including minute ventilation (VE) were measured on a breath-by-breath basis throughout the test. RESULTS: There were no differences in VE (10.7 +/- 1.5 vs. 11.0 +/- 1.7 l/min) or among any of the other hemodynamic or respiratory gas variables studied in the control and NO tests, with the exception of the end-tidal CO(2) partial pressure (5.0 +/- 0.4 vs. 4.8 +/- 0.5%; p = 0.018). The % magnitude of oscillation (i.e., the difference between the peak and nadir of oscillating VE, divided by the mean VE) was 40.0 +/- 22.4% in RA and not influenced by inhaled NO (43.9 +/- 20.8%, p = 0.57). CONCLUSION: Inhaled NO at a concentration of 30 ppm did not attenuate periodic breathing in awake patients with mild heart failure.

Administration, Inhalation↗
PubMed1991

Inhibin and oestradiol in the control of FSH secretion in the sheep.

In the sheep both FSH and LH are necessary for development of large antral follicles. The secretion of FSH is controlled by the negative feedback effect of two ovarian hormones, oestradiol and inhibin, acting at the level of the anterior pituitary. Both are derived from the granulosa cells of large antral follicles which are present in sheep ovaries throughout the oestrous cycle. FSH stimulates growth and mitosis and so the fully differentiated granulosa cells of the large preovulatory follicles acquire receptors for LH, have maximal aromatase activity and produce large amounts of inhibin. The number of these large antral follicles (oestrogenic) which have the potential for ovulation corresponds to the ovulation rate specific for each particular breed of sheep. Over 90% of the oestradiol secreted by the ovaries is derived from these chosen follicles. In contrast, inhibin (and androstenedione) is also secreted by large antral follicles which have lost or not yet acquired maximal aromatase activity. The secretion of oestradiol by the preovulatory follicle(s) is dependent on the supply of androgen precursors produced by the theca which is stimulated by LH. When the concentration of progesterone falls at the end of the luteal phase the increased secretion of LH stimulates the progressive increase in secretion of oestradiol which occurs during the follicular phase. At this stage of the cycle there is a modest inconsistent rise in inhibin, the secretion of which is not stimulated by LH but is related to the increase in the number of large antral follicles. It is suggested that inhibin with its long half-life sets the overall level of negative feedback while oestradiol is responsible for the day-to-day fluctuations in the concentration of FSH which determines the number of ovulatory follicles. This dual control of FSH is adapted to monitor both the total number of large antral follicles in the ovaries (inhibin) and the number which are selected for ovulation (oestradiol).

Animals↗
PubMed1994

Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor-dependent mechanism.

In the adult female rat, the densities of dendritic spines and synapses on hippocampal CA1 pyramidal cells are dependent upon the ovarian steroid estradiol; moreover, spine and synapse density fluctuate naturally as ovarian steroid levels vary across the estrous cycle. To determine whether the effects of estradiol on dendritic spine density require activation of specific neurotransmitter systems, we have treated animals concurrently with estradiol and one of four selective neurotransmitter receptor antagonists: MK 801, a noncompetitive NMDA receptor antagonist; CGP 43487, a competitive NMDA receptor antagonist; NBQX, an AMPA receptor antagonist; or scopolamine, a muscarinic receptor antagonist. Our results indicate that the effects of estradiol can be blocked by treatment with either of the NMDA receptor antagonists, but treatment with an AMPA or muscarinic receptor antagonist has no effect on spine density. Thus, we have concluded that estradiol exerts its effect on hippocampal dendritic spine density via a mechanism requiring activation specifically of NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

The influence of sequential, in vitro passage on secretion of matrix metalloproteinases by human brain tumour cells.

Matrix metalloproteinases (MMP) are a family of zinc-dependent enzymes which degrade various components of the extracellular matrix (ECM) and play an important role in facilitating tumour cell invasion of the normal brain. The family includes the gelatinases, stromelysins and collagenases. Preliminary studies have shown that there is a differential expression four metalloproteinases in human brain tumour cell lines derived from neoplasms of various histological types and grades of malignancy. Morphological and antigenic changes in human glioma-derived cell lines over many serial in vitro passages have been reported in earlier studies. When established cell lines are maintained in culture over a long period, it is possible that the secretion of enzymes such as metalloproteinases may differ according to the passage level examined. This report presents a study on the secretion of four matrix metalloproteinases - interstitial collagenase (MMP-), 72-kDa and 92-kDa gelatinases (MMP-2 and MMP-9 respectively), and stromelysin (MMP-3) - in three human brain tumour-derived cell lines at sequentially increasing passage numbers, ranging from passage 2 to passage 50; foetal astrocytes were used as a positive control. Reverse zymography and substrate degradation analysis were employed to demonstrate the presence of these enzymes in cell- conditioned culture medium. Aminophenyl mercuric acetate (APMA) was used to activate latent zymogen. Results demonstrate that there is no definite pattern of change in the levels of enzyme secretion common to all cell lines studied. Instead, the fluctuations in APMA- activated metalloproteinase activity in serial passage seems to vary considerably depending on the cell line and the type of enzyme studied. The variation in metalloproteinase expression observed on serial passage may be due to in vitro selection processes or karyotype evolution where the transcription of either the enzyme and/or its inhibitor may be affected. Thus an imbalance of the two products could be occurring in serial passage. Ideally, experiments requiring the measurement of relative enzyme activities should use cultures as near to the biopsy stage as possible, i.e. very low passages, to avoid artifacts that may arise on prolonged culturing.

Astrocytoma↗
PubMed2006

GABAergic mechanisms in regulating the activity state of substantia nigra pars reticulata neurons.

Substantia nigra reticulata is the major output structure of the basal ganglia involved in somatosensory integration and organization of movement. While previous work in vitro and in anesthetized animal preparations suggests that these neurons are autoactive and points to GABA as a primary input regulating their activity, single-unit recording coupled with iontophoresis was used in awake, unrestrained rats to further clarify the role of tonic and phasic GABA input in maintenance and fluctuations of substantia nigra reticulata neuronal activity under physiologically relevant conditions. In contrast to glutamate, which was virtually ineffective at stimulating substantia nigra reticulata neurons in awake rats, all substantia nigra reticulata neurons tested were inhibited by iontophoretic GABA and strongly excited by bicuculline, a GABA-A receptor blocker. The GABA-induced inhibition had short onset and offset latencies, a fading response pattern (a rapid decrease in rate followed by its relative restoration), and was independent of basal discharge rate. The bicuculline-induced excitation was inversely related to discharge rate and current (dose)-dependent in individual units. However, the average discharge rate during bicuculline applications at different currents increased to a similar plateau ( approximately 60 impulses/s), which was about twice the mean basal rates. The excitatory effects of bicuculline were phasically inhibited or completely blocked by brief GABA applications and generally mimicked by gabazine, another selective GABA antagonist. These data as well as neuronal inhibitions induced by nipecotic acid, a selective GABA uptake inhibitor, suggest that substantia nigra reticulata neurons in awake, quietly resting conditions are under tonic, GABA-mediated inhibition. Therefore, because of inherent autoactivity and specifics of afferent inputs, substantia nigra reticulata neurons are very sensitive to phasic alterations in GABA input, which appears to be the primary factor determining fluctuations in their activity states under physiological conditions. While these cells are relatively insensitive to direct activation by glutamate, and resistant to a continuous increase in GABA input, they appear to be very sensitive to a diminished GABA input, which may release them from tonic inhibition and determine their functional hyperactivity.

Action Potentials↗
PubMed2004

Androgen replacement therapy: present and future.

The major goal of androgen substitution is to replace testosterone at levels as close to physiological levels as is possible. For some androgen-dependent functions testosterone is a pro-hormone, peripherally converted to 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol (E2), of which the levels preferably should be within normal physiological ranges. Furthermore, androgens should have a good safety profile without adverse effects on the prostate, serum lipids, liver or respiratory function, and they must be convenient to use and patient-friendly, with a relative independence from medical services. Natural testosterone is viewed as the best androgen for substitution in hypogonadal men. The reason behind the selection is that testosterone can be converted to DHT and E2, thus developing the full spectrum of testosterone activities in long-term substitution. The mainstays of testosterone substitution are parenteral testosterone esters (testosterone enantate and testosterone cipionate) administered every 2-3 weeks. A major disadvantage is the strongly fluctuating levels of plasma testosterone, which are not in the physiological range at least 50% of the time. Also, the generated plasma E2 is usually supraphysiological. A major improvement is parenteral testosterone undecanoate producing normal plasma levels of testosterone for 12 weeks, with normal plasma levels of DHT and E2 also. Subcutaneous testosterone implants provide the patient, depending on the dose of implants, with normal plasma testosterone for 3-6 months. However, their use is not widespread. Oral testosterone undecanoate dissolved in castor oil bypasses the liver via its lymphatic absorption. At a dosage of 80 mg twice daily, plasma testosterone levels are largely in the normal range, but plasma DHT tends to be elevated. For two decades transdermal testosterone preparations have been available and have an attractive pharmacokinetic profile. Scrotal testosterone patches generate supraphysiological plasma DHT levels, which is not the case with the nonscrotal testosterone patches. Transdermal testosterone gel produces fewer skin irritations than the patches and offers greater flexibility in dosage. Oromucosal testosterone preparations have recently become available. Testosterone replacement is usually of long duration and so patient compliance is of utmost importance. Therefore, the patient must be involved in the selection of type of testosterone preparation. Administration of testosterone to young individuals has almost no adverse effects. With increasing age the risk of adverse effects on the prostate, the cardiovascular system and erythropoiesis increases. Consequently, short-acting testosterone preparations are better suited for aging androgen-deficient men.

Animals↗
PubMed1990

Levodopa delivery from controlled-release polymer matrix: delivery of more than 600 days in vitro and 225 days of elevated plasma levels after subcutaneous implantation in rats.

Parkinson's disease is commonly treated with orally applied levodopa (l-dopa). However, because this treatment modality is associated with a number of undesirable side effects, some due to plasma fluctuations, we have developed a slow-release polymer system that can be used to deliver l-dopa continuously for extended periods of time in vitro (greater than 600 days) and in vivo (at least 225 days) in rats. In vitro l-dopa release was evaluated using polymer matrices with appropriately selected parameters (loading and geometry), and zero-order (linear) release of l-dopa was observed for more than 600 days (in highly loaded, noncoated material first-order kinetics), in some instances in mg quantities per day. This was achieved even in polymer matrices, which did not possess a dissolution limiting barrier. Scanning electron-microscopic analysis suggests that the mechanism of release is dissolution through channels and pores within the polymer matrix. To assess in vivo release, l-dopa was quantified in plasma from rats given s.c. implants of l-dopa polymer matrices using high-performance liquid chromatography. We observed release of l-dopa for a period of at least 225 days after an initial burst of release. Continuous release of l-dopa from s.c. implanted slow-release polymer matrices has several advantages over oral delivery: 1) l-dopa plasma fluctuations are eliminated, 2) patient compliance issues are reduced and 3) the gastrointestinal tract is circumvented, thus requiring a lower dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1970

Temporal phenotypic heterogeneity as a substrate for selection.

The interaction of temporal phenotypic heterogeneity with a population level fitness function was explored through the use of a simple model. The model, based upon experimental data, assumes that the exploitation of pollinators, and seed-set within plant populations are dependent upon the frequency of a pink flower morph in populations composed of pink and white morphs. An increase in pink frequency is accompanied by an increase in seed-set for both morphs. The model also assumes that seed-set within a population is the same for pink and white individuals. In perennials and annuals with long-lived seeds, fluctuations in morph balance from one season to another may lead to reproductive pulses or drags, depending upon which morph was in excess. The reproductive differential which stems from different levels of pollinator service leads to an increase in pink frequency and an attendant fitness gain. The perennial habit and long-lived seeds provide a population with a memory which permits the current population image to compete with images of previous years. As a consequence, fitness gains may be achieved in the absence of interplant or interpopulation selection.

Journal Article↗
PubMed1998

Seasonal values of selected blood parameters of farm-raised channel catfish (Ictalurus punctatus) in the Mississippi Delta.

Hematocrit, sodium, chloride, potassium, calcium, glucose, and pH were measured in whole blood of 1,522 channel catfish collected from 3 commercial food-fish ponds in the Mississippi Delta. Samples were collected from March 1995 to March 1996 to monitor seasonal fluctuations. A total of 10-20 fish were arbitrarily collected with snag lines from each pond on each sample day. The mean monthly hematocrits fluctuated seasonally from a low of 14.5% in midwinter to a high of 25.7% in midsummer (annual x = 21%, SE = 0.15). Sodium levels were consistent throughout the year with a mean (SE) of 134 (0.13) mM/liter. Mean chloride values for the year were 120 (0.14) mM/liter but increased to 132 mM/liter in midwinter. By March 1996, the chloride levels had returned to levels observed during spring 1995. Potassium and glucose levels varied throughout the year with means of 4.43 (0.06) mM/liter and 26.9 (0.46) mg/dl, respectively, and coefficients of variation of 51.8% and 63.3%, respectively. Calcium and pH values were fairly stable with means of 1.31 (0.004) mM/liter and 7.13 (0.004), respectively. All parameters except glucose and potassium may be adequately evaluated with a sample size of 25 or less. These data were collected to provide baseline information for ongoing pond health studies.

Agriculture↗
PubMed2004

Polygenic variation maintained by balancing selection: pleiotropy, sex-dependent allelic effects and G x E interactions.

We investigate three alternative selection-based scenarios proposed to maintain polygenic variation: pleiotropic balancing selection, G x E interactions (with spatial or temporal variation in allelic effects), and sex-dependent allelic effects. Each analysis assumes an additive polygenic trait with n diallelic loci under stabilizing selection. We allow loci to have different effects and consider equilibria at which the population mean departs from the stabilizing-selection optimum. Under weak selection, each model produces essentially identical, approximate allele-frequency dynamics. Variation is maintained under pleiotropic balancing selection only at loci for which the strength of balancing selection exceeds the effective strength of stabilizing selection. In addition, for all models, polymorphism requires that the population mean be close enough to the optimum that directional selection does not overwhelm balancing selection. This balance allows many simultaneously stable equilibria, and we explore their properties numerically. Both spatial and temporal G x E can maintain variation at loci for which the coefficient of variation (across environments) of the effect of a substitution exceeds a critical value greater than one. The critical value depends on the correlation between substitution effects at different loci. For large positive correlations (e.g., rho(ij)2>3/4), even extreme fluctuations in allelic effects cannot maintain variation. Surprisingly, this constraint on correlations implies that sex-dependent allelic effects cannot maintain polygenic variation. We present numerical results that support our analytical approximations and discuss our results in connection to relevant data and alternative variance-maintaining mechanisms.

Data Interpretation, Statistical↗
PubMed1996

Effects of muscarinic agents on cultured human trabecular meshwork cells.

Intracellular calcium measurements were performed in cultured human trabecular meshwork cells preloaded with the cell permeant dye fura 2-AM. Fluctuations in calcium levels were then monitored with microscope-based ratio fluorometry. Carbachol increased intracellular calcium in a dose-dependent manner; as did oxotremorine-M, aceclidine, and pilocarpine. Carbachol's effect was blocked by the non-selective muscarinic antagonist atropine, as well as by muscarinic receptor subtype-selective antagonists such as pirenzepine (M1-selective), p-fHHSiD (M3-selective), and 4-DAMP (M1, M3 subtypes). Rank order of potencies for the antagonists' effects was atropine = 4-DAMP > p-fHHSiD > pirenzepine, a profile suggesting that the M3 receptor subtype is essential in the carbachol effect. Phospholipase C activity was estimated via measurement of total production of inositol phosphates in cultured human trabecular meshwork cells pre-exposed to 3H-myoinositol. In these cells, carbachol also stimulated phosphoinositide production in a dose-dependent manner, and an antagonist profile similar to that seen for calcium response was obtained when carbachol was used as the effector. The data indicate that muscarinic effects on cultured human trabecular meshwork calcium mobilization and phospholipase C activity are mediated by an M3-like receptor subtype. Therefore, the muscarinic M3 receptor may play a role in trabecular meshwork cell function(s).

Adolescent↗
PubMed2005

Methodologies for the study of ocular surface disease.

The ability to obtain reliable results from clinical trials of therapies for ocular allergic disease and dry eye disease is often limited because of inadequate control of variables, such as environment, patient life style, compliance, and individual fluctuations that occur from one assessment visit to another. The controlled allergen challenge (CAC) model of allergic conjunctivitis allows signs and symptoms of the disease to be elicited in a physiologically accurate and reproducible manner. The rigid criteria for subject selection, the controlled allergic reaction, and the standardized and quantified grading systems allow for a reproducible baseline from which statistically and clinically significant differences between formulations can be assessed. Similarly, the controlled adverse environment (CAE) model for dry eye mimics the environmental stimuli that lead to ocular surface drying. Preselected subjects have a reproducible, homogeneous baseline reaction from which the effects of various treatments can be significantly evaluated and compared. CAC and CAE provide accurate means to study highly variable and individual ocular surface disease.

Journal Article↗
PubMed1980

Material-specific perceptual interference for visual words and faces: implications for models of capacity limitations, attention, and laterality.

Four experiments were conducted to test the hypothesis that perceptual interference effects would be greatest among items that are processed by the same hemisphere than among items processed by different hemispheres. Recognition of two peripheral faces, flanked on either side of a central item that also had to be identified, was worse when the item was a face than when the item was a word. The opposite results were obtained for peripheral word identification by naming (Experiment 1). Identical results were obtained when a nonsense form was substituted for the central face (Experiment 2). Since unfamiliar faces and nonsense forms are processed primarily by the right hemisphere and words are processed by the left, the results are consistent with the hypothesis. The interference effect was the same even when the central nonsense shape was identified by naming, suggesting that the locus of the effect is not at response selection (Experiment 3). Ignoring the central item only reduces the interference effects but does not eliminate it (Experiment 4). Although in general words were perceived better in the right visual field, and faces were perceived better in the left, small fluctuations in the magnitude but not in the direction of perceptual asymmetries were sometimes noted with changes in the central item. The fluctuations were usually opposite to those predicted by attentional models of perceptual asymmetries.

Attention↗
PubMed2004

Outcome signature genes in breast cancer: is there a unique set?

MOTIVATION: Predicting the metastatic potential of primary malignant tissues has direct bearing on the choice of therapy. Several microarray studies yielded gene sets whose expression profiles successfully predicted survival. Nevertheless, the overlap between these gene sets is almost zero. Such small overlaps were observed also in other complex diseases, and the variables that could account for the differences had evoked a wide interest. One of the main open questions in this context is whether the disparity can be attributed only to trivial reasons such as different technologies, different patients and different types of analyses. RESULTS: To answer this question, we concentrated on a single breast cancer dataset, and analyzed it by a single method, the one which was used by van't Veer et al. to produce a set of outcome-predictive genes. We showed that, in fact, the resulting set of genes is not unique; it is strongly influenced by the subset of patients used for gene selection. Many equally predictive lists could have been produced from the same analysis. Three main properties of the data explain this sensitivity: (1) many genes are correlated with survival; (2) the differences between these correlations are small; (3) the correlations fluctuate strongly when measured over different subsets of patients. A possible biological explanation for these properties is discussed. CONTACT: eytan.domany@weizmann.ac.il SUPPLEMENTARY INFORMATION: http://www.weizmann.ac.il/physics/complex/compphys/downloads/liate/

Biomarkers, Tumor↗
PubMed2001

Are the parameters of various stabilization factors estimated from mutant human lysozymes compatible with other proteins?

The various factors which contribute to protein stability have been extensively examined using mutant proteins, but the same kinds of substitutions have given different results depending on the substitution sites. Recently, the contributions of some stabilization factors have been quantitatively derived as parameters by a unique equation, considering the conformational changes due to the mutations using mutant human lysozymes [Funahashi et al. (1999) Protein ENG: 12, 841-850]. To evaluate these parameters estimated from the mutant human lysozymes, stability-structure datasets for the mutant T4 lysozymes were selected. The stabilities for the mutant T4 lysozymes could be roughly estimated using these parameters. Notable differences between the estimated and experimental stabilities were caused by the uncertainty in part of the structures due to some Arg and Lys residues fluctuating on the surface of the T4 lysozyme. Excluding these atoms from the estimation gave a good correlation between the estimated and experimental stabilities. These results suggest that the parameters of the various stabilization factors derived from the mutant human lysozymes are compatible with the mutant T4 lysozymes, although they should be improved with respect to some points using more information.

Amino Acid Substitution↗
PubMed2002

Prolongation of hippocampal miniature inhibitory postsynaptic currents in mice lacking the GABA(A) receptor alpha1 subunit.

GABA(A) receptors (GABA(A)-Rs) are pentameric structures consisting of two alpha, two beta, and one gamma subunit. The alpha subunit influences agonist efficacy, benzodiazepine pharmacology, and kinetics of activation/deactivation. To investigate the contribution of the alpha1 subunit to native GABA(A)-Rs, we analyzed miniature inhibitory postsynaptic currents (mIPSCs) in CA1 hippocampal pyramidal cells and interneurons from wild-type (WT) and alpha1 subunit knock-out (alpha1 KO) mice. mIPSCs recorded from interneurons and pyramidal cells obtained from alpha1 KO mice were detected less frequently, were smaller in amplitude, and decayed more slowly than mIPSCs recorded in neurons from WT mice. The effect of zolpidem was examined in view of its reported selectivity for receptors containing the alpha1 subunit. In interneurons and pyramidal cells from WT mice, zolpidem significantly increased mIPSC frequency, prolonged mIPSC decay, and increased mIPSC amplitude; those effects were diminished or absent in neurons from alpha1 KO mice. Nonstationary fluctuation analysis of mIPSCs indicated that the zolpidem-induced increase in mIPSC amplitude was associated with an increase in the number of open receptors rather than a change in the unitary conductance of individual channels. These data indicate that the alpha1 subunit is present at synapses on WT interneurons and pyramidal cells, although differences in mIPSC decay times and zolpidem sensitivity suggest that the degree to which the alpha1 subunit is functionally expressed at synapses on CA1 interneurons may be greater than that at synapses on CA1 pyramidal cells.

Animals↗
PubMed2005

Using the EDAC test to monitor abstinence and relapses during outpatient treatment.

The main objective of this study is to show the performance of the EDAC test in monitoring alcohol consumption during outpatient treatment. The EDAC is a new approach that uses routine laboratory tests to identify binge drinking as well as chronic drinking. The overall diagnostic performance of the EDAC fluctuates around 80 to 90% for both specificity and sensitivity. Close to two thousand subjects have been tested by the EDAC since the early eighties; 300 of these were patients undergoing treatment at different institutions across the U.S. This article selected five case studies to represent examples of classical drinking behaviors encountered in most outpatient clinics. The first four cases illustrate the use of the EDAC alone and the last case represents the use of the EDAC combined with CDT. These five case studies illustrate the use of the EDAC to detect relapse episodes, to monitor abstinence during outpatient treatment and to recognize a slip early enough to prevent more severe drinking. The use of biomarkers to monitor drinking behavior in alcohol dependent patients is gaining popularity because they provide objective information on a patient's drinking status when used as an adjunct to self-report.

Adult↗
PubMed2000

Prevalence of allergic bronchopulmonary aspergillosis in patients with bronchial asthma.

Two Hundred patients with bronchial asthma were studied to identify the prevalence of allergic bronchopulmonary aspergillosis (ABPA). The patients selected required intermittent short courses of steroids and their mean duration of illness was 12 years. Absolute eosinophil count was > 500/mm3 in 53% of the cases. Chest X-rays showed small homogenous shadows with patchy infiltrations in 25% and fluctuating pneumonic shadows in 14% of the cases. Raised specific IgG and positive serum precipitin against Aspergillus fumigatus (AF) were present in 24% and 13%, respectively. Cases with radiological and immunological suspicion were further investigated for ABPA. Skin tests for Type-I and Type-III reactivity were positive with AF extract in 87% (n = 47) and 36% (n = 47) of the cases. A thorax CT of 31 patients showed central bronchiectasis in 24 cases, labeling these patients as ABPA-CB (ABPA with central bronchiectasis) and an other 7 as ABPA-S (serological positive). CT was not done in one case who, because of other positive findings, was also labeled as ABPA-S. Thus, these 32 asthmatics were found to have ABPA. Among them, there was raised specific IgG (100%) and raised specifc IgE against AF (100%), positive skin test for Type-I and Type-III reactivity (100% and 53%) against AF. There was elevated total IgE (100%, n = 29), a positive family history of asthma (63%), peripheral eosinophilia (100%) and a history of passage of brownish plugs (31%). Radiological findings suggested soft shadow with infiltration in 31% and fluctuating pneumonic shadows in 69% of cases. CT Thorax (n = 31) showed central bronchiectasis in 78% of theses patients. Based on the present data, the prevalence of ABPA in bronchial asthma patients is 16% (12% with central bronchiectasis and 4% only serologically positive). Therefore, patients should be investigated and diagnosed in an early phase of ABPA (ABPA-S) and should be treated to prevent permanent lung damage.

Adolescent↗