Effect of itraconazole therapy in allergic bronchopulmonary aspergillosis.
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BACKGROUND: Tubercular brain abscess (TBA) is a rare manifestation of CNS tuberculosis. It is characterised by an encapsulated collection of pus, containing viable tubercular bacilli without evidence of tubercular granuloma. PRESENTATION AND HISTORY: Patients may present with features of raised intracranial pressure and focal neurological deficit commensurate with the site of the abscess. A history of pulmonary tuberculosis may be present, as documented in one of our six cases; three of our six children developed TBA despite 3-weeks to 12-month courses of antitubercular chemotherapy prescribed for post-TBM hydrocephalus. DIAGNOSIS: Contrast CT head, MRI, MR spectroscopy is helpful in making the diagnosis and planning the treatment. TBA may be unilocular or multilocular on contrast CT scan. A relatively long clinical history and an enhancing capsule with thick wall are suggestive of TBA. Pyogenic abscess, however, has a thin rim on contrast CT. The capsule of TBA is formed of vascular granulation tissue containing acute and chronic inflammatory cells, particularly polymorphs. Proof of tubercular origin must be demonstrated either by presence of acid fast bacilli in culture or staining of pus or wall. TREATMENT: Treatment options include simple puncture, continuous drainage, fractional drainage, repeated aspiration through a burr hole, stereotactic aspiration and total excision of the abscess. Total excision usually becomes necessary in multilocular noncommunicating and thick-walled abscesses. Antitubercular therapy is the mainstay of management. The development of fulminant tubercular meningitis is sometimes problematic following surgical excision of TBA, as seen in one of our four operated cases. Mortality is reported to be high despite progress in treatment, while five of the six children treated by us responded well to the treatment.
Terminal myelocystocele is an unusual form of occult spinal dysraphism. It consists of a cystic dilatation of a low-lying terminal cord herniated posteriorly through a skin covered lumbosacral spina bifida. This condition is often associated with OEIS complex i.e. opmphalocele, exstrophy of the bladder, imperforate anus and spinal abnormality. We studied 4 cases of terminal myelocystocele. They revealed no preoperative neurological deficit. None of these had associated OEIS complex. One of the cyst was unique due to presence of copious amount of pus in its cavity. All four cases underwent successful repair and surgery remained uneventful in all of them. No child showed neurological deterioration during the follow-up.
Epicoccum nigrum (EN) is an important fungal allergen for nasobronchial allergy. Fungal extracts should contain all the relevant allergen components from spores, mycelium and culture medium for the purpose of allergy diagnosis and therapy. EN extract from spore-mycelial mass has been standardized, but the culture filtrate (CF) allergens of EN have not been studied as EN grows poorly in synthetic medium. The objective of the present study was to obtain a standard CF extract of EN by cultivating the source material in a modified semi-synthetic medium and to compare this with the EN cellular extract. Sabouraud's medium containing yeast extract (50 mg/l) was filtered using 10-kDa cut-off membrane and the lower molecular mass media components were used to cultivate EN. The CF obtained after removing the spore-mycelia was dialyzed to remove media components. The CF extract was characterized by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot. It was compared with EN spore-mycelial extract by enzyme-linked immunosorbent assay (ELISA), ELISA inhibition and by intradermal testing on allergy patients. The CF extract of EN resolved into 30 protein bands on SDS-PAGE. About 27 IgG bands were detected using anti-EN rabbit antibodies and 12 IgE bands by EN-sensitive pooled patients' sera. Periodate modification of CF proteins showed that the carbohydrate moieties are not important for IgE binding. Protein components of 26, 34 and 43 kDa were recognized as the major CF allergens. Three different batches of CF extract required 7.5-9 ng of self protein for 50% inhibition of binding to anti-EN rabbit antibodies in ELISA. Intradermal testing with CF extract showed comparable allergenic potency to standardized EN spore-mycelial extract, although it contained some allergenic proteins in higher amounts as compared to the spore-mycelial extract. In summary, the semi-synthetic medium has been suitably modified for obtaining EN CF antigens. This medium can be an important substitute for producing potent CF allergens of fungi that grow poorly in synthetic medium. The EN CF extract elicited good allergenic reactivity and may be used for allergy diagnosis along with spore-mycelial extract.
Epidemiologic studies in India show that the prevalence of asthma is increasing, but no genetic studies have been reported on the Indian population thus far. We selected the IFNG locus on 12q21 as a candidate gene for asthma on the basis of its role in pathophysiology and positive linkage demonstrated in other populations. The aim of this study was to investigate association of a CA-repeat marker in this gene with asthma and total serum IgE levels in the North Indian population. The repeat region was PCR-amplified from patients and control subjects and analyzed through use of GeneScan. The distributions of allele sizes were found to be significantly different between patients and control subjects (Kolmogorov-Smirnov test, P < 10(-6)). Alleles 10 and 11 were found to be overrepresented in individuals with asthma, whereas alleles 13 and 15 were less likely in asthmatic individuals. We found that the CA-repeat polymorphism in the IFNG gene was significantly associated with total serum IgE levels (ANOVA, P < 10(-4) for control subjects and P =.0036 for patients). Furthermore, a previously reported promoter polymorphism at the -333 base pair position was not detected in our population. This is the first report on the association of a candidate gene with asthma from the Indian subcontinent.
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder induced by Aspergillus species colonizing the bronchial tree. Thirty one patients fulfilling criteria of ABPA were evaluated in the present study. Eleven patients were diagnosed as ABPA-S (serological positive) and 20 patients as ABPA-CB (with central bronchiectasis). The two groups of patients were compared on the basis of clinical, serological, and radiographic observations. Serum anti Aspergillus fumigatus IgG was positive in 72% of cases of ABPA-S and 85% of ABPA-CB patients at the time of presentation. Specific IgE against A. fumigatus and total IgE were significantly lower in ABPA-S (specific IgE= 7.42 IU and total IgE= 1127 ng/mL) as compared to ABPA-CB (specific IgE = 44 IU and total IgE = 2874 ng/mL). The spirometric changes in ABPA-S (normal 80%, mild obstruction 10%, and severe obstruction 10%) were milder than in ABPA-CB (normal 40%, mild obstruction 10%, moderate obstruction 20%, and severe obstruction 30%). These patients were monitored closely for seasonal exacerbation with new pulmonary infiltrates which gave lower recordings in ABPA-S patients. No patient in the ABPA-S group progressed to end-stage lung disease. This may be due to early recognition and treatment. The present data suggest that ABPA-S represents the early stage of an apparently less aggressive form of ABPA than ABPA-CB.
BACKGROUND: Curvularia lunata is an important inhalant allergen. The present study was undertaken to investigate the shared IgG- and IgE-binding components among seven Curvularia species prevalent in the aerospora. METHODS: Seven different Curvularia species were grown in a semisynthetic medium for 13 days. The extracts were analyzed by SDS-PAGE, immunoblot and ELISA/immunoblot inhibition using sera from C. lunata-positive patients and anti-C. lunata rabbit serum. RESULTS: Different Curvularia species showed 11-19 protein bands on SDS-PAGE. Proteins of 12, 20, 31, 45, 53, 78 and 97 kD were present in all the species. Eight out of 98 nasobronchial patients exhibited positive skin tests to C. lunata and to at least five Curvularia species. ELISA using these sera showed IgE binding with Curvularia species. Immunoblot using pooled anti-C. lunata sera from patients showed 5-12 allergenic proteins. Proteins of 12, 31, 45, 53 and 78 kD showed IgE binding in Curvularia species. Antibodies against C. lunata detected 6-14 antigenic proteins on immunoblot. Proteins of 31, 45 and 53 kD showed IgG binding in all the species. Proteins of 31 and 53 kD showed complete IgE/IgG binding inhibition. IgE/IgG ELISA inhibition showed dose-dependent inhibition in Curvularia species. C. lunata extract required 0.17 and 0.11 microg of protein for 50% IgE and IgG inhibition, respectively. C. clavata and C. pallescens required 10 times more protein to exhibit the same inhibition and other species required similar protein levels as those required by C. lunata. CONCLUSIONS: A high degree of cross-reactivity was observed between C. lunata and the six other Curvularia species tested. C. lunata and C. senegalensis shared maximum allergenic and antigenic components.
OBJECTIVE: To describe the clinical features and surgical outcome of a combined anomaly, i.e. split cord malformation (SCM) with meningomyelocele (MMC), and to propose an addition to Pang's classification of SCM to accommodate a combined form of anomaly. METHODS: We retrospectively analyzed 16 cases of such a combination, out of a total of 106 cases of spinal dysraphism treated and studied prospectively for outcome at our center. The clinical profile and outcome of these cases are described. RESULTS: All cases had SCM and MMC. Nine patients were males, and the mean age of presentation was 3.9 years. Twelve patients had Pang's type I SCM and the other 4 were of type II. The MMC sac was lumbar in 11 cases. In all the patients, SCM was present either at the same level as the MMC or one to two segments above it. Nine patients had motor weakness, 6 had hypoesthesia, 4 had urinary incontinence and 3 had trophic ulcers. Nine patients had neuroorthopedic syndrome. All cases, except 3 (who were operated on at birth, at which time 'superficial surgery' was performed without relevant imaging), underwent repair of the MMC and excision of the spur/septum at the same sitting. The 3 cases who had undergone superficial surgery, however, were operated on for SCM following investigation at our center, obviously at a second sitting. After an average follow-up of 7.2 months, 4 patients showed improvement in motor weakness, 5 in hypoesthesia and 3 in urinary symptoms, whereas trophic ulcers had healed in all cases. CONCLUSION: With respect to the occurrence of SCM at or above the level of an MMC, we feel it is apt to screen the entire spinal/neuraxis by MRI in children with MMC. We labeled this combined pathology 'complex spina bifida', and feel it is necessary to make a minor modification to Pang's classification to accommodate the pure/combined anomalies together.
From July 1996 to August 2001, we operated on 23 children (age 4-12 years) with congenital atlantoaxial dislocation (AAD). Sixteen had reducible AAD and 6 had the fixed type, while a single patient had basilar invagination. Preoperatively, these children were divided into four functional grades depending on the level of neurological deficits and dependence on others for activities of daily living (Di Lorenzo grades I-IV). There were only 2 patients with no deficits (grade I), while 15 of the 23 children presented with severe neurological deficits and were completely dependent for all activities of daily living (grade IV). Stigmata suggestive of congenital AAD were documented in 6 children and radiological osseous anomalies in 18 children. Transoral decompression and posterior stabilization was performed in 7 children, while 16 patients underwent the posterior stabilization procedure only. All patients were immobilized with a hard cervical collar postoperatively. Six children developed one or other treatable complications, of whom reoperation was indicated in 3, but could only be undertaken in 2 children. Retightening of the wire was done in 1 and further decompression of the odontoid process was carried out in the other. There was no postoperative deterioration in patients with no preoperative deficits (grade I). Ten out of the 15 children who were completely dependent for all activities in the preoperative period (grade IV) improved, and 6 children achieved normalcy or near normalcy (grade I or II). Three children deteriorated in the postoperative period, of whom 2 subsequently improved at follow-up. There were 2 deaths in the series; both these patients belonged to the severely compromised group (grade IV) and in addition had respiratory compromise. Bony fusion at the posterior stabilization site could be seen in 14 out of 16 patients screened. The various problems faced by the authors in managing these very fragile and severely compromised children with cervicomedullary compression due to congenital atlantoaxial dislocation in a setting with limited resources are discussed.
Six cases of unusual neuroenteric (NE) cysts, occurring in children aged 15 months to 18 years, are reported here. Three of the cysts were extramedullary, while the other three were intramedullary. Two of the extramedullary cysts were located at the lumbosacral region, an unusual site. Only one patient had the cyst located in a ventral relation to the cord in the cervicothoracic region. None of the patients had communication with the mediastinum or intraabdominal viscera. Stigmata of spinal dysraphism were seen in three patients. All the children had variable neurological involvement and it was difficult to differentiate NE cyst from other causes of spinal cord or cauda equina lesion, particularly in the absence of some dysraphic marker. One patient presented with minimal neurological deficits and painful torticollis; this patient was suspected to have an atlantoaxial dislocation. All patients were investigated with MRI, and the only diagnostic feature of an NE cyst was an intradural cyst with an anterior vertebral body anomaly in a single case. It was not possible to radiologically differentiate NE cyst from other intraspinal cysts in the rest of the patients. All patients were operated on by the posterior route; an attempt to excise the cyst nearly in toto was made. Evidence of neural tethering most probably due to cyst contents was seen in three patients. All patients improved after surgery. None showed recurrence of the cyst at follow-up of 3 months to 2 years.
Seven premature hydrocephalics presenting with lambdoid positional moulding (LPM) were reviewed. All were treated for hydrocephalus secondary to aqueductal stenosis, Dandy Walker Syndrome and infection. Parenchymal hemorrhage, intraventricular bleed, cortical atrophy, septal agenesis, cortical anomalies and subdural hygroma were the other common associations. These children did not show expected improvement in their higher mental functions at 6 months to 5.4 years of follow-up, following the management of hydrocephalus. It was not the LPM but associated intracranial anomalies, which were most probably responsible for their poor outcome. The differentiation from posterior plagiocephaly is also highlighted.
The cerebellopontine angle (CPA) is a rare site for the growth of choroid plexus papilloma (CPP). The clinicoradiological diagnosis of this tumor in the CPA is difficult because of the nonspecific clinical presentation and radiological features. Five cases of choriod plexus papilloma (3 males, 2 females) operated upon at this center are reviewed. All the cases were operated upon by retromastoid suboccipital craniectomy. As they all presented with a typical CPA syndrome without any distinctive radiological feature, a clinicoradiological diagnosis of CPP could not be reached in any of these. The diagnosis of CPP could only be suspected at the operation table and established on histopathological examination. Two patients developed recurrences at the primary site following surgery. One patient developed recurrence twice despite gross total excision of tumor in each sitting. Subsequently, this patient remained symptom free for a follow-up period of 1 year. Another patient developed recurrence 2 years following surgery, but he died due to septicemia and aspiration pneumonitis. Therefore definitive surgery could not be performed. Radiotherapy was offered to one of the patients having residual mass post operatively, to render her symptom free for a 4 year follow-up. The remaining two patients have also showed progressive improvement in their symptoms following surgery for 4 years on follow-up. Hydrocephalus was a common feature in all the cases preoperatively, but only one required shunt CSF diversion, because of rapid deterioration in visual equity. In all other cases, hydrocephalus was managed conservatively. Surgery remains the main modality of treatment for CPP, both for primary and recurrent tumors, but radiotherapy may have a role in cases of recurrence, which are quite frequent.
A retrospective study of 22 children with intramedullary mass lesions (neoplastic and nonneoplastic) was performed to see the frequency of different histotypes of tumors/lesions and the functional outcome in Indian children. The age of the children varied from 1.5 to 16 years with a median of 8 years. The male to female ratio was 2.7:1. The children having a minimum follow-up of 3 months and a complete clinicopathological record were entered into this study. McCormick functional grading was applied retrospectively to assess the preoperative grade and postoperative functional outcome of the children. Histopathologically, these 22 cases were astrocytomas (n = 6, 27.3%), ependymomas (n = 3, 13.6%), dermoids (n = 3, 13.6%), epidermoids (n = 2, 9.1%), ependymal cysts (n = 2, 9.1%), and myxopapillary ependymoma, neurenteric cyst, ganglioglioma, teratoma, tuberculoma and anteriovenous malformation one each (4.55%). Near-total or gross-total resection was achieved in 13 (59%) and subtotal resection in 7 patients (32%), while complete excision of tuberculoma was achieved in 1 patient. Coagulation of perimedullary vessels was done in another single patient with anteriovenous malformations. Fourteen of the 22 cases having had functional grade IV or V preoperatively, improved to grade I or II (n = 7) and to grade III (n = 4, all astrocytomas) following surgery. Two patients died (1 within 2 days and 1 after 3 months due to recurrence of the tumor) and 1 case deteriorated at the follow-up of 4 months. Eight out of the 22 patients who had been admitted with functional grade II or III improved to grade I or II following surgery. The following conclusions were drawn after evaluation of these cases: (1) astrocytomas and ependymomas constituted only 50% of intramedullary tumors; (2) nonneoplastic, malformative tumors like dermoid and epidermoid showed a higher incidence (23%) in comparison with the Western World where all congenital intramedullary tumors (including dermoids and epidermoids) account for 5-8% only; (3) extremely rare cystic lesions like ependymal cyst and inflammatory granuloma may manifest as an intramedullary lesion; (4) even neurenteric cyst, though rare, may manifest as a pure intramedullary lesion without the stigmata of spinal dysraphism, and (5) delayed presentation was the cause of unfavorable outcome in a developing milieu.
Twenty-five children with benign intradural extramedullary tumors/lesions were retrospectively analyzed to see the frequency of different histotypes in this location and their variation from the Western world. The duration of symptoms, clinical profile and surgical outcome of these cases were evaluated. The age of children ranged from 1.5 to 18 years, with a mean age of 7.5 years. Thirteen amongst them were male. Follow-up ranged from 3 months to 5 years with a mean of 19 months. McCormick functional grading was used retrospectively to find out the functional outcome in these children. Sixty-eight percent of these cases presented with functional grade IV or V. The mean duration from the appearance of the first symptoms to admission to our hospital in these children was 13 months. Improvement in the functional grade following surgical excision was noted amongst all, except one, who presented with schwannoma, and did not improve from grade III even after a 14-month follow-up. Reoperation/two-staged operation was required in 3 children. The following conclusions were drawn from this study: (1) approximately half (48%) of intradural extramedullary benign tumors are nerve sheath tumors, i.e. neurofibromas, neurilemomas and schwannomas. Giant neurofibromas with giant extraforaminal extension may rarely manifest with a large extraspinal mass; (2) meningioma is an infrequent tumor in this location; (3) developmental cystic dysraphic lesions (neurenteric cyst, arachnoid cysts), unassociated with the stigmata of spinal dysraphism, are significantly more frequent (28%) than reported in the literature; (4) the possibility of infective lesions (granuloma, abscess) causing compressive features cannot be denied even in intradural extramedullary tumors; (5) long-standing lesions, with a long segment involvement, also have a good outcome following a good microsurgical excision, and (6) more than half of the children (68%) present with a severe neurological compromise, either because of ignorance and poor education or due to the scanty diagnostic facilities available at the peripheral hospitals of the developing milieu.
The aqueous-ethanolic extract (AEE) of high altitude Podophyllum hexandrum has earlier been reported to render a radioprotective effect against lethal gamma radiation in in vitro model. AEE has also been reported to possess metal chelating and DNA protecting properties. The present study was undertaken to isolate and characterize the bioactive principle present in AEE and investigate its role in radiation protection. A novel molecule was found to be present in AEE and was assigned as 3-O-beta-D-galactoside of quercetin by acid hydrolysis, LC-MS, LC-APCI-MS/MS and 13C NMR spectra. Various biological activities were investigated at in vitro level. The antioxidant potential of AEE in lipid and aqueous phase was determined against numerous stresses. AEE was found to be significantly (p < 0.05) protective, i.e., against Fe2+ and Cu2+-induced linoleic acid degradation, respectively. Radiation-induced lipid oxidation studies revealed that AEE maximally works at a [lignan]/0.25 kGy ratio 400 (ratio of concentration of AEE divided by the radiation dose, i.e., 0.25 kGy) and no drug-induced lipid oxidation at all concentrations tested was found. In a time-dependent study, total antioxidant activity was maximally exhibited at 1 mg/ml. The site-specific and non-site-specific deoxyribose degradation assay exhibited a dose-dependant hydroxyl scavenging potential of AEE (0.05-500 microg/ml). The anti-lipid peroxidation ability of AEE against radiation (0.25 kGy)-induced lipid peroxidation was higher in case of neural tissue homogenate as compared to kidney homogenate [activity ratio: 0.039 (brain) < 0.24 (kidney)]. The protein protection study using bovine serum albumin was also done for two time intervals (2 h and 4 h) and significant (p < 0.05) protection was observed at 500 microg/ml (> 97%). This study implies that 3-O-beta-D-galactoside present in AEE renders radioprotection by protecting lipids, proteins in renal and neural model system against supra-lethal (0.25 kGy) gamma radiation.
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INTRODUCTION: A well-accepted vaccination schedule for preterm babies is not available. We therefore studied the response to hepatitis B vaccine in preterm babies. METHODS: 60 babies born to HBsAg-negative mothers were studied. Group I (n=20) consisted of term babies with birth weight >2.5 Kg, group II (n=20) included preterm babies with birth weight between 1.8 and 2.49 Kg, and group III (n=20) included preterm babies with birth weight between 1.2 and 1.79 Kg. Mean gestational age in the three groups was 38.5 (1.1), 33.5 (1.4) and 32.7 (2.1) weeks, respectively. All babies received 3 doses (10 microg/0.5 mL) of a recombinant HBV vaccine within 3 days of birth, and at 6 weeks and 6 months of life. Anti-HBs levels were measured one month after the 2nd and 3rd doses each; the immune response was categorized as good responders (anti-HBs >100 mIU/mL, low responders (anti-HBs 10-100 mIU/mL) and non-responders (anti-HBs <10 mIU/mL). RESULTS: Good antibody response after the second dose was seen in 95% of babies in group I, 60% of those in group II and 10% of those in group III. This increased to 100%, 90% and 45%, respectively after the third dose. The response was influenced by gestational age (r=0.73); 94% of babies with gestational age 34-36 weeks attained good antibody response compared to only 55% of babies with gestational age of 31-33 weeks. Birth weight had no independent influence on the antibody response. CONCLUSION: The response to hepatitis B vaccine is influenced by gestational age. Hence, in preterm babies, it is advisable to check antibody titers one month after the third dose to assess the need for a booster dose.
The present series reports an audit on the patterns of presentation, radiation treatment techniques, failure pattern and outcome in the 36 patients treated at a single institution. Patients were accrued between October 1991 and September 1999. They underwent total or subtotal resection along with craniospinal irradiation. The dose to the cranium ranged from 30 to 43Gy (median- 36Gy), to the spine from 20 - 36Gy (median- 36Gy) and the posterior fossa boost, which was delivered in 32 cases, ranged from 14 to 24Gy (median -18Gy). Simulator film evaluation was carried out at the time of analysis based on the French Medulloblastoma Group guidelines, which revealed a significant under-dosage in the region of posterior fossa and cribriform plate in 27% and 19% respectively. Adjuvant chemotherapy was administered in 7 patients. Salvage treatment in the form of chemotherapy (5 cases) and re-irradiation (2 cases) were attempted but were ineffective. The overall survival (OS) and progression free survival (PFS) rates were 54% and 40% respectively, with the median being 75 and 29 months respectively. Amongst all the prognostic factors considered, on univariate analysis, duration of symptoms was significant for PFS with a trend towards significance for OS, while extent of debulking had a trend towards significance for PFS. No factor emerged significant on multivariate analysis.