Revisiting epidermal growth factor receptor in glioblastoma multiforme: Does it play a role in response to therapy.

Background and Aim: Glioblastoma multiforme (GBM) are the most aggressive class of cancer of central nervous system with hallmark characteristics that include rampant proliferation, necrosis, and endothelial proliferation. Epidermal growth factor receptor (EGFR) has been implicated as the primary contributor to glioblastoma initiation and succession. The present study was designed to evaluate EGFR protein expression in GBM as predictor of response to therapy and survival. Materials and Methods: Epidermal growth factor receptor was assessed by immunohistochemistry as a percentage of positive tumor cells in hot spots (10 high-power fields). The study group comprised of 35 cases of GBM. All cases underwent surgical resection and subsequently underwent radiotherapy (n = 17) or radiotherapy with adjuvant temozolomide chemotherapy (n = 18). Immediate response to therapy was assessed at 3 months using World Health Organization response evaluation criteria in solid tumors criteria and cases followed up for survival. Results: Twenty-four cases (68.6%) expressed EGFR while 11/35 (31.4%) cases were negative. Response to therapy was evident in 21/35 cases (60.0%) and 14/35 were (40.0%) nonresponders. Mean EGFR protein expression in responders was 37.23 ± 33.70 and in nonresponders was 59.5 ± 39.46 (P = 0.542). The percentage of responders which were EGFR negative was 72.7% and while response in EGFR positive cases was observed in 54.2%. Mean survival in EGFR positive and negative GBM was 394.37 ± 189.11 and 420.54 ± 191.23 days, respectively. Conclusion: The EGFR negative cases appear to respond better to therapy, however, the difference is not statistically significant (P = 0.298). Further, EGFR protein expression does not play a definitive role in predicting survival. This is an original study evaluating EGFR in terms of therapeutic response.

A study on human leukocyte antigen class I molecules in paediatric bronchial asthma.

Childhood asthma, often associated with atopy, is more common in boys and may persist throughout life in 50% of cases. This case-control study was carried out to examine if any association of paediatric bronchial asthma with human leukocyte antigen (HLA) class I antigens. Thirty-six children with bronchial asthma diagnosed on basis of Global Initiative for Asthma (GINA) criteria and an equal number of healthy controls without history of bronchial asthma were studied. Low resolution HLA- ABC typing was performed by sequence specific primers (SSP) and the frequency of HLA–ABC antigens in the two groups was compared. Total serum immunoglobulin E (IgE) estimation was done as a marker of atopy by ELISA. The study included 24 boys and 12 girls aged 13 months to 11 yrs, of which 16 (44%) had positive family history. Serum IgE levels were elevated in 20 (55%) of the cases and 33% of controls with peak values of 4877 and 627 IU/ml, respectively. No statistically significant correlation was observed between childhood asthma and HLA class I antigens, however, a statistically significant correlation was observed between serum IgE levels and asthma, which was elevated in cases, as compared to normal population. Serum IgE levels did not show a linear trend, in that a direct correlation with the severity of disease was not observed.

Trichophyton rubrum onychomycosis in an 8-week-old infant.

An 8-week-old infant presented with 7 weeks history of nail involvement and discoloration. Lesions started over the middle fingernail of right hand at 1 week of age, spreading over to other nails within 2 weeks. Only two nails of the feet were spared. On KOH examination, fungal hyphae were seen and culture showed growth of Trichophyton rubrum. The purpose is to report the earliest case of onychomycosis having multiple nail involvement of fingers and toes (18 nails).

Proliferating cell nuclear antigen, p53 and micro vessel density: Grade II vs. Grade III astrocytoma.

Histological classification and grading are prime procedures in the management of patients with astrocytoma, providing vital data for therapeutic decision making and prognostication. However, it has limitations in assessing biological tumor behavior. This can be overcome by using newer immunohistochemical techniques. This study was carried out to compare proliferative indices using proliferating cell nuclear antigen (PCNA), extent of p53 expression and micro vessel morphometric parameters in patients with low grade and anaplastic astrocytoma. Twenty-five patients, each of grade II and grade III astrocytoma were evaluated using monoclonal antibodies to PCNA, p53 protein and factor VIII related antigen. PCNA, p53-labeling indices were calculated along with micro vessel morphometric analysis using Biovis Image plus Software. Patients with grade III astrocytoma had higher PCNA and p53 labeling indices as compared with grade II astrocytoma (29.14 plus/minus 9.87% vs. 16.84 plus/minus 6.57%, p 0.001; 18.18 plus/minus 6.14% vs. 6.14 plus/minus 7.23%, p 0.001, respectively). Micro vessel percentage area of patients with grade III astrocytoma was also (4.26 plus/minus 3.70 vs. 1.05 plus/minus 0.56, p 0.001), higher along with other micro vessel morphometric parameters. Discordance between histology and one or more IHC parameters was seen in 5/25 (20%) of patients with grade III astrocytoma and 9/25 (36%) of patients with grade II disease. PCNA and p53 labeling indices were positively correlated with Pearson's correlation, p less than 0.001 for both). Increased proliferative fraction, genetic alterations and neovascularization mark biological aggressiveness in astrocytoma. Immunohistochemical evaluation scores over meet the challenge of accurate prognostication of this potentially fatal malignancy.

Implications of contrast-enhanced CT-based and MRI-based target volume delineations in radiotherapy treatment planning for brain tumors.

Delineation of various target volumes using contrast-enhanced magnetic resonance imaging (MRI) and/or computed tomography (CT) constitutes the primary step for radiation therapy planning (RTP) in brain tumors. This study presents a quantification and comparative evaluation of the various clinical target volumes (CTV) and gross target volumes (GTV) as outlined by contrast-enhanced CT and MRI, along with its implications for postoperative radiotherapy of brain tumors. Twenty-one patients of gliomas were considered for this prospective study. Peritumoral edema as CTV and residual tumor as GTV were delineated separately in postoperative contrast-enhanced CT and MRI. These volumes were estimated separately and their congruence studied for contrast-enhanced CT and MRI. Compared to MRI, CT underestimated the volumes, with significant differences seen in the mean CTV (mean +/- SD: -62.92 +/- 93.99 cc; P = 0.006) and GTV (mean +/- SD: -21.08 +/- 36.04 cc; P = 0.014). These differences were found to be significant for high-grade gliomas (CTV: P = 0.045; GTV: P = 0.044), while they were statistically insignificant for low-grade gliomas (CTV: P = 0.080; GTV: P = 0.117). The mean differences in the volumes for CTV and GTV were estimated to be -106.7% and -62.6%, respectively, taking the CT volumes as the baseline. Thus, even though, electron density information from CT is essential for RTP, target delineation during postoperative radiotherapy of brain tumors, especially for high-grade tumors, should be based on MRI so as to avoid inadvertent geographical misses, especially in the regions of peritumoral edema.

Imaging features of central nervous system fungal infections.

Fungal infections of the central nervous system (CNS) are rare in the general population and are invariably secondary to primary focus elsewhere, usually in the lung or intestine. Except for people with longstanding diabetes, they are most frequently encountered in immunocompromised patients such as those with acquired immunodeficiency syndrome or after organ transplantation. Due to the lack of inflammatory response, neuroradiological findings are often nonspecific and are frequently mistaken for tuberculous meningitis, pyogenic abscess or brain tumor. Intracranial fungal infections are being identified more frequently due to the increased incidence of AIDS patients, better radiological investigations, more sensitive microbiological techniques and better critical care of moribund patients. Although almost any fungus may cause encephalitis, cryptococcal meningoencephalitis is most frequently seen, followed by aspergillosis and candidiasis. The biology, epidemiology and imaging features of the common fungal infections of the CNS will be reviewed. The radiographic appearance alone is often not specific, but the combination of the appropriate clinical setting along with computed tomography or magnetic resonance may help to suggest the correct diagnosis.

Epilepsy with focal cerebral calcification: role of magnetization transfer MR imaging.

BACKGROUND: Some patients with focal cerebral calcification (FCC) have no seizure or a benign course of epilepsy, whilst others with a similar lesion have uncontrolled epilepsy. AIMS: To look for perilesional hyperintensity, presumed to be indicative of gliosis, around FCC on magnetization transfer (MT) MRI and to correlate seizure outcome with its presence. SETTING AND DESIGN: Case control study. MATERIAL AND METHODS: Fifty-one patients with epilepsy and 30 controls with single calcified cerebral lesion on CT were studied. Clinical and treatment details were noted. EEG and T1, T2, MT and contrast enhanced MRI were done. STATISTICAL ANALYSIS USED: Student's t test. RESULTS: On MT MRI, perilesional gliosis was seen around the focal calcified lesion in 17 (33.3%) patients. None of the controls had perilesional gliosis. The mean monthly seizure frequency was significantly higher in the 17 patients having perilesional gliosis (2.63+1.15) as compared to the 34 patients without it (0.59+0.63; P= 0.0014). Perilesional gliosis was seen in 8 out of 11 (72.7%) patients who were on 2 AEDs and in all 5 (100%) patients who were on 3 or more AEDs. It was present only in 4 (11.4%) out of 35 patients who were on one AED. CONCLUSION: Gliosis around a cerebral calcified lesion as seen on T1 weighted MT MRI indicates poor seizure control.

Neurocysticercosis in clinically suspected and MRI proven cases: evidence of sub-optimal antibody response.

Neurocysticercosis (NCC) has a worldwide distribution mainly in the developing countries like India. The study was done to find the seroprevalence of anti-cysticercus antibodies in clinically suspected and MRI proven cases and to corroborate the serological findings with radiological findings (MRI). A hospital based study among 204 suspected patients during January, 1996 to August, 2001 showed that 77 (32.2%, M:F = 2.2:1) had serological evidence of NCC. Of the total 189 sera, tested at 1:100 dilution 68 (35.9%) and of the total 50 CSF, tested at 1:5 dilution 9 (18%) were positive for anti-cysticercus IgG antibodies. In 35 cases where both were tested 13 sera (37.1%), 9 CSF (25.7%) and in 7 (20%) both sera and CSF were positive. In CSF from 62 patients with tubercular meningitis (disease control) 2 (3.2%) samples whereas in sera of 60 normal blood donors (normal control) 7 (11.7%) samples had anti-cysticercus IgG antibodies. In 33 MRI-positive cases, anti-cysticercus antibodies were seen in 15 (45.4%) patients. Antibodies were seen in 6 of 14 (42.8%) cases with single cortical cyst, 4 of 11 (36.3%) with 2-3 cysts and in 5 of 8 (62.5%) with multiple cysts. Alternatively, 18 of 33 (54.5%) MRI positive cases lacked anti-cysticercus antibodies. Six MRI negative cases were found to be seropositive and were treated successfully. Hence, immune response was sub-optimal even in MRI positive cases and conversely, few MRI negative cases were seropositive. Since positive response with MRI or serology depends on the stage of the disease, therefore both tests should be done together to confirm or to rule out NCC.

An evaluation of salmeterol in the treatment of chronic obstructive pulmonary diseases.

BACKGROUND: Salmeterol has been shown a useful drug for the treatment of chronic obstructive pulmonary disease (COPD). However, its positioning in the current treatment of COPD remains to be defined. The present study was carried out to evaluate its role as an add-on drug to the current first-line drug, ipratropium. METHODS: A double-blind randomized, parallel group, placebo-controlled design was used in an outpatient setting. Thirty-three patients with moderate or severe COPD were included. After a run-in period of two weeks on 40 microg four-times-daily ipratropium and 400 microg twice-daily beclomethasone dipropionate, they were randomized into two groups to receive either salmeterol (50 microg twice daily) or placebo for eight weeks. The outcome parameters were: (i) spirometry, (ii) six-minute walking test, (iii) SF-36 health-related quality of life (HRQoL) questionnaire score, (iv) baseline dyspnoea index (BDI), (v) patient's self-assessment and (vi) supplemental use of salbutamol. RESULTS: The mean FEV1 and FVC increased significantly over the initial values in the salmeterol group but not in the placebo group. Salmeterol produced greater improvements in almost all the dimensions of HRQoL as well as in the BDI and the supplemental use of salbutamol was lower in this group. However, the six-minute walk distance was similar in the two groups. CONCLUSIONS: The present study shows that eight weeks treatment with salmeterol 50 microg twice-daily added to the existing regimen of ipratropium bromide and beclomethasone dipropionate provides greater symptomatic relief and improvement in lung function than placebo. This is accompanied by an improvement in the health-related quality of life.