The effect of hyperthermia on the repair of radiation damage in plateau phase cells.

Hyperthermia (41 degrees C for 1 hr.) completely inhibited both sublethal and potentially lethal radiation damage repair by plateau phase cells taken from V79 Chinese hamsters. This suggests that there may be disadvantages in combining x-ray and heat therapies for the treatment of tumors.     

Loss of expression of death-inducing signaling complex (DISC) components in lung cancer cell lines and the influence of MYC amplification

We have previously reported that the key apoptosis related gene caspase 8 (CASP8) is frequently silenced in small cell lung cancer (SCLC) tumors and cell lines usually, but not always, by aberrant promoter methylation. Because CASP8 is a key component of the death-inducing signaling complex (DISC) when specific death receptors (including DR4, DR5, FAS) are activated by their specific ligands (TRAIL/FASL), we examined expression of the components of the DISC complex in lung cancer cell lines. MYC family members are frequently amplified (MYC+ve) in SCLC, and MYC is a potent inducer of apoptosis. We examined 34 SCLC lines (12 of which were MYC+ve) and 22 NSCLC lines. CASP8 gene expression was frequently lost (79%) at message and protein levels in SCLC but not in non-SCLC (NSCLC). MYC amplification was present in 45% of SCLC cell lines, which had lost CASP8 expression, but not in any of the CASP8 positive lines. The frequency of CASP8 loss was significantly higher in MYC+ve SCLC compared to MYC-ve SCLC or in NSCLC. Analyses of other DISC components showed significantly higher rates of loss of expression of CASP10, DR5, FAS and FASL in SCLC compared to NSCLC. The loss of expression of proapoptotic DISC components was significantly higher in MYC+ve SCLC cell lines and these lines were completely resistant to TRAIL. Expression of CASP10 (a caspase closely related to CASP8) was frequently absent at the protein level in both SCLC and NSCLC lines. Expression of c-FLIP (proteolytically inactive homolog of CASP8) was inversely related to expression of CASP8. Our major conclusions are: (a) The death receptor pathway is differently inactivated at multiple levels in lung cancer cell lines; and (b) MYC amplification in SCLC is associated with inactivation of most components of the DISC complex, with resistance to TRAIL and with expression of c-FLIP. These findings may have considerable clinical and therapeutic implications.     

Differential inactivation of caspase-8 in lung cancers

Caspase-8 (CASP8) is an apoptosis inducing cysteine protease which is activated through the formation of a death-inducing signaling complex when death receptors are complexed to their specific ligands. Recent reports indicate that CASP8 expression is lost via a combination of promoter methylation and allelic loss in subset of neuroblastomas. We investigated the state of the gene in lung tumors and cell lines. RT-PCR studies indicated that gene expression was lost in most (27 of 34, 79%) of small cell lung carcinoma (SCLC) cell lines, but expression was retained in all 22 non-SCLC (NSCLC) lines tested. Loss of gene expression at the RNA level was associated with absent protein expression by Western blotting and lack of CASP8 enzymatic activity. Methylation of the promoter region of the CASP8 gene was present in 16 of 27 (59%) of the SCLC lines lacking gene expression. All methylated cell lines lacked the presence of an unmethylated allele indicating biallelic methylation or loss of non-methylated allele. Promoter methylation was absent in all SCLC and NSCLC cell lines retaining gene expression, and all of these lines had the unmethylated form of the gene. One non-expressing SCLC cell line, NCI-H82, had a homozygous deletion at 2q33 encompassing the chromosomal location of the CASP8 gene. The mechanism of gene inactivation in the remaining 10 of 27 (37%) non-expressing SCLC cell lines is unknown. Using five polymorphic markers for 2q33 a high frequency of allelic loss was present in SCLC lines. Analyses of fresh tumors showed that 15 of 43 (35%) of the SCLC, seven of 40 (18%) of bronchial carcinoids and none of 44 NSCLC tumors had CASP8 promoter methylation. Because only approximately 60% of SCLC cell lines lacking CASP8 expression were methylated, extrapolating from the cell line data, we estimate that approximately 58% of SCLC and 30% of bronchial carcinoids lack CASP8 expression. Thus, CASP8 expression is absent in a subset of both high grade (SCLC) and low grade (carcinoid) neuroendocrine lung tumors but not in NSCLC, which usually lack neuroendocrine features. CASP8 may function as a tumor suppressor gene in neuroendocrine lung tumors.     

Asymmetric pigment dispersion in a patient with the unilateral Adie pupil

PURPOSE: Pigmentary glaucoma is a bilateral disorder. When it occurs asymmetrically or unilaterally, a cause should be sought because it may help us to understand the pathophysiology of this condition better. We describe a patient with unilateral pigmentary glaucoma and the Adie pupil in the same eye and discuss the possible role of the Adie pupil in the development of the pigmentary glaucoma. METHODS: A case report. A 37-year-old woman presented with asymmetric pigment dispersion resulting in pigmentary glaucoma in the right eye and an unilateral Adie pupil in the same eye. RESULTS: We believe that the dilated Adie pupil in the right eye might have resulted in a decreased amount of relative pupillary block. This, then, might have led to an increased contact between the posterior iris and the zonules, resulting in greater pigment dispersion and trabecular obstruction in the right eye. CONCLUSION: It has been proposed that the pigment is liberated from the iris pigment epithelium because of the mechanical rubbing of the posterior iris against the anterior zonular packets. Our case supports this proposed mechanism of pigment release.     

Pupil block glaucoma in phakic and pseudophakic patients after vitrectomy with silicone oil injection

PURPOSE: To describe pupil block glaucoma in phakic and pseudophakic patients after vitrectomy with silicone oil injection. DESIGN: Interventional case series. METHODS: Cases were collected from January 1997 to July 2000 from three tertiary referral centers. RESULTS: Seven phakic patients (seven eyes) and one pseudophakic patient (one eye) presented 1 to 90 days after vitrectomy and silicone oil injection with intraocular pressures of 36 to 70 mm Hg. Five patients had an observed or potential weakness of the iris-lens diaphragm. Treatment with Nd:YAG-laser peripheral iridotomy or inferior iridectomy provided a temporary reduction in intraocular pressure for some patients, but all eventually required removal of silicone oil. CONCLUSION: Pupil block glaucoma after silicone oil injection is well recognized in aphakic patients, but ophthalmologists should be aware that it can occur in phakic and pseudophakic patients, particularly in complicated cases and patients with a weakness of the iris-lens diaphragm.     

Efficacy of naturopathy and yoga in bronchial asthma--a self controlled matched scientific study

Asthma is one of the common psychosomatic illness influenced by many factors. Bronchodilators give temporary relief and have side effects. The present study is aimed at finding the efficacy of a non-pharmacological approach of naturopathy and Yoga in bronchial asthma. A total no of 37 patients (19 men, 18 women) with mean age 35.06 yrs (men), 40.74 yrs (women) admitted to INYS, Bangalore, for the period of 21 days. The treatment included 1. Diet therapy 2. Nature cure treatment and 3. Yoga therapy. The various parameters including lung function test were measured on admission and once a week. Results showed the significant improvement in PEFR, VC, FVC, FEV1, FEV/FEC %, MVV, ESR and absolute eosinophil count. The patients reported a feeling of well being, freshness and comfortable breathing. Naturopathy and yoga helps in inducing positive health, alleviating the symptoms of disease by acting at physical and mental levels.     

Traumatic distal anterior cerebral artery aneurysm in a child: a case report

Traumatic intracranial aneurysms constitute less than 1% of all intracranial aneurysms. A case of traumatic distal anterior cerebral artery aneurysm in 18 months old child, treated successfully by microsurgical excision of aneurysm is being reported, along with review of the literature.     

Pleurx tunneled catheter in the management of malignant ascites

The authors report their experience with the Pleurx tunneled catheter in patients with end-stage abdominal carcinomatosis and intractable ascites. Ten patients with intractable ascites and abdominal carcinomatosis underwent placement of tunneled Pleurx catheters. The catheters were placed with combined US and fluoroscopic guidance. Patients' charts were reviewed for procedural complications, serum albumin levels, infection, efficacy of catheters in providing effective drainage of ascites, and duration of catheter patency. There were no procedural complications. The serum albumin level decreased from 2.7 g/L to 2.3 at 3 weeks and 2.4 g/L at 6 weeks. There were no catheter infections. Some patients required continuous drainage, whereas others were successfully treated by drainage once per week. Mean catheter survival was 70 days. In patients with end-stage abdominal carcinomatosis complicated by malignant ascites, the Pleurx tunneled catheter can provide effective palliation and alleviated the need for repeated percutaneous paracentesis.     

A validated RP-HPLC method for the determination of mosapride citrate in bulk drug samples and pharmaceutical formulations

Mosapride citrate, a selective serotonin 5-HT4 agonist, is a novel and potent gastroprokinetic drug. So far no assay procedure has been reported for the estimation of this drug either in bulk drug samples, pharmaceutical formulations or in biological samples. A rapid and sensitive high-performance liquid chromatographic method was developed for the estimation of mosapride citrate in bulk drug samples and pharmaceutical dosage forms. Risperidone was used as an internal standard (ISD). A HPLC system consisting of gradient pump, reverse phase C-18 analytical column, a variable UV-visible detector set at 274 nm and an integrator was used. The mobile phase consisted of acetonitrile: 0.02 M potassium dihydrogen phosphate buffer (pH adjusted to 4.0 with o-phosphoric acid) in the ratio of 50:50 (v/v), and was pumped at 1 ml/min at 40 degrees C. The drug and ISD were eluted at 8.10 and 2.27 min, respectively. The peak drug/ISD area ratio versus drug concentration relationship was linear (r = 0.9998). The method was validated for its linearity, precision and accuracy. The calibration curve was linear in the range of 0.5 to 30 micrograms/ml. The lower detection limit was found to be 0.23 microgram/ml. The intra- and inter-day variation was found to be less than 1% showing high precision of the assay method. The mean recovery of the drug from the solutions containing 2, 4 or 10 micrograms/ml was 101.55 +/- 0.97% indicating high accuracy of the proposed HPLC method.     

Red Cell Distribution Width in the Diagnosis of Iron Deficiency Anemia

Objective: 1. To compare peripheral smear (PS) and Red cell distribution width (RDW) in diagnosis of Iron deficiency anemia (IDA) in various grades. 2. To study the changes in RDW and PS after therapy.Methods : Children in the age group of six months to five years with microcytic (MCV < 80fl) anemia (Hemoglobin < 11g%) were evaluated. Those who had received blood transfusion and /or were already on iron therapy were excluded. Evaluation included clinical examination, complete blood count (CBC), RDW estimation microscopic examination of peripheral smear, measurement of serum iron and transferrin saturation. Children with IDA were treated with oral iron for 8 weeks and PS, CBC including RDW were repeated.Result: Of the 100 children evaluated, 89 had IDA. 48% had mild, 42% had moderate and 10% had severe anemia. Transferrin saturation correlated with severity of anemia. Peripheral smear showed microcytosis and hypochromia in all cases with severe anemia, 61.5% and 22.5% of those with moderate and mild anemia respectively. RDW was suggestive of iron deficiency in 100%, 82.05% and 100% of patient with mild, moderate and severe anemia respectively.Conclusion : In the diagnosis of mild and moderate iron deficiency anemia, RDW had a higher sensitivity than PS. Red cell morphology, Hb, PCV and RDW showed significant improvement after iron-therapy