Outcomes of surgical versus non-surgical treatment of resectable T4a laryngeal and hypopharyngeal carcinoma.

OBJECTIVE: Surgery is the recommended treatment for resectable T4a laryngeal and hypopharyngeal carcinoma. Non-surgical treatment is an option in a select few patients. METHOD: This retrospective study was undertaken to assess the treatment outcomes in patients with resectable T4a carcinoma of the larynx and hypopharynx who received either surgical or non-surgical treatment at our institute and to assess factors influencing these outcomes. RESULTS: A total of 120 patients were included in the study. They were divided into groups A, B and C based on the presence of extralaryngeal spread through laryngeal membrane, cartilage or both. The overall survival was better among patients who received surgery than those who received non-surgical treatment in the three groups. The factor influencing overall survival was the treatment given in the form of surgical versus non-surgical treatment. CONCLUSION: Surgery is the preferred treatment for T4a laryngeal and hypopharyngeal carcinoma, even in patients with extralaryngeal spread without cartilage erosion.

Lane-Hamilton syndrome - Is it really a needle in a haystack?

Introduction: The association of pulmonary hemosiderosis with celiac disease (Lane-Hamilton syndrome) is extremely rare. Case Details: A five-year-old female child presented with fever, cough, breathlessness, and pallor for 20 days, without any previous history of recurrent lower respiratory tract infections, tuberculosis, or cardiac disease. There was no history of pica, chronic diarrhea, bleeding, or personal or family history of repeated blood transfusions. She had tachycardia, tachypnea, severe pallor, stunting, rickets, and bilateral fine lung crepitations. Peripheral smear and blood indices revealed dimorphic anemia. Anti-tissue transglutaminase IgA antibody levels were high (>200 U/mL) and the upper gastrointestinal endoscopy with duodenal biopsy confirmed the diagnosis of celiac disease. The child was discharged on a gluten-free diet (GFD) and oral hematinic, but her dietary compliance was poor. Interestingly, the child had persistent bilateral pulmonary infiltrates, which was initially attributed to congestive cardiac failure (CCF), which persisted even despite treatment. HRCT chest revealed interstitial thickening and bilateral alveolar shadows and bronchoalveolar lavage showed a few inflammatory cells. The child was readmitted four times with similar complaints and was given packed red cell transfusions. In the fourth admission, a lung biopsy was done, which revealed extensive pulmonary hemosiderosis. The patient was given a course of oral steroids for 6 weeks, with a gluten-free diet, following which both the anemia and the pulmonary infiltrates resolved. Conclusion: Pulmonary hemosiderosis is an important cause of anemia in cases of celiac disease and may be misdiagnosed as CCF due to severe anemia. A strict GFD, with or without corticosteroids, can reverse the clinical and radiological picture.

Inclusion body fibromatosis - A report of four cases and review of literature.

Inclusion body fibromatosis (IBF) also called the "Reye tumor" is a rare spindle cell proliferation with distinct clinicopathological features. This is a report of four cases of IBF from a single institute. Typical location, age, size of the lesion, bland histology, and paranuclear inclusions are the distinguishing features of this entity. Medical literature search reveals very few series of cases of IBF, the remaining cases being in the form of case reports. The aim of this report is to highlight the typical features of this rare entity.

Giant chondroid lipoma of breast.

Lipomas are benign tumors composed of mature fat, usually encapsulated. Vast majority of lipomas are small, weighing only a few grams, and grow slowly. Lipoma occur rarely in breast causing diagnostic dilemma. Chondroid lipoma is a rare variant of lipoma which is benign in nature. We present a case of 65 year old female patient presented with lump in right breast, underwent surgical excision and histopathology reported as chondroid lipoma.

Evolutionary dynamics of the American African genotype of dengue type 1 virus in India (1962-2005).

Dengue is a major health problem in India with all four serotypes represented. Recently there has been an increase in the occurrence of dengue-1 outbreaks. It is possible that there have been changes in the genetics of dengue virus-1 (DENV-1), either by fresh introductions or by evolution in situ. The studies on DENV-1 evolution so far have no Indian sequences included. To gain insight into the dynamics of DENV-1 in India, the envelope (E) gene of thirteen virus isolates representative of the period 1962-2005 were sequenced and analyzed together with the available sequences of 40 globally representative isolates. All the Indian DENV-1 isolates were found to belong to the American African (AMAF) genotype. With the addition of 13 Indian isolates, the AMAF genotype can now be called Cosmopolitan. The Indian isolates were distributed into four lineages, India I, II, III and the Africa lineage, now called Afro-India. Of these, India III was the oldest and extinct lineage; the Afro-India was a transient lineage while India I, imported from Singapore and India II, evolving in situ, were the circulating lineages. Despite the extinction and introduction of lineages, no specific codon site was observed to be under selection pressure. The rate of nucleotide substitution estimated for DENV-1 was 6.5 × 10(-4) substitutions/site/year, and the time to the most recent common ancestor (tMRCA) was estimated to be 78-180 years (1825-1925), similar to previous estimates. The tMRCA for the AMAF/Cosmopolitan genotype was 56-98 years (1907-1949), a period that covers World War I and II. The two imports from Africa (1953-1968) and Singapore (1964-1975) and an export to the Americas (1955-1965) prove that there have been changes in the lineage of the DENV-1 viruses circulating in India which has contributed to the global dynamics of DENV-1 evolution and perhaps to the changing epidemiology of dengue in India.

Clinical profile of chikungunya fever in patients in a tertiary care centre in Maharashtra, India.

BACKGROUND & OBJECTIVE: In India a chikungunya fever outbreak started in December 2005 when the country experienced more than 13 lakhs of chikungunya infected cases. We undertook this study to study detailed clinical profile of chikungunya fever in both indoor and outdoor patients in a tertiary care hospital in Nagpur, Maharashtra in 2006. METHODS: Suspected cases of chikungunya fever (n=405) during the period of July to September 2006, having clinical triad of fever, arthralgia and/or rashes were included in the study. Clinical profile was studied in all the cases. Of the 405 samples collected, 166 were tested for serum CHIK IgM antibodies. RESULTS: Of the 166 samples tested for CHIKV IgM antibodies, 87 (52.4%) were positive (confirmed cases). Male: female ratio was 2.3:1. Fever and arthralgia were present in all cases. Rash was present in 27 (31%) confirmed and 38 (12%) suspected cases. Lymphadenopathy was present in 12 (13.8 %) confirmed and 4 of suspected cases. Chronic polyarthritis was seen in 22 (25.3%) confirmed and 75 (23.6%) suspected cases. Neurological manifestations were observed in 08 (9%) confirmed and 10 (3.14%) suspected cases. Mortality was 7 (2.2%) in 318 suspected cases and 3 (3.4%) in 87 confirmed cases. INTERPRETATION & CONCLUSION: Our findings showed that about half of the serum samples for CHIKV IgM antibody tested positive from cases suspected to have chikungunya fever. Fever, joint pain and headache were major symptoms. Certain rare manifestations like lymphodenopathy, oral ulcers and encephalitis were also seen. Mortality in confirmed cases was about 3.4 per cent.

Clinico-epidemiological profile of cases of fever with arthritis (Chikugunya) attending Urban Health Centre, Solapur.

This communication describes the findings of a hospital and community survey conducted in the UHC catchment area of solapur city to find out clinico-epidemiological profile of cases of chikungunya fever during mid 2006. A total of 208 cases who attended UHC and 962 community members were studied. 20-44 was the mostly affected age-group and Females outnumber male hospital attendees. Major presenting features were fever, joint pain, bodyache, headache, nausea. In majority of patients, joint pain lasted for two months and subsided by 6th month. Of 21 samples tested, 19 showed IgM positivity for chikungunya.

The steady-state development of splenic dendritic cells.

Dendritic cells (DCs) are a heterogenous population of cells that can be grouped into the conventional DCs (cDCs) and plasmacytoid DCs (pDCs), or interferon-producing cells. pDCs are thought to develop in the bone marrow and migrate to the periphery as mature cells. In contrast, cDC precursors are thought to migrate to the periphery, where they further differentiate into cDCs. In the case of migratory cDCs, these precursors are thought to be monocytes, whereas resident cDCs derive from a different precursor. Recent activity on this subject has shed some light on the precursors that differentiate into resident cDCs and pDCs, but often with conflicting findings. Here, we review some of these findings and discuss some of the outstanding issues in the field.

Response of avian embryonic brain to spatially segmented x-ray microbeams.

Duck embryo was studied as a model for assessing the effects of microbeam radiation therapy (MRT) on the human infant brain. Because of the high risk of radiation-induced disruption of the developmental process in the immature brain, conventional wide-beam radiotherapy of brain tumors is seldom carried out in infants under the age of three. Other types of treatment for pediatric brain tumors are frequently ineffective. Recent findings from studies in Grenoble on the brain of suckling rats indicate that MRT could be of benefit for the treatment of early childhood tumors. In our studies, duck embryos were irradiated at 3-4 days prior to hatching. Irradiation was carried out using a single exposure of synchrotron-generated X-rays, either in the form of parallel microplanar beams (microbeams), or as non-segmented broad beam. The individual microplanar beams had a width of 27 microm and height of 11 mm, and a center-to-center spacing of 100 microm. Doses to the exposed areas of embryo brain were 40, 80, 160 and 450 Gy (in-slice dose) for the microbeam, and 6, 12 and 18 Gy for the broad beam. The biological end point employed in the study was ataxia. This neurological symptom of radiation damage to the brain developed within 75 days of hatching. Histopathological analysis of brain tissue did not reveal any radiation induced lesions for microbeam doses of 40-160 Gy (in-slice), although some incidences of ataxia were observed in that dose group. However, severe brain lesions did occur in animals in the 450 Gy microbeam dose groups, and mild lesions in the 18 Gy broad beam dose group. These results indicate that embryonic duck brain has an appreciably higher tolerance to the microbeam modality, as compared to the broad beam modality. When the microbeam dose was normalized to the full volume of the irradiated tissue. i.e., the dose averaged over microbeams and the space between the microbeams, brain tolerance was estimated to be about three times higher to microbeam irradiation as compared with broad beam irradiation.

Evaluation of truncated areas in the assessment of bioequivalence of immediate release formulations of drugs with long half-lives and of Cmax with different dissolution rates.

PURPOSE: To Evaluate truncated AUC in place of AUCt or extrapolated AUCinf, for drugs with long half-lives and to study the relationship between Cmax and in vitro dissolution rates. METHODS: Monte-Carlo simulations were conducted using actual mean plasma concentrations of five long half-life drug products. The simulations were based on a catenary pharmacokinetic system in which the drug disposition in the body was represented by a one-or two-compartment model, characterizing the observed mean profiles. The influence of dramatic changes in the in vitro dissolution rate constant 'kd', was simulated in scenarios consisting of 20 crossover trials with 24 subjects per trial, comparing a fast dissolving reference and a hypothetical, slow dissolving test formulation. RESULTS: The AUC's truncated after the completion of distribution phase were found surrogate to the AUCt or AUCinf measures. Except for Phenylbutazone, the Cmax measure was insensitive to the changes in the in vitro dissolution rate. The Cmax measure was found to be useful in the bioequivalence assessment since it reflected both the rate and extent of absorption. (Cmax/AUCt) measure was specific to absorption rate. CONCLUSIONS: For the bioequivalence determination of long half-life drug products, (1) the use of truncated AUC's after completion of the distribution phase instead of AUCinf, appears feasible. (2) Cmax measure may be insensitive to input rate changes, if the absorption rate is not constrained by the input rate in relation to the distribution or elimination rate. (3) (Cmax/AUCt) may be more specific to 'ka' differences, but Cmax reflects differences in both rate and extent of absorption.

In vitro dissolution profile comparison--statistics and analysis of the similarity factor, f2.

PURPOSE: To describe the properties of the similarity factor (f2) as a measure for assessing the similarity of two dissolution profiles. Discuss the statistical properties of the estimate based on sample means. METHODS: The f2 metrics and the decision rule is evaluated using examples of dissolution profiles. The confidence interval is calculated using bootstrapping method. The bias of the estimate using sample mean dissolution is evaluated. RESULTS: 1. f2 values were found to be sensitive to number of sample points, after the dissolution plateau has been reached. 2. The statistical evaluation of f2 could be made using 90% confidence interval approach. 3. The statistical distribution of f2 metrics could be simulated using 'Bootstrap' method. A relatively robust distribution could be obtained after more than 500 'Bootstraps'. 4. A statistical 'bias correction' was found to reduce the bias. CONCLUSIONS: The similarity factor f2 is a simple measure for the comparison of two dissolution profiles. But the commonly used similarity factor estimate f2 is a biased and conservative estimate of f2. The bootstrap approach is a useful tool to simulate the confidence interval.

In vitro dissolution profile comparison and IVIVR. Carbamazepine case.

Dissolution data for the immediate or modified release drug products are usually collected as percent dissolved at multiple time points. Once an in-vitro/in-vivo relationship is established on a drug product, the dissolution profile becomes meaningful and important. In that context, if a firm desires to modify its formulation on which the in-vitro/in-vivo association has been established, a meaningful insight into the pharmacokinetics may be obtained by comparing the dissolution profiles of the two lots. In this presentation, we demonstrated a model dependent dissolution profile comparison approach using example of carbamazepine tablet dissolution data. Once a mathematical function was selected to describe the dissolution data coming from various standard lots, a similarity region could be constructed using the model parameter variances. To compare the test and reference lot dissolution profiles, a statistical distance was calculated between the mean parameters. A confidence region generated around the normalized mean statistical distance could then be compared with the similarity region to assess the similarity or dissimilarity of the dissolution profiles.