A direct comparison of women's perceptions and acceptability of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol in the management of young postmenopausal women, under 45 years of age.

OBJECTIVE: To assess the acceptability and perception of postmenopausal women, to two different hormone replacement therapy regimens, in relation to the control of their symptoms and development of adverse effects. STUDY DESIGN: Prospectively recruited postmenopausal women, <45 years, were randomised to one of two treatment arms for 12-months: cyclical micronised progesterone or medroxyprogesterone acetate in combination with transdermal oestradiol. A self-reported questionnaire with matrix rating scales was completed and repeated after 3, 6 and 12-months. MAIN OUTCOME MEASURES: Symptom control and development of adverse effects. RESULTS: Seventy-one individuals were screened, with baseline data available for 67 subjects. A total of 190 questionnaires were returned. The most commonly reported symptoms were low energy levels, vasomotor symptoms and sexual dysfunction. The prevalence of adverse effects ranged between 57.89 and 87.50%, with a reduction seen in the transdermal oestradiol + micronised progesterone arm (73.91% at 3-months, decreasing to 57.89% at 12-months; p = 0.33), compared to the transdermal oestradiol + medroxyprogesterone acetate arm (76.92% at 3-months, increasing to 87.50% at 12-months; p = 0.69). The main reported adverse effects were bloating, weight change and psychological symptoms. A significant difference was documented between the groups after set intervals, with a greater proportion reporting breast tenderness after 3-months (p = 0.01), lower numbers reporting mood swings at 6-months (p = 0.01) and irritability at 12-months (p = 0.03) in the transdermal oestradiol + micronised progesterone arm compared to the transdermal oestradiol + medroxyprogesterone acetate arm. CONCLUSIONS: The acceptability of both regimens was high despite adverse effects, but tolerability of transdermal oestradiol combined with micronised progesterone appeared to be better with fewer women reporting psychological concerns.

Anorectal malformations: Role of MRI in preoperative evaluation.

PURPOSE: To evaluate the spectrum of magnetic resonance imaging (MRI) findings in pediatric patients with anorectal malformation (ARM) and compare the accuracy of MRI and distal cologram (DC) findings using surgery as reference standard. MATERIALS AND METHODS: Thirty pediatric patients of age less than 14 years (19 boys and 11 girls) with ARM underwent preoperative MRI. MRI images were evaluated for the level of rectal pouch in relation to the pelvic floor, fistula, and development of sphincter muscle complex (SMC). Associated spinal and other anomalies in lumbar region and pelvis were also evaluated. DC was done in 26 patients who underwent colostomy. Ultrasound of abdomen and pelvis was also done for associated anomalies. RESULTS: Overall accuracy of MRI and DC to detect the exact level of rectal pouch including cloacal malformation was 93.33% and 76.9% respectively. MRI and DC could correctly identify presence or absence of fistula in 76.6% and 76.9% cases respectively. MRI and DC correctly identified the anatomy of fistula in 76% and 65% cases respectively. On MRI, correlation of development of levator ani and puborectalis with the level of rectal pouch as found on surgery was significant (P = 0.008; 0.024 respectively). Subjective assessment of sphincter muscle development on MRI correlated well with the surgical assessment [P = 0.019 and 0.016 for puborectalis and external anal sphincter (EAS) respectively]. Lumbosacral spine anomalies were present in 33.3% of patients and were most common in high type of ARM. Vesicoureteric reflux and renal agenesis were the most common renal and urinary tract anomalies and were present in 40% of cases. CONCLUSION: MRI allows reliable preoperative evaluation of ARM and should be considered as a complementary imaging modality for preoperative imaging in ARM.

Myeloid translocation genes differentially regulate colorectal cancer programs.

Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1-/- mice have progressive depletion of all intestinal secretory cells, and Mtg16-/- mice have a decrease in goblet cells. Furthermore, both Mtgr1-/- and Mtg16-/- mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc1638/+-dependent intestinal tumorigenesis. Mtgr1-/- mice, but not Mtg16-/- mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of chromatin immunoprecipitation sequencing data sets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1-/- tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context-dependent effect on intestinal tumorigenesis.

Evaluation and Validation of Neo-Adjuvant Response Index (NRI) and It's Correlation with Various Predictive Biomarkers and RECIST in Locally Advanced Breast Cancer.

BACKGROUND: Response evaluation following neo-adjuvant chemotherapy in breast cancer is usually done without taking in to account the axillary response and the available tools like 'response evaluation criteria in solid tumors' (RECIST) have this limitation. These criteria rely solely on the response observed in the primary tumour. Neoadjuvant response index is one such attempt to have a comprehensive assessment of response both in the primary tumour and the axilla. METHODS: 30 cases of locally advanced breast cancer (LABC) were assessed for response using 'Neo-adjuvant Response Index'. The index always gives score between '0' (no response or progressive disease) and '1' (pathological complete response i.e. no invasive tumor in breast as well as axilla). This index includes axillary response as well and provides a spectrum of response rather than dividing patients into simply responders and non-responders . RESULTS: Mean reading of index was found to be 0.2925 in this study. Three patients achieved an index of 1. This index correlates significantly with the existing scales for assessing response. Hormone negative tumors were found to be more chemo responsive with higher rates of pathological complete response (pCR) while ER/PR + Her2- tumors showed a very poor response to NACT. CONCLUSIONS: Based on the observations of the present study it may be submitted that Neoadjuvant Response Index (NRI) is a reliable and simple tool that can serve as a comprehensive and accurate method of assessing response to neo-adjuvant chemotherapy as it takes in to consideration both the tumor and axillary response unlike the existing RECIST, binary system (responders are those with greater than 50 % reduction), RCB method and the available biomarkers. This study being first of it's kind in Indian population, in spite of it's limitations, could prove to be a launching ground for further reasearch and contribute substantially to the evidence base.

Computed tomography in chronic suppurative otitis media: value in surgical planning.

The present study was conducted prospectively to evaluate how accurately high resolution computed tomography scanning could define the extent and severity of the underlying disease in patients with chronic suppurative ear disease, thus, helping convert a surgical exploration into a planned procedure. Sixty adult consecutive cases of chronic suppurative otitis media underwent a detailed high resolution computed tomography by a single radiologist. The recorded radiological findings in various heads were then compared to the surgical findings during mastoid exploration of these patients by a single otologist and the two statistically compared. The presence and distribution of soft tissue in the middle ear cleft and mastoid could confidently be predicted using this modality. The malleus, body and short process of incus were well visualized, but not the long process of incus and the stapes suprastructure. Lateral semicircular canal fistulae could be demonstrated with an acceptable degree of accuracy. It was possible to detect facial nerve dehiscence and defects in tegmen tympani in significant number of cases although, statistical values were low for these structures. High resolution scanning is a modality which can accurately image the pathological anatomy in unsafe chronic suppurative otitis media. Otologists should use it more often, especially in complicated cases as an adjunct to better preoperative assessment, and thus, the surgical outcome. Its accuracy is likely to improve with larger studies and better experience, wherein its routine use may become justifiable.

Functional variants of IL4 and IL6 genes and risk of tobacco-related oral carcinoma in high-risk Asian Indians.

BACKGROUND: Tobacco-related oral squamous cell carcinoma (OSCC) is one of the most common cancers involving Indian males. We assessed the association of IL4 promoter -589 T>C, -33 T>C, and IL6-174 G>C functional genetic polymorphisms with tobacco-related OSCC in Asian Indians. PATIENTS AND METHODS: The IL4 and IL6 promoter polymorphisms were assessed in 140 patients with OSCC and 120 normal subjects by PCR-RFLP technique, and significance of the data was determined using chi-square test. RESULTS: The frequency of TC, CC genotype, and C allele at IL4 promoter sites -589 and -33 were higher in patients when compared with controls. Consequently, TC/CC genotypes and C allele at both sites appeared as susceptible. However, IL6-174 G>C single-nucleotide polymorphisms (SNP) appeared to be protective in patients with OSCC. Of eight haplotypes, five were associated with two- to seven-fold increased risk of tobacco-related OSCC. These SNPs further showed heterogeneity among different ethnic population, but their distribution in Asian Indians stand closer to other Asian populations. CONCLUSIONS: In this study, IL4-589 CC, -33 CC genotype, and *C allele at both sites appeared to be susceptible, while IL6-174 CC genotype and *C allele appeared to be protective in patients with OSCC; hence, these SNPs may be a potential prognostic markers for tobacco-related OSCC in Asian Indians.

Claudin-2 expression increases tumorigenicity of colon cancer cells: role of epidermal growth factor receptor activation.

Claudin-2 is a unique member of the claudin family of transmembrane proteins, as its expression is restricted to the leaky epithelium in vivo and correlates with epithelial leakiness in vitro. However, recent evidence suggests potential functions of claudin-2 that are relevant to neoplastic transformation and growth. In accordance, here we report, on the basis of analysis of mRNA and protein expression using a total of 309 patient samples that claudin-2 expression is significantly increased in colorectal cancer and correlates with cancer progression. We also report similar increases in claudin-2 expression in inflammatory bowel disease-associated colorectal cancer. Most importantly, we demonstrate that the increased claudin-2 expression in colorectal cancer is causally associated with tumor growth as forced claudin-2 expression in colon cancer cells that do not express claudin-2 resulted in significant increases in cell proliferation, anchorage-independent growth and tumor growth in vivo. We further show that the colonic microenvironment regulates claudin-2 expression in a manner dependent on signaling through the EGF receptor (EGFR), a key regulator of colon tumorigenesis. In addition, claudin-2 expression is specifically decreased in the colon of waved-2 mice, naturally deficient in EGFR activation. Furthermore, genetic silencing of claudin-2 expression in Caco-2, a colon cancer cell line, prevents the EGF-induced increase in cell proliferation. Taken together, these results uncover a novel role for claudin-2 in promoting colon cancer, potentially via EGFR transactivation.

Clinical management of supernumerary teeth: a report of two cases.

Supernumerary tooth may closely resemble the teeth of the group to which it belongs, i.e. molars, premolars or anterior teeth, or it may bear little resemblance in size or shape to which it is associated. Many complications can be associated with supernumeraries, like impaction, delayed eruption or ectopic eruption of adjacent teeth, crowding, development of median diastema and eruption into floor of the nasal cavity. This may also cause the formation of follicular cysts with significant bone destruction. Early intervention to remove it is usually required to obtain reasonable alignment and occlusal relationship. This article will present the clinical management of an (i) impacted supernumerary tooth impeding the eruption of maxillary central incisor and (ii) erupted supernumerary tooth with midline diastema.

Natural history of solitary cerebral cysticercosis cases after albendazole therapy: a longitudinal follow-up study from India.

OBJECTIVES: To find out natural course of solitary cerebral cysticercosis (SCC) cases after treating them with 2 weeks albendazole therapy. MATERIAL AND METHODS: All patients with SCC were treated with 2 weeks of albendazole therapy with follow-up radiological scan at 6 months and 2 years. The evolution of lesion was noted as complete resolution, calcification or persistent active. Antiepileptic drugs (AED) prophylaxis was given for 1 year in patients with complete resolution and for 2 years in calcified lesion, respectively. AED was continued in persistent lesion group till it became calcified or resoluted completely. One-year follow-up was done in all after stopping AED. RESULTS: Among 345 cases, 226 (65.5%) had complete resolution with very low seizure relapse rate with 1 year of seizure free period on AED treatment. On the contrary, 105 (30.5%) had calcified lesion with high seizure relapse rate after stopping AED treatment with 2 years of seizure free period. Fourteen patients (4%) could not stop their antiepileptic medication at all because of active lesion. CONCLUSION: Two-third of patients with SCC have favorable outcome with complete resolution and needs short-term AED prophylaxis and the rest one-third requires long AED treatment to prevent seizures.

Comparison of the efficacy of clinical examination, ultrasound neck and computed tomography in detection and staging of cervical lymph node metastasis in head and neck cancers.

There are many modalities, which are being used for detection of cervical lymph nodes in head and neck cancers clinical examination, computed tomography, ultrasound, magnetic resonance imaging and radionuclide scintigraphy. Various studies in past have highlighted their benefits and drawbacks used singly or in comparison with others. Here we present the study of 100 patients comparing the result of clinical examination, computed tomography and ultrasound.

Is the routine drainage after surgery for thyroid necessary? A prospective randomized clinical study [ISRCTN63623153].

BACKGROUND: Drains are usually left after thyroid surgery to prevent formation of hematoma and seroma in the thyroid bed. This is done to reduce complications and hospital stay. Objective evaluation of the amount collected in the thyroid bed by ultrasonography (USG) can help in assessing the role of drains. METHODS: A randomized prospective control study was conducted on 94 patients undergoing 102 thyroid surgeries, over a period of fifteen months. Patients included in the study were randomly allocated to drain and non-drain group on the basis of computer generated random number table. The surgeon was informed of the group just before the closure of the wound Postoperatively USG neck was done on first and seventh postoperative day by the same ultrasonologist each time. Any swelling, change in voice, tetany and tingling sensation were also recorded. The data was analyzed using two-sample t-test for calculating unequal variance. RESULTS: Both groups were evenly balanced according to age, sex, and size of tumor, type of procedure performed and histopathological diagnosis. There was no significant difference in collection of thyroid bed assessed by USG on D1 & D7 in the two groups (p = 0.313) but the hospital stay was significantly reduced in the non-drain group (p = 0.007). One patient in the drain group required needle aspiration for collection in thyroid bed. No patient in either group required re-operation for bleeding or haematoma. CONCLUSION: Routine drainage of thyroid bed following thyroid surgery may not be necessary. Not draining the wound results in lesser morbidity and decreased hospital stay.

Complete nucleotide sequence analysis of a vaccine strain and a field isolate of foot-and-mouth disease virus serotype Asia1 with an insertion in VP1 genomic region.

Complete nucleotide sequences except the poly (C) tract and poly (A) tail of a vaccine strain (IND 491/97) and an atypical field isolate (IND 321/01) of Foot-and-mouth disease virus (FMDV) serotype Asia1 are described. Amino acid (aa) sequence analysis of the VP1 protein of the field isolate revealed that the latter has 212 instead of 210 or 211 aa found in the so far available sequences of other FMDV isolates of Asia1 serotype. The insertion was localized in the hypervariable region of aa 130-160 of VP1 protein. Nucleotide sequencing of the entire genome was therefore carried out to detect changes in other parts of the genome, if any, besides VP1, which could contribute to its fitness. An 8.16 kb sequence of IND 491/97 and an 8.162 kb sequence of IND 321/01 were compared with each other and also with the known sequence of IND 63/72, another vaccine strain of serotype Asia1. Comparison of the entire polyprotein coding (L to 3D) region of IND 321/01 with those of the two Asia1 vaccine strains (IND 63/72 and IND 491/97) revealed no significant differences. A similar comparison of IND 491/97 with IND 63/72 revealed variability across the entire length of the genome. In addition to the capsid-coding region, sequence variability was also observed in non-structural proteins albeit to different extent. This study shows that in the gene pool of serotype Asia1 at least three groups of isolates/strains are present with respect to the length of VP1 protein.

FNAC of papillary and solid epithelial neoplasm of pancreas--a case report.

A case of solid papillary epithelial neoplasm (PSEN) of pancreas in a young woman is reported in which the nature of tumour was recognised pre-operatively by ultrasound guided Fine needle aspiration. The pre-operative cytologic diagnosis enabled prompt and appropriate surgical treatment. FNAC revealed large cell clumps in the aspirate showing branching papillary appearance in which multiple layers of tumour cells surrounded central vascular stalks. The above was confirmed on histopathological examination of the excised tumour tissue.

Candida sepsis and association with retinopathy of prematurity.

OBJECTIVE: To assess the association of Candida sepsis with retinopathy of prematurity (ROP) in extremely low birth weight infants. METHODS: We prospectively identified 253 infants admitted to the Critical Care Nursery at Georgetown University Hospital with birth weights

Comparative tissue toxicity evaluation of four endodontic sealers.

The tissue toxicity of zinc oxide-eugenol, Tubli seal, Sealapex, and Endoflas F.S. was investigated by injecting them into the subcutaneous connective tissue of the dorsal surface of rats and studying the tissue response histologically. Animals were killed after time intervals of 48 h, 7 days, 14 days, 1 month, and 3 months; tissue sections were taken from the injection sites. Histological examination of the tissue sections revealed that all of the sealers caused some inflammation that decreased with time, except in the case of zinc oxide-eugenol where it increased from the 48th hour to the 7th day and after that showed a decreasing trend. Overall, Sealapex showed the least inflammatory reaction compared with other sealers used, because it showed moderate inflammation at 48 h that became mild in later periods. Zinc oxide-eugenol, Tubli seal, and Endoflas F.S. were severely toxic at 48 h and 7 days. This toxicity decreased gradually in later time periods. No inflammatory reaction was seen at 3 months with any of the sealers used.

Three-year experience with neonatal ventilation from a tertiary care hospital in Delhi.

Ninety neonates were ventilated over a period of 33 months of whom 50 (55.5%) survived. Fifty seven babies received IPPV while 33 CPAP. IPPV mode was being used more frequently recently and survival rates have steadily improved over past 3 years. Survival was cent per cent in babies above 1.5 kg on CPAP mode while 16/26 (57.7%) survived on IPPV mode. Of 22 extremely VLBW (< 1 kg) babies, six survived. HMD was the commonest indication of ventilation (50%), of which 53% (24/45) survived. The other important indications of ventilation were apnea in 13 and transient tachypnea in 11 babies. All babies requiring ventilation for transient tachypnea survived. Nosocomial infections were common in association with ventilation 34/90 (37.7%), out of which in 14 was responsible for about a third of deaths. Pulmonary air leaks developed in 12 babies of which 6 died. Two babies developed BPD and one ROP. Neonatal ventilation should be ventured in centres where basic facilities for level II care already exist. It may not be cost effective to ventilate extremely low birth weight neonates.

PIP: During January 1989-September 1991, in India, neonatologists prescribed assisted ventilation (intermittent positive pressure ventilation [IPPV] and continuous positive airway pressure [CPAP]) for 90 neonates born and treated at a tertiary hospital in Delhi. All neonates requiring more than 168 hours of ventilation received IPPV. The smallest surviving neonate weighed 830 g at birth and was born at 26 weeks' gestation. This neonate received 510 hours of ventilation. One neonate received 48 days of ventilation (gestational age at birth, 28 weeks; birth weight, 800 g). This neonate eventually died due to necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), and sepsis. This infant was the only infant to develop NEC. A total of two newborns developed BPD. One infant developed retinopathy of prematurity (ROP). Indications for ventilation were hyaline membrane disease (HMD) (45/90), apnea (13/90), and transient tachypnea of the newborn (TTNB) (11/90). Almost all HMD cases who weighed more than 1.5 kg at birth on CPAP survived. CPAP successfully treated all TTNB cases. Nine neonates developed pneumothorax. Three of them survived. 34 neonates developed sepsis, the most common complication. 20 sepsis cases also had underlying pneumonia. Sepsis was responsible for 35% of deaths (14/40). Five infants on IPPV developed persistent pulmonary hypertension (persistent fetal circulation). 35 infants developed infection during ventilation, 34 of whom had a nosocomial infection. The nosocomial infection rate was 37.7%. Nosocomial infection was responsible for 35% of deaths. 12 babies (13%) developed pulmonary air leaks, 50% of whom died. 25 of the 33 infants on CPAP survived. Few CPAP cases developed pulmonary air leak, BPD, and ROP. Six of 22 very low birth weight (VLBW) infants (1 kg) survived. These findings led the researchers to recommend that medical centers with basic facilities for level II care should provide neonatal ventilation. They proposed that ventilation may not be cost effective for VLBW newborns, however.