Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis.

Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti-programmed cell death 1 (PD-1) pembrolizumab has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin-domain containing-3 (Tim-3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim-3 and PD-1 on subsets of peripheral blood NK (CD56dim/neg CD16bright/dim/neg and CD56bright CD16dim/neg ) and T cells. The percentages of these cells were increased in women with cervical cancer and pre-malignant lesions. PD-1+ NK and T cells were likely to co-express TIGIT and/or Tim-3. These cells, with an apparently 'exhausted' phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)- and DNAX accessory molecule 1 (DNAM-1)-positive. PD-1int and PD-1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD-L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD-L1 and PD-1+ T cells in women with low-grade lesions. Within the cancer group, there were no significant correlations between sPD-L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD-L1 and total T cells and a correlation between sPD-L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre-cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies.

Association of Hypertension with Serum Estrogen Level in Postmenopausal Women.

Hypertension is a chronic and debilitating disease. Its complications give rise to cardiovascular diseases, stroke in Postmenopausal women. Estrogen deficiency that develops during menopause is likely the etiological factor for development of hypertension in postmenopausal women. Increased incidence of cardiovascular diseases in postmenopausal women may be due to hypertension caused by lower level of estrogen hormone. The study was carried out to observe the association of hypertension with serum estrogen level in postmenopausal women. This cross sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka, during the period of January 2011 to December 2011. A total number of 90 female subjects were selected from different areas of Dhaka city. Among them, 60 postmenopausal women with age ranging from 50 to 60 years were taken as study group and 30 apparently healthy premenopausal women with age ranging from 20 to 30 years were included as control group for comparison. Systolic blood pressure and diastolic blood pressure were recorded in both groups. Serum estrogen level was estimated in order to assess the hormonal level of both groups. Data was analyzed by Unpaired Student's 't' test and Pearson's co-efficient (r) test as applicable. The value of systolic blood pressure was higher in postmenopausal women than those of premenopausal women and result was statistically significant. The level of diastolic blood pressure was also significantly (p<0.001) higher in postmenopausal women in comparison to those of premenopausal women. In postmenopausal women serum estrogen level was lower than premenopausal women and serum estrogen level showed negative correlation with systolic and diastolic blood pressure levels. All these correlation were statistically non significant. Present study revealed that there is association of hypertension with serum estrogen level in postmenopausal women.

Demonstration and imaging of cryogenic magneto-thermoelectric cooling in a van der Waals semimetal.

Attaining viable thermoelectric cooling at cryogenic temperatures is of considerable fundamental and technological interest for electronics and quantum materials applications. In-device temperature control can provide more efficient and precise thermal environment management compared with conventional global cooling. The application of a current and perpendicular magnetic field gives rise to cooling by generating electron-hole pairs on one side of the sample and to heating due to their recombination on the opposite side, which is known as the Ettingshausen effect. Here we develop nanoscale cryogenic imaging of the magneto-thermoelectric effect and demonstrate absolute cooling and an Ettingshausen effect in exfoliated WTe2 Weyl semimetal flakes at liquid He temperatures. In contrast to bulk materials, the cooling is non-monotonic with respect to the magnetic field and device size. Our model of magneto-thermoelectricity in mesoscopic semimetal devices shows that the cooling efficiency and the induced temperature profiles are governed by the interplay between sample geometry, electron-hole recombination length, magnetic field, and flake and substrate heat conductivities. The observations open the way for the direct integration of microscopic thermoelectric cooling and for temperature landscape engineering in van der Waals devices.

Effect of vitamins C and E on antioxidant status of breast-cancer patients undergoing chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Reactive oxygen/nitrogen species generated by antineoplastic agents are prime suspects for the toxic side-effects of acute or chronic chemotherapy. The present study was undertaken to test whether vitamins C and E (VCE) supplementation protect against some of the harmful effects of commonly used anticancer drugs in breast-cancer patients. METHODS: In a randomized 5-month study, the activity of various antioxidant enzymes (superoxide dismutase, catalase, glutathione-S-transferase and glutathione reductase) and the levels of malondialdehyde and reduced glutathione were measured in forty untreated breast-cancer patients (stage II) and compared with those of healthy controls. The degree of DNA damage was also assessed in the peripheral lymphocytes of the patients by alkaline single cell gel electrophoresis. The untreated patients were then randomly assigned to either treatment with chemotherapy alone (5-fluorouracil 500 mg/m(2) i.v. day 1, doxorubicin 50 mg/m(2) i.v. day 1 and cyclophosphamide 500 mg/m(2) i.v. day 1, every 3 weeks for six cycles) or to the same chemotherapy regimen supplemented with VCE (vitamin C 500 mg tablet and vitamin E 400 mg gelatin capsule). On completion of the treatments, both the groups were studied again for the levels of the markers measured prior to treatment. RESULTS AND DISCUSSION: The untreated group showed significantly lower levels of antioxidant enzymes (P < 0·001) and reduced glutathione (P < 0·001), and more extensive lipid peroxidation (P < 0·001) and DNA damage than healthy controls. Similar but less pronounced patterns were observed in the patients receiving chemotherapy alone. The group of patients receiving VCE supplementation had all the marker levels moving towards normal values. Activities of superoxide dismutase, catalase, glutathione-S-transferase and glutathione reductase, and the levels of reduced glutathione were significantly increased (P < 0·01) while, the levels of malondialdehyde and DNA damage were significantly (P < 0·01) reduced in the VCE supplemented group relative to those of patients receiving chemotherapy alone as well as relative to the pretreatment levels. WHAT IS NEW AND CONCLUSION: Co-administration of VCE restored antioxidant status, lowered by the presence of breast-cancer and chemotherapy. DNA damage was also reduced by VCE. The results suggest that VCE should be useful in protecting against chemotherapy-related side-effects and a randomized control trial to evaluate the effectiveness of VCE in breast-cancer patients using clinical outcomes would be appropriate.

Preparation, nutritional composition, functional properties and antioxidant activities of multigrain composite mixes.

Multigrain composite mixes were prepared from different cereals, legumes, millets, nuts along with condiments by different processes. Multigrain composite mixes had 10 to 12% moisture, 56 to 61% carbohydrate, 15 to 20% protein, 9 to 13% crude lipid and 2 to 3% ash. Energy value ranged from ~1600 to 1700 kJ/100 g. Among the vitamins studied, thiamine and riboflavin content varied from 0. 23 to 0.45 mg% and from 8.7 to 21.6 microgram% respectively. Dietary fibre was in the range of 12.4-16.5%. Swelling power of these mixes was about 10; however solubility varied from 17 to 22%. In-vitro Starch digestibility varied from 60 to 76%. Phytic acid content in these multigrain composite mixes varied from 0.6 to 0.8%. Poly-phenols ranged from 1.2 to 1.5%, DPPH free radical scavenging activity ranged from 75.2-86.2% and metal chelating activity ranged from 1.9 to 3.9%. Pasting profile by a Brabender Viscograph of these mixes indicated that they have cross linked starch type behaviour. These multigrain composite mixes can be used for the preparation of food formulations, savory products, pan cake, snacks preparation like muruku and chakli.

Role of Transabdominal Ultrasonogram for Evaluation of Placental Maturity in Relation with Fetal Gestational Age.

In this study our main goal is to evaluate the role of ultrasonography (USG) for determination of placental maturity and fetal gestational age. This cross-sectional study was done at the Department of Radiology and Imaging (USG section) Mymensingh Medical College and Hospital, Mymensingh from July 2008 to June 2010, where 60 patients included in this study, who was attending in the department of Radiology & Imaging for transabdominal ultrasonography with early and late pregnancy related complaints. In this study among the 60 patients, the youngest one was eighteen years and oldest one was thirty-nine years old age. Thirty five percent (35.0%) patients were from 26-30 years age group. About 33 patients out of 60(55.0%) were house wives. Most of the patients were presented with amenorrhea (65.0%) 39 out of 60. Among 60 patients, 20 patients (33.3%) were in gestational age within 12-28 weeks, 20 patients (33.3%) were in gestational age within 29-36 weeks and 20 patients (33.3%) were within >36 weeks gestational age. Among them, 20 patients (33.3%) had grade III placenta, 20 patients (33.3%) had grade II placenta, 12 patients (20%) had grade I placenta and 08 patients (13.3%) had grade 0 placenta. Out of 60 patients, 18 patients (30.0%) were in high risk group and 70.0% were normal. Six (6) patients (10.0%) suffered from HTN, 3 patients had RH negative (5.0%) blood group, 3(5.0%) patients suffered from APH, 3 patients suffer from DM and 3 from IUGR. In this study showed hypertension and IUGR had strong correlation with accelerated placental maturation. Maternal DM and Rh sensitization were associated with delayed maturation of the placenta. This study concludes that, USG appears to be the best imaging modality for the evaluation of placenta and its grading. USG is relatively less expensive and it is good considering the diagnostic accuracy in pregnancy profile. It is noninvasive procedure without any radiation hazards and better visualization of the lesion in different section, but this study is not a complete reflection of overall incidence and statistics regarding the ailment in our country. For this a more extensive study over a longer period covering different section of society is very much needed for better outcome.

Anorectal Malformations and Associated Anomalies in Children.

Anorectal malformations (ARM) incorporate a broad spectrum of diseases, can affect both sexes, and involve the distal anus and rectum as well as the uro-genital tracts. Defects range from the minor which can be treated easily with an excellent outcome, to those are complex and often associated with other anomalies are difficult to manage with poor functional prognosis. This study was done to observe the hospital incidence of Anorectal malformations, frequency of types, sex distribution and spectrum of associations with ARM. The effects of presence of associated anomalies on morbidity and mortality also observed. Detailed history, clinical examinations and relevant investigations were performed for the primary and as well as the associated anomalies. A total of 80 patients were admitted in the department of pediatric surgery in Mymensingh Medical College Hospital during the period of June 2016 to May 2017. Age of the patients was ranging from 1-180 days with the mean age of 0.49±1.002 months. Male: Female ratio was 1.6: 1. Among them 48(60%) were high and 32(40%) were low variety of ARM. In male 37(46.2%) had high and 13(13.7%) were low variety whereas in female 11(13.7%) were high and 19(23.7%) had low ARM. Associated anomalies were seen in 25(31.2%) patient -18 in males and 7 in females; 20 in high and 5 in low ARM. Associated anomalies were uro-genital 11(13.8%), cardiovascular 10(12.5%), vertebral 4(5%), limb defects 3(3.5%) and others 2(2.5%). Four patients have more than one anomaly. Anorectal malformations occur more in boys than girls. Males were more likely to have high lesions and without fistula was the common defect. Low variety ARM were found more in females with Anovestibular fistula is the commonest defect. The most common associated anomalies were recto urinary fistula (13.8%). Associations were more in high than low ARM but not significant (p>0.05). Post operative complications were more in high ARM in both sexes with associated anomalies. The effects of types and associations on morbidity and mortality were significantly different (p<0.05).

Pesticides and their degradates in groundwater reflect past use and current management strategies, Long Island, New York, USA.

Long Island, New York, has a mix of urban/suburban to agricultural/horticultural land use and nearly 3 million residents that rely on a sole-source aquifer for drinking water. The analysis of shallow groundwater (<40 m below land surface) collected from 54 monitoring wells across Long Island detected 53 pesticides or pesticide degradates. Maximum concentrations for individual pesticides or pesticide degradates ranged from 3 to 368,000 ng/L. The highest concentrations and most frequent pesticide detections occurred in samples collected from the pesticide management (PM) network, set in an agricultural/horticultural area in eastern Long Island with coordinated pesticide management by state and local agencies. The other two networks (Suffolk and Nassau/Queens) were set in suburban and urban areas, respectively, and had less frequent detections and lower pesticide concentrations than the PM network. Pesticide detections and concentration patterns (herbicide, insecticide, or fungicide) differed among the three networks revealing broad differences in land use. The predominance of fungicides metalaxyl, 1H-1,2,4-triazole (propiconazole/myclobutanil degradate), and 4-hydroxychlorothalonil (HCTL, chlorothalonil degradate) in samples from the PM network reflects their intensive use in agricultural settings. Total fungicide concentrations in the PM network ranged from <10 to >300,000 ng/L. The widespread detection of imidacloprid and triazine herbicides, simazine and atrazine, reveal a mixture of current and past use pesticides across the Long Island region. Low concentrations (<200 ng/L) of the triazines in the Suffolk and Nassau/Queens networks may reflect a change in land use and application. Acetanilide herbicides and aldicarb have been discontinued for 20 and 40 years, respectively, yet the concentrations of their degradates were among the highest observed in this study. Acetanilide (total concentrations up to 10,000 ng/L) and aldicarb degradates (up to 270 ng/L) are present in the PM network at much lower concentrations than previous Long Island studies and reflect changes in agricultural practices and pesticide management.

Glycosylation of purified buffalo heart galectin-1 plays crucial role in maintaining its structural and functional integrity.

A buffalo heart galectin-1 purified by gel filtration chromatography revealed the presence of 3.55% carbohydrate content, thus it is the first mammalian heart galectin found to be glycosylated in nature and emphasizes the need to perform deglycosylation studies. Physicochemical comparative analysis between the properties of the native and deglycosylated proteins was carried out to understand the significance of glycosylation. The deglycosylated protein exhibited lesser thermal and pH stability compared to the native galectin. When exposed to thiol blocking reagents, denaturants, and detergents, remarkable differences were observed in the properties of the native and deglycosylated protein. Compared to the native glycosylated protein, the deglycosylated galectin showed enhanced fluorescence quenching when exposed to various agents. CD and FTIR analysis showed that deglycosylation of the purified galectin and its exposure to different chemicals resulted in significant deviations from regular secondary structure of the protein, thus emphasizing the significance of glycosylation for maintaining the active conformation of the protein. The remarkable differences observed in the properties of the native and deglycosylated galectin add an important dimension to the significance of protein glycosylation and its associated biological and clinical relevance.

Evaluation of Breast Lump - Comparison between True-cut Needle Biopsy and FNAC in MMCH: A Study of 100 Cases.

One-fourth of all women suffer from breast disease in their lifetime. World Health Organization estimated that over 508,000 women died in 2011 due to breast cancer worldwide.For several years, fine needle aspiration cytology (FNAC) was the most practiced method for the pathological diagnosis of breast lump specially differentiation of benign from malignant. The advent of core needle or True-Cut biopsy (TCB) in the new millennium has resulted in many surgeons switching to TCB since it provides a sufficient amount of tissue for pathologists to make an accurate histological diagnosis.During the study period, patients present with clinically palpable breast lump admitted in different surgicalunits of MMCH, among them 100 patients selected purposively. Then a prospective comparative study was carried out in the Department of Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from September 2017 to February 2018. Out of a total of 100 patients, who presented with suspicious breast lump, as clinically diagnosed 68 patients had benign breast lump and 32 patients had malignant breast lump. FNAC confirmed the diagnosis of breast carcinoma in 27 patients with sensitivity 89.65% and specificity 66.66%. True-cut biopsy confirmed the diagnosis of breast carcinoma in 29 patients with sensitivity 96.66% and specificity 100%. It also gave the definitive histological type and grade which correlated with the final histopathology report in 29 out of the 30 patientsTCB also provides adequate tissue for the evaluation of molecular markers which have extreme therapeutic value.

Legg-Calve-Perthes Disease: Correlation between Computed Radiography and Magnetic Resonance Imaging.

The purpose of this study is to diagnose Legg-Calve-Perthes disease by computed radiography and Magnetic resonance imaging and accurate staging and correlating the findings of these two modalities. Thirty five (35) patients complaining pain in groins and painful walking, after thorough physical examinations were sent to Department of Radiology & Imaging, Mymensingh Medical College Hospital, Mymensingh, Bangladesh for computed radiography and Magnetic Resonance Imaging examination. This cross sectional study was conducted in the Department of Radiology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2016 to June 2018. Legg-Calve-Perthes disease among the selected 35 cases were started at the age of 5(2.9%) and age range of the patients were 5-13 years; mean age was (9.63±1.82) years and most of them belonged to 8-10 years of age (51.4%). Patients with Legg-Calve-Perthes disease had been suffering from pain in right and left groins forvarious durations. Maximum duration was 1-2 years (~88.57%). Maximum proportion of diagnosed patients was delivered by normal delivery (60%) and maximum proportion of patients was premature (65.7%). Most of the patients were low birth weight baby (65.7%). Here chi-square test was done and found no significant relationship between delivery mode and birth weight in case of Legg-Calve-Perthesdisease (x²=1.712) (P=0.191). The result of the X-ray and MRI findings by cross table of chi square test found fair inter relationship between two diagnostic instruments. Result found fine difference in staging of the disease between X-ray and MRI findings. It can be said that MRI definitely a better tool for early diagnosis of Legg-Calve-Perthes disease and its staging but X-ray modality can be used. A primary tool for diagnosis and staging of the disease can be done where the MRI facility is not available or cost expensive for patient.

Influence of the Interval between Antenatal Corticosteroid Therapy and Delivery on the Incidence of Respiratory Distress Syndrome in Neonate.

In spite of the recommendation for rescue antenatal corticosteroids (ACS), the optimal time interval between primary and rescue courses has not been clearly demonstrated. The aim of this retrospective study was to determine the effects of the interval between a single ACS (Dexamethasone) course and delivery on the incidence of respiratory distress syndrome (RDS) in neonates at Mymensingh Medical College Hospital Center from 1st January 2017 to 30th June 2017. Injection Dexamethasone 2 doses (12.5mg IM 12 hourly for 2 doses) or 4 doses (6mg IM every 12 hours for 4 doses) use to arrest preterm labor as well as to prevent RDS delivered beyond 48 hours after ACS administration between 24 and 34 weeks gestation. The risk of RDS was compared between patients who delivered within seven days (Group I) and 7-14 days (Group II) after ACS administration. We included 140 and 60 patients in Group I and Group II respectively. After adjusting for confounders, the ACS delivery interval was significantly associated with RDS in Group II (adjusted odds ratio 12.8, 95% confidence interval 1.31-164.7). A longer ACS delivery interval is associated with a higher risk of RDS. Thus, the use of a rescue course could be expected to reduce the incidence of RDS in patients beyond seven days after ACS administration who remain at risk for preterm delivery within seven days, especially in cases of placenta previa and/or women bearing a male fetus.

The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro.

BACKGROUND: Fascin is overexpressed in many cancers, including colorectal, but its role in the malignant transformation of benign colorectal adenomas is unclear. METHODS: Immunohistochemical analysis of fascin expression was carried out in resected human colorectal adenoma specimens. The effects of forced overexpression of fascin on adenoma cell motility were also analysed. RESULTS: We show fascin overexpression in adenomas increasing with tumour size, histological type, and degree of dysplasia and increased cell motility in adenoma cell lines following fascin transfection. CONCLUSION: These data suggest an important role for fascin in the malignant progression of colorectal tumours.

Incidence of Negative Appendicectomy in Clinically Diagnosed Patients of Acute Appendicitis.

This study was conducted in the department of Surgery, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2016 to December 2017 and performed to assess the negative appendicectomy on histopathology followed by clinically and laboratory investigations based diagnosed acute appendicitis. To perform this prospective study 200 patients with pain in right iliac fossa of both sexes randomly selected and were evaluated by history, clinical examination, laboratory investigations (USG, CBC) and scoring system. Among 200 patients male 124 and female 76 under went appendicectomy 36 were histopathologically normal appendix. Over all negative appendicectomy (NAR) 18%, among them 14.5% (18/124) were male & 23.67% (18/76) were female.

Motor Outcome of Stroke Patients with Low Dose Levodopa Therapy.

Stroke is one of the leading cause of disability worldwide. Motor function deficits due to stroke contribute to overall low quality of life. The objective was of this study is to observe functional motor outcome after stroke with low dose Levodopa therapy. This prospective follow up study was carried out in the Department of Neurology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh from July 2014 to June 2016 to see the effect of low dose of Levodopa (110mg) on motor outcome after stoke disability. Motor deficit was measured by Medical Research Council (MRC) grading and Rivermead Mobility Index (RMI) score. Two groups were selected by simple random method, consisted of both ischemic and hemorrhagic stroke. All the patients of both the groups were suffering from at least some post stroke motor disability and attended full course of physiotherapy. The group (L) received 110mg Levodopa with physiotherapy. On the other hand (NL) group received only physiotherapy. They were all followed up for four times within two months of time and were assessed for recovery of motor function. Mean age was 59.03±11.56 years in Levodopa (L) group and 57.10±12.41 years in the Non Levodopa (NL) group; Males were predominant in both groups. Ninety three (77.50%) cases had ischemic stroke and 27(22.50%) cases had hemorrhagic stroke. Most common risk factors were hypertension and smoking. No known risk factor was detected in 8 (6.67%) patients. Single or multiple risk factors were confirmed in 112 patients (93.33%). MRC score was significantly higher both in affected upper and lower limb in Levodopa group comparing non Levodopa group at 4th visit. RMI score was also significantly higher in Levodopa group comparing non Levodopa group at 4th visit. The Levodopa (L) group showed better recovery pattern than Non Levodopa (NL) group. It can be concluded that motor recovery was better with administration of a single low dose of Levodopa in combination with physiotherapy. Motor outcome was significantly higher in levodopa group than non-levodopa group.

Susac Syndrome: A Rare Case Report.

Susac syndrome is a rare autoimmune disease, which is characterized by microangiopathic changes that affects the brain, retina and cochlea. A 60-years-old female Muslim housewife, hypertensive, non-diabetic patient was admitted into Ophthalmology department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh on 18 December 2017 presented with the complains of gross dimness of vision of left eye for 10 years, vitiligo over the whole body for 5years,hearing loss with tinnitus in both ear for one year. Fluoresce in fundus angiography of Left eye shows Central retinal artery occlusion & was treated by Pan retinal photocoagulation in left eye, Magnetic resonance image of brain shows hyper intense lesions in periventricular white matter & corpus callosum, pure tone audiometry shows bilateral sensorineural type of hearing loss. Early diagnosis and early initiation of treatment is important in reducing the permanent disability.

Inhibition of COX-2 with NS-398 decreases colon cancer cell motility through blocking epidermal growth factor receptor transactivation: possibilities for combination therapy.

UNLABELLED: The use of non-steroidal anti-inflammatory drugs has proved of great interest in the prevention and treatment of colorectal cancer, although their precise mechanisms of action remain unclear. Overexpression of cyclooxygenase-2 (COX-2) and subsequent prostaglandin production promote metastasis and have been shown to increase cell motility in vitro. OBJECTIVE: We have aimed to elucidate whether specific inhibition of COX-2 with NS-398 (NS-398 is a selective inhibitor of COX-2) would be able to inhibit motility of colorectal cancer cells and whether this was modulated through epidermal growth factor receptor (EGFR) transactivation. MATERIALS AND METHODS: A transwell filter assay was used to study cell motility. Expression of COX-2, EGFR phosphorylation and prostaglandin E(2) (PGE(2)) receptors were assessed by Western blot analysis and reverse transcriptase-polymerase chain reaction. PGE(2) concentrations after NS-398 treatment were estimated by enzyme immunoassay. RESULTS: Treatment with NS-398 significantly reduced PGE(2) levels and reduced cell migration in the HT29 and HCA7 colorectal carcinoma cell lines and this effect was rescued by addition of PGE(2). Furthermore, specific inhibition of COX-2 with NS-398 reduced EGFR phosphorylation in colorectal cancer cells. Direct inhibition of EGFR activity with AG1478 reduced PGE(2)-stimulated motility, clearly demonstrating that PGE(2 )acts via the EGFR-signalling pathway. The novel combination of NS-398 and AG1478 dramatically reduced migration of colorectal cancer cells. CONCLUSION: The data presented indicate that the use of NS-398 in chemoprevention and adjuvant therapy for colorectal cancer may work in part, through the inhibition of cell motility. Furthermore, our data suggest that the combined use of non-steroidal anti-inflammatory drugs with EGFR antagonists could be explored further for future use in the clinic.

Hepatitis B viral infection with nephrotic syndrome treated with lamivudine.

A 04 years old boy with 02 months history of generalized oedema and scanty micturition was diagnosed as nephrotic syndrome with hepatitis B viral infection. He had evidence of active viral replication. After 01 month treatment with oral lamivudine, his urine became protein free and after 04 months, he had seroconversion from HBeAg+ve to HBeAg-ve. Lamivudine was continued for 01 year. He had no relapse after discontinuation of therapy and remained well after 36 months of completion of therapy. He had no evidence of active viral replication during this period, however HBsAg remained positive indication carrier state. As most children with HBV associated nephropathy have no evidence of chronic hepatitis, all such children must undergo HBV screening and for chronic liver disease if HBV screening is positive. As such children do not respond to prednisolone or other immunosuppresive therapy which might harm them, antiviral therapy should be considered. Lamivudine is a suitable alternative to IFN alpha owing to its low cost, ease of administration and fewer side effects.

Camptomelic dysplasia with sex reversal.

Camptomelic dysplasia is a disorder of the newborn characterized by congenital bowing and angulation of long bones together with other skeletal and extraskeletal defects. The affected newborn had dysmorphic features with bowing of the legs and bilateral talipes equinovarus. Radiology showed marked anterior bowing of both tibia with disproportionately short fibula, anterolateral bowing of the femurs and wide pelvic outlet with small iliac wings. She had sex reversal with normal female genitalia and 46, XY karyotype. Camptomelic dysplasia is generally considered to be a lethal skeletal dysplasia and most patients die in the neonatal period due to severe respiratory distress. Survivors may have learning difficulties, developmental delay, conductive hearing loss, myopia and recurrent chest infections. Because of its high associated mortality, prenatal diagnosis of camptomelic dysplasia is mandatory. The birth of a child with skeletal dysplasia is an emotionally difficult experience for parents.

The nature of an accessory cell in bone marrow stimulating murine megakaryocytopoiesis.

The nature of accessory cells in unstimulated mouse bone marrow that modulates in vitro megakaryocytopoiesis by releasing megakaryocyte potentiator (Mk-potentiator) activity was investigated. An active cell class was identified by the 7/4 and Ia cellular antigens. Bone marrow macrophages were obtained by their defined outgrowth in the presence of growth factors. Bone marrow macrophages grown in the presence of interleukin 3 (IL-3) were more active in producing Mk-potentiator than were macrophages grown in the presence of colony-stimulating factor 1 (CSF-1). The data indicate that the accessory cells producing Mk-potentiator are a select population of bone marrow macrophages that may be responsible for inducing megakaryocyte maturation under steady-state conditions.