MUC 1 core protein as a marker of gallbladder malignancy.

AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer.     

Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity.

PURPOSE: Myeloid suppressor (Gr-1(+)/CD11b(+)) cells accumulate in the spleens of tumor-bearing mice where they contribute to immunosuppression by inhibiting the function of CD8(+) T cells and by promoting tumor angiogenesis. Elimination of these myeloid suppressor cells may thus significantly improve antitumor responses and enhance effects of cancer immunotherapy, although to date few practical options exist. EXPERIMENTAL DESIGN: The effect of the chemotherapy drug gemcitabine on the number of (Gr-1(+)/CD11b(+)) cells in the spleens of animals bearing large tumors derived from five cancer lines grown in both C57Bl/6 and BALB/c mice was analyzed. Suppressive activity of splenocytes from gemcitabine-treated and control animals was measured in natural killer (NK) cell lysis and Winn assays. The impact of myeloid suppressor cell activity was determined in an immunogene therapy model using an adenovirus expressing IFN-beta. RESULTS: This study shows that the chemotherapeutic drug gemcitabine, given at a dose similar to the equivalent dose used in patients, was able to dramatically and specifically reduce the number of myeloid suppressor cells found in the spleens of animals bearing large tumors with no significant reductions in CD4(+) T cells, CD8(+) T cells, NK cells, macrophages, or B cells. The loss of myeloid suppressor cells was accompanied by an increase in the antitumor activity of CD8(+) T cells and activated NK cells. Combining gemcitabine with cytokine immunogene therapy using IFN-beta markedly enhanced antitumor efficacy. CONCLUSIONS: These results suggest that gemcitabine may be a practical strategy for the reduction of myeloid suppressor cells and should be evaluated in conjunction with a variety of immunotherapy approaches.     

Synthesis and Structure-Activity Relationships of Vasicine Analogues as Bronchodilatory Agents

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 13-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect.     

Devastating salt‐wasting crisis in a four‐month‐old male child with congenital adrenal hyperplasia,highlighting the essence of neonatal screening

Congenital adrenal hyperplasia (CAH) is a rare condition usually referred to as a group of genetic disorders resulting due to a deficiency of steroid enzymes required by adrenal glands to produce cortisol and mineralocorticoid hormones. It has an autosomal recessive mode of inheritance and is further categorized into two types—Classic and Non‐Classic. Non‐Classic CAH is a more common milder form that presents late after puberty. Classic CAH, although more severe, is rare and detected at birth and is associated with the life‐threatening adrenal crisis in both sexes and virilization of the external genitalia in females (46, XX) patients, whereas in males, no overt abnormality of the external genitalia is present. We present a case of a four‐month‐old male child with the classic form of CAH who was brought with complaints of loose stools, projectile non bilious vomiting, decreased urine output, and failure to feed for 3 days. The child had a clinical presentation of salt wasting with hypoglycemia and hyperpigmentation of his genitalia. The USG findings revealed increased anteroposterior diameter of renal pelvis indicative of a growth in the suprarenal area. 17‐hydroxyprogesterone (17‐OHP) was found to be elevated confirming the diagnosis. He was treated with hydrocortisone with gradual improvement in his glucose and electrolytes. The patient was discharged home on replacement therapy consisting of oral prednisolone and fludrocortisone acetate and followed up as outpatient with significant improvement in the clinical findings. The fact that the child was not screened for CAH at birth led to the critical consequences of the disease in this case. To prevent life‐threatening adrenal crisis and help perform appropriate sex assignments for affected female patients, newborn screening (NBS) programs for the classical form of CAH should be made mandatory even in low‐ and middle‐income countries.     

Effect of intravenous immune globulin on natural killer cell activity: possible association with autoimmune neutropenia and idiopathic thrombocytopenia

Natural killer cell (NK) activity was assessed in patients before and after treatment with intravenously administered immune globulin (IVIG). In eight patients with hypogammaglobulinemia or agammaglobulinemia receiving 300 mg/kg/dose IVIG every 4 weeks, NK activity was significantly lower after therapy than before. In two patients, one with idiopathic thrombocytopenic purpura and one with autoimmune neutropenia, receiving high doses (2 gm/kg) of IVIG, NK activity was unusually high before therapy. After treatment, NK activity decreased in correlation with the clinical response and elevation of peripheral cell counts. These data show that IVIG diminishes NK activity in vivo and that reduction of NK activity may be associated with clinical improvement in idiopathic thrombocytopenic purpura and autoimmune neutropenia. NK activity of lymphocytes obtained from healthy volunteers was reduced by the same concentrations of maltose or sucrose present in Gamimune or Sandoglobulin, respectively; IVIG preparations, however, were more inhibitory. The diminution of NK activity therefore may be related to two components of IVIG preparations, monomeric IgG and maltose or sucrose.     

Genital tuberculosis: an important cause of Asherman’s syndrome in India

Objective To demonstrate the association between genital endometrial tuberculosis and Asherman's syndrome. Materials and methods A total of 28 women who underwent hysteroscopy with or without laparoscopy for suspected Asherman’s syndrome from symptoms (amenorrhoea or oligomenorrhoea, and or primary or secondary infertility) and who were found to have genital tuberculosis on endometrial biopsy (histopathology or culture) or positive polymerase chain reaction (PCR) on endometrial aspirate or positive findings of tuberculosis on laparoscopy or hysteroscopy were enrolled in this retrospective study. Results The mean age and parity were 26.5 years and 0.3, respectively. There was past history of TB in 67.8% women. All women had menstrual dysfunction, with oligomenorrhoea and hypomenorrhoea in 16 (57%) women and amenorrhoea in 12 (42.8%). All women had primary (n = 19, 67.8%) or secondary (n = 9, 32%) infertility. On hysteroscopy, there were various grades of adhesions in all women, with grade I in 17.8%, grade II in 28.5%, grade III in 28.5% and grade IV in 17.5% women. Only four women (14.3%) had open ostia, while others had bilateral (28.5%) or unilateral (21.3%) blocked ostia or inability to see ostia (28.5%). On laparoscopy performed on 18 women, there were varying grades of adhesions in 16 (88.8%) women, with beading (33.3%), tubercles (33.3%), caseation (11.1%) and tubo-ovarian masses (11.1%). The diagnosis of genital TB was made by histopathology (tuberculous granuloma) on endometrial biopsy in 28.6%, positive culture in 3.6%, positive polymerase chain reaction (PCR) in 46.4% and observation of tubercles, beading or caseation on laparoscopy in 17.8% or shaggy cavity with caseation on hysteroscopy in 3.6% women. Conclusion Genital tuberculosis appears to be an important and common cause of Asherman's syndrome in India, causing oligomenorrhoea or amenorrhoea with infertility.     

Control of presacral venous bleeding, using thumbtacks

Background Massive life threatening bleeding from presacral venous plexus in gynecological surgery, though uncommon can be fatal when conventional methods fail. Case In the present case, a 55-year-old woman undergoing radical hysterectomy for cancer cervix was saved using thumbtacks to control bleeding from presacral vessels when conventional methods were ineffective. Conclusion Use of thumbtacks in such patients is simple, cost effective and life saving.     

Diabetes in pregnancy: a review of current evidence

PURPOSE OF REVIEW: There is controversy about the best approach to screening and management for gestational diabetes. In the recent Confidential Enquiry in Maternal and Child Health (CEMACH) the outcome of women with diabetes compared with women without diabetes. The results were exceptionally poor, suggesting the need for a new management approach. The aim of this review is to address these findings and our suggested care pathways. RECENT FINDINGS: The CEMACH report showed the congenital malformation rate was four to 10-fold higher, the perinatal mortality rate was four to seven-fold higher, stillbirth was five times more common, and babies were three times more likely to die in the first 3 months of life. Only 39% of women with established diabetes took folic acid and only 37% had some documentation of glycaemic control before pregnancy. Overall, less than a fifth of NHS trusts in the UK had any kind of multidisciplinary preconception services. The results for women with type 2 diabetes were as bad as those for type 1. Caesarean delivery rates were very high (67%). SUMMARY: Prepregnancy counselling and multidisciplinary team management is the key in achieving good pregnancy outcomes. There is emerging evidence about the safety and efficacy of oral hypoglycaemics like metformin in pregnancy.