Recombinant human interleukin-11 stimulates multilineage hematopoietic recovery in mice after a myelosuppressive regimen of sublethal irradiation and carboplatin

Interleukin-11 (IL-11) is a novel multifunctional hematopoietic cytokine capable of stimulating cells of the myeloid, lymphoid, erythroid, and megakaryocytic lineages in vitro. We have tested the pleiotropic properties of this cytokine on the hematopoietic recovery of mice after a combined regimen of sublethal irradiation and carboplatin administration. This regimen results in severe myelosuppression, characterized by a prolonged period of thrombocytopenia and severe anemia. Administration of recombinant human IL-11 (rhIL-11; 250 micrograms/kg/d) had multilineage effects on bone marrow and spleen hematopoietic activity, increasing the number of megakaryocyte, erythroid, granulocyte, and macrophage progenitors compared with the vehicle-treated controls. This was reflected in the peripheral circulation by a reduction of both the platelet and hematocrit nadirs and a significantly reduced period of thrombocytopenia and anemia in the rhIL-11-treated mice. The results from this study support the broad spectrum of biologic activities that have been attributed to rhIL-11 in vitro and suggest that this cytokine may be an effective agent in the treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.     

Outcome of injection sclerotherapy using absolute alcohol in patients with cirrhosis, non-cirrhotic portal fibrosis, and extrahepatic portal venous obstruction

In order to assess the comparative efficacy and safety of endoscopic injection sclerotherapy in patients with portal hypertension of different etiology, i.e., cirrhosis, non-cirrhotic portal fibrosis, and extrahepatic portal venous obstruction, 87 patients with variceal bleeding were initiated on sclerotherapy using absolute alcohol. There was no significant difference in the success rate of sclerotherapy as well as in the number of sessions and volume of alcohol required for variceal obliteration between the three groups. Major complications included esophageal ulcers (30.0%), symptomatic strictures (18.6%), and interval re-bleed (17.1%) with similar complication rates for the three groups (p greater than 0.05). There was no difference between patients with Child's class A cirrhosis compared with classes B and C together with respect to efficacy and complications of sclerotherapy. Fifty patients (25 cirrhosis, 11 non-cirrhotic portal fibrosis, and 14 extrahepatic portal venous obstruction) with complete variceal obliteration were followed up for a mean period of 16.5 months. Sixteen patients (32%) had variceal recurrence, but bleeding due to recurrent varices occurred in only one case. There was no difference among the three groups for overall variceal recurrence, although recurrence tended to be somewhat later in extrahepatic portal venous obstruction (9.4 +/- 4.0 months) compared with that in cirrhosis (5.1 +/- 3.6 months) and non-cirrhotic portal fibrosis (4.8 +/- 2.6 months).     

Capsule endoscopy:Present status and future expectation

Video capsule endoscopy(CE)since its introduction 13years back,has revolutionized our approach to small intestinal diseases.Obscure gastrointestinal bleed(OGIB)continues to be the most important indication for CE with a high sensitivity,specificity as well as positive and negative predictive values.It is best performed during ongoing bleed or immediately thereafter.Overt OGIB has a higher diagnostic yield than occult OGIB.However,even in iron deficiency anemia,CE is emerging as important investigation after initial negative work up.In suspected Crohn’s disease(CD),CE has been shown superior to traditional imaging and endoscopic technique and should be considered after a negative ileocolonoscopy.Although CE has also been used for evaluating established CD,a high capsule retention rate precludes its use ahead of cross-sectional imaging.Celiac disease,particularly where gastro-duodenoscopy cannot be performed or is normal,can also be investigated by CE.Small bowel tumor,hereditary polyposis syndrome,and non-steroidal anti-inflammatory drugs induced intestinal damage are other indications for CE.Capsule retention is the only significant adverse outcome of CE and occurs mostly in presence of intestinal obstruction.This can be prevented by use of Patency capsule prior to CE examination.Presence of cardiac pacemaker and intracardiac devices continue to be relative contraindications for CE,though data do not suggest interference of CE with these devices.Major limitations of CE today include failure to control its movement from outside,inability of CE to acquire tissue for diagnosis,and lack of therapeutic help.With ongoing interesting and exciting developments taking place in these areas,these issues would be solved in all probability in near future.CE has the potential to become one of the most important tools in diagnostic and possibly in the therapeutic field of gastrointestinal disorder.     

A conservative approach in the management of inflammatory dentigerous cyst in transitional dentition: a case report

Dentigerous cysts are benign odontogenic cysts that develop from the reduced enamel epithelium related to the crown of an unerupted and/or impacted tooth. Inflammatory dentigerous cyst is a variety of dentigerous cyst that is mostly found in the mixed dentition, and the treatment modalities range from enucleation to marsupialization. By extracting the infected primary teeth, opening the cyst, and ensuring continuous drainage, spontaneous eruption of the involved permanent teeth occurs into the dental arch even if they are severely dislocated. The purpose of this report is to describe the successful treatment of a large dentigerous cyst by conservative surgical management.     

The burden of diabetes and impaired fasting glucose in India using the ADA 1997 criteria: prevalence of diabetes in India study (PODIS)

This random multistage cross sectional population survey was undertaken to determine the prevalence of diabetes mellitus (DM) and impaired fasting glycemia/glucose (IFG) in subjects aged 25 years and above in India. The study was carried out in 108 centers (49 urban and 59 rural) to reflect the size and heterogeneity of the Indian population. 41,270 (20,534 males and 20,736 females) subjects were studied. 21,516 (10,865 males and 10,651 females) were from urban areas and 19,754 (9669 males and 10,085 females) from rural areas. Blood samples were taken after a fast of 10-12h and the subjects were categorized as having IFG or DM using the 1997 American Diabetes Association criteria. The age and gender standardized prevalence rate for DM and IFG in the total Indian population was 3.3 and 3.6% respectively (P < 0.001). The standardized prevalence of DM and IFG in urban areas was significantly higher than that for the rural population (urban DM prevalence 4.6% versus rural DM prevalence 1.9%, P < 0.001; urban IFG prevalence 4.8% versus rural IFG prevalence 2.5%, P < 0.001). There was no statistically significant difference in the prevalence between DM (4.6%) and IFG (4.8%) in the urban population. The rural prevalence of IFG (2.5%) was significantly (P <0.001) more than the rural prevalence of DM (1.9%). Type 2 diabetes is a major health problem is India.     

Adiponectin levels are high in children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency

Objective: It has been shown that adiponectin serves as an insulin-sensitizing adipokine. Serum concentrations of adiponectin are low in children with obesity, and increase with fat mass loss, indicating that adiponectin can serve as a biomarker. Since the prevalence of overweight and obesity is increased in children with congenital adrenal hyperplasia (CAH), our study aimed to evaluate serum levels of adiponectin in a cohort of CAH children and adolescents, and their associations with clinical parameters such as chronological age (CA), body mass index (BMI), Tanner stage (TS), medication and metabolic control.
Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI.
Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 μg/L) compared to the matched controls (6.7 μg/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage.
Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients.     

Hyaline‐vascular type Castleman’s disease of the pararenal retroperitoneum: Multidetector CT findings

We describe the case of a 40‐year‐old woman who presented with a pararenal hyaline‐vascular type Castleman’s disease that had an arterial supply from the renal artery and a draining vein as showed by multidetector CT. Identification of the renal artery relationship to the feeding vessel of the mass is critical to prevent potential surgical complications.