Paediatric rehabilitation in a developing country—India in relation to aetiology,consequences and outcome in a group of 459 burnt children

Age, aetiology of burn, percentage body surface area burnt and post-burn sequelae have a direct relationship to the rehabilitative necessity in burnt children in a developing country—India. In spite of the gross disfigurements and sequelae, only adolescent children required psychosocial rehabilitation. These are the results following a retrospective analysis of 459 paediatric burn patients in Madras, India.     

Fos and Jun potentiate individual release sites and mobilize the reserve synaptic-vesicle pool at the Drosophila larval motor synapse

In all nervous systems, short-term enhancement of transmitter release is achieved by increasing the weights of unitary synapses; in contrast, long-term enhancement, which requires nuclear gene expression, is generally thought to be mediated by the addition of new synaptic vesicle release sites. In Drosophila motor neurons, induction of AP-1, a heterodimer of Fos and Jun, induces cAMP- and CREB-dependent forms of presynaptic enhancement. Light and electron microscopic studies indicate that this synaptic enhancement is caused by increasing the weight of unitary synapses and not through the insertion of additional release sites. Electrophysiological and optical measurements of vesicle dynamics demonstrate that enhanced neurotransmitter release is accompanied by an increase in the actively cycling synaptic vesicle pool at the expense of the reserve pool. Finally, the observation that AP-1 mediated enhancement eliminates tetanus-induced forms of presynaptic potentiation suggests: (i) that reserve-pool mobilization is required for tetanus-induced short-term synaptic plasticity; and (ii) that long-term synaptic plasticity may, in some instances, be accomplished by stable recruitment of mechanisms that normally underlie short-term synaptic change.     

MDA-7/IL-24 suppresses human ovarian carcinoma growth in vitro and in vivo

Background  

Previous studies showed that the human melanoma differentiation-associated gene-7 (mda-7), also known as interleukin-24 (IL-24), has potent antitumor activity against human and murine cancer cells. However, the majority of these studies were limited to in vitro testing. In the present study, we investigated the antitumor activity of mda-7/IL-24 against human ovarian cancer cells both in vitro and in vivo.     

Long term results of a phase II trial of Induction Chemotherapy with Uracil-Ftegafur (UFT), Vinorelbine and Cisplatin (UFTVP) followed by Radiotherapy concomitant with UFT and Carboplatin (RT/UFTJ) in Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma

Purpose. To evaluate the response of advanced squamous cell head and neck carcinoma to a combination of induction chemotherapy and radiotherapy. Methods. We present long-term results of a phase II trial of Induction Chemotherapy with UFT 200 mg/m² p.o. days 1 to 21, Vinorelbine 25 mg/m² i.v. days 1 and 8 and Cisplatin 100 mg/m² i.v. day 1 (UFTVP) each 21 days for 4 courses, followed by Radiotherapy concomitant with UFT 100 mg/m² p.o. daily and Carboplatin AUC = 0.5 i.v. weekly (RT/UFTJ) in patients (pts) with Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma (IV-B-SCHNC). Primary endpoint was Complete Response to induction UFTVP and secondary endpoints were Disease Free Status Rate after locoregional treatment and long-term Overall Survival. Between 1994 and 1997, 32 pts were included. Results. Complete Response to Induction UFTVP was 59% (95% CI: 48%-70%). Main toxicity of UFTVP was G 3,4 neutropenia (94% of pts; 25% developed febrile neutropenia and 1 of this pts dead). After Induction Chemotherapy with UFTVP, 30 pts received radiotherapy and 25 of them received cocomitant Carboplatin and UFT (RT/UFTJ): main toxicity was mucositis (G3-4: 72%) and one patient died during RT/UFTJ because pneumonia. Twenty-five pts (78%) were alive and disease free at the end of the whole treatment. Actuarial 5 year Overall survival is 32%. Conclusion. Although toxicity is important, this approach has interesting activity and deserves further investigation. In the January issue of Clin Transl Oncol the following article was published with a wrong reference: Fernando Rivera, María E Vega-Villegas, Marta F. López-Brea, Almudena García-Casta?o, Ana de Juan, Francisco Javier Ramos, Antonio Collado, Piedad Galdós, Antonio Rubio, Adolfo del Valle, Julio Rama, Marta Mayorga and Jaime Sanz-Ortiz Long term results of a phase II trial of Induction Chemotherapy with Uracil-Ftegafur (UFT), Vinorelbine and Cisplatin (UFTVP) followed by Radiotherapy concomitant with UFT and Carboplatin (RT/UFTJ) in Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma and Peripheral Blood Stem Cell Support (PBSCS) with Febrile Neutropenia Clin Transl Oncol. 2007 Jan;9:40-47 DOI 10.1007/s12094-007-0008-5 The correct reference should be as follows: Fernando Rivera, María E Vega-Villegas, Marta F. López-Brea, Almudena García-Casta?o, Ana de Juan, Francisco Javier Ramos, Antonio Collado, Piedad Galdós, Antonio Rubio, Adolfo del Valle, Julio Rama, Marta Mayorga and Jaime Sanz-Ortiz Long term results of a phase II trial of Induction Chemotherapy with Uracil-Ftegafur (UFT), Vinorelbine and Cisplatin (UFTVP) followed by Radiotherapy concomitant with UFT and Carboplatin (RT/UFTJ) in Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma Clin Transl Oncol. 2007 Jan;9:40-47The original article can be found online at     

Autocrine stimulation by insulin-like growth factor 1 and insulin-like growth factor 2 mediates chondrocyte survival in vitro

OBJECTIVE: To determine the role of autocrine stimulation by insulin-like growth factor 1 (IGF-1) and IGF-2 in mediating chondrocyte survival and to determine whether chondrocytes from older individuals are more susceptible to cell death when IGF action is blocked. METHODS: Survival was assessed in human and monkey chondrocytes cultured in suspension in alginate under serum-free conditions. The role of IGFs in mediating survival was determined by treating cultures with neutralizing antibodies to IGF-1 and IGF-2, an antibody that blocks the type 1 IGF receptor, and antisense oligonucleotides to inhibit IGF-1 production. Survival was measured in chondrocyte cultures from young and old adult monkeys in the presence and absence of the IGF receptor blocking antibody and ceramide to induce cell death. RESULTS: Cell survival of >90% was noted when chondrocytes were cultured for as long as 107 days in alginate in a supplemented serum-free medium. Compared with controls, survival was significantly reduced by treatment with neutralizing antibodies to IGF-1 (25% cell death), neutralizing antibodies to IGF-2 (18% cell death), antibody to the IGF receptor (45% cell death), and IGF-1 antisense oligonucleotides (28% cell death). Cell death from inhibition of the type 1 IGF receptor was associated with an increase in caspase 3 activity and with positive DNA fragmentation, consistent with apoptotic cell death. Chondrocytes from old adult monkeys were more susceptible to cell death than were those from young adult monkeys when the IGF receptor was blocked and cell death was further stimulated by ceramide. CONCLUSION: Autocrine production of IGFs helps to maintain chondrocyte survival in vitro and could play a similar role in vivo. With aging, chondrocytes may become more susceptible to factors that induce cell death.     

Percutaneous endopyeloplasty: a novel technique

BACKGROUND AND PURPOSE: Despite a 10% to 15% failure rate, endopyelotomy remains the treatment of choice for most patients with ureteropelvic junction (UPJ) obstruction. We present a novel technique of percutaneous endopyeloplasty, wherein a precise, full-thickness approximation of a standard longitudinal endopyelotomy incision is performed in a horizontal Heineke-Mikulicz fashion through the conventional solitary percutaneous tract via a nephroscope. We assess the feasibility and efficacy of percutaneous endopyeloplasty in a chronic porcine bilateral UPJ obstruction model and compare outcome data with those#10; of conventional endopyelotomy and laparoscopic pyeloplasty. MATERIALS AND METHODS: Partial UPJ obstruction was created in 20 kidneys (11 pigs) by laparoscopic ligation of the upper ureter over a 5F ureteral catheter. After development of hydronephrosis over a period of 4 to 6 weeks, percutaneous endopyeloplasty (N = 10), conventional percutaneous endopyelotomy (N = 5), or laparoscopic pyeloplasty (N = 5) was performed. The essential steps of percutaneous endopyeloplasty include retrograde ureteral catheterization, standard percutaneous endopyelotomy incision, mobilization of the distal ureteral lip, horizontal suturing of the endopyelotomy incision through the nephroscope, and nephrostomy drainage and ureteral stenting. Suturing was performed using a modified 5-mm laparoscopic device (Sew Right 5 SR; LSI Solutions, Rochester, NY), which was passed through the nephroscope. RESULTS: Percutaneous endopyeloplasty was technically successful in all 10 kidneys with a mean total operative time of 81.4 minutes (range 51-117 minutes). The mean endopyeloplasty suturing time was 29.4 minutes (range 20-64 minutes). Three kidneys required two sutures, while seven kidneys required three sutures to complete the endopyeloplasty. The solitary complication was a lower-pole infundibular stenosis. Over a mean follow-up of 7.7 weeks, all renal units showed relief of obstruction, as evidenced by regression of hydronephrosis,#10; improvement in T(1/2) and glomerular filtration rate on renogram, and a low intrapelvic pressure on Whitaker test. At autopsy, the endopyeloplasty site showed a fine, well-healed transverse scar with no evidence of residual suture on the mucosal surface. The mean caliber of the UPJ following endopyeloplasty (13.8F +/- 2.2F) was significantly greater (P = 0.01) than that following endopyelotomy (7.5F +/- 1.9F). Intraoperative extravasation on completion of endopyeloplasty was absent (N = 6) or mild (N = 4) compared with that seen in all five kidneys following endopyelotomy. CONCLUSION: Percutaneous endopyeloplasty is feasible, simple, reproducible, and effective. Its advantages over conventional endopyelotomy include transrenal performance of a Fenger-plasty, wider caliber of the UPJ, absence of extravasation, and shorter duration of ureteral stenting.     

Hyperhomocysteinemia,and low intakes of folic acid and vitamin B12 in urban North India

Summary Background and Aim An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy in subjects living in an urban slum of North India and healthy subjects from urban non-slum area. Methods Group I consisted of 46 subjects (22 males and 24 females) living in an urban slum, while group II consisted of healthy subjects (n = 26, 13 males and 13 females) living in the adjacent non-slum area. Anthropometric measurements, biochemical profile (fasting blood glucose, total cholesterol, serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and fasting serum levels of Hcy were measured. Dietary intakes of folic acid, vitamin B12, vitamin B1, and iron were calculated by the 24-hour dietary recall method. Serum levels of Hcy were correlated with dietary intakes of nutrients, anthropometry, and metabolic variables. Results Sex-adjusted serum levels of Hcy in mmol/L (Mean ± SD) were high, though statistically comparable, in both the groups (group I: 20.8 ± 5.9 and group II: 23.2 ± 5.9). Overall, higher than normal serum levels of Hcy (> 15 μmol/L) were recorded in 84 % of the subjects. A substantial proportion of subjects in both groups had daily nutrient intakes below that recommended for the Asian Indian population (folic acid: 93.4 % in group I and 96.7 % in group II, vitamin B12: 76.1 % in group I and 88.4 % in group II). However, between the two groups, average daily dietary intakes of both the nutrients were statistically comparable. As compared to non-vegetarians, vegetarians showed lower intakes of folic acid (p < 0.01) and vitamin B12 (p < 0.01) in both groups. On multivariate linear regression analysis with serum Hcy as the response variable and vegetarian/non-vegetarian status and sex (male/female) as predictor variables, higher serum levels of Hcy were observed in vegetarians vs non-vegetarians (β = 4.6, p < 0.05) and males vs females (β = 5.3, p < 0.01). Conclusions Low intakes of folic acid and vitamin B12, and hyperhomocysteinemia, in both the healthy population living in urban slums and adjacent urban non-slum areas, are important observations for the prevention of nutritional and cardiovascular diseases in the Indian subcontinent. Received: 30 October 2001, Accepted: 14 January 2002     

Clavosolides A and B, dimeric macrolides from the Philippines sponge Myriastra clavosa

A specimen of the sponge Myriastra clavosa from the Philippines contained two dimeric macrolides, clavosolides A and B. Clavosolide A is a symmetrical dimer, while clavosolide B is rendered unsymmetrical by the replacement of one of the methoxyl groups by a hydroxyl group. The structures of the clavosolides were elucidated by interpretation of spectroscopic data.     

Consumption of L-arginine mediated by Entamoeba histolytica L-arginase (EhArg) inhibits amoebicidal activity and nitric oxide production by activated macrophages

In this study we discuss the cloning and expression of Entamoeba histolytica arginase (EhArg), an enzyme that catalyses the hydrolysis of L-arginine to L-ornithine and urea. L-norvaline, a competitive inhibitor of E. histolytica L-arginase, inhibits the growth of the parasite, which suggests that the catabolism of L-arginine mediated by EhArg is essential. Nitric oxide (NO) is an antimicrobial agent that inhibits some key enzymes in the metabolism of Entamoeba histolytica. NO is synthesized by activated macrophages from L-arginine, the substrate of NO synthase (NOS-II). We show that E. histolytica inhibits NO mediated amoebicidal activity of activated macrophages by consuming L-arginine present in the medium.