Possibilities and limitations of fibrin glue usage in nephron-sparing surgery: experimental study

INTRODUCTION: The possibilities and limitations of fibrin glue (FG) usage in nephron-sparing surgery were studied. MATERIALS AND METHODS: A prospective experimental study was carried out in 50 pigs: 30 with polar resection, and 20 with mediorenal wedge resection of the kidney. Hemostatic sutures, FG, and FG with a muscle 'cup' in animals with polar resection of the kidney were compared. FG and sutures in animals with the wedge resection of the kidney were studied as well. Bleeding, hot ischemia time, complication rate, and additional scarring were also analyzed. RESULTS: Suture hemostasis is safe but with significant adverse effects in both polar and wedge resection of kidney. FG was not efficient as a sole hemostatic agent for polar resection. It was as efficient as hemostatic suture for wedge resection of the kidney. FG with a muscle 'cup' on a pole of the kidney achieved good results in animals with polar resection of the kidney. Histological analysis confirmed better results with FG because of both the less intense and smaller area of additional scarring. CONCLUSION: FG is a reliable and efficient hemostatic agent for nephron-sparing surgery whenever both sided gluing is possible.     

Vaccinia virus mediated p53 gene therapy for bladder cancer in an orthotopic murine model

PURPOSE: We determined if vaccinia virus (VV) mediated delivery of human tumor suppressor p53 is safe and effective for bladder tumor therapy in an orthotopic murine model. MATERIALS AND METHODS: We used recombinant VV (rVV) vectors to express transgenes in murine bladder cancer MB-49 cells in culture and those growing orthotopically in syngeneic mice. Cultured MB-49 cells were infected with rVV expressing reporter genes (rVV-L15) or p53 (rVV-TK-53) to measure virus infection and apoptosis induction. Orthotopic MB-49 tumors in C57/Bl6 mice were treated with intravesical instillation of rVV, and the tumor incidence, survival and transgene expression were determined. RESULTS: Productive virus infection in vitro was observed in MB-49 cells, although at somewhat lower efficiency than in African Green Monkey kidney CV-1 cells (American Type Culture Collection, Manassas, Virginia). Expression of transgenes in vitro correlated with the virus dose. Cells infected with rVV underwent apoptosis with rVV-TK-53 inducing far greater cell death than rVV-L15. The rVV-L15 virus had no effect on tumor incidence but it increased mean survival compared with control. Instillation of rVV-TK-53 decreased the tumor incidence and 33% of mice survived treatment. At necropsy all nonsurviving mice had bladder tumor, whereas 2 survivors in the rVV-TK-53 treated group were tumor-free. Immunohistochemistry of tumors detected expression of the human p53 gene product in tumor cells. CONCLUSIONS: To our knowledge we report for the first time that recombinant vaccinia virus expressing human p53 can induce the death of MB-49 tumor cells in vivo, not only through the lytic effect of the virus, but also through expression of the death inducing p53 transgene. Further studies are needed to shed light on the mechanisms of rVV-TK-53 mediated tumor apoptosis and the antitumor immune response.     

Cloning and characterization of cyclooxygenase-1b (putative cyclooxygenase-3) in rat

A splice variant of cyclooxygenase-1 (COX-1), COX-1b (previously termed as COX-3), has been identified in canine tissues as an acetaminophen-sensitive isoform, but the sequence of COX-1b mRNA and the encoded protein are not known in rats. We cloned and sequenced rat COX-1b mRNA from cerebral endothelial cells. Sequence analysis indicated that the 98-base pair intron-1 of COX-1 gene remains unprocessed in the COX-1b mRNA, causing a frameshift mutation and a 127-amino acid open reading frame with no sequence similarity with known cyclooxygenases. Transient and permanent transfection of COS-7 cells with a vector containing the rat COX-1b cDNA resulted in synthesis of a protein of the expected size. We generated an affinity-purified polyclonal antibody against the rat COX-1b protein. Western blot analysis of rat tissues using this antibody demonstrated the likely existence of rat COX-1b protein in vivo with the highest expression in heart, kidney, and neuronal tissues. Our results on both stable and on transiently transfected COS-7 cells suggest that rat COX-1b does not have cyclooxygenase activity and does not have any effect on the inhibition of prostaglandin production by acetaminophen. Because this protein has a completely different amino acid sequence than COX-1 and COX-2 and it does not have cyclooxygenase activity, we suggest a name cyclooxygenase variant protein to distinguish it from the known prostaglandin-synthesizing cyclooxygenase isoforms.     

Child and adolescent suicides in Virginia: 1987 to 2003

OBJECTIVES: The aim of this study was to better understand suicides in children and adolescents using records from the Office of the Medical Examiner of Virginia from 1987 to 2003. MAIN FINDINGS, KEY DATA, AND STATISTICS: Suicide accounted for 16.8% of unnatural deaths. Suicide rates were highest for Caucasians. Guns were the most common method of death for suicides, followed by hanging and poisoning. Poisoning other than carbon monoxide accounted for 7.8% of suicides, with tricyclic antidepressants (TCAs) the most identifiable poison. Female youths were 10 times more likely to die from TCAs than male youths, after adjusting for race and age. CONCLUSIONS: Guns and hanging were the principal methods of suicide. Among the antidepressants, TCAs have been the most common poisons used in suicide. Increasing age was a powerful determinant of suicide. Some patients may have stockpiled their TCAs for a while before their TCA overdose. Other suicide victims may have used TCA supplies from family members. Hence, some of the suicide victims may not have taken TCAs on a regular basis before committing suicide. Further exploration of TCA-induced suicidal thoughts is needed. Conclusions cannot be made at the time about the precise role that TCAs played in TCA-induced suicide reported in our study.     

Body mass index (BMI) in newly admitted child and adolescent psychiatric inpatients

INTRODUCTION: Obesity is a major problem among children and adolescents suffering from chronic mental illness. State-of-the-art measures such as body mass index (BMI) and growth-related weight charts are now readily available to clinicians and investigators interested in psychotropic drug-associated weight gain in the pediatric population. However, no reports that utilize such measures in large series of children and adolescents with psychiatric disorders are available. METHODS: The authors employed the Nutstat module of the Centers for Disease Control and Prevention (CDC) Epi Info software to assess BMI in a psychiatry inpatient child and adolescent population in Central Virginia. The authors also developed a scoring system to relate psychotropic administration to BMI. RESULTS: Children and adolescents with chronic mental illness had greater BMI measurements than the general pediatric population. Our scoring system found a relationship between antipsychotic drug administration and increased BMI that almost reached a level of significance (p=0.062). CONCLUSIONS: The present methodology using absolute weight to assess psychotropic drug-associated increase in body weight for children and adolescents is unsatisfactory. The authors offer a new and convenient methodology to correct this problem.     

Responding to the threat of chronic diseases in India

At the present stage of India's health transition, chronic diseases contribute to an estimated 53% of deaths and 44% of disability-adjusted life-years lost. Cardiovascular diseases and diabetes are highly prevalent in urban areas. Tobacco-related cancers account for a large proportion of all cancers. Tobacco consumption, in diverse smoked and smokeless forms, is common, especially among the poor and rural population segments. Hypertension and dyslipidaemia, although common, are inadequately detected and treated. Demographic and socioeconomic factors are hastening the health transition, with sharp escalation of chronic disease burdens expected over the next 20 years. A national cancer control programme, initiated in 1975, has established 13 registries and increased the capacity for treatment. A comprehensive law for tobacco control was enacted in 2003. An integrated national programme for the prevention and control of cardiovascular diseases and diabetes is under development. There is a need to increase resource allocation, coordinate multisectoral policy interventions, and enhance the engagement of the health system in activities related to chronic disease prevention and control.     

Flat and polypoid adenocarcinomas of the colorectum: A comparative histomorphologic analysis of 47 cases

"Flat" colorectal adenomas and adenocarcinomas are well documented in the Japanese literature but only sporadically reported in the English literature. The present study involved systematic morphological analysis of a large series of colorectal carcinomas (CRCs) to determine the frequency of these "flat" CRCs (FCRCs) and analyze their pathological characteristics and associated patient survival. The study group comprised 47 patients (19 females and 28 males) with primary CRC who underwent colorectal resection at the H. Lee Moffitt Cancer Center between 1997 and 2002. These cases were selected based on the gross appearance of the tumors and after review of all of the hematoxylin and eosin-stained tumor sections in a series of 190 consecutive colorectal resections for CRCs. Application of strict morphological criteria classified 22 tumors as FCRCs. For comparison, 25 "polypoid" CRCs (PCRCs) were also identified. Cases of ulcerative fungating annular CRCs and CRCs with mixed gross appearance were excluded from this analysis. Clinicopathologic data, including patient survival, were compared for FCRCS and PCRCs. Statistical analyses were carried out using the chi(2) or Fisher's exact test and log-rank tests. Overall, 22 of 190 CRCs (11%) were found to meet the morphological criteria of FCRCs. Mean patient age was 70.6 years (range, 55 to 87) for FCRCs versus 68.5 years (range, 54 to 91) for PCRCs, and mean tumor size was 4.7 cm (range, 1.6 to 9) for FCRCs versus 4.4 cm (range, 0.5 to 10) for PCRCs. None of the 22 FCRCs and only 1 of 25 (4%) PCRCs were well differentiated; 17 of 22 (77%) FCRCs and 23 of 25 (92%) PCRCs were moderately differentiated; and 5 of 22 (22%) FCRCs and 1 of 25 (4%) PCRCs were poorly differentiated (P = 0.0087). FCRC cases were staged as 0 stage T1, 3 (14%) stage T2, and 19 (86%) stage T3; PCRC cases, as 4 (16%) stage T1, 14 (56%) stage T2, and 7 (28%) stage 3 (P = 0.000031). Similarly, angiolymphatic invasion was identified in 12 of 22 (54%) FCRCs versus 4 of 25 (16%) PCRCs (P = 0.0123). Although some differences between FCRCs and PCRCs were observed on resection in terms of nodal status (N), presence of metastases (M), and perineural invasion, these differences were not statistically significant. In comparison with PCRCs, FCRCs were associated with significantly shorter postresection patient survival at 1 to 5 years (P = 0.028). We have demonstrated in this report that a proportion of primary CRCs resected at our institution were indeed "flat." Furthermore, these FCRCs exhibited higher histological grades, higher T stage, more frequent angiolymphatic invasion, and shorter patient survival compared with PCRCs. Based on these data, FCRC appears to be a worse subtype of colon cancer than PCRC. Further appraisal of FCRCs and additional studies to further elucidate the molecular mechanisms underlying their morphogenesis are warranted.     

Rapid communication: water disinfection by-products enhanced apoptotic activity in human lymphocytes

The apoptosis-inducing activity of concentrated sediments of disinfected and non-disinfected water samples from the waterworks in Budapest, Hungary, was investigated using cultures of human peripherial blood lymphocytes. Chlorine-treated water and untreated (raw) water sediments were concentrated with the use of Amberlite XAD-2 resin columns. The concentrates were dissolved in dimethyl sulfoxide and added to cultures of human peripherial blood lymphocytes. Apoptotic index was determined in lymphocytes after treatment with the raw or disinfected concentrates by flow cytometry. Disinfected water concentrates of 100 microl/ml increased the apoptotic ratio of lymphocyte culture. The same amount of raw water concentrate also enhanced apoptosis. Both raw water and disinfected water contain substances that induced a significant rate of apoptosis in lymphocyte cultures.     

Leptospirosis in children

Leptospirosis has a broad spectrum of clinical manifestations varying, from inapparent influenza like illness to fulminant fatal disease with hepato-renal dysfunction and hemorrhagic phenomena. Our cases had fever, puffiness, respiratory distress and bleeding diathesis as leading manifestations. Leptospirosis was suspected in view of epidemic situation prevailing in the city. We report four cases here, three of which survived and one died.