Intrathecal Nalbuphine versus Ketamine with Hyperbaric Bupivacaine in Lower Abdominal Surgeries.

BACKGROUND: Spinal anesthesia is an effective method of anesthesia with fewer side effects. The main limitations include the shorter duration of action and shorter postoperative analgesia when performed only with local anesthetics. AIM: The aim of this study is to compare adjuvants nalbuphine and ketamine to hyperbaric bupivacaine in spinal anesthesia with respect to the duration of analgesia, sensory and motor onset, hemodynamic status, and side effects. SETTINGS AND DESIGN: This was a prospective, randomized, double-blind study. MATERIALS AND METHODS: After ethical committee's clearance and informed consent, 90 patients of the American Society of Anesthesiologists physical status I and II were randomly allocated in three groups N, K, and B who received 3 ml hyperbaric bupivacaine with 0.8 mg nalbuphine, 3 ml hyperbaric bupivacaine with 25 mg ketamine (preservative free), and 3 ml hyperbaric bupivacaine with 0.5 ml normal saline, respectively. STATISTICAL ANALYSIS: Data were analyzed using paired t-test. Results were analyzed and compared to previous studies. SPSS-22 version of software was used, released 2013, IBM Corp., Armonk, NY, USA. RESULTS: Mean duration of analgesia in Group N, K, and B was 290 ± 6.09, 220 ± 5.03, and 154 ± 6.04 min, respectively. Mean time of sensory onset in Group N, K, and B was 2.08 ± 0.34, 3.5 ± 0.25, and 4.5 ± 0.37 min, respectively. Time of motor onset was 7.60 ± 0.58, 7.79 ± 0.37, and 7.82 ± 0.53 min in Group N, K, and B, respectively. CONCLUSION: Nalbuphine is an effective adjuvant in spinal anesthesia with respect to sensory onset, duration of analgesia, and hemodynamic stability.

Cytomegalovirus Immediate-Early Proteins Promote Stemness Properties in Glioblastoma.

Glioblastoma (GBM) is the most common and aggressive human brain tumor. Human cytomegalovirus (HCMV) immediate-early (IE) proteins that are endogenously expressed in GBM cells are strong viral transactivators with oncogenic properties. Here, we show how HCMV IEs are preferentially expressed in glioma stem-like cells (GSC), where they colocalize with the other GBM stemness markers, CD133, Nestin, and Sox2. In patient-derived GSCs that are endogenously infected with HCMV, attenuating IE expression by an RNAi-based strategy was sufficient to inhibit tumorsphere formation, Sox2 expression, cell-cycle progression, and cell survival. Conversely, HCMV infection of HMCV-negative GSCs elicited robust self-renewal and proliferation of cells that could be partially reversed by IE attenuation. In HCMV-positive GSCs, IE attenuation induced a molecular program characterized by enhanced expression of mesenchymal markers and proinflammatory cytokines, resembling the therapeutically resistant GBM phenotype. Mechanistically, HCMV/IE regulation of Sox2 occurred via inhibition of miR-145, a negative regulator of Sox2 protein expression. In a spontaneous mouse model of glioma, ectopic expression of the IE1 gene (UL123) specifically increased Sox2 and Nestin levels in the IE1-positive tumors, upregulating stemness and proliferation markers in vivo. Similarly, human GSCs infected with the HCMV strain Towne but not the IE1-deficient strain CR208 showed enhanced growth as tumorspheres and intracranial tumor xenografts, compared with mock-infected human GSCs. Overall, our findings offer new mechanistic insights into how HCMV/IE control stemness properties in GBM cells.

HCMV glycoprotein B is expressed in primary glioblastomas and enhances growth and invasiveness via PDGFR-alpha activation.

Our laboratory first demonstrated that human cytomegalovirus (HCMV) is associated with the most deadly form of primary brain tumor, glioblastoma (GBM). We showed that HCMV glycoprotein B (gB) mediates viral cellular entry via the receptor tyrosine kinase PDGFR-alpha (PDGFRα), resulting in activation of the PI3K/Akt pathway, a critical signaling axis gliomagenesis. Here, we investigated the effects of gB overexpression on glioma progression. We demonstrate that gB is endogenously expressed in primary GBM samples and show that ectopic gB expression in glioma cells induced sustained phosphorylation of PDGFRα, Akt, and Src. Recombinant gB protein and the whole virus enhanced invasion of primary glioblastoma cells into Matrigel and rat brain slices, and this effect was specifically inhibited by neutralizing antibodies to either gB or PDGFRα. Importantly, neutralizing antibodies to gB significantly inhibited the invasiveness of patient-derived HCMV-positive glioblastoma cells, suggesting that functional inhibition of this viral protein could hinder glioblastoma progression. gB overexpression promoted in vivo glioma growth and enhanced phosphor-Akt levels and tumor cell dispersal relative to controls. Taken together, our results demonstrate that HCMV gB promotes key hallmarks of glioblastoma and suggest that targeting gB may have therapeutic benefits for patients with HCMV-positive gliomas.

Id-1 is a key transcriptional regulator of glioblastoma aggressiveness and a novel therapeutic target.

Glioblastoma is the most common form of primary adult brain tumors. A majority of glioblastomas grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control glioblastoma invasiveness and target them therapeutically. We show here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of glioblastoma cell lines and primary glioblastoma cells. Id-1 expression levels positively correlate with glioma cell invasiveness in culture and with histopathologic grades in patient biopsies. Id-1 knockdown dramatically reduces glioblastoma cell invasion that is accompanied by profound morphologic changes and robust reduction in expression levels of "mesenchymal" markers, as well as inhibition of self-renewal potential and downregulation of glioma stem cell markers. Importantly, genetic knockdown of Id-1 leads to a significant increase in survival in an orthotopic model of human glioblastoma. Furthermore, we show that a nontoxic compound, cannabidiol, significantly downregulates Id-1 gene expression and associated glioma cell invasiveness and self-renewal. In addition, cannabidiol significantly inhibits the invasion of glioblastoma cells through an organotypic brain slice and glioma progression in vivo. Our results suggest that Id-1 regulates multiple tumor-promoting pathways in glioblastoma and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of patients with glioblastoma.

Factors associated with hydrocarbon ingestion in children.

OBJECTIVE: To investigate the types of hydrocarbon ingested by children and identify factors associated with hydrocarbons ingestion. PATIENTS AND METHODS: It was a hospital based case control study in which medical records of sixty seven children with hydrocarbon ingestion, admitted through emergency department between January 2001 to December 2005 of Aga Khan Hospital were reviewed. Variables such as age, sex, types of hydrocarbons, amount ingested, socioeconomic status, family size, number of children, type of containers, trend of ingestion during hot weather, length of stay at hospital along with the outcomes were evaluated. RESULTS: Out of 67 patients, 53 (79%) were male and 14 (21%) were female. Majority of children 36 (54%) were between the ages 2-5 years. Kerosene oil 59 (88%) was the most commonly ingested hydrocarbons. Socioeconomically 48 (71%) children belonged to lower middle class. Children with large family size (> or = 3 siblings/family) were more commonly affected. Hydrocarbon were mostly 41 (61%) stored in beverages and mineral water bottles. The accident occurred in 43 (65%) during summer, whereas 34 (56%) patients had presented with fever and cough. Consolidation of lungs was found in 38 (56%) cases. Majority 53 (79%) of the patients were discharged from the hospital within the first 24 hours of admission. Male, age < 2 years, large family size, poor socioeconomic status, hot weather (afternoon and summer vacations), kerosene oil, unsafe containers were the major factors loading to hydrocarbon ingestion in this study. CONCLUSION: There is a need for strategic planning with parent awareness programs to reduce the hydrocarbon poisoning in our children.

Awareness about common diseases in selected female college students of Karachi.

OBJECTIVE: To determine the level of awareness about five common diseases, namely: Tuberculosis (TB), Typhoid, Hepatitis B, Hepatitis C and HIV/AIDS among college female students of Karachi. METHODS: A cross-sectional survey of female students aged 16-21 years from three colleges selected by convenient sampling method was conducted from January to May 2004. Data was collected through a self-administered questionnaire. RESULTS: A large number of students (71%) knew that typhoid spreads by eating contaminated food and drinking infected water. Majority (84%) knew about cough as a mode of spread for TB whereas 69% thought that TB could spread through sneeze of a TB patient. Regarding AIDS, 90% knew that it is sexually transmitted. Majority (87%) knew about the association of hepatitis B and contaminated needles; 64% were aware of hepatitis C and abuse of contaminated needles; 88% knew about the spread of HIV by the use of contaminated needles. A large number (92%) mentioned television as their main source of information. CONCLUSION: The general level of awareness regarding HIV/AIDS transmission was satisfactory among college girls in this study. The level of awareness of the young educated females about the modes of spread of typhoid, TB, hepatitis B and C is low. This study emphasizes the effectiveness of health education campaign regarding common infectious diseases, especially in young girls.