Gamma-linolenic acid therapy of human gliomas

OBJECTIVES: We investigated the effect of intratumoral administration of gamma-linolenic acid (GLA) in human gliomas. METHODS: We evaluated the effect of the administration of 1 mg of GLA for 7 d via a cerebral reservoir placed into the tumor bed or by direct intratumoral delivery in nine patients who had grade 4 disease and recurrent glioma after surgery, radiation, or chemotherapy. RESULTS: There was some, but not dramatic, improvement in patients' survival. No significant prolongation of life span was expected considering the advanced nature of the disease. Nevertheless, it was encouraging that GLA produced no significant side effects in any patient. Regression of the cerebral gliomas was visualized on computed tomography and magnetic resonance imaging. CONCLUSIONS: Based on results of the present and previous studies, we believe that GLA is a safe antitumor agent and that higher doses of GLA should be investigated in future studies.     

Human papillomavirus and risk factors for cervical cancer in Chennai,India: a case-control study

To evaluate the role of human papillomavirus (HPV) and other risk factors in the aetiology of invasive cervical carcinoma (ICC), we conducted a hospital-based case-control study in Chennai, Southern India. A total of 205 ICC cases (including 12 adenocarcinomas) and 213 frequency age-matched control women were included. HPV DNA in cervical cells was evaluated by means of a polymerase chain-reaction assay. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed by means of unconditional multiple logistic regression models. HPV infection was detected in all but one ICC cases and in 27.7% of control women (OR = 498). Twenty-three different HPV types were found. HPV 16 was the most common type in either cases or controls, followed by HPV 18 and 33. The association of ICC with HPV 18 and HPV 16-associated types was somewhat stronger than the one with HPV 16. Multiple HPV infections did not show a higher OR for ICC than single infections. Other than HPV infection, high parity (OR for >4 vs. /=45 years = 4.2) were significantly associated with ICC, also after restricting the analysis to HPV-positive cases and controls. Poor hygienic conditions were associated with an increased risk of HPV infection among control women but not with ICC risk among HPV-positive women. A vaccine against HPV 16 and 18 may be effective in more than three-quarters of ICC in the study area.     

Technique of ultrasonic detection and mapping of abdominal wall adhesions

Summary A technique for noninvasive ultrasound examination to detect and map abdominal wall adhesions is described. The examination is based on the demonstration of movement of abdominal viscera during real-time imaging. This movement is called viscera slide and either occurs spontaneously as a result of respiratory movement or may be induced by manual compression. Abdominal wall adhesions produce a restriction of viscera slide. Ultrasonic demonstration of restricted viscera slide has been used for the precise localization and mapping of abdominal wall adhesions prior to abdominal surgery. The technique may be particularly useful in providing safe initial access in patients undergoing laparoscopy who are at increased risk for trocar injury of viscera due to abdominal wall adhesions resulting from previous surgery or peritonitis.     

Generalisability in unbalanced,uncrossed and fully nested studies

Medical Education 2010: 44 : 367–378 Objectives There is growing interest in multi‐source, multi‐level feedback for measuring the performance of health care professionals. However, data are often unbalanced (e.g. there are different numbers of raters for each doctor), uncrossed (e.g. raters rate the doctor on only one occasion) and fully nested (e.g. raters for a doctor are unique to that doctor). Estimating the true score variance among doctors under these circumstances is proving a challenge. Methods Extensions to reliability and generalisability (G) formulae are introduced to handle unbalanced, uncrossed and fully nested data to produce coefficients that take into account variances among raters, ratees and questionnaire items at different levels of analysis. Decision (D) formulae are developed to handle predictions of minimum numbers of raters for unbalanced studies. An artificial dataset and two real‐world datasets consisting of colleague and patient evaluations of doctors are analysed to demonstrate the feasibility and relevance of the formulae. Another independent dataset is used for validating D predictions of G coefficients for varying numbers of raters against actual G coefficients. A combined G coefficient formula is introduced for estimating multi‐sourced reliability. Results The results from the formulae indicate that it is possible to estimate reliability and generalisability in unbalanced, fully nested and uncrossed studies, and to identify extraneous variance that can be removed to estimate true score variance among doctors. The validation results show that it is possible to predict the minimum numbers of raters even if the study is unbalanced. Discussion Calculating G and D coefficients for psychometric data based on feedback on doctor performance is possible even when the data are unbalanced, uncrossed and fully nested, provided that: (i) variances are separated at the rater and ratee levels, and (ii) the average number of raters per ratee is used in calculations for deriving these coefficients.     

Plumbagin,a medicinal plant (Plumbago zeylanica)-derived 1,4-naphthoquinone,inhibits growth and metastasis of human prostate cancer PC-3M-luciferase cells in an orthotopic xenograft mouse model

We present here first time that Plumbagin (PL), a medicinal plant-derived 1,4-naphthoquinone, inhibits the growth and metastasis of human prostate cancer (PCa) cells in an orthotopic xenograft mouse model. In this study, human PCa PC-3M-luciferase cells (2 × 10⁶) were injected into the prostate of athymic nude mice. Three days post cell implantation, mice were treated with PL (2 mg/kg body wt. i.p. five days in a week) for 8 weeks. Growth and metastasis of PC-3M-luciferase cells was examined weekly by bioluminescence imaging of live mice. PL-treatment significantly (p = 0.0008) inhibited the growth of orthotopic xenograft tumors. Results demonstrated a significant inhibition of metastasis into liver (p = 0.037), but inhibition of metastasis into the lungs (p = 0.60) and lymph nodes (p = 0.27) was not observed to be significant. These results were further confirmed by histopathology of these organs. Results of histopathology demonstrated a significant inhibition of metastasis into lymph nodes (p = 0.034) and lungs (p = 0.028), and a trend to significance in liver (p = 0.075). None of the mice in the PL-treatment group showed PCa metastasis into the liver, but these mice had small metastasis foci into the lymph nodes and lungs. However, control mice had large metastatic foci into the lymph nodes, lungs, and liver. PL-caused inhibition of the growth and metastasis of PC-3M cells accompanies inhibition of the expression of: 1) PKCε, pStat3Tyr705, and pStat3Ser727, 2) Stat3 downstream target genes (survivin and Bcl_xL), 3) proliferative markers Ki-67 and PCNA, 4) metastatic marker MMP9, MMP2, and uPA, and 5) angiogenesis markers CD31 and VEGF. Taken together, these results suggest that PL inhibits tumor growth and metastasis of human PCa PC3-M-luciferase cells, which could be used as a therapeutic agent for the prevention and treatment of human PCa.     

Mouse skin tumor promoting activity of orange peel oil and d-limonene: a re-evaluation

Orange peel oil has previously been shown to be a promoter ofmouse skin tumors. It has been assumed that this activity isdue to its major (95%) constituent, d-limonene. We have testedboth orange peel oil and purified d-limonene as skin tumor promotersin a two-stage skin carcinogenesis model in which tumors wereinitiated with 7, 12-dimethylbenz[a]-anthracene. We confirmedthat topically applied orange peel oil is a very weak promoterof both skin papillomas and carcinomas. However, this promotionalactivity could not be accounted for by topically applied d-limonene.We thus feel that one or more minor components of orange peeloil has promotional activity. Neither orange peel oil nor d-limonenehad promotional activity when given via the diet.