Female circumcision (female genital mutilation): a problem for brachytherapy in cervical cancer

Female circumcision is a traditional practice common in African countries. It involves partial or total removal of external female genitalia. It has led to many complications, in particular, the scarring of the external genitalia. The consequence is a very narrow introitus making the intracavitary brachytherapy treatment component difficult when these women develop cancer of cervix. We present two such cases from our institution. Our aim is to make the radiation and gynecological oncologists, both in developed and developing countries, aware of this practice and the problems they can encounter in the management of such cases. Intracavitary brachytherapy is an important component in the potentially curative role of radiation therapy for cervical cancer. Every effort should be made to ensure that the sequelae of genital mutilation does not deprive these women of the same standard of care as the general population.     

Temozolomide pharmacodynamics in patients with metastatic melanoma: dna damage and activity of repair enzymes O6-alkylguanine alkyltransferase and poly(ADP-ribose) polymerase-1.

PURPOSE: Temozolomide, a DNA methylating agent used to treat melanoma, induces DNA damage, which is repaired by O6-alkylguanine alkyltransferase (ATase) and poly(ADP-ribose) polymerase-1 (PARP-1)-dependent base excision repair. The current study was done to define the effect of temozolomide on DNA integrity and relevant repair enzymes as a prelude to a phase I trial of the combination of temozolomide with a PARP inhibitor. EXPERIMENTAL DESIGN: Temozolomide (200 mg/m2 oral administration) was given to 12 patients with metastatic malignant melanoma. Peripheral blood lymphocytes (PBL) were analyzed for PARP activity, DNA single-strand breakage, ATase levels, and DNA methylation. PARP activity was also measured in tumor biopsies from 9 of 12 patients and in PBLs from healthy volunteers. RESULTS: Temozolomide pharmacokinetics were consistent with previous reports. Temozolomide therapy caused a substantial and sustained elevation of N7-methylguanine levels, a modest and sustained reduction in ATase activity, and a modest and transient increase in DNA strand breaks and PARP activity in PBLs. PARP-1 activity in tumor homogenates was variable (828 +/- 599 pmol PAR monomer/mg protein) and was not consistently affected by temozolomide treatment. CONCLUSIONS: The effect of temozolomide reported here are consistent with those documented in previous studies with temozolomide and similar drug, dacarbazine, demonstrating that a representative patient population was investigated. Furthermore, PARP activity was not inhibited by temozolomide treatment and this newly validated pharmacodynamic assay is therefore suitable for use in a proof-of-principle phase I trial a PARP-1 inhibitor in combination with temozolomide.     

Book reviews

History

The End of History and the Last Man By Francis Fukuyama. Hamish Hamilton, London, 1992, 418 pp., £20.00, ISBN 0–24–1301–1

Aeskulap oder Mars? [Asdepius or Mars] (subtitle: Doctors against War) Edited by T.M. Ruprecht and C. Jenssen. (In German). Donat Verlag, Bremen, 1991, 604pp., 48.00DM, ISBN 3–924444–51‐X.

The Gulf War

Hidden Casualties, Volume II: The Environmental, Health and Political Consequences of the Persian Gulf War Edited by Saul Bloom, John M. Miller and Philippa Winkler, with Ross Mirkarimi. ARC/Arms Control Research Center, 942 Market St, Suite 202, San Francisco CA 94102, USA, 1993, 350pp.

Medicine and War

Wounded Healthy Cities: Searching for Health and Human Dignity A report by the Croatian Healthy Cities Network. Compiled by Ivana Eterovi?, Selma Sogori?, and Slobodan Lang. Edited by John Middleton. Sandwell Public Health Publications, 1992, PO Box 1953, Lyndon, West Bromwich, West Midlands, B71 4NA, pp. 68, £5.95 incl. p&;p, ISBN 0–9517035–4–4.

Public Health

Health through Public Policy, the Greening of Public Health Edited by Peter Draper. Greenprint, London, 1991, x + 258 pp., £9.99, ISBN 1–85425–045–0.

Economics

The Culture of Contentment By John Kenneth Galbraith. Sinclair Stevenson, London, 1992, 195pp., £14.95, ISBN 1–85619–147–8.

Beyond the Limits: Global Collapse or a Sustainable Future By Donella Meadows, Dennis Meadows and Jorgen Randers. Earthscan, London, 1992, xix + 300 pp., £19.95, ISBN 1–85383–130–1 (hbk), £11.95, ISBN 1–85383–131‐X (pbk).

Human Rights

Refugees: Rationing the Right to Life By David Keen. Zed Books, London, 1992, 86pp., £29.9S(hbk), ISBN 1–85649–091–2, £9.95(pbk), ISBN 1–85649–092–0.

Deadly Silence: Black Deaths in Custody Institute of Race Relations, London, 1991, 75pp., £4 (pbk), ISBN 085001–038–1.

Torture and Its Consequences: Current Treatment Approaches Edited by Metin Ba?o?lu. Cambridge University Press, Cambridge, 1992, xxiii + 527pp., £55.00, ISBN 0–521–39299–3

Militarism and the Environment

Taking Stock: The Impact of Militarism on the Environment Working Group on Militarism and the Environment. Science for Peace, 1992, 30pp., Can$ 4.00 (available from WGME, University College, University of Toronto, Ontario, Canada M5S 1A1).

AIDS

The AIDS Epidemic: Economic, Political and Security Implications By Alan Whiteside and David FitzSimons. Research Institute for the Study of Conflict and Terrorism, London, 1992, 43pp., £9.00, ISSN 0069–8792 (available from 136 Baker Street, London W1M 1FH)     

Validation of the National Institute of Neurological Disorders and Stroke Spinal Cord Injury MRI Common Data Elements Instrument

BACKGROUND AND PURPOSE:The National Institute of Neurological Disorders and Stroke common data elements initiative was created to provide a consistent method for recording and reporting observations related to neurologic diseases in clinical trials. The purpose of this study is to validate the subset of common data elements related to MR imaging evaluation of acute spinal cord injury.MATERIALS AND METHODS:Thirty-five cervical and thoracic MR imaging studies of patients with acute spinal cord injury were evaluated independently in 2 rounds by 5 expert reviewers. Intra- and interrater agreement were calculated for 17 distinct MR imaging observations related to spinal cord injury. These included ordinal, categoric, and continuous measures related to the length and location of spinal cord hemorrhage and edema as well as spinal canal and cord measurements. Level of agreement was calculated using the interclass correlation coefficient and kappa.RESULTS:The ordinal common data elements spinal cord injury elements for lesion center and rostral or caudal extent of edema or hemorrhage demonstrated agreement ranging from interclass correlation coefficient 0.68 to 0.99. Reproducibility ranged from 0.95 to 1.00. Moderate agreement was observed for absolute length of hemorrhage and edema (0.54 to 0.60) with good reproducibility (0.78 to 0.83). Agreement for the Brain and Spinal Injury Center score showed the lowest interrater agreement with an overall kappa of 0.27 (0.20, 0.34). For 7 of the 8 variables related to spinal cord injury, agreement improved between the first and second evaluation. Continuous diameter measures of the spinal cord and spinal canal using interclass correlation coefficient varied substantially (0.23 to 0.83).CONCLUSIONS:Agreement was more consistent for the ordinal measures of spinal cord injury than continuous measures. Good to excellent agreement on length and location of spinal cord hemorrhage and edema can be achieved with ordinal measures alone.

In 2006, the National Institute of Neurological Disorders and Stroke (NINDS) began a process to develop common data elements (CDEs) to provide a standardized method for the collection of clinical data related to neurologic diseases.^1-3 Recognizing that there is a lack of clear and consistent terminology for spine disorders, particularly spinal cord injury (SCI), in 2014, the NINDS convened a workgroup comprising expert stakeholders for the development of SCI CDE instruments that included clinical care assessments and imaging.^3-8 This new set of SCI CDE instruments aimed to increase the efficiency and value of clinical research studies and treatment, increase data quality, facilitate data sharing, and help educate new clinical investigators.³ Investigators are expected to incorporate the CDE modules in grant applications and National Institutes of Health–funded research.The MR imaging SCI CDE subset was created to be a comprehensive and standardized terminology for describing MR imaging findings in patients with SCI. This collection consists of a case report form (CRF) containing 35 discrete measures and responses divided into 4 main categories: general imaging characteristics, spinal injury features, canal and cord measurements, and chronic SCI features. The responses are of 3 types: Boolean, categoric, and an ordinal range representing specific anatomic locations. These measures were chosen to represent both objective and subjective assessment derived from routine clinical MR images. The workgroup codified these features using existing CDEs that have proved value in the published literature, and when ones did not exist, the workgroup developed the feature and the response parameters.As with the development of any CRF used for a clinical trial or research, the goal is to provide an instrument that provides useful data representations that are reproducible across trained observers and institutions, require minimal cognitive effort, minimize ambiguity, and are both accurate and precise. Reproducibility of the observations through rigorous testing by multiple observers is a needed step to validate the instrument before clinical or research use. However, the evaluation process may not entirely reproduce the clinical environment in which it is meant to be used such that datasets and observers are overly prepared or optimized. Therefore, the goal of this study is to determine the inter- and intrarater reliability of the NINDS MR imaging CDEs when assessed by MR imaging experts with familiarity with SCI. We hypothesize that there will be good to excellent agreement (kappa >0.4) among the expert raters after limited training.     

Interaction between blood type,smoking and factor V Leiden mutation and risk of venous thromboembolism: a Danish case‐cohort study

See also Lowe GDO. Epidemiology of venous thromboembolism: the need for large (including prospective) studies and meta‐analyses. This issue, pp 2186–8 and Rosendaal FR. Etiology of venous thrombosis: the need for small original studies. This issue, pp 2189–90.     

Percutaneous nephrolithotripsy under assisted local anaesthesia for high risk patients: Is it effective?

ObjectivesThe aim of the present study is to evaluate the feasibility and safety of performing PNL under local anesthesia in a selected group of patients who are at high risk for general anesthesia.Patients and methodsForty seven patients underwent PNL under local anesthesia. There were 38 males and 9 females with a mean age of 62 years. All patients were at medical high-risk for general anesthesia, with an American Society of Anesthesiologists (ASA) score of 3. The indications for local anesthesia in this study were obstructed single functioning kidney with azotemia in 29 patients, hepatic insufficiency in 8 patients, cardiac problems in 7 patients and 3 patients had hepatocellular carcinoma. The mean stone size was 2.7 cm (range 2–3.1 cm). Local infiltration with 10–20 cc of 2% lidocaine at the site of puncture was used in all cases. Narcotics were given 30 min prior to the procedure and medazolam was given intraoperatively upon demand. Utrasound guided puncture was performed in all cases and tract dilatation was then done under fluoroscopy using high pressure balloon catheter in 35 and Alken's metal dilators in 12 cases. Stones were then retrieved after disintegration in the same cession in 33 patients, while the other 14 patients underwent staged PNL, where a 12 Fr. nephrostomy tube was placed in the first stage, followed by tract dilatation and stone retrieval one week later.ResultsOut of 47 patients included, 44 had successful PNL either one stage (30 patients) or two stages (14 patients). Only 3 patients could not tolerate pain and the procedure was terminated after placement of nephrostomy tube and stone retrieval was completed later under general anesthesia.ConclusionOur results demonstrated that PNL under local anesthesia with narcotics and sedatives seems to be a satisfying solution for the treatment of a selected group of patients with renal pelvic stones and who have high anesthetic risk. However, additional studies with different groups of patients are required to validate our results.