Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin

A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3–5 days later by 100–150 g of indium-111 streptavidin, at the specific activity of 280–370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1–8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1–30:1) and 45:1 (range 12:1–120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1–30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01–0.3) for recurrences and 0.05 for primary tumour (range 0.005–0.2). Over 24–48 h 14% i.d. (range 8–18% i.d.) was found in the urine, 14% i.d. (range 629% i.d.) in the blood and 63% i.d. (range 56–70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer. Offprint requests to: G. Paganelli     

Fatal shoulder dystocia: a review of 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy

Objective To use information collected by the Confidential Enquiry into Stillbirths and Deaths in Infancy to help obstetric, midwifery and paediatric practice in the management of shoulder dystocia.
Design Review of casenotes by a multidisciplinary focus group.
Sample All 56 cases reported to the Confidential Enquiry into Stillbirths and Deaths in Infancy from England, Wales and Northern Ireland in 1994 and 1995, where stillbirth or neonatal death was attributed to shoulder dystocia.
Main outcome measures Case notes were reviewed with respect to a range of perinatal variables. Comparisons were made with normative data from other studies when appropriate.
Results Maternal obesity and big babies were over-represented in pregnancies complicated by fatal shoulder dystocia. Fetal compromise was recorded in 26% of labours. The median time interval between delivery of the head and the rest of the body was only five minutes. The lead professional at the time the head was delivered was a midwife in 65% of cases. Middle grade or senior obstetric staff were supervising 47% of cases by the time the body was delivered.
Conclusions Antenatal prediction of shoulder dystocia is imprecise, and the majority of deliveries are attended by midwives. A relatively brief delay in delivery of the shoulders may be associated with a fatal outcome.     

Therapeutic plasma exchange for thrombotic thrombocytopenic purpura with refractory thrombocytopenia

Thrombotic thrombocytopenic purpura (TTP) is an acute, life‐threatening illness with disseminated platelet‐rich thromboses of small vessels that variably presents with the classic clinical “pentad” of microangiopathic hemolytic anemia, thrombocytopenia, fever, altered mental status, and acute kidney injury. Most cases are caused by an acquired autoantibody to ADAMTS13, a metalloproteinase that cleaves large von Willebrand Factor (vWF) multimers. The mainstay of treatment is daily therapeutic plasma exchange (TPE), sometimes with adjunctive pharmacologic immunosuppression. TPE is generally continued until the platelet count is greater than 150 × 10³/µL and the lactate dehydrogenase is near normal for 2‐3 consecutive days. Unfortunately, there is no clear guidance for when thrombocytopenia is refractory for a prolonged period of time. The following case describes such a scenario in which consecutive ADAMTS13 activity and inhibitor levels were used to guide the decision to stop treatment with TPE in a patient who failed to recover their platelet count.     

Myocardial Perfusion Single-Photon Emission Tomography (SPET) and Positron Emission Tomography–Computed Tomography (PET-CT) Imaging for Congenitally Corrected Transposition of Great Arteries

Congenitally corrected transposition of great arteries (ccTGA) consists of both atrioventricular and ventriculo-arterial discordance. In patients with ccTGA, the pulmonary artery arises from the left ventricle, whereas the aorta arises from the right ventricle. The burden of the systemic blood pressure on the right ventricle involves an increased risk of coronary artery disease (CAD) and, as a long-term consequence, myocardial hypertrophy and gradual failure. This report describes the case of an adult patient affected by ccTGA who was referred for an episode of atypical chest pain while at rest. First-line diagnostic examinations were inconclusive. Myocardial perfusion single-photon emission tomography (SPET) was performed to exclude CAD, but the congenital abnormalities of the patient??s heart made interpretation of the images particularly difficult. A perfusion positron emission tomography?Ccomputed tomography (PET-CT) scan with ¹³N-ammonia then was suggested, which unmasked an unexpected artifact. The case report demonstrates that hybrid imaging techniques such as SPET-CT and PET-CT should be used systematically when CAD is suspected for patients with abnormal anatomy of the heart, including ccTGA.     

Exploring the Positions of German and Israeli Patient Organizations in the Bioethical Context of End-of-Life Policies

Patient organizations are increasingly involved in national and international bioethical debates and health policy deliberations. In order to examine how and to what extent cultural factors and organizational contexts influence the positions of patient organizations, this study compares the positions of German and Israeli patient organizations (POs) on issues related to end-of-life medical care. We draw on a qualitative pilot study of thirteen POs, using as a unit of analysis pairs comprised of one German PO and one Israeli PO that were matched on the basis of organizational category. Bioethical positions that emanated from the interviews concerned advance directives—general views, recent legal framework, and formalization; as well as active and passive euthanasia, withholding and withdrawing of treatment, and physician-assisted suicide. In addition to the unifying, within-country impact of cultural factors, we found that constituency-based organizations and partner organizations in both countries often share common views, whereas disease-based support organizations have very heterogeneous positions. We conclude by discussing how organizational contexts provide a source of uniformity as well as diversity in the positions of POs.     

ASSOCIATION BETWEEN SMOKING,CRACK COCAINE ABUSE AND THE DISCONTINUATION OF COMBINATION ANTIRETROVIRAL THERAPY IN RECIFE,PERNAMBUCO, BRAZIL

Despite the effectiveness of combination antiretroviral therapy in the treatment of people living with HIV/AIDS (PLWHA), nonadherence to medication has become a major threat to its effectiveness. This study aimed to estimate the prevalence of self-reported irregular use of antiretroviral therapy and the factors associated with such an irregularity in PLWHA. A cross-sectional study of PLWHA who attended two referral centers in the city of Recife, in Northeastern Brazil, between June 2007 and October 2009 was carried out. The study analyzed socioeconomic factors, social service support and personal habits associated with nonadherence to antiretroviral therapy, adjusted by multivariable logistic regression analysis. The prevalence of PLWHA who reported irregular use of combination antiretroviral therapy (cART) was 25.7%. In the final multivariate model, the irregular use of cART was associated with the following variables: being aged less than 40 years (OR = 1.66, 95%-CI: 1.29-2.13), current smokers (OR = 1.76, 95%-CI: 1.31-2.37) or former smokers (OR = 1.43, 95%-CI: 1.05-1.95), and crack cocaine users (OR = 2.79, 95%-CI: 1.24-6.32). Special measures should be directed towards each of the following groups: individuals aged less than 40 years, smokers, former smokers and crack cocaine users. Measures for giving up smoking and crack cocaine should be incorporated into HIV-control programs in order to promote greater adherence to antiretroviral drugs and thus improve the quality of life and prolong life expectancy.     

Thermotolerant mycobiota of Israeli soils

Composition of thermotolerant mycobiota in the soil of Israeli deserts and northern territories was examined in spatiotemporal dynamics. A total of 165 species from 82 genera were isolated at 37 °C using the soil dilution plate method. Aspergilli (Aspergillus fumigatus and A. niger) and teleomorphic ascomycetes (Canariomyces notabilis, Chaetomium nigricolor, and Ch. strumarium) comprised the basic part of the thermotolerant communities. The desert communities remarkably differed from the northern communities by a much higher abundance of A. fumigatus and teleomorphic species, as well as by a lower abundance of A. niger and Rhizopus arrhyzus. Seasonal dynamics revealed for the southern Negev was expressed mainly in the variations of species richness (substantially lower in the winter), and abundances of A. fumigatus (dominant in the summer) and A. niger (dominant in the winter). The composition of thermotolerant mycobiota was almost entirely different from the composition of mesophilic mycobiota at 25 °C. Melanin‐containing fungi with many‐celled conidia that dominated mesophilic communities in the deserts did not grow at 37 °C, while prevailing aspergilli accompanied by teleomorphic species with perithecial fruit bodies were apparently able not only to survive but also to germinate at this temperature and be active during a long hot period in the desert.