A phase II irinotecan–cisplatin combination in advanced pancreatic cancer

We report a cisplatin and irinotecan combination in patients with biopsy-proven advanced pancreatic adenocarcinoma. Patients were selected from a specialist centre and required good performance status (KPS>70%), measurable disease on CT scan, and biochemical and haematological parameters within normal limits. Based on a two-stage phase II design, we aimed to treat 22 patients initially. The study was stopped because of the death of the 19th patient during the first treatment cycle, with neutropenic sepsis and multiorgan failure. A total of 89 treatments were administered to 17 patients. Serious grade 3/4 toxicities were haematological (neutropenia) 6%, diarrhoea 6%, nausea 7% and vomiting 6%. Using the clinical benefit response (CBR) criteria, no patients had an overall CBR. For responses confirmed by CT examination, there was one partial response (5%), three stable diseases lasting greater than 6 weeks (16%), with an overall 22% with disease control (PR+SD). The median progression-free and overall survival was 3.1 months (95% CI: 1.3-3.7) and 5.0 (95% CI: 3.9-10.1) months, respectively. Although this synergistic combination has improved the response rates and survival of other solid tumours, we recommend caution when using this combination in the palliation of advanced pancreatic cancer, because of unexpected toxicity

A multiplicative hazard regression model to assess the risk of disease transmission at hospital during community epidemics

<p>Abstract</p> <p>Background</p> <p>During community epidemics, infections may be imported within hospital and transmitted to hospitalized patients. Hospital outbreaks of communicable diseases have been increasingly reported during the last decades and have had significant consequences in terms of patient morbidity, mortality, and associated costs. Quantitative studies are thus needed to estimate the risks of communicable diseases among hospital patients, taking into account the epidemiological process outside, hospital and host-related risk factors of infection and the role of other patients and healthcare workers as sources of infection.</p> <p>Methods</p> <p>We propose a multiplicative hazard regression model to analyze the risk of acquiring a communicable disease by patients at hospital. This model derives from epidemiological data on communicable disease epidemics in the community, hospital ward, patient susceptibility to infection, and exposure of patients to infection at hospital. The model estimates the relative effect of each of these factors on a patient's risk of communicable disease.</p> <p>Results</p> <p>Using individual data on patients and health care workers in a teaching hospital during the 2004-2005 influenza season in Lyon (France), we show the ability of the model to assess the risk of influenza-like illness among hospitalized patients. The significant effects on the risk of influenza-like illness were those of old age, exposure to infectious patients or health care workers, and a stay in a medical care unit.</p> <p>Conclusions</p> <p>The proposed multiplicative hazard regression model could be an interesting epidemiological tool to quantify the risk of communicable disease at hospital during community epidemics and the uncertainty inherent in such quantification. Furthermore, key epidemiological, environmental, host, or exposure factors that influence this risk can be identified.</p

Semen cryopreservation, utilisation and reproductive outcome in men treated for Hodgkin's disease

Between 1978 and 1990, 122 men underwent semen analysis before starting sterilising chemotherapy for Hodgkin's disease. Eighty-one (66%) had semen quality within the normal range, 25 were oligospermic (<20×106 sperm per ml) and five were azoospermic (no sperm in the ejaculate). Semen from 115 men was cryopreserved and after a median follow-up time of 10.1 years, 33 men have utilised stored semen (actuarial rate 27%) and nine partners have become pregnant resulting in 11 live births and one termination for foetal malformation. Actuarial 10 year rates of destruction of semen before death or utilisation and death before utilisation are 19% and 13% respectively. This retrospective cohort study demonstrates that approximately one-quarter of men utilising cryopreserved semen after treatment for Hodgkin's disease obtain a live birth. The high non-utilisation rate is intriguing and warrants further investigation

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3&gt;2.1×10-12¿¿s/eV at 90% C.L

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Health care professionals' views on discussing sexual wellbeing with patients who have had a stroke: A qualitative study

OBJECTIVES: To examine the experiences of health care professionals discussing sexual wellbeing with patients who have had a stroke. DESIGN: In-depth qualitative interview study with purposive sampling and thematic analysis. PARTICIPANTS: 30 health care professionals purposively recruited to include different roles and settings along the stroke patient pathway in secondary and primary care. SETTING: Two hospitals and three general practices in the West Midlands, UK. RESULTS: Sexual wellbeing was a topic that participants did not raise with patients and was infrequently raised by patients. Barriers to raising discussion were on four levels: structural, health care professional, patient, and professional-patient interface. Barriers within these levels included: sexual wellbeing not present within hospital stroke policy; the perception that sexual wellbeing was not within participants' role; participants' concern that raising the issue could cause harm to the patient; and the views that discussion would be inappropriate with older people or unimportant to women. Resources exist to aid discussion but many participants were unaware of them, and most of those that were, did not use them routinely. CONCLUSIONS: Participants lacked motivation, ownership, and the confidence and skills to raise sexual wellbeing routinely after stroke. Similar findings have been reported in cancer care and other taboo subjects such as incontinence potentially resulting in a sub-optimal experience for patients. Normalisation of the inclusion of sensitive topics in discussions post-stroke does not seem to need significant structural intervention and simple changes such as information provision and legitimisation through consideration of the issue in standard care policies may be all that is required. The experiences recounted by professionals in this study suggest that such changes are needed now

Radiolucent lines in low-contact-stress mobile-bearing total knee arthroplasty: a blinded and matched case control study

<p>Abstract</p> <p>Background</p> <p>Low-contact-stress (LCS) mobile-bearing total knee arthroplasty (TKA) (Johnson & Johnson, New Brunswick, NJ; previously: DePuy, Warsawa, USA) provides excellent functional results and wear rates in long-term follow-up analyses. Radiological analysis shows radiolucent lines (RLL) appearing immediately or two years after primary implantation, indicative of poor seat. Investigations proved RLL to be more frequent in uncemented TKA, resulting in a consensus to cement the tibial plateau, but their association with clinical findings and patients discomfort and knee pain is still unknown.</p> <p>Methods</p> <p>553 patients with 566 low-contact-stress (LCS) total knee prostheses were screened for continuous moderate knee pain. We compared tibial stress shielding classified by Ewald in patients suffering from pain with a matched, pain-free control group on blinded X-rays. We hypothesized a positive correlation between pain and radiolucency and higher frequency of such radiolucent lines in the most medial and most lateral zones of the tibial plateau.</p> <p>Results</p> <p>Twenty-eight patients suffered from knee pain in total. Radiolucencies were detected in 27 of these cases and in six out of 28 matched controls without knee pain. We could demonstrate a significant correlation of knee pain and radiolucencies, which appeared significantly more frequently in the outermost zones of the tibial plateau.</p> <p>Conclusion</p> <p>Our findings suggest that radiolucent lines, representing poor implant seat, about the tibial plateau are associated with knee pain in LCS patients. Radiolucencies are observed more often in noncemented LCS, and cementing the tibial plateau might improve implant seat and reduce both radiolucent lines and associated knee pain.</p

A combination of gemcitabine and 5-fluorouracil in advanced pancreatic cancer, a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

In a randomized clinical trial, gemcitabine (GEM) was more effective than 5-fluorouracil (5-FU) in advanced pancreatic cancer patients. GEM and 5-FU have different mechanisms of action and their combination, from a theoretical point of view, could result in a higher activity. To test activity and feasibility of such a combination, a multi-institutional phase II study was initiated in November 1996 by the Italian Group for the study of Digestive Tract Cancer (GISCAD). Primary objectives of this study were to determine the activity in terms of response rate and clinical benefit, while the secondary objective was toxicity. According to the optimal two-stage phase II design, 54 patients were enrolled. Schedule was: GEM 1000 mg m(-2) intravenous (i.v.), and 5-FU 600 mg m(-2) bolus i.v. weekly for 3 weeks out of every 4. All the 54 patients were symptomatic (pain, weight loss, dyspepsia). A clinical benefit was obtained in 28 patients (51\%) (95\% confidence interval (CI) 38-64\%). Two patients achieved a partial response and 34 a stable disease. Median survival for all the patients was 7 months. Side-effects were mild: no gastrointestinal or haematological grade 3-4 toxicity (WHO) were recorded. We observed only six episodes of grade 2 (WHO) leukopenia and seven episodes of thrombocytopenia. Although the non-randomized design of this study suggests caution in the interpretation of these data, in consideration of the low incidence of toxicity and the favourable results obtained in terms of clinical benefit, it may be worthwhile to test more active schedules of 5-FU (continuous infusion) in combination with gemcitabine

Selenium Toxicity to Honey Bee (Apis mellifera L.) Pollinators: Effects on Behaviors and Survival

We know very little about how soil-borne pollutants such as selenium (Se) can impact pollinators, even though Se has contaminated soils and plants in areas where insect pollination can be critical to the functioning of both agricultural and natural ecosystems. Se can be biotransferred throughout the food web, but few studies have examined its effects on the insects that feed on Se-accumulating plants, particularly pollinators. In laboratory bioassays, we used proboscis extension reflex (PER) and taste perception to determine if the presence of Se affected the gustatory response of honey bee (Apis mellifera L., Hymenoptera: Apidae) foragers. Antennae and proboscises were stimulated with both organic (selenomethionine) and inorganic (selenate) forms of Se that commonly occur in Se-accumulating plants. Methionine was also tested. Each compound was dissolved in 1 M sucrose at 5 concentrations, with sucrose alone as a control. Antennal stimulation with selenomethionine and methionine reduced PER at higher concentrations. Selenate did not reduce gustatory behaviors. Two hours after being fed the treatments, bees were tested for sucrose response threshold. Bees fed selenate responded less to sucrose stimulation. Mortality was higher in bees chronically dosed with selenate compared with a single dose. Selenomethionine did not increase mortality except at the highest concentration. Methionine did not significantly impact survival. Our study has shown that bees fed selenate were less responsive to sucrose, which may lead to a reduction in incoming floral resources needed to support coworkers and larvae in the field. If honey bees forage on nectar containing Se (particularly selenate), reductions in population numbers may occur due to direct toxicity. Given that honey bees are willing to consume food resources containing Se and may not avoid Se compounds in the plant tissues on which they are foraging, they may suffer similar adverse effects as seen in other insect guilds

Distortion Product Otoacoustic Emissions Evoked by Tone Complexes

Distortion product otoacoustic emissions (DPOAEs) are traditionally evoked by two-tone stimuli. In this study, emission data from Mongolian gerbils are reported that were obtained with stimuli consisting of six to 10 tones. The stimuli were constructed by replacing one of the tones of a tone pair by a narrowband multitone complex. This produced rich spectra of the ear canal sound pressure in which many of the third-order DPOAEs originated from the interaction of triplets of stimulus components. A careful choice of the stimulus frequencies ensured that none of these DPOAE components coincided. Three groups of DPOAEs are reported, two of which are closely related to DPOAEs evoked by tone pairs. The third group has no two-tone equivalent and only arises when using a multitone stimulus. We analyzed the relation between multitone-evoked DPOAEs and DPOAEs evoked by tone pairs, and explored the new degrees of freedom offered by the multitone paradigm