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Time for medicine's re-entry.
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Proton scattering from an excited nucleus (18Fm,J pi =5(+),Ex=1.1 MeV) using a gamma -ray-tagged secondary isomeric nuclear beam.
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The detection of hepatitis B antigen in hepatic parenchyma by the fluorescent antibody technic.
Tissue sections from 42 specimens of liver were examined by indirect immunofluorescence microscopy for the presence of hepatitis B antigen (HB Ag). In all cases the serologic status of HB Ag was known. Fourteen of the specimens were also examined by electron microscopy. In four biopsies from three patients positive cytoplasmic fluorescence was detected using antisera prepared in animals and 20-nm. nuclear particles were found by electron microscopy. These patients were all seropositive for HB Ag, all had chronic aggressive hepatitis or active cirrhosis, and all were receiving immunosuppressive therapy at the time of examination. Nuclear fluorescent staining was demonstrated when one of these biopsies was re-examined using a human antiserum.
The arthropod Offacolus kingi (Chelicerata) from the Silurian of Herefordshire, England: computer based morphological reconstructions and phylogenetic affinities.
The small, non-biomineralized, three-dimensionally preserved arthropod Offacolus kingi Orr et al. from the Wenlock Series (Silurian) of Herefordshire, England, is re-evaluated, and the new family Offacolidae erected. This new study is based on specimens which have been serially ground, reconstructed by computer and rendered in the round as coloured models. Offacolus possesses a prosomal appendage array similar to that of Limulus, but also bears robust and setose exopods on appendages II-V which are unlike those found in any other arthropods. Opisthosomal appendages are similar in number and morphology to the book-gills of Limulus. Cladistic analysis places Offacolus basally within the Chelicerata, as a sister taxon to the eurypterids and extant chelicerates, but more derived than the Devonian Weinbergina.
Is there a bound dineutron in 11Li?
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Post-treatment sexual and prevention behaviours of adolescents with sexually transmitted infections.
OBJECTIVE: To evaluate sexual behaviour (including abstinence), sex partner change, and condom use during the 3 month period following treatment for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, or non-gonococcal urethritis. METHODS: 251 14-21 year old participants (83% female; 83% African-American) diagnosed with gonorrhoea, chlamydia, trichomonas, or non-gonococcal urethritis or sexual contacts of infected partners. Participants were clients of a public sexually transmitted diseases clinic or primary care adolescent clinics. Data were collected by structured interview at treatment, 1 month post-treatment, and 3 months post-treatment. At each visit, participants were asked about coital frequency and condom use for each recent partner. At 1 month, participants were asked when coitus occurred following treatment. At each follow up visit, sex partners were compared to partners named at treatment and classified as "same partner(s)," "new partner(s)," or both "same and new partner(s)." RESULTS: Post-treatment abstinence was reported by 26% and 19% for the 1 month and 3 month visits, respectively. Abstinence was associated with greater likelihood of infection at enrolment although abstainers reported fewer lifetime STI and fewer lifetime sex partners. A substantial proportion of participants reported additional sexual contact with a previous partner. The average proportion of condom protected coital events increased from about 45% at enrolment to 64% at 1 month and 58% at 3 months (p<0.05). Higher levels were sustained for the 3 months following treatment. CONCLUSIONS: Many adolescents adopt, at least temporarily, risk reduction behaviours such as abstinence or increased condom use. Sexual re-exposure to potentially untreated previous partners may increase risk of subsequent reinfection.
Electromagnetic excitation of 11Li.
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Coulomb dissociation of 11Li.
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Re-programming of expression of the KGFR and bek variants of fibroblast growth factor receptor 2 during limb regeneration in newts (Notophthalmus viridescens).
We have previously shown, by in situ hybridization, that fibroblast growth factor receptor 2 (FGFR2) is present in the basal layer of wound epithelium during limb regeneration in newts (Notophthalmus viridescens). In contrast, FGFR1 expression is observed throughout the blastema mesenchyme but is distinctly absent from the wound epithelium (Poulin et al. [1993] Development 119:353-361). Sequence analysis revealed that we have isolated both the KGFR and bek variants of FGFR2. These two variants differ only in the second half of the last of their three (or two) Ig-like domains. In this report, we show the expression patterns of FGFR2 variants during limb regeneration by in situ hybridization. During the pre-blastema stages of regeneration, FGFR2 expression was observed in the basal layer of the wound epithelium and in the cells of the periosteum. The wound epithelial hybridization was observed when the KGFR-specific probe was used while the bek-specific probe hybridized to mRNA in the cells of the periosteum. As regeneration progresses to the blastema stages, KGFR expression continued to be observed in the basal layer of the wound epithelium with additional hybridization seen in the blastema mesenchyme closely associated with the bisected bones. The bek-specific hybridization pattern observed at this stage corresponds specifically to the mesenchymal hybridization. In the differentiation stages of regeneration, the mesenchymal expression of FGFR2 becomes restricted to the cells of the condensing cartilage and later to the perichondrium. Interestingly, there appears to be a dorsoventral gradient of the expression of both KGFR and bek variants of FGFR2, which are opposite each other at the later stages of regeneration. Thus, re-programming of expression of the two FGFR2 variants is required during the initial wound closure of limb regeneration. Remarkably, the expression patterns of KGFR and bek mimic those observed in the mouse limb bud during early embryonic development (Orr-Urtreger et al. [1993] Dev. Biol. 18:475-486). Moreover, our results suggest that the two FGFR2 variants have distinct roles in limb regeneration. Further investigation regarding the potential sources of the FGF ligands will help establish the roles that FGFs and FGFRs play in limb regeneration.
Dose-intense phase II study of weekly cisplatin and epidoxorubicin plus medroxyprogesterone acetate and recombinant interleukin 2 in stage IIIB-IV non-small cell lung cancer.
The purpose of the study was to evaluate the effectiveness in terms of response rates, toxicity and survival of the combination chemotherapy regimen cisplatin and epidoxorubicin (epirubicin) including medroxyprogesterone acetate (MPA), recombinant IL-2 (rIL-2) and antioxidants in patients with advanced (stage IIIB-IV) non-small cell lung cancer (NSCLC). Thirty-three chemotherapy-naive patients with NSCLC were enrolled in the study and 30 of them were evaluable. The mean age of the patients was 61 years. Twenty (66.7%) out of 30 patients were >or=60 years, and 5 (16.7%) patients were >or=70 years. The ECOG performance status was 0 to 1 in 30 patients and 2 in 3 patients. Twenty-six patients (78.8%) had stage IIIB disease and 7 (21.2%) had stage IV; histology was mainly squamous cell carcinoma (72.7%). The treatment consisted of cisplatin 40 mg/m2/week and epirubicin 40 mg/m2/week both intravenously on day 1, rIL-2 1.8 MIU/day subcutaneously, MPA 1 g/day orally, alpha-lipoic acid 300 mg/day orally and N-acetyl cysteine 1.8 g/day orally. The treatment was administered for 6 weeks. Patients with a complete response (CR), partial response (PR) or stable disease (SD) continued the treatment, according to response re-evaluation, until 15 weeks. The present study reports the results of 6, 9, 12 and 15-week treatment. After 6 weeks, 30 patients were assessable for response: no CR was observed, a PR was achieved in 15 patients (50%; ORR 50%). After 15 weeks, 1 CR and 8 PR were observed (ORR 30.0%). The median follow-up period was 13 months. The median duration of response was 9 months. The median overall survival (OS) was 15 months. The one-year survival rate was 55.8%. The median progression-free survival (PFS) was 10 months. The toxicity was, as expected, mainly hematologic: neutropenia was the most significant symptom. The non-hematologic toxicity was quite low. Therefore, the treatment's toxicity was quite acceptable. There was no toxic death. The 30.0% ORR, the 15 month OS and the 10 month PFS obtained in this study are comparable with those observed with cisplatin plus epirubicin (ORR 39-54%) in phase II studies and in a previous phase III study (ORR 33%, OS 10.5 months). Moreover, the toxicity was acceptable and it was mainly hematologic. Serum levels of proinflammatory cytokines significantly decreased after treatment.
Development of a mental health programme in the Central Coast of New South Wales, Australia.
The Central Coast Programme is considered to have begun in December 1969 with the arrival and commitment of Dr Donald Scott-Orr (specialist psychiatrist) in the Central Coast, and with the parallel commitment of the then Medical Superintendent of Morisset Hospital, Dr Howard Gorton to support the development of a regional programme for the Central Coast. It was decided not to re-establish any clinics and so avoid waiting lists. There was an emphasis on groups as a means of interaction and a family orientation in the work. In the early years the role of the nurse was changing. Initially, the extramural role was expected by the hospital to be 'following-up' patients. However, the service was based on commitment to a community rather than hospital. Increasingly the nurses' work was directly referred to them independently of hospital admissions. Staff visited general practitioners (GPs) on the Central Coast in their surgeries and regular letters were sent keeping the GPs informed of changes in the service. Consultations and transactions were recorded on referral forms and files were opened on all persons concerning whom the service was consulted. A client's name was always linked with the name of their general practitioner who was encouraged to make telephone contact freely to seek consultative support in connection with problems in their practice. Priority for crisis intervention and orientation towards family and group was backed up by domiciliary visits and widespread communication and consultation. The attempt was made to use therapeutic community principles for the in-patient programme. The processes of care were seen as being as important as the content of care in assuring an optimum quality care. There is a continuing need to focus on the flexible interchange between intra- and extra-mural staff in providing continuity for clients in care and integration with primary care services and agencies. In January 1978 Dr Max Chapman was appointed director of the psychiatric and mental health services on the Central Coast and he is currently in that position.
Long-wavelength equation for vertically falling films.
An equation is derived for describing wave evolution on the surface of a vertically falling viscous film. The traditional long-wavelength scaling is replaced by a new scaling to reduce the (We) must be used instead of the Reynolds number (Re) to distinguish between viscous and inertia dominated regimes for vertically falling films. This equation includes viscous dissipation and pressure correction terms that are missing in the existing single evolution equations at the same order. Comparison of the neutral stability curves and growth rates predicted by different models to that of the Orr-Sommerfeld (OS) equation shows that our equation matches with the OS results better than the existing single evolution equations. However, our equation is not free from finite time blowup. Selective regularization leads to a two mode model in flow rate and film thickness. The regularized equation is free from finite time blowup and predicts two families of solitary waves. Numerical simulations of the derived equation and its regularized version in the traveling wave coordinate show the transition of wave structure from regular (periodic) to chaotic profiles. Model predictions on maximum wave amplitude on the low celerity branch show good agreement with experimental data.
Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM).
BACKGROUND: The aim of the study was to test the clinical efficacy and toxicity profile of gemcitabine (GEM) in combination with cisplatin (CDDP) in a series of patients affected by unresectable and/or metastatic biliary tree carcinoma (BTC) previously untreated with chemotherapy. PATIENTS AND METHODS: Overall 38 consecutive patients who satisfied eligibility criteria (10 with gall-bladder carcinoma and 28 with bile duct carcinoma) were included in this phase II study. Median age was 61 years with median PS 1. Treatment included GEM 1000 mg/m(2)/week as 30 min i.v. on days 1 and 8, and CDDP 75-80 mg/m(2) on day 1 with adequate hydration protocol and forced diuresis. Treatment was repeated every 3 weeks for three cycles before first re-evaluation of disease status. RESULTS: According to an intent-to-treat analysis a complete response (CR) was achieved in 1 patient (3%) with duration of 8 months. A partial response (PR) was recorded in 11 cases (29%; 95% CI 6% to 48%) with a median duration of 6.4 months (range 5-11 months) for an overall response rate (ORR) of 32%. Stable disease (SD) was seen in eight cases (21%), while the remaining 18 patients showed progressive disease (PD). Tumor growth control rate was 53%. Objective responses were recorded at loco-regional disease, liver and nodal metastases. Lung and peritoneal metastases did not respond. Time-to-progression was 4 months (range 2-11 months) and median overall survival was 8+ months (range 2-15 months). Side-effects were mild with few cases of grade 4 hematological toxicity. Transient and reversible liver toxicity was recorded in nearly one-quarter of patients. Infection without severe grade 4 neutropenia was observed in three cases. In no case was chemotherapy withdrawn for toxicity. CONCLUSION: The GEM/CDDP regimen is active against advanced and/or metastatic BTC with a favourable toxicity profile. This regimen represents a reasonable therapeutic choice for palliation of advanced BTC. Inferences concerning overall survival are difficult to draw due to the phase II nature of the study.
Monoclonal antibody therapy for B-cell lymphoma: clinical trials of an anti-CD20 monoclonal antibody for B-cell lymphoma in Japan.
Twelve patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (B-NHL) were enrolled in a phase I study of rituximab; 4 received rituximab 250 mg/m2 and 8 received rituximab 375 mg/m2 once weekly for 4 weeks. Grade 1 or 2 infusion-related toxicity was observed. Of the 11 eligible patients, 2 achieved complete responses and 5 achieved partial responses. The elimination half-life (T1/2) of rituximab was 445 +/- 361 hours, and serum rituximab levels were detectable at 3 months. Thereafter, 90 relapse patients with indolent B-NHL or mantle cell lymphoma (MCL) were enrolled in a phase II study and treated with rituximab at 375 mg/m2 per infusion in 4 weekly infusions. Sixteen patients were ineligible in protocol compatible analyses. The overall response rates (ORR) in indolent B-NHL and MCL were 61% (37 of 61 patients) and 46% (6 of 13 patients), respectively. Factors affecting response and progression-free survival (PFS) were analyzed for 77 patients whose histopathology was centrally confirmed as indolent B-NHL or MCL. The ORR in patients receiving 1 prior chemotherapy regimen was higher than the ORR in those receiving > or = 2 regimens (P < .05). The median PFS was shorter in MCL patients, in those with extranodal disease, and in those receiving > or = 2 prior chemotherapy regimens (P < .01). The PFS of patients with higher serum rituximab levels (> or = 70 microg/mL) immediately before the third infusion was longer than that of other patients (P < .01). Several pretreatment factors and serum rituximab levels are useful for predicting the efficacy of rituximab monotherapy. Rituximab re-treatment was well tolerated in 13 patients with no grade 3 or 4 nonhematological toxicities. A partial response was observed in 5 patients (38%), and the median PFS after re-treatment was 5.1 months. In conclusion, rituximab is a highly effective agent in relapsed indolent and aggressive B-NHL and MCL and has acceptable toxicities.
Effects of aspirin and prostaglandin E2 on secondary phase aggregation responses of schizophrenic patients treated with chlorpromazine.
We investigated the effects of oral aspirin 900 mg upon the platelet aggregation responses to 5-hydroxytryptamine, dopamine or N-dimethyl dopamine in schizophrenic patients chronically treated with chlorpromazine. Most subjects showed enchanced aggregation responses (that is appearance of secondary phase aggregation) to these agents prior to aspirin administration. When aggregation was re-tested 23.5 h after aspirin the secondary phase of the enhanced aggregation responses was abolished. Addition of 0.14-0.3 mumol/l prostaglandin E2 15 s after inducing aggregation partially restored the secondary phase. The observed secondary phase of aggregation may be due to increased prostaglandin synthesis or release.
An electrochemically driven poly(dimethylsiloxane) microfluidic actuator: oxygen sensing and programmable flows and pH gradients.
We describe the fabrication and performance of an integrated microelectrochemical reactor-a design possessing utility for multiple applications that include electrochemical sensing, the generation and manipulation of in-channel microfluidic pH gradients, and fluid actuation and flow. The device architecture is based on a three-electrode electrochemical cell design that incorporates a Pt interdigitated array (IDA) working (WE), a Pt counter (CE), and Ag pseudo-reference (RE) electrodes within a microfluidic network in which the WE is fully immersed in a liquid electrolyte confined in the channels. The microchannels are made from a conventional poly(dimethylsiloxane)(PDMS) elastomer, which serves also as a thin gas-permeable membrane through which gaseous reactants in the external ambient environment are supplied to the working electrode by diffusion. Due to the high permeability of oxygen through PDMS, the microfluidic cell supports significantly (>order of magnitude) higher current densities in the oxygen reduction reaction (ORR) than those measured in conventional (quiescent) electrochemical cells for the same electrode areas. We demonstrate in this work that, when operated at constant potential under mass transport control, the device can be utilized as a membrane-covered oxygen sensor, the response of which can be tuned by varying the thickness of the PDMS membrane. Depending on the experimental conditions under which the electrochemical ORR is performed, the data establish that the device can be operated as both a programmable pH gradient generator and a microfluidic pump.
The Cdt1 protein is required to license DNA for replication in fission yeast.
To maintain genome stability in eukaryotic cells, DNA is licensed for replication only after the cell has completed mitosis, ensuring that DNA synthesis (S phase) occurs once every cell cycle. This licensing control is thought to require the protein Cdc6 (Cdc18 in fission yeast) as a mediator for association of minichromosome maintenance (MCM) proteins with chromatin. The control is overridden in fission yeast by overexpressing Cdc18 (ref. 11) which leads to continued DNA synthesis in the absence of mitosis. Other factors acting in this control have been postulated and we have used a re-replication assay to identify Cdt1 (ref. 14) as one such factor. Cdt1 cooperates with Cdc18 to promote DNA replication, interacts with Cdc18, is located in the nucleus, and its concentration peaks as cells finish mitosis and proceed to S phase. Both Cdc18 and Cdt1 are required to load the MCM protein Cdc21 onto chromatin at the end of mitosis and this is necessary to initiate DNA replication. Genes related to Cdt1 have been found in Metazoa and plants (A. Whitaker, I. Roysman and T. Orr-Weaver, personal communication), suggesting that the cooperation of Cdc6/Cdc18 with Cdt1 to load MCM proteins onto chromatin may be a generally conserved feature of DNA licensing in eukaryotes.