Continuous infusional topotecan in advanced breast and non-small-cell lung cancer: no evidence of increased efficacy

Two open, phase II studies were performed to evaluate the activity and toxicity of infusional topotecan in patients with advanced non-small-cell lung carcinoma (NSCLC) and advanced breast cancer who had not received previous chemotherapy for metastatic disease. Twenty-five patients with an ECOG performance score < 2 were treated with infusional topotecan administered as a daily, continuous intravenous infusion starting at 0.6 mg m(-2) day(-1) (NSCLC) and 0.5 mg m(-2) day(-1) (breast cancer) for 21 days every 4 weeks. Three patients achieved a partial response as defined by WHO criteria: one with NSCLC (8%; 95% CI 0-39%) and two with advanced breast cancer (15%; 95% CI 2-45%). The major toxicities were neutropenia and thrombocytopenia, with one episode of neutropenic sepsis. These data suggest that topotecan delivered as a continuous intravenous infusion over 21 days as single-agent therapy does not appear to offer a clinical advantage over conventional 5-day schedules against advanced NSCLC and advanced breast cancer.     

Typology of prolonged anxious-phobic disorders with agoraphobia

There were studied 23 schizophrenic and cyclothymic patients with stable agoraphobia in the structure of anxiousphobic disorders (APD). No absolute correlation was found between stability of agoraphobia and severity of panic disorder (frequency and intensity of panic attacks). It was established that APD with manifestations of agoraphobia had been, perhaps, conditioned by the presence of comorbid disturbances in their structure which had determined peculiarities of the patients' behavior. Two types of prolonged APD with agoraphobic phenomena were recognized. Retention of agoraphobic disturbances in conditions of the first type was related to symptoms of generalized somatic disorder (generalized somatic anxiety) in clinical pattern of APD. Manifestations similar to panphobias prevailed, agoraphobic avoidance included all the situations in which the patient could find himself without help. In the states of the second type retention of agoraphobic disorders was conditioned by comorbidity of APD with asthenohypochondriac manifestations with somato-psychic fragility in their structure. Anxiety of expectation was formed in situations with emotional or physical tension. Agoraphobic avoidance in conditions of this type had displayed the character of preventive measures and one of manifestations of hypochondriac development of personality. The presence of pronounced anxiety (intensive panic attacks, generalized anxiety) in clinical pattern of prolonged agoraphobic conditions can serve a predictor of a favourable development of the disease.     

Texturing 3D-reconstructions of the human brain with EEG-activity maps

There is only a limited amount of definite knowledge on the course of schizophrenic psychoses, although 100 years have passed since they were first described by Kraepelin as "Dementia praecox". The main reason for this is that most studies done thus far suffer from more or less serious methodological shortcomings: samples were often highly selective; investigations were often not direct, not prospective and almost never continuous, which would be of utmost importance in an episodic disease such as schizophrenia; assessments in older studies were neither standardized nor tested for validity or reliability; in more recent studies they were often not conducted by experienced psychiatrists; patients who refused to participate or who died during the study period were widely neglected. Nevertheless, we have learned that schizophrenic psychoses do not have a steadily deteriorating course ending in "dementia". On the contrary, the course of these psychoses seems very heterogeneous. Due to their methodological shortcomings, studies done thus far even seem to have underestimated heterogeneity by partly neglecting patients with very good outcome, on the one hand, and very poor outcome, on the other hand.     

Effect of polymerization temperature and time on the residual monomer content of denture base polymers

The aim of this study was to investigate the effect of polymerization time and polymerization temperature on the residual methyl methacrylate (MMA) content of two heat-cured and two autopolymerized denture base polymers. Gas chromatography was used to determine the residual MMA content of three test specimens of each type of polymer. Increasing the polymerization temperature for the autopolymerized denture base resins from 30 degrees C to 60 degrees C decreased the residual MMA content of the polymer from an average of 4.6 wt% to 3.3 wt%. With the heat-cured denture base resins, a curing cycle at a polymerization temperature of 70 degrees C followed by a period at 100 degrees C significantly reduced the residual monomer content of the polymer when compared with a resin cured at 70 degrees C only. Polymerizing the heat-cured denture base resin at 100 degrees C only for various lengths of time significantly affected the residual MMA content of the polymer. The lowest residual MMA content (0.07 wt%) was obtained by polymerizing the heat-cured denture base resin at 100 degrees C for 12 h. The results of this study suggest that the polymerization temperature and polymerization time considerably affect the residual MMA content of denture base polymers.     

Antinociceptive analogs of orphanin FQ/nociceptin(1-11)

The presence of pairs of basic amino acids within the sequence of orphanin FQ/nociceptin (OFQ/N) peptide, the endogenous ligand for the ORL1/KOR-3 receptor, has raised the possibility that processing might generate pharmacologically important truncated peptides, including OFQ/N(1-11). OFQ/N(1-11) is pharmacologically active in vivo with a potency comparable to OFQ/N. Several tyrosine-containing analogs of OFQ/N(1-11) have been synthesized and examined for antinociceptive activity. Like OFQ/N(1-11), [Tyr1]OFQ/N(1-11), [Tyr10]OFQ/N(1-11) and [IodoTyr10]OFQ/N(1-11) given supraspinally in mice were antinociceptive in the tailflick assay in mice. The tyrosine analogs showed similar potencies as OFQ/N(1-11) but longer durations of action. This response was readily reversed by the opioid antagonist naloxone despite poor affinities for these analogs at opioid receptors. Another compound, [Tyr11]OFQ/N(1-11) was highly epileptogenic, inducing naloxone-sensitive seizures in greater than 50% of the mice tested at doses comparable to those examined with the other analogs. These results indicate that it is possible to make analgesic OFQ/N(1-11) analogs. The activity of [IodoTyr10]OFQ/N(1-11) suggests that it may prove useful as a radioligand in exploring potential OFQ/N(1-11) binding sites.     

Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

OBJECTIVE: It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. METHODS: HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE). RESULTS: In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22). CONCLUSIONS: The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.     

Obstetric analgesia in Norwegian hospitals]

We report the results of a questionnaire sent to anaesthetists and midwives on the use of obstetric analgesia and anaesthesia in Norwegian hospitals in 1996. 95% of the 49 hospitals involved responded to the questionnaire, representing a total of 56,884 births. The use of epidural analgesia in labour varied from 0 to 25% in the different hospitals with a mean value of 15%. Epidural analgesia was much more widely used in university and regional hospitals than in local hospitals (p < 0.001). Five of the local hospitals did not offer epidural analgesia during labour at all. The combination of low-dose local anaesthetic and an opioid (either sufentanil or fentanyl) had not been introduced in nine of the hospitals (20%). The optimal use of epidural analgesia to relieve labour pain was judged to be more frequent by the anaesthetists than by the midwives (19% versus 11%, p < 0.01). In response to what factors limited the frequency of epidural analgesia, the anaesthetists specified factors related to the attitude of the midwife, and the midwives specified factors related to the anaesthetist. Only five of the hospitals provided written information on the various analgesic methods that could be employed during labour. The majority of midwives considered the analgesic methods employed on their maternity ward to be good or excellent. The frequency of Caesarean section was 12%; spinal anaesthesia was used in 55%, epidural anaesthesia in 17%, and general anaesthesia in 28% of the cases.     

Liulin-type spectrometry-dosimetry instruments

The main purpose of Liulin-type spectrometry-dosimetry instruments (LSDIs) is cosmic radiation monitoring at the workplaces. An LSDI functionally is a low mass, low power consumption or battery-operated dosemeter. LSDIs were calibrated in a wide range of radiation fields, including radiation sources, proton and heavy-ion accelerators and CERN-EC high-energy reference field. Since 2000, LSDIs have been used in the scientific programmes of four manned space flights on the American Laboratory and ESA Columbus modules and on the Russian segment of the International Space Station, one Moon spacecraft and three spacecraft around the Earth, one rocket, two balloons and many aircraft flights. In addition to relative low price, LSDIs have proved their ability to qualify the radiation field on the ground and on the above-mentioned carriers.