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BACKGROUND: Anxiety adversely affects quality of life and is common in adults with advanced life-limiting disease. There are no UK-wide guidelines on the assessment and management of anxiety in this specific population and there is little evidence regarding drug treatments. This study aimed to explore how palliative care physicians assess and manage anxiety in their patients, and to identify barriers encountered. METHODS: A cross-sectional survey was undertaken of all physicians working in specialist palliative care in the UK who were members of the Association for Palliative Medicine. This was conducted in February 2014 using an online questionnaire. RESULTS: The response rate was 23% (230/980) and 61% of respondents were consultants. Most did not use tools to screen for anxiety (87%) and almost all used the clinical interview to diagnose anxiety (99%). Only 8% used psychiatric criteria. Most physicians reported difficulties managing anxiety (93%). Only 33% thought they had adequate training in this area. Most had difficulty accessing psychological and/or psychiatric services (71%, 64% respectively). The majority used a combination of pharmacological and non-pharmacological treatments for anxiety. The most frequently prescribed first-line medications for patients with a prognosis of days to weeks were benzodiazepines (93%), usually lorazepam. The use of benzodiazepines over antidepressants was statistically significant (p < 0.001). For patients with a prognosis of months, antidepressants were most frequently prescribed first-line (60%), significantly more than benzodiazepines (p < 0.001). However, benzodiazepine use was still common in this prognostic group with 47% prescribing it first-line, sometimes in combination with an antidepressant. CONCLUSION: This is the first national survey on the assessment and management of anxiety in palliative care. Findings demonstrate the infrequent use of screening tools, variation in prescribing practice, potentially inappropriate use of benzodiazepines for patients with a prognosis of months, training gaps and poor access to psychological and psychiatric services in the UK. This highlights the need for formal training, further research into the pharmacological management of anxiety in this population and evidence-based national guidance to support clinical decision-making and service development.

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Karyotypic studies of eight endometrioid carcinomas of the endometrium in this laboratory, four colorectal polyps (from this laboratory or reported in the literature), and four early carcinomas of the ovary (from the literature), provide evidence that clonal evolution leading to malignant neoplasms at these sites originates when a cell acquires a single additional chromosome. In different tumors, different chromosomes may be involved in this change from euploidy to aneuploidy. Since the resultant clones of trisomic cells occur at an early stage of tumor development, their presence is only likely to be determined when they are at a location that is accessible for study. As aneuploidy is a virtually constant feature of malignancy, the possibility that the concept of a single trisomy as the initial event in the development of all malignant solid neoplasias should be addressed.

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Recent interest has focused on endometrioid carcinomas of the endometrium in view of the frequent occurrence of microsatellite stability, accompanied by a favorable prognosis, and by near-diploidy when studied by flow cytometry. The latter feature fails to address the question whether (and to what extent) the karyotypes of the tumor cells may or may not be truly diploid, an important feature on which there is virtually no information. A reconsideration of earlier published and unpublished work in this laboratory on near-diploid carcinomas of the endometrium, and comparable studies on near-diploid ovarian carcinomas (a site where endometrioid carcinomas are also commonly found) has therefore been undertaken. In the endometrium, these studies have clearly shown that carcinomas with near-diploid chromosomes are in fact commonly hyperdiploid, often of endometrioid histology, and in many instances show a single additional chromosome, differing in different tumors, as the apparently sole chromosome change. By contrast, similar studies on the ovary (which also included several endometrioid carcinomas) revealed a tendency towards hypodiploidy, with loss of a few chromosomes, as well as the presence of structural chromosome changes and a generally poor prognosis.

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Unlike aneuploidy, considered to be the cardinal feature of malignant tumors ever since the chromosomal analysis of neoplastic cells became technically feasible, a second pathway toward malignancy has emerged over the past decade that is not characterized by gross aneuploidy but, instead, by inactivation of the DNA mismatch repair system, leading to a hypermutable state in which simple repetitive DNA sequences are unstable during DNA replication. Although mutations of many of these microsatellite sequences are presumably innocuous, because they do not occur in the coding or regulatory regions of genes, other such sequences are critically located in the coding regions of genes involved in the regulation of cell growth. First discovered in the rather uncommon hereditary nonpolyposis colorectal cancer syndrome, where there is an inactivating germline mutation in one of the DNA mismatch repair genes and most of the tumors show microsatellite instability, the latter phenomenon has since been implicated in about 15% of sporadic colorectal cancers, as well as in cancers at several other sites, such as the endometrium. Tumors showing microsatellite instability are generally near-diploid, are at a low stage of development, have a favorable prognosis, and, in the colon, are commonly located on the right side. In recent years, epigenetic phenomena, including hypermethylation and loss of imprinting, have come to be recognized as having a significant bearing on the development of these tumors.

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OBJECTIVES: (1) To measure the extent of use of preventer medications (ie, inhaled corticosteroids or cromones) and possession of written asthma management plans (AMPs) among people with asthma in New South Wales in 1997. (2) To assess factors associated with underuse of preventer medications and AMPs. DESIGN AND SETTING: A cross-sectional survey by computer-assisted telephone interviews of a stratified random sample of the adult population of New South Wales, Australia. PARTICIPANTS: People aged 16 to 54 years with asthma diagnosed by a doctor and causing symptoms or requiring treatment in the preceding year (n = 1,372). RESULTS: Although 55.2% of survey participants had used preventer medications in the preceding year, only 27.8% had used them regularly. Only 34.7% had a written AMP. Preventer medications were judged to be indicated for 54% of the study population, but only 42.5% of this group had used them regularly (43.1% had a written AMP). Younger adults were less likely to use preventer medications regularly, but there was no difference in use of preventer medications by sex, urban/rural residence, or manner of purchasing reliever medications (either on prescription or "over the counter"). Past smokers used preventers more commonly than current smokers, with never smokers having an intermediate prevalence of regular preventer use. Age, sex, urban/rural residence, and manner of purchasing reliever medications were not related to the possession of an AMP. CONCLUSION: Despite the trend towards increased use of preventer medications and written AMPs during the 1990s, undertreated asthma remains a major public health problem in Australia.

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Changes in gellan polymer morphology during the sol-gel transition were directly visualized by transmission electron microscopy and a model incorporating these changes and existing physical data is proposed. Our observations suggest that the most thermodynamically stable conformations of gellan polymers in solution, in the absence of added cations, are the double helix and double-helical duplexes. We have demonstrated two forms of lateral aggregation of gellan helices in the presence of Ca(2+) and K(+) ions. One type forms junction zones that lead to network formation and gelation, while the second type leads to the formation of isolated fibers of aggregated helices and inhibition of gelation. The proposed model of gellan gelation is based on these observations where thermoreversibility, gel strength, and endothermic transitions of gellan gels can be explained.

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Recent molecular evidence points to defects in cell cycle checkpoints as one of the most important events in the transformation of normal to malignant cells. A byproduct of, if not a critical step brought about by, these defects is the occurrence of polyploidization; near-tetraploid and near-octoploid cells are a common feature of cancers, and the neoplastic stemline may itself attain a high (e.g., near-tetraploid) value. This short review cites cases in which polyploidization is frequent, even at an early stage of tumor development, and considers the probability that, once a high stemline has arisen, there is increased instability with the likelihood of further chromosome changes. A possible example of the latter is a lymphoma in which tetraploid and hypotetraploid metaphases were found, the latter, interestingly, showing an apparently preferential loss from tetraploidy of chromosome 10. It appears, therefore, that a stemline was emerging consequent to (a) chromosome doubling resulting in tetraploid cells, and (b) the appearance of a hypotetraploid line in which chromosome 10 was under-represented. Alternately, there might have been a repeated loss of chromosomes from tetraploid cells that preferentially included chromosomes 10.

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Two chromosomes that undergo nonrandom changes in carcinoma of the cervix and have been studied for several decades in this laboratory are discussed. The first, chromosome 5, is discussed in view of the frequent appearance of an isochromosome for 5p, often in two or more copies and commonly associated with fewer that the expected number of normal copies of this chromosome. The second is chromosome 17, where a translocation involving another chromosome may result in a 17p+, and the significant change appears to be a loss from 17p that may include the p53 gene (TP53) and/or other tumor-suppressor genes located on this chromosome arm.

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Deletions of the long arm of chromosome 6 (6q) are frequent chromosome aberrations in non-Hodgkin lymphomas (NHLs) and acute lymphoblastic leukemias (ALLs). It is presumed that one or more tumor suppressor genes are localized on 6q. By means of fluorescence in situ hybridization (FISH), we attempted to detect and delineate deletions of 6q in leukemias and lymphomas. We performed FISH on 148 cases of lymphoma and acute leukemia using a panel of 36 YAC probes distributed from 6q12 to 6q27 and a centromeric probe of chromosome 6 as internal control. Deletions of 6q that included a 7-cM commonly deleted region in 6q21 were detected in 59 patients who had B- and T-cell low-grade and high-grade NHL and ALL. FISH with two YAC probes flanking this region was performed on an additional 97 cases of NHL and leukemia. Deletions in 6q21 were detected in an additional 21 cases. In five cases of high-grade B- and T-cell NHL and ALL, the deletion breakpoints were located within the commonly deleted region. To define the deletion breakpoints exactly and to narrow this region further, FISH was performed with six additional YAC probes that have been physically localized within this region. A 3-cM (4-5 Mb) commonly deleted region in 6q21 was delineated. Our study suggests that this commonly deleted region harbors a putative tumor suppressor gene involved in the pathogenesis of both low-grade and high-grade NHL and ALL. Genes Chromosomes Cancer 27:52-58, 2000.

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OBJECTIVE: We aimed to assess whether GP input into discharge planning for high-risk aged in-patients admitted under the care of a geriatrician results in improved patient outcomes. METHODS: We conducted a prospective randomized controlled trial in Sydney, Australia. The subjects were 364 patients aged 60 years and over. The main outcome measures included community service referral, accommodation changes, length of stay, readmission rate, length of time to first readmission and patient satisfaction with discharge arrangements. RESULTS: No significant differences were found with regard to length of stay, readmission rates or time to first readmission. Test-group subjects were significantly more likely to be recommended for community services at discharge and to report that hospital personnel had discussed their discharge plan with them. Significantly more of the test group reported that their return home was well prepared. CONCLUSIONS: Although GP pre-discharge visits did not alter the likelihood of 'hard outcomes such as risk of readmission', the results suggest that quality of care is enhanced amongst patients receiving a pre-discharge visit and that GPs can perform a key role in planning post-discharge care with other services.

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Cytogenetic studies over the past 35 years have made a major contribution towards the understanding of the nature of Hodgkin's disease by demonstrating unequivocally the consistent presence of a clonal population of cells that have the cardinal features of malignancy e.g. more or less gross aneuploidy, frequently with complex chromosomal changes and showing considerable variation from case to case, thus comparable to the findings in carcinomas and other solid cancers. The mode is frequently in the triploid-tetraploid region, as we found in 17 of 27 cases studied in this laboratory by Feulgen microspectrophotometry, compared to only 10 cases with neardiploid modes. It is disappointing that no specific change, such as a translocation that could give a clue to the chromosomal location of a gene or genes involved in the etiology of Hodgkin's disease, has yet been found. Nevertheless it is clear that a number of nonrandom changes, including several that are also common in other malignancies including the non-Hodgkin's lymphomas, are frequently present, e.g., deletions of 1p, 6q, and 7q. Interestingly, deletions of 4q, with loss of 4q25 --> q27, that have also been reported may show some specificity for Hodgkin's disease.

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We describe a diffuse large cell (Kiel-1) lymphoma in a 76-year-old man that is noteworthy because, apart from a missing Y, the only chromosome change was a hitherto undescribed reciprocal translocation, t(9;11)(p21-22;q13). It is interesting that the breakpoints lay in the vicinity of genes that encode proteins engaged in cell cycle control: CCND1 situated at 11q13 and p15 and p16 at 9p21.

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OBJECTIVE: To compare GPs' willingness to participate in a GP pre-discharge project as measured by a survey, with actual participation rates. To identify the characteristics of GPs likely to make a pre-discharge visit to frail, aged inpatients admitted under the care of a geriatrician. METHOD PRE-IMPLEMENTATION GP SURVEY: Survey of a random sample of 100 GPs from the Central Sydney area using a standardised questionnaire. PRE-DISCHARGE VISIT PROJECT: Information on actual participation rates and GPs who declined to make a pre-discharge visit was obtained from an audit of Division of General Practice records. Information on Patient characteristics was obtained from patient interviews and medical records. The survey was conducted at the Balmain Hospital and Concord Repatriation and General Hospitals located within the Central Sydney Area Health Service. The subjects were GPs practising in central Sydney and patients admitted under the care of a geriatrician at Balmain and Concord Hospitals. RESULTS: Twenty-nine per cent of GPs reported that they were willing to undertake visits without remuneration and 71% reported they were willing to make a pre-discharge visit if remunerated. Fifty-three per cent of GPs actually complied with a request to make a remunerated pre-discharge visit. This was 18% less than the rate determined by the survey. GPs were less likely to make a visit if they were solo practitioners and not members of the Division. Patients who were more dependent, as measured by total Barthel's score, and those from nursing homes were less likely to receive a visit. CONCLUSION: GP surveys may overestimate participation rates in Division projects. In reality, it appears difficult for GPs to accommodate pre-discharge visits in a general practice routine and the offered remunerations may not be adequate compensation for time lost when undertaking a pre-discharge visit. Lastly, some GPs may not see a benefit in visiting more dependent patients.

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Cytogenetic studies on carcinoma of the cervix have shown the nonrandom involvement in structural changes of a number of chromosomes, particularly chromosomes 1, 3, 5, 11, and 17. Apart from chromosome 5, where a short-arm isochromosome is the commonest derivative, these chromosomes most often undergo short-arm deletions. Notably, chromosome 17 may have undergone structural changes that result in loss of the tumor suppressor gene TP53 on 17p; chromosomal translocations may in some tumors perform the function that in others is provided by human papillomavirus protein complexing with and inactivating this gene. The chromosome 1 changes may sometimes result in the duplication of long-arm material. Although there have been few comparable studies on the preinvasive stages of cancer of the cervix, it is clear from earlier chromosome and quantitative DNA studies that, except perhaps in the "mild dysplasias," there already is clonal development that has resulted in an aneuploid population with a mode that, as in carcinomas, is either in the diploid or (in 50% or more) triploid-tetraploid range; spindle defects are prominent and may result in unequal segregation of the chromosomes into the daughter cells. Further characterization of the chromosomal changes in carcinoma of the cervix, and more particularly its preinvasive stages, using the new molecular DNA techniques is eagerly awaited.

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Fluorescence in situ hybridization using centromeric probes for chromosomes 7 and 10 in a follicular lymphoma revealed only one signal in about 40% of interphases, whereas two copies of each chromosome were consistently seen in metaphases. In four out of 18 metaphases both copies of chromosome 7 were situated close to one another. In contrast, two signals for chromosome 1 were seen in 94% of interphases, consistent with observations on metaphases. The findings suggest chromosome-specific somatic pairing, the functional significance of which is at present unknown, and reinforce previous evidence suggesting that care should be taken in the interpretation of interphase signal numbers using centromeric probes in neoplastic as well as normal material.

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Specific human papilloma virus (HPV) types appear to be necessary etiological factors for most cervical cancers, yet additional genetic alterations seem to be required for their development and progression. The aim of this study is to determine the likely chromosomes location of tumorigenicity suppressor-like genes, the loss of function of which might be important in the origin or progression of cervical carcinomas. PCR with primers for 75 highly polymorphic microsatellite loci located on the major autosome arms were used to estimate the incidence of loss of heterozygosity (LOH) in 38 tumors. The HPV status of the tumors was also determined. LOH was found to involve 19 chromosome arms in 20-43% of the tumors. Chromosome arms 6p, 3p, and 18q are most frequently involved in LOH in 43, 39, and 35% of the informative carcinomas, respectively. The respective regions involved are 6p21.1-23, 3p13-25.3, and 18q12.2-21.2. LOH is generally limited to specific band segments within these regions. Similar high incidences of LOH of the same 3p segments have been reported in cervical carcinomas from different parts of the world. The same 3p and 6p segments are involved in many types of common cancers, whereas 18q changes are less frequent in other cancers. Chromosome arms 1q, 2q, 3q, 4p, 4q, 5p, 5q, 6q, 7q, 8p, 8q, 11q, 13q, 16p, 18p, and 19p are involved in LOH in 20-33% of the cervical tumors. Chromosome 11 alterations are among the most frequently found in many different types of neoplasias. In this study, 11p was involved in 16% of the tumors, and 11q was involved in 22%. Chromosome 17 alterations are found in more cancers than those of any other chromosome, frequently involving the p53 gene on 17p. LOH of 17p was found in 5 (15%) cervical tumors; 2 of these were HPV negative and expressed mutant p53. In such HPV-negative tumors, direct mutation of the wild-type p53 appears to replace the inactivation of the p53 product by oncogenic HPV types. Tumors with LOH at many loci were, on the average, at more advanced stages, as were tumors with mutant p53. The higher overall incidence of LOH in cervical carcinomas as compared to other cancers, and the diversity of LOH patterns found, suggest that different cervical carcinomas probably arise and/or progress, in part, because of the loss of function of different yet finite sets of tumorigenicity suppressor genes and genes that are involved in tumor progression and metastasis. The findings also indicate that certain chromosome segments that are often altered in cervical carcinomas are also frequently altered in several other types of cancers. It remains to be determined whether the same or different genes located within these segments are involved in the different cancer types.

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