Association between psychological distress and cancer type in patients referred to a psycho-oncology service.

Psychological distress is common in patients with cancer and psychological well-being is increasingly seen as an important component of cancer care. The aim of this study was to examine the relationship between cancer type and subjective distress. The following data were collected from a database of consecutive psycho-oncology referrals to the Liaison Psychiatry service in Cork University Hospital from 2006 to 2015: demographics, cancer diagnosis, Distress Thermometer (DT) score. 2102 out of 2384 referrals were assessed. Of those assessed, the most common cancer diagnoses were breast (23%, n=486) followed by haematological (21%, n=445). There were significant difference in DT score between the different cancer types, (?2(13)=33.685, p=0.001, Kruskal-Wallis test). When adjusted for age, gender and whether or not the cancer was recently diagnosed, there was no significant association between cancer type and psychological distress. In conclusion, cancer type is not associated with level of distress in cancer.

ß-Catenin is required for intrinsic but not extrinsic BCR-ABL1 kinase-independent resistance to tyrosine kinase inhibitors in chronic myeloid leukemia.

Activation of nuclear ß-catenin and expression of its transcriptional targets promotes chronic myeloid leukemia (CML) progression, tyrosine kinase inhibitor (TKI) resistance, and leukemic stem cell self-renewal. We report that nuclear ß-catenin has a role in leukemia cell-intrinsic but not -extrinsic BCR-ABL1 kinase-independent TKI resistance. Upon imatinib inhibition of BCR-ABL1 kinase activity, ß-catenin expression was maintained in intrinsically resistant cells grown in suspension culture and sensitive cells cultured in direct contact (DC) with bone marrow (BM) stromal cells. Thus, TKI resistance uncouples ß-catenin expression from BCR-ABL1 kinase activity. In ß-catenin reporter assays, intrinsically resistant cells showed increased transcriptional activity versus parental TKI-sensitive controls, and this was associated with restored expression of ß-catenin target genes. In contrast, DC with BM stromal cells promoted TKI resistance, but had little effects on Lef/Tcf reporter activity and no consistent effects on cytoplasmic ß-catenin levels, arguing against a role for ß-catenin in extrinsic TKI resistance. N-cadherin or H-cadherin blocking antibodies abrogated DC-based resistance despite increasing Lef/Tcf reporter activity, suggesting that factors other than ß-catenin contribute to extrinsic, BM-derived TKI resistance. Our data indicate that, while nuclear ß-catenin enhances survival of intrinsically TKI-resistant CML progenitors, it is not required for extrinsic resistance mediated by the BM microenvironment.

Spondyloarthropathy in the community: differences in severity and disease expression in Alaskan Eskimo men and women.

OBJECTIVES: To determine the relative severity and compare the clinical expression of spondyloarthropathy (SpA) in men and women. METHODS: A clinical study was conducted in 43 women and 40 men who made up 80% of all individuals identified as having SpA in a community-wide epidemiologic study of Alaskan Eskimos. The study included interviews, physical, laboratory, radiographic and electrocardiographic examinations, record reviews, and functional assessments. A measure of relative severity was developed to evaluate disease impact in individual patients. The results in men and women were compared. RESULTS: No significant differences between men and women were found in many features, including the age of onset, frequency of inflammatory joint swelling or inflammatory back pain, physical signs of sacroiliitis, presence of skin changes, or positive family history of SpA. Women were less likely to have sacroiliac joint fusion, advanced spinal changes, uveitis, severe cardiac conduction and valvular abnormalities, and elevated erythrocyte sedimentation rates. According to our relative severity measure, a smaller proportion of women had severe disease than men. CONCLUSION: Although as many women as men were affected by SpA in the communities studied, severe disease was seen more often in men and a number of disease manifestations were more frequent or more marked in men. These discrepancies in disease severity and expression may contribute to the underdiagnosis of SpA in women and the long standing impression that SpA is a disease predominantly of men.

Spondyloarthropathy in the community: clinical syndromes and disease manifestations in Alaskan Eskimo populations.

OBJECTIVE: To define the clinical spectrum and disease manifestations of spondyloarthropathy (SpA) as seen in a community, rather than a referral setting. METHODS: Eighty percent (83/104) of all individuals identified as having SpA in a community wide epidemiologic study of Alaskan Eskimos and 83 age and sex matched controls from the same regions participated in a 5 year clinical study. The study included baseline and followup interviews, physical, radiographic, and electrocardiographic examinations, record reviews, and functional assessment. The medical records of an additional 83 age and sex matched controls were reviewed and followed over the same 5 year period. RESULTS: The spectrum of disease varied from very mild undifferentiated SpA (USpA) to incapacitating ankylosing spondylitis (AS). Most cases were mild. Overlapping clinical features were common in the different syndromes; 10% of the cases met more than 1 set of disease criteria. Axial signs and symptoms were more frequent in patients with AS, but occurred in over half of the patients with USpA and reactive arthritis (ReA) also. Peripheral joint involvement was noted in 85% of the AS cases, usually early in the course of disease. The patterns of joint involvement and enthesopathy were similar in SpA subjects with different syndromes and significantly different from those in control subjects. Patients with AS had a higher frequency of uveitis and of aortic root disease than patients with other syndromes. CONCLUSION: The results illustrate the extent of shared clinical features in the different SpA syndromes, and describe the frequency of different features associated with SpA in patients and matched controls in a community setting. ReA and USpA were more prevalent and less severe than AS in these populations.

Prevalence of rheumatoid arthritis in circumpolar native populations.

OBJECTIVE: To compare the prevalence of rheumatoid arthritis (RA) in related, but geographically separate, indigenous circumpolar populations. METHODS: Cases were identified by community survey in Russia and by examination of cases located through arthritis registries, a computerized patient information database, and query of local health care providers in Alaska. All possible cases were verified by examination and application of the American College of Rheumatology 1987 criteria. RESULTS: The prevalence rates of RA (age standardized to US population of 1980) varied from 0.62% in the Alaskan Yupik to 1.78% in the Alaskan Inupiat. The Russian Chukchi rate was 0.73% and that of the Siberian Eskimo was 1.42%. CONCLUSION: The Alaskan Yupik Eskimo and Chukchi natives had prevalence rates of RA within the usual range of North American Caucasian groups, in contrast to the Russian Siberian Eskimo and the Alaskan Inupiat Eskimo of the Barrow region, whose high rates approached those of unrelated North American native groups living in very different environments. The Alaskan Inupiat rate was significantly higher than that of the Alaskan Yupik (OR = 2.51, 95% CI 1.25-5.07; p = 0.013), but statistical inferences are limited in the Russian study populations by the small case numbers. The high prevalence rates probably have a genetic basis, although an environmental influence cannot be excluded.

The synthesis of new adenosine A3 selective ligands containing bioisosteric isoxazoles.

The synthesis and purinergic receptor binding of novel adenosine A3 ligands is described. Many selective A3 receptor agonists e.g. N-(3-iodobenzyl)adenosine-5'-methyluronamide (IB-MECA) contain a 4'-ribosylalkylamide moiety. We found that this amide and other 4'-functional groups could be replaced with an isosteric isoxazole, and the target molecules retained potent binding to the recombinant human A3 receptor.

A comparison of patients with spondyloarthropathy seen in specialty clinics with those identified in a communitywide epidemiologic study. Has the classic case misled us?

BACKGROUND: Undiagnosed cases of seronegative spondyloarthropathy (Spa) are often observed during epidemiologic studies. OBJECTIVE: To determine the extent of and the reasons for the underdiagnosis of Spa. METHODS: We studied 2 groups of Alaskan native patients with Spa using a standardized protocol that included an interview, physical examination, medical record review, and radiographic and laboratory examinations. One group consisted of patients identified in a communitywide epidemiologic study; the other group consisted of patients from related but geographically separate populations who had been diagnosed by a specialist in the hospital or a specialty clinic. All cases met the current classification criteria for Spa. The clinical and demographic features of the cases in the 2 groups were compared. RESULTS: Fifty-five (72%) of the 76 community cases that we identified in the epidemiologic study had not been diagnosed previously as Spa. Among the undiagnosed patients were 34 (94%) of the 36 women, 11 (65%) of the 17 patients with ankylosing spondylitis, 12 (36%) of the 33 patients with reactive arthritis, and 24 (100%) of those with undifferentiated Spa. The community and specialty clinic patient groups were similar in age of onset of joint and back pain and in overall symptoms. The specialty clinic group had a higher proportion of men, more severe disease, and a higher frequency of iritis. CONCLUSIONS: The diagnosis of Spa was missed more often than not in the primary care setting, probably because most of the cases were of mild or moderate severity and did not fit the classic descriptions of spondyloarthropathic disorders. The higher proportion of men among the specialty clinic cases probably reflects provider expectation as well as a slightly milder disease course in women.

Urban birth and residence as risk factors for psychoses: an analysis of 1880 data.

It is known that social drift to cities increases the urban prevalence for severe mental illnesses. Recent studies in England and Sweden have reported that being born in, or raised in, an urban area is also a risk factor for later developing schizophrenia. The present study utilized 1880 census data, the most complete enumeration of severely mentally ill individuals ever done in the United States, to examine the association of urban residence and severe mental illnesses. Individuals identified as having one of seven forms of 'insanity' (n = 91959) were allocated to their county of origin (n = 2661) in the census. Rates of 'insane' persons per 1000 population were calculated for each county. The counties were then divided by degree of urbanization based on the largest cities and the percentage of population living in towns of 4000 or more. The point prevalence of 'insanity' in the United States as a whole in 1880 was 1.8 per 1000. There was a significant association between 'insanity' by county and degree of urbanization, with odds ratios of 1.66 for urban, 1.46 for semi-urban, and 1.44 for semi-rural, and 1.37 for rural, using completely rural counties as a baseline. Most completely rural counties with high rates included mining camps, lumbering camps, or fishing villages, and not farming areas. In addition to urban drift, urban birth and residence appear to be risk factors for developing severe mental illnesses. Psychological and biological explanations have both been proposed. However, recent studies reporting winter birth and urban birth or residence as synergistic risk factors favor the latter.

Class I HLA antigens in spondyloarthropathy: observations in Alaskan Eskimo patients and controls.

OBJECTIVE: To assess the role of HLA-B27 and other class I histocompatibility antigens in overall risk and clinical manifestations of spondyloarthropathy (SpA) in Alaskan Eskimos. METHODS: Class I antigens were studied in 104 patients with SpA and in 111 controls. The frequencies of HLA-A, B, and Cw antigens were determined in patients with SpA with various clinical manifestations and compared to frequencies observed in controls. RESULTS: Only HLA-B27 differed significantly in cases and controls. Except for B27, no association of particular antigens with specific syndromes or disease features was found. Patients with B27 had more extraarticular manifestations than patients who lacked B27 antigen. Patients putatively homozygous for B27 did not appear to have more severe disease than those who were heterozygotic. B27 was most closely associated with ankylosing spondylitis [odds ratio (OR) = 210], less so with reactive arthritis (OR = 12.9) and undifferentiated SpA (OR = 4.6). CONCLUSION: Observations in other population groups that implicated B27 cross reactive group (CREG) and other A, B, and Cw antigens as risk factors for developing SpA were not confirmed in Alaskan Eskimos. Nor were CREG or other B antigens either alone or in combination with B27 associated with specific clinical syndromes. Only HLA-B27 was strongly associated with disease and with extraarticular manifestations.

Spondylarthropathic diseases in indigenous circumpolar populations of Russia and Alaska.

AIMS: To compare the nature and frequency of spondylarthropathy in geographically separated but genetically related populations with a high prevalence of HLA-B27. METHODS: Using a common questionnaire and disease criteria, cases were ascertained through cross-sectional community surveys in Russia and by examination and study of possible cases identified through rheumatic disease registries and the Native Health Service's computerized patient care data system in Alaska. RESULTS: Similar overall prevalences of spondyloarthropathy (2.0-3.4%) and a similar spectrum of disease were found, including reactive arthritis, ankylosing spondylitis and undifferentiated spondylarthropathy. Psoriatic arthritis was very rare. CONCLUSION: No predisposition to one particular form of spondyloarthropathy was observed; genetic and microbial settings for a spectrum of disease were present. Among adults positive for the presence of HLA-B27 the prevalence of all types of spondylarthropathies was estimated to be 4.5%, all populations combined, and the prevalence of AS was estimated to be 1.6%.

Spondyloarthropathies in circumpolar populations: II. Characterization of the populations.

For epidemiologic studies of spondyloarthropathy in circumpolar peoples of Chukotka, Russia and Alaska, we gathered demographic, physical and laboratory data to provide a background for evaluating and comparing factors that may influence susceptibility and clinical expression of disease. The study groups included the Chukchi and Siberian Eskimo of Russia and the Inupiat and Yupik Eskimo of Alaska. The 4 groups were remarkably similar in population structure, educational attainment, mean hemoglobin concentrations and frequency of the Class I histocompatibility antigen HLAB27. The Alaskan and Chukotkan groups were similar in mean height, but the Alaskans had higher body weights and significantly greater body mass indexes, probably a reflection of a shift away from traditional lifestyle and diet. Differences in the frequencies of ABO and MN blood group antigens were also apparent, with higher frequencies of blood group M in the Alaskan populations, particularly the Inupiat.

Discrepancies between patient recall and the medical record. Potential impact on diagnosis and clinical assessment of chronic disease.

BACKGROUND: During a case-control study, data necessary for fulfilling diagnostic and classification criteria for spondyloarthropathy were collected from 121 patients. OBJECTIVE: To study the potential impact of differences between patient recall and the medical record on diagnosis and clinical characterization of spondyloarthropathy as a model of chronic disease. METHODS: The study was conducted among four Alaskan Eskimo populations served by the Alaska Native Health Service. Two sets of historical data were compiled for each subject, one acquired during the interview and the other derived from the medical record. Paired items from the interview and the medical record were analyzed to determine discrepancies and consequent effects on diagnosis, classification, and disease characterization. RESULTS: Significant differences were observed in the reporting of genitourinary or diarrheal illnesses preceding or associated with arthritis, the occurrence of eye inflammation in association with joint pain, the occurrence of joint pain and back pain together, and the age at onset of back pain all of which are important to the diagnosis and classification of spondyloarthropathy. In contrast, for information needed to establish the probable inflammatory nature of back pain, patient interview was more helpful than the medical records, which did not provide adequate details to differentiate inflammatory from mechanical back pain. CONCLUSIONS: Patient recall bias can substantially affect diagnosis and clinical assessment of chronic disease, as exemplified by spondyloarthropathy. Reliance on records alone, however, may lead to underestimation of features that require subjective appraisal by the patient.

Clearance of chylomicron-like lipid emulsions is increased in normal rabbits but not in heterozygous Watanabe heritable hyperlipidaemic rabbits following treatment with cholestyramine or pravastatin.

1. Cholestyramine and pravastatin are two potent hypocholesterolaemic drugs which lower plasma cholesterol by increasing the clearance of low density lipoproteins by high affinity uptake mechanisms. 2. We gave heterozygous Watanabe heritable hyperlipidaemic rabbits (hz-WHHL) cholestyramine and/or pravastatin for a two week period to try and ameliorate slow clearance of chylomicron remnants, which occurs because of reduced expression of the apolipoprotein B100/E receptor. 3. In hz-WHHL rabbits the clearance of chylomicron-like lipid emulsions, traced by the decrease in plasma cholesteryl oleate radioactivity was not improved following treatment with either of the cholesterol lowering drugs. 4. In contrast, control rabbits had significantly less chylomicron-like emulsion cholesteryl-ester radioactivity remaining at each time of blood sampling. 5. Similarly, the clearance of chylomicron-like emulsion triolein was enhanced in normal rabbits receiving cholestyramine or pravastatin, whereas there was no detectable increase in clearance in hz-WHHL rabbits. 6. Combined treatment with cholestyramine and pravastatin increased the rate of receptor-mediated uptake in vivo in control rabbits but not in hz-WHHL rabbits. 7. The plasma lipid profiles of control and hz-WHHL rabbits paralleled the patterns of chylomicron-like emulsion clearance. Moderate hypertriglyceridaemia was identified in hz-WHHL rabbits compared to controls and there was no change in plasma triglyceride or cholesterol following drug therapy. In contrast, control rabbits had decreased plasma lipids following cholestyramine or pravastatin treatment. 8. It appears that therapy with lipid lowering drugs increased chylomicron remnant clearance in control rabbits by up-regulation of the apolipoprotein B100/E receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Link between pregnancy complications and minor physical anomalies in monozygotic twins discordant for schizophrenia.

OBJECTIVE: The aim of the current study was to explore the relevancy of early pregnancy complications for the development of minor physical anomalies in monozygotic twins discordant and concordant for schizophrenia. METHOD: Pregnancy complications and minor physical anomalies were independently assessed in 22 discordant, 10 concordant, and six normal comparison monozygotic twin pairs. RESULTS: Complications occurring during early pregnancy were associated with a higher frequency of minor physical anomalies in the total group and in the discordant twin pairs particularly. While no significant differences in anomaly rates were observed among the discordant, concordant, and normal comparison groups, the discordant ill twins showed a trend toward having more anomalies than their well co-twins. CONCLUSIONS: Complications occurring early in pregnancy are relevant for the development of minor physical anomalies and may be of particular importance for the development of these anomalies in twin pairs discordant for schizophrenia.

Obstetric complications in histories of monozygotic twins discordant and concordant for schizophrenia.

Histories of obstetric complications (OCs) during pregnancy, labor-delivery and the neonatal period were investigated by detailed maternal report for 23 monozygotic (MZ) twin pairs discordant for schizophrenia, 10 MZ twin pairs concordant for schizophrenia and 7 normal MZ control pairs. Statistically significant differences in OC rates were found across these 3 groups. OCs being most frequent in discordant pairs and least frequent in normal control pairs. Labor complications were significantly more frequent in discordant than concordant pairs. OC rates were equivalent in sick and well discordant twins. The results provide evidence for the role of OCs in the development of schizophrenia, complications at the time of birth being especially associated with the development of schizophrenia in discordant twins.

Prenatal origin of schizophrenia in a subgroup of discordant monozygotic twins.

Neuropathological, obstetrical, and epidemiological evidence increasingly suggest that some cases of adult-onset schizophrenia have prenatal or neonatal etiological roots. We evaluated the developmental histories of 23 monozygotic twin pairs discordant for schizophrenia to determine when they markedly and permanently began diverging from each other in motor skills or unusual behavior. Seven of the twins (30%) who later developed schizophrenia had become permanently different from their cotwins by age 5 years. The early divergence group differed from the others by multivariate tests (p = 0.002) for within-twin pair effects and by univariate tests for physical anomaly scores (p = 0.01), total finger ridge counts (p = 0.001), family history of psychosis (p = 0.004), and serious perinatal complications or low birth weight (p = 0.05). It is concluded that some cases of adult-onset schizophrenia are associated with prenatal events, which may include neurodevelopmental abnormalities or specific insults such as anoxia or infectious agents.

Handedness in twins with schizophrenia: was Boklage correct?

Boklage's report of increased non-right handedness among monozygotic twins with schizophrenia has been cited as evidence to support an association of abnormal brain lateralization with the development of schizophrenia. The present study found no such association. Two previous attempts to replicate Boklage's findings (Luchins et al. 1980; Lewis et al. 1989) also reported little support. Studies of twin handedness do not appear to support an association of brain lateralization and schizophrenia.

Seasonality of schizophrenia and stillbirths.

A study of the birth pattern of 30,467 patients with schizophrenia and 428,406 stillbirths in New York State showed a significant winter-month excess in both schizophrenia births (p = 0.0000) and stillbirths (p = 0.0000). Excess births of individuals with schizophrenia in November and December provided additional evidence to refute the age-incidence explanation for the observed seasonality. Time series spectral analysis showed coherence in the pattern of schizophrenia births and stillbirths of 0.898 (p < 0.003) with schizophrenia births preceding stillbirths by 13 days. These results suggest that a common etiological seasonal factor affects a subgroup of births of individuals who later develop schizophrenia and a subgroup of stillbirths. Nutritional factors, temperature, and infectious agents known to cause both central nervous system disease and stillbirths are possible candidates.

Improving the quality of emergency department documentation using the voice-activated word processor: interim results.

We examined whether voice-activated word processors provide an acceptable means for emergency physicians to create medical records. Our study addressed three areas of inquiry: whether physicians can be induced to try this new technology, whether they will continue to use it after outside technical support is withdrawn, and the factors contributing to adoption and substantial use of voice-activated computers by practicing emergency physicians. This paper presents findings from the first half of the study, reflecting physicians' reported experiences while receiving onsite training followed by technical support for three months after system installation. Based on preliminary assessments, the keys to successful use appear to include physician and group commitment, acceptance of a steep learning curve, and flexibility in adapting the computer software and/or practice habits.