Natural history of idiopathic erythrocytosis - A retrospective case series review

Idiopathic Erythrocytosis (IE) is a diagnosis given to patients who have an absolute erythrocytosis (red cell mass more than 25% above their mean normal predicted value) but who do not have a known form of primary or secondary erythrocytosis (BCSH guideline, 2005). We report here the results of a follow-up study of 80 patients (44 male and 36 female) diagnosed with IE from the United Kingdom and the Republic of Ireland over a 10 year period. Baseline information was initially collected when investigating for molecular causes of erythrocytosis in this group. The diagnosis of IE was made on the basis of a raised red cell mass >25% above mean normal predicted value, absence of Polycythaemia Vera (PV) based on the criteria of Pearson and Messinezy (1996), and the exclusion of secondary erythrocytosis (oxygen saturation >92% on pulse oximetry, no history of sleep apnoea, no renal or hepatic pathology, and a normal oxygen dissociation curve (if indicated). The average age at diagnosis of erythrocytosis was 34.5 (2–74 years). Erythropoietin levels were available for 77/80 of the patients and were low in 18 (23%) and normal or high in 59 (74%). Ultrasound imaging was carried out in 67 patients (84%) at time of diagnosis and no significant abnormalities found. Fourteen patients had a family history of erythrocytosis. These patients have now been followed up for an average of 9.4 years (range 1–39). Out of 80 patients 56 patients can still be classified as having IE, of whom 52 are living (cause of death in the other 4 - lung cancer, RTA, sepsis, unknown). Thirty-five of these patients are regularly venesected, 3 take hydroxyurea (one also venesected), 11 receive no treatment while treatment is unknown in 2. Twenty take aspirin, 1 warfarin and 31 no thromboprophylaxis. Four of these patients had suffered thromboembolic complications (3 with CVA/TIAs and 1 with recurrent DVT) at or before their original diagnosis. Since diagnosis 8 patients have had 9 thrombotic events of which 7 were arterial (1 CVA, 3 TIAs, 1 MI, 2 PVD) and 2 venous (DVT/PE). Twenty take aspirin, 1 dipyridamole, 1 warfarin and 30 take no thromboprophylaxis. Out of the 24 patients who now have a diagnosis other than IE, 8 have been diagnosed with myelo-proliferative disease. Thirteen patients have a molecular abnormality which is likely to account for their erythrocytosis (11 VHL, 1 PHD-2, 1 EPO-receptor mutations). Three patients have secondary erythrocytosis. Older case studies identified a heterogenous group of patients, some of whom probably had apparent erythrocytosis and some who had either primary polycythaemia or secondary causes later identified (Modan and Modan, Najean et al). More recent reviews have identified a more homogenous group with low rates of transformation to myelofibrosis/acute leukaemia and low rates of thrombosis of around 1% patient-year. Follow up of our initial patient group does indeed reveal a heterogeneous group of patients with 10% now diagnosed with an MPD, although when analysis is confined to those patients who continue to fulfil the criteria for IE, the clinical course has been more stable. There has been no progression to MDS or leukaemia in this group (one patient with PV progressed to AML). The rate of thrombosis is 1.6% patient-years which is lower than the rate seen in PV and is consistent with the rate identified in other series. Molecular defects continue to be identified in this group and future investigation is likely to reveal further abnormalities.

It runs in the family : the Bradfords, print, and liberty (1680-1810)

En se basant sur l’histoire des Bradfords, l’une des plus grandes familles d’imprimeurs de l’histoire américaine, ce mémoire étudie la relation entre l’imprimé, les imprimeurs, et divers discours sur la liberté au cours du « long » 18e siècle. Il retrace la transition entre une ère de la « liberté de parole, » née des débats sur la liberté de presse et d’expression de la période coloniale, et une ère de la « parole de la liberté, » née au cours de la Révolution et entretenue sous la jeune république. Cette transition fut le produit de la transformation du discours des contemporains sur la liberté, mais s’effectua également en lien avec la transformation du milieu de l’imprimerie et de la culture de l’imprimé. Selon les circonstances politiques, sociales, économiques et culturelles particulières des périodes coloniale, révolutionnaire, et républicaine, l’imprimé et les imprimeurs américains furent appelés à disséminer et à contribuer au discours sur la liberté. Ils établirent ainsi une forte association entre l’imprimé et la liberté dans la culture de l’imprimé du 18e siècle, qui était destinée à être transmise aux siècles suivants. Mots-

A family study of co-morbidity between generalized social phobia and generalized anxiety disorder in a non-clinic sample

Background: High rates of co-morbidity between Generalized Social Phobia (GSP) and Generalized Anxiety Disorder (GAD) have been documented. The reason for this is unclear. Family studies are one means of clarifying the nature of co-morbidity between two disorders. Methods: Six models of co-morbidity between GSP and GAD were investigated in a family aggregation study of 403 first-degree relatives of non-clinical probands: 37 with GSP, 22 with GAD, 15 with co-morbid GSP/GAD, and 41 controls with no history of GSP or GAD. Psychiatric data were collected for probands and relatives. Mixed methods (direct and family history interviews) were utilised. Results: Primary contrasts (against controls) found an increased rate of pure GSP in the relatives of both GSP probands and co-morbid GSP/GAD probands, and found relatives of co-morbid GSP/GAD probands to have an increased rate of both pure GAD and comorbid GSP/GAD. Secondary contrasts found (i) increased GSP in the relatives of GSP only probands compared to the relatives of GAD only probands; and (ii) increased GAD in the relatives of co-morbid GSP/GAD probands compared to the relatives of GSP only probands. Limitations: The study did not directly interview all relatives, although the reliability of family history data was assessed. The study was based on an all-female proband sample. The implications of both these limitations are discussed. Conclusions: The results were most consistent with a co-morbidity model indicating independent familial transmission of GSP and GAD. This has clinical implications for the treatment of patients with both disorders. (C) 2006 Elsevier B.V. All fights reserved.

Family, locality and nationality: vernacular adaptations of the Expugnatio Hibernica from late medieval Ireland

This paper examines two late medieval abridgements of Gerald of Wales’ Expugnatio Hibernica, one in Hiberno-English and one in Irish. The manuscripts in which these adaptations survive all date from the late fifteenth century and appear to bear witness to a sudden and pronounced interest in Gerald’s text. Drawing on evidence from the extant manuscripts, this paper explores the readerships of, and the nature of their interest in, these adaptations. A key conclusion is that the Expugnatio, which gives prominence to Gerald's own relatives, the Fitzgeralds, was valued as a family history by the Fitzgerald Earls of Kildare and their allies. The Earls were at the height of their power in the period in which these manuscripts were produced. Examination of this neglected evidence of the adaptation and readership of the Expugnatio in late medieval Ireland suggests that, for some medieval readers at least, the primary identities Gerald’s text expressed were familial and local rather than colonial or national.

No evidence of genetic anticipation in a large family with Lynch syndrome.

Lynch syndrome is the commonest inherited cause of colorectal cancer (CRC). Genetic anticipation occurs when the age of onset of a disorder decreases in successive generations. It is controversial whether this occurs in Lynch syndrome. Previous studies have included heterogenous groups of subjects from multiple families, including subjects with a clinical diagnosis (based on family history) as well as those with proven germline mismatch repair gene mutations. The purpose of this study was to determine whether genetic anticipation occurs in mismatch repair gene carriers from a single Lynch syndrome family. This study includes members of a single family known to carry an MLH1 gene mutation who are proven germline mutation carriers or obligate carriers (based on their offspring's mutation status). Evidence of genetic anticipation (determined by age of onset of first CRC) was sought in two ways: Firstly, subjects were grouped as parent-child pairs and individuals were compared with their own offspring; secondly they were grouped by generation within the family tree. The Kaplan-Meier technique was used to adjust for variable follow up times. The family tree consisted of 714 subjects. Ninety-two subjects over five generations were included in the study. There was no evidence of genetic anticipation over the generations. (P = 0.37). Similarly, in the 75 parent-child pairs identified, age of onset of CRC was similar for parents and children (P = 0.51). We could not identify any evidence of genetic anticipation in mutation carriers from a single family with Lynch syndrome.

Exploring family and community involvement to protect Thai youths from alcohol and illegal drug abuse

Youth substance abuse is widely recognized as a major public health issue in Thailand. This study explores family and community risk and protective factors relevant to alcohol and illegal drug misuse in 1,778 Thai teenagers. Strong family attachment and a family history of antisocial behaviors were strongly associated with nearly all forms of substance abuse, with adjusted odds ratios ranging from 5.05 to 8.45. Community disorganization was strongly associated with self-reported substance use, although involvement in prosocial activities acted as a protective factor. The findings suggest that interventions that promote family cohesion and encourage community involvement may have considerable benefits in reducing substance abuse in Thai adolescents.

Parent and family factors associated with service use by young people with mental health problems: a systematic review

AIM: To conduct a systematic review of parent and family factors associated with service use for young people with mental health problems, to inform early intervention efforts aimed at increasing service use by young people. METHODS: A systematic search of academic databases was performed. Articles were included in the review if they had: a sample of young people aged between 5 and 18 years; service use as the outcome measure; one or more parental or family variables as a predictor; and a comparison group of non-service using young people with mental health problems. In order to focus on factors additional to need, the mental health symptoms of the young person also had to be controlled for. Stouffer's method of combining P-values was used to draw conclusions as to whether or not associations between variables were reliable. RESULTS: Twenty-eight articles were identified investigating 15 parental or family factors, 7 of which were found to be associated with service use for a young person with mental health needs: parental burden, parent problem perception, parent perception of need, parent psychopathology, single-parent household, change in family structure and being from the dominant ethnic group for the United States specifically. Factors not found to be related to service use were: family history of service use, parent-child relationship quality, family functioning, number of children, parent education level, parent employment status, household income and non-urban location of residence. CONCLUSIONS: A number of family-related factors were identified that can inform effective interventions aimed at early intervention for mental health problems. Areas requiring further research were also identified.

Dacus Family Papers - Accession 251 - M106 (136)

The Dacus Family Papers consist of a brief family history prepared by Mrs. James E. Rugg, together with wills and claims of Nathaniel Dacus (born around 1749 and died around 1831) of Greenville District, SC, and correspondence relating to the family history.

Epidemiology of masked and white-coat hypertension: the family-based SKIPOGH study

Objective We investigated factors associated with masked and white-coat hypertension in a Swiss population-based sample. Methods The Swiss Kidney Project on Genes in Hypertension is a family-based cross-sectional study. Office and 24-hour ambulatory blood pressure were measured using validated devices. Masked hypertension was defined as office blood pressure<140/90 mmHg and daytime ambulatory blood pressure≥135/85 mmHg. White-coat hypertension was defined as office blood pressure≥140/90 mmHg and daytime ambulatory blood pressure<135/85 mmHg. Mixed-effect logistic regression was used to examine the relationship of masked and white-coat hypertension with associated factors, while taking familial correlations into account. High-normal office blood pressure was defined as systolic/diastolic blood pressure within the 130–139/85–89 mmHg range. Results Among the 652 participants included in this analysis, 51% were female. Mean age (±SD) was 48 (±18) years. The proportion of participants with masked and white coat hypertension was respectively 15.8% and 2.6%. Masked hypertension was associated with age (odds ratio (OR) = 1.02, p = 0.012), high-normal office blood pressure (OR = 6.68, p<0.001), and obesity (OR = 3.63, p = 0.001). White-coat hypertension was significantly associated with age (OR = 1.07, p<0.001) but not with education, family history of hypertension, or physical activity. Conclusions Our findings suggest that physicians should consider ambulatory blood pressure monitoring for older individuals with high-normal office blood pressure and/or who are obese.

Development and preliminary validation of the cancer family impact scale for colorectal cancer

This study aimed to develop and validate The Cancer Family Impact Scale (CFIS), an instrument for use in studies investigating relationships among family factors and colorectal cancer (CRC) screening when family history is a risk factor. We used existing data to develop the measure from 1,285 participants (637 families) across the United States who were in the Johns Hopkins Colon Cancer Genetic Testing study. Participants were 94% white with an average age of 50.1 years, and 60% were women. None had a personal CRC history, and eighty percent had 1 FDR with CRC and 20% had more than one FDR with CRC. The study had three aims: (1) to identify the latent factors underlying the CFIS via exploratory factor analysis (EFA); (2) to confirm the findings of the EFA via confirmatory factor analysis (CFA); and (3) to assess the reliability of the scale via Cronbach's alpha. Exploratory analyses were performed on a split half of the sample, and the final model was confirmed on the other half. The EFA suggested the CFIS was an 18-item measure with 5 latent constructs: (1) NEGATIVE: negative effects of cancer on the family; (2) POSITIVE: positive effects of cancer on the family; (3) COMMUNICATE: how families communicate about cancer; (4) FLOW: how information about cancer is conveyed in families; and (5) NORM: how individuals react to family norms about cancer. CFA on the holdout sample showed the CFIS to have a reasonably good fit (Chi-square = 389.977, df = 122, RMSEA= 0.058 (.052-.065), CFI=.902, TLI=.877, GF1=.939). The overall reliability of the scale was α=0.65. The reliability of the subscales was: (1) NEGATIVE α = 0.682; (2) POSITIVE α = 0.686; (3) COMMUNICATE α = 0.723; (4) FLOW α = 0.467; and (5) NORM α = 0.732. ^ We concluded the CFIS to be a good measure with most fit levels over 0.90. The CFIS could be used to compare theoretically driven hypotheses about the pathways through which family factors could influence health behavior among unaffected individuals at risk due to family history, and also aid in the development and evaluation of cancer prevention interventions including a family component. ^

Screening for hypercholesterolemia in family practice

The purpose of this study was twofold: (1) To see if there was any difference in screening for hypercholesterolemia in a Family Practice setting after two national recommendations of 1985 and 1988. (2) To see if presence of coronary heart disease (CHD) risk factors e.g. smoking, hypertension, family history of heart disease, diabetes mellitus, and obesity influenced screening for hypercholesterolemia.^ A retrospective chart auditing was done at the Baylor College of Medicine, Family Practice Center, Houston for the years of 1985, 1986 and 1989. Statistically significant improvement in screening was observed in 1989 (after the second NCEP recommendations of 1988) compared to 1986 data (after the first national recommendations of 1985). But the proportion of target population screened (about 35%) was still far below the NCEP recommendations. Probably due to the small number of patients with CHD risk factors, no significant statistical differences were found in screening for hypercholesterolemia in 1985, 1986 and 1989 in patients with any CHD risk factor. ^

History of Richard and Francina (Hart) Phillips and their descendants : including a brief account of their ancestry, collateral lines, and items of interest /

Mode of access: Internet.

Gleanings of Virginia history. An historical and genealogical collection, largely from original sources.

pt. 1, Historical. From 1607 to 1744 -- pt. 2, Revolutionary war records, 1775-1791 -- pt. 3, Family history and genealogy.

Hereditary pancreatitis in a family of Aboriginal descent

Hereditary pancreatitis is an autosomal dominant condition characterized by recurrent episodes of acute pancreatitis, usually starting in childhood. We present a family who was ascertained when an 11-year-old girl presented with an episode of acute pancreatitis. Her father and other family members had also had recurrent bouts of acute pancreatitis. Genetic testing revealed a pathogenic mutation in the cationic trypsinogen gene in the proband, her father and her paternal grandmother. As far as we are aware, this is the first Aboriginal kindred with mutation-proven hereditary pancreatitis. Hereditary pancreatitis is an important differential diagnosis to consider in a patient with recurrent episodes of acute pancreatitis with no obvious precipitating cause. This family is of Aboriginal descent and the implications of the family's background are also discussed when considering the aetiology of the condition. We emphasize the need to ascertain a full family history from patients with a history of repeated episodes of acute pancreatitis and also emphasize the need to avoid ethnic stereotypes when assessing patients.