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Lifetime Risk (lifetime + risk)

Distribution by Scientific Domains

Medical Sciences	96%

Distribution within Medical Sciences

Psychiatry	22%
Dermatology	7%
14 Other Subdomains	71%

Selected Abstracts

Residual Lifetime Risk of Fractures in Women and Men,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007
Nguyen D Nguyen
Abstract In a sample of 1358 women and 858 men, ,60 yr of age who have been followed-up for up to 15 yr, it was estimated that the mortality-adjusted residual lifetime risk of fracture was 44% for women and 25% for men. Among those with BMD T-scores , ,2.5, the risks increased to 65% in women and 42% in men. Introduction: Risk assessment of osteoporotic fracture is shifting from relative risk to an absolute risk approach. Whereas BMD is a primary predictor of fracture risk, there has been no estimate of mortality-adjusted lifetime risk of fracture by BMD level. The aim of the study was to estimate the residual lifetime risk of fracture (RLRF) in elderly men and women. Materials and Methods: Data from 1358 women and 858 men ,60 yr of age as of 1989 of white background from the Dubbo Osteoporosis Epidemiology Study were analyzed. The participants have been followed for up to 15 yr. During the follow-up period, incidence of low-trauma, nonpathological fractures, confirmed by X-ray and personal interview, were recorded. Incidence of mortality was also recorded. BMD at the femoral neck was measured by DXA (GE-LUNAR) at baseline. Residual lifetime risk of fracture from the age of 60 was estimated by the survival analysis taking into account the competing risk of death. Results: After adjusting for competing risk of death, the RLRF for women and men from age 60 was 44% (95% CI, 40,48) and 25% (95% CI, 19,31), respectively. For individuals with osteoporosis (BMD T-scores , ,2.5), the mortality-adjusted lifetime risk of any fracture was 65% (95% CI, 58,73) for women and 42% (95% CI, 24,71) for men. For the entire cohort, the lifetime risk of hip fracture was 8.5% (95% CI, 6,11%) for women and 4% (95% CI, 1.3,5.4%) for men; risk of symptomatic vertebral fracture was 18% (95% CI, 15,21%) for women and 11% (95% CI, 7,14%) for men. Conclusions: These estimates provide a means to communicate the absolute risk of fracture to an individual patient and can help promote the identification and targeting of high-risk individuals for intervention. [source]

Cancer/testis antigen MAGE-A4 expression pattern differs in epithelial skin tumors of organ-transplant recipients and immunocompetent patients

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2007
Beda Muehleisen
Background:, Lifetime risk for squamous cell carcinoma (SCC) of the skin is 1:30. Risk in organ-transplant recipients (OTR) is increased over 60-fold through long-term drug-induced immunosuppression. MAGE family-derived peptides are cancer/testis antigens recognized by specific CD8+ T cells and employed for immunotherapy. We were interested in the frequency and distribution of MAGE-A4 in epithelial skin tumors of OTR and immunocompetent patients. Methods:, mAb 57B predominantly recognizing MAGE-A4 was used to stain 119 formalin-fixed, paraffin-embedded epithelial skin tumors (actinic keratosis, bowenoid actinic keratosis, Bowen's disease, and SCC; n = 17, 25, 61, 16, respectively) in immunocompetent patients (n = 84) and OTR (n = 35). Results:, All four epithelial skin tumors showed comparable immunoreactivity ranging from (25,71%, p = 0.361). Scattered immunoexpression pattern was more frequent in OTR (p = 0.025). SCC showed polarized immunoreactivity basally (p = 0.002). Conclusion:, MAGE-A4 was expressed in a large part of epithelial skin tumors with predominantly scattered immunoexpression pattern in OTR. The difference in immunoexpression pattern for immune status was limited, suggesting important non-immunosuppressor-mediated mechanisms for increased skin carcinogenesis in OTR. mAb 57B may be a helpful tool for immunohistochemistry and micrographic surgery using formalin-fixed paraffin-embedded tissue. [source]

Persistent high rates of hysterectomy in Western Australia: a population-based study of 83 000 procedures over 23 years

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 7 2006
K Spilsbury
Objective, To investigate incidence trends and demographic, social and health factors associated with the rate of hysterectomy and morbidity outcomes in Western Australia and compare these with international studies. Design, Population-based retrospective cohort study. Setting, All hospitals in Western Australia where hysterectomies were performed from 1981 to 2003. Population, All women aged 20 years or older who underwent a hysterectomy. Methods, Statistical analysis of record-linked administrative health data. Main outcome measures, Rates, rate ratios and odds ratios for incidence measures and length of stay in hospital and odds ratios for morbidity measures. Results, The age-standardised rate of hysterectomy adjusted for the underlying prevalence of hysterectomy decreased 23% from 6.6 per 1000 woman-years (95% CI 6.4,6.9) in 1981 to 4.8 per 1000 woman-years (95% CI 4.6,4.9) in 2003. Lifetime risk of hysterectomy was estimated as 35%. In 2003, 40% of hysterectomies were abdominal. The rate of hysterectomy to treat menstrual disorders fell from 4 per 1000 woman-years in 1981 to 1 per 1000 woman-years in 1993 and has since stabilised. Low socio-economic status, having only public health insurance, nonindigenous status and living in rural or remote areas were associated with increased risk of having a hysterectomy for menstrual disorders. Indigenous women had higher rates of hysterectomy to treat gynaecological cancers compared with nonindigenous women, particularly in rural areas. The odds of a serious complication were 20% lower for vaginal hysterectomies compared with abdominal procedures. Conclusion, Western Australia has one of the highest hysterectomy rates in the world, although proportionally, significantly fewer abdominal hysterectomies are performed than in most countries. [source]

Method for moderation: measuring lifetime risk of alcohol-attributable mortality as a basis for drinking guidelines

INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2008
Jürgen Rehm
Abstract The objective of this paper was to determine separately the lifetime risk of drinking alcohol for chronic disease and acute injury outcomes as a basis for setting general population drinking guidelines for Australia. Relative risk data for different levels of average consumption of alcohol were combined with age, sex, and disease-specific risks of dying from an alcohol-attributable chronic disease. For injury, combinations of the number of drinks per occasion and frequency of drinking occasions were combined to model lifetime risk of death for different drinking pattern scenarios. A lifetime risk of injury death of 1 in 100 is reached for consumption levels of about three drinks daily per week for women, and three drinks five times a week for men. For chronic disease death, lifetime risk increases by about 10% with each 10-gram (one drink) increase in daily average alcohol consumption, although risks are higher for women than men, particularly at higher average consumption levels. Lifetime risks for injury and chronic disease combine to overall risk of alcohol-attributable mortality. In terms of guidelines, if a lifetime risk standard of 1 in 100 is set, then the implications of the analysis presented here are that both men and women should not exceed a volume of two drinks a day for chronic disease mortality, and for occasional drinking three or four drinks seem tolerable. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Cancer risk from diagnostic radiology in a deliberate self-harm patient

ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010
L. J. Norelli
Norelli LJ, Coates AD, Kovasznay BM. Cancer risk from diagnostic radiology in a deliberate self-harm patient. Objective:, Patients who engage in recurrent deliberate self-harm (DSH) behaviours have increased morbidity and mortality and use emergency services more than others. Unrecognized iatrogenic injury may play a role. Specifically, we call attention to the potential danger of cumulative radiation exposure. Method:, Case presentation and discussion. Results:, A 29-year-old woman with multiple episodes of deliberate foreign body ingestion received over 400 diagnostic radiology examinations during a 12 year period. The patient's calculated total radiation dose reached an average of 20.5 mSv per year, a dose comparable to atomic bomb survivors and nuclear industry workers, populations in which there is a significant excess cancer risk. Conclusion:, Patients with recurrent self-injurious behaviours, frequent users of healthcare services who often undergo repeated medical assessment and treatment, are likely at higher risk for iatrogenic adverse events. Multiple diagnostic radiology examinations have recently come under scrutiny for causing increased lifetime risk of cancer. Healthcare providers, in particular psychiatrists and emergency department physicians, should consider the cumulative risks of radiological procedures when assessing and treating patients with DSH. [source]

The serotonin transporter 5-HTTPR polymorphism is associated with current and lifetime depression in persons with chronic psychotic disorders

ACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009
J. Contreras
Objective:, Variation in the serotonin transporter gene (SLC6A4) promoter region has been shown to influence depression in persons who have been exposed to a number of stressful life events. Method:, We evaluated whether genetic variation in 5-HTTLPR, influences current depression, lifetime history of depression and quantitative measures of depression in persons with chronic psychotic disorders. This is an association study of a genetic variant with quantitative and categorical definitions of depression conducted in the southwest US, Mexico and Costa Rica. We analyzed 260 subjects with a history of psychosis, from a sample of 129 families. Results:, We found that persons carrying at least one short allele had a statistically significant increased lifetime risk for depressive syndromes (P < 0.02, odds ratio 2.18, 95% CI 1.10,4.20). Conclusion:, The ,ss' or ,sl' genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of psychotic individuals to develop major depression during the course of their illness. [source]

Type 2 diabetes in families and diabetes prevention

EUROPEAN DIABETES NURSING, Issue 2 2008
FRCP Professor of Diabetic Molecular Medicine, M Walker MD
Abstract Type 2 diabetes frequently clusters in families. Non-diabetic first-degree relatives (offspring and siblings) of patients with type 2 diabetes have a three-fold increased lifetime risk of developing diabetes compared with the background population. This increased diabetes risk results from the combined effects of shared genetic and lifestyle factors. Extensive studies of non-diabetic relatives of type 2 diabetic families show that impaired insulin secretion, insulin resistance and an adverse cardiovascular risk factor profile exist well before the development of frank diabetes. Despite this well-documented adverse metabolic predisposition, patients with type 2 diabetes and their non-diabetic relatives generally have a limited understanding of the risks. Several large-scale studies, such as the Finnish Diabetes Prevention and Diabetes Prevention Program studies, indicate unequivocally that lifestyle modification through dietary change and exercise can dramatically decrease risk of progression to diabetes in high-risk subjects. However, such individuals pursue lifestyle changes only if they understand their own risk of developing diabetes. Further work is therefore needed to investigate and develop optimal ways of improving knowledge of diabetes risk in families of patients with type 2 diabetes, so that they can appreciate the potential benefits of diabetes prevention strategies. Copyright © 2008 FEND [source]

Genetic aspects of the Paget's disease of bone: concerns on the introduction of DNA-based tests in the clinical practice.

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2010
Advantages, disadvantages of its application
Eur J Clin Invest 2010; 40 (7): 655,667 Abstract Background, A large amount of genetic studies have clearly demonstrated the existence of a genetic susceptibility to Paget's disease of bone (PDB). Although the disease is genetically heterogeneous, the SQSTM1/p62 gene, encoding a protein with a pathophysiological role in both osteoclast differentiation and activity, has been found worldwide to harbour germline mutations in most of the PDB patients from geographically distant populations originating from different areas of Europe, both in sporadic and familial cases. Materials and Methods, Thus, SQSTM1/p62 gene mutations may confer an increased lifetime risk of developing PDB. Results, Several different genotype-phenotype analyses have shown a high penetrance for such mutations. These results suggest the opportunity to perform genetic testing in affected individuals and then, after the identification of a SQSTM1/p62 gene germline mutation, in their relatives as a real and concrete strategy to increase the diagnostic sensitivity in most of the asymptomatic mutant carriers. However, it is of note to underlie that an incomplete penetrance for SQSTM1/p62 gene mutations has also been reported. Conclusions, In light of all these contradictory evidences, a review on whether, when and why apply the DNA test to those subjects, its interpretation and clinical application is necessary. In fact, a growing number of preventive care options are now available to affected patients and families and the process of systematically assessing risk is becoming increasingly important for both patients and physicians. [source]

Constitutional NF1 mutations in neurofibromatosis 1 patients with malignant peripheral nerve sheath tumors,,

HUMAN MUTATION, Issue 5 2003
Lan Kluwe
Abstract Neurofibromatosis type 1 (NF1) patients have 10% of lifetime risk for developing malignant peripheral nerve sheath tumors (MPNST), one of the most aggressive cancers. We examined the spectrum of constitutional NF1 mutations among 24 NF1 patients with MPNST. We found mutations in 18 patients: four megabase deletions involving the NF1 gene, 13 truncating mutations, and only one missense mutation. One deletion included both exonic and intronic sequences. No typical splicing mutation was found. Five of these mutations were novel: c.3686delA, c.197_204+9del17, c.3044T>C (p.Leu1015Pro), c.2497delT, and c.6020_6027dup. The proportion of megabase deletions of the NF1 gene found in patients with MPNST (17%=4/24) was higher than that in a group of unselected NF1 patients (5.4%=27/500). © 2003 Wiley-Liss, Inc. [source]

The ,oestrogen hypothesis', where do we stand now?,

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2003
Richard M. Sharpe
Summary The original ,oestrogen hypothesis' postulated that the apparent increase in human male reproductive developmental disorders (testis cancer, cryptorchidism, hypospadias, low sperm counts) might have occurred because of increased oestrogen exposure of the human foetus/neonate; five potential routes of exposure were considered. This review revisits this hypothesis in the light of the data to have emerged since 1993. It addresses whether there is a secular increasing trend in the listed disorders and highlights the limitations of available data and how these are being addressed. It considers whether new data has emerged to support the suggestion that increased oestrogen exposure could cause these abnormalities and reviews new data on potential routes via which such increased exposure could have occurred. Secular trends: The disorders listed above are now considered to represent a syndrome of disorders (testicular dysgenesis syndrome, TDS) with a common origin in foetal life. Testicular cancer has increased in incidence in Caucasian men worldwide and lifetime risk is 0.3,0.8%. Secular trends in cryptorchidism are unclear but it is by far the commonest (2,4% at birth) congenital abnormality in either sex. Secular trends for hypospadias are not robust, although most studies suggest a progressive increase; registry data probably under-estimates incidence, but based on this data hypospadias is the second most common (0.3,0.7% at birth) congenital malformation. Retrospective analyses of sperm count data show a global downward trend but this is inconclusive , prospective studies using standardized methodology show significant differences between countries and very low sperm counts in the youngest cohort of men. For all disorders, other then testis cancer, standardized prospective studies are the best way forward and are in progress across Europe. Oestrogen effects: Evidence that foetal exposure to oestrogens can induce the above disorders has strengthened. New pathways via which such changes could be induced have been identified, including suppression of testosterone production by the foetal testis, suppression of androgen receptor expression and suppression of insulin-like factor-3 (InsL3) production by foetal Leydig cells. Other evidence suggests that the balance between androgen and oestrogen action may be important in induction of reproductive tract abnormalities. Oestrogen exposure: Although many new environmental oestrogens have been identified, their uniformly weak oestrogenicity excludes the possibility that they could induce the above disorders. However, emerging data implicates various environmental chemicals in being able to alter endogenous levels of androgens (certain phthalates) and oestrogens (polychlorinated biphenyls, polyhalogenated hydrocarbons), and the former have been shown to induce a similar collection of disorders to TDS. Other mechanisms via which increased fetal exposure to pregnancy oestrogens might occur (increasing trend in obesity, dietary changes) are also discussed. [source]

Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: An update

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2006
Jacek Gronwald
Abstract Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of ,80%, and following the first diagnosis the10-year risk of contralateral breast cancer is ,30%. It has been shown that both tamoxifen and oophorectomy prevent contralateral breast cancer, but it is not clear whether there is a benefit in giving tamoxifen to women who have previously undergone an oophorectomy. Furthermore, the relative degree of protection in BRCA1 and BRCA2 carriers has not been well evaluated. We studied 285 women with bilateral breast cancer and a BRCA1 or BRCA2 mutation, and 751 control women with unilateral breast cancer and a BRCA1 or BRCA2 mutation in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of breast cancer and had been followed for as long as the case for a second primary breast cancer. The history of tamoxifen use for treating the first breast cancer was compared between bilateral and unilateral cases. The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0.50 for carriers of BRCA1 mutations (95% CI, 0.30,0.85) and was 0.42 for carriers of BRCA2 mutations (95% CI, 0.17,1.02). The protective effect of tamoxifen was not seen among women who had undergone an oophorectomy (OR = 0.83; 95%CI, 0.24,2.89) but this subgroup was small. In contrast, a strong protective effect of tamoxifen was apparent among women who were premenopausal or who had undergone natural menopause (OR = 0.44; 95% CI, 0.27,0.65). © 2005 Wiley-Liss, Inc. [source]

Method for moderation: measuring lifetime risk of alcohol-attributable mortality as a basis for drinking guidelines

Studying the incidence of depression: an ,interval' effect

INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 4 2000
Jane M. Murphy
Abstract A review of studies about the incidence of depression suggested that the length of the ,interval' of follow up may influence the findings. Exploration of these issues is carried out using data from the Stirling County Study, an investigation of psychiatric epidemiology in a general population. The study's customary method of diagnosis, DePression and AnXiety (DPAX), and the Diagnostic Interview Schedule (DIS) were used in an incidence investigation whose ,interval' was less than three years. Average annual incidence rates of depression for both DPAX and DIS were about 15 per 1000. Where longer intervals were used in the Stirling Study, rates were close to four per 1000. Projected lifetime risk based on the lower rates was more congruent with reported lifetime prevalence than that based on the higher rates. Irrespective of method, 90% or more of the incident cases gave an onset that predated the initial interview, suggesting poor reliability. This was often due to the fact that information given in the first interview met some but not all of the criteria for diagnosis. Being in the ,borderline' category at the beginning of the study significantly increased incidence. Thus, evidence from the Stirling County Study replicated findings that suggest an ,interval effect' and pointed to the need in incidence studies for distinguishing between the onset of the prodrome and the onset of diagnosable depression. Copyright © 2000 Whurr Publishers Ltd. [source]

Residual Lifetime Risk of Fractures in Women and Men,,

Evidence From Data Searches and Life-Table Analyses for Gender-Related Differences in Absolute Risk of Hip Fracture After Colles' or Spine Fracture: Colles' Fracture as an Early and Sensitive Marker of Skeletal Fragility in White Men,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2004
Patrick Haentjens
Abstract Based on data searches and life-table analyses, we determined the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture after sustaining a Colles' or spine fracture and searched for potential gender-related differences. In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility. Introduction: Colles' fracture occurrence has been largely ignored in public health approaches to identify target populations at risk for hip fracture. The aim of this study was to estimate the long-term and short-term absolute risks of hip fracture after sustaining a Colles' or spine fracture and to search for potential gender-related differences in the relationship between fracture history and future fracture risk. Materials and Methods: To determine the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture, we applied life-table methods using U.S. age- and sex-specific hip fracture incidence rates, U.S. age-specific mortality rates for white women and men, pooled hazard ratios for mortality after Colles' and spine fracture, and pooled relative risks for hip fracture after Colles' and spine fracture, estimated from cohort studies by standard meta-analytic methods. Results: Our results indicate that the estimated remaining lifetime risks are dependent on age in both genders. In women, remaining lifetime risks increase until the age of 80 years, when they start to decline because of the competing probabilities of fracture and death. The same pattern is found in men until the age of 85 years, the increment in lifetime risk being even more pronounced. As expected, the risk of sustaining a hip fracture was found to be higher in postmenopausal women with a previous spine fracture compared with those with a history of Colles' fracture. In men, on the other hand, the prospective association between fracture history and subsequent hip fracture risk seemed to be strongest for Colles' fracture. At the age of 50, for example, the remaining lifetime risk was 13% in women with a previous Colles' fracture compared with 15% in the context of a previous spine fracture and 9% among women of the general population. In men at the age of 50 years, the corresponding risk estimates were 8%, 6%, and 3%, respectively. Similar trends were observed when calculating 5- and 10-year risks. Conclusions: In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility. The gender-related differences reported in this analysis should be taken into account when designing screening and treatment strategies for prevention of hip fracture in men. [source]

Genetic Polymorphisms Related to Delirium Tremens: A Systematic Review

ALCOHOLISM, Issue 2 2007
Barbara C. Van Munster
Background: Delirium tremens (DT) is one of the more severe complications of alcohol withdrawal (AW), with a 5 to 10% lifetime risk for alcohol-dependent patients. The 2 most important neurosystems involved in AW are , -aminobutyric acid and glutamate. It is unknown whether these neurosystems are involved in the pathophysiology of DT as well. The candidate gene approach in DT could contribute to this knowledge and demonstrate a possible genetic predisposition for DT. The purpose of this study is to give an overview of all studied genetic polymorphisms in the diverse candidate genes related to DT and to summarize what these studies contribute to insights into the pathophysiology of DT. Methods: The inclusion criteria for this literature study were articles in English analyzing the association between a genetic polymorphism and DT without other AW syndromes. Studies were identified until February 2006 in MEDLINE and EMBASE databases. Results: We found 25 studies dealing with 30 polymorphisms, located in 19 different genes. Positive associations were found in 3 different candidate genes involved in the dopamine transmission, 1 gene involved in the glutamate pathway, 1 neuropeptide gene, and 1 cannabinoid gene. Two candidate genes involved in the dopamine transmission, dopamine receptor D3, and solute carrier family 6, were each associated with DT in 2 different study populations. The other 4 positive associations were not replicated in other studies. Conclusions: A total of 8 positive associations out of 30 polymorphisms makes a genetic base for DT plausible. Understanding the pathophysiological process of the development of DT has, indeed, been augmented by the reviewed genetic association studies. These studies suggest that the regulation of dopaminergic neurotransmission may play an important role. [source]

Assessing the role of DRD5 and DYT1 in two different case,control series with primary blepharospasm

MOVEMENT DISORDERS, Issue 2 2007
Jordi Clarimon PhD
Abstract Primary blepharospasm is a common adult-onset focal dystonia. Polymorphisms of the genes encoding TorsinA (DYT1) and the D5 dopamine receptor (DRD5) have previously been associated with lifetime risk for focal dystonia. We describe here experiments testing common variability within these two genes in two independent cohorts of Italian and North American patients with primary blepharospasm. We have failed to identify a consistent association with disease in the two patient groups examined here; however, analysis of the Italian group reveals an association with the same risk genotype in DYT1 as previously described in an Icelandic population. We have also found global significant DYT1 haplotype differences between patients and controls in the Italian series. These data suggest that further examination is warranted of the role genetic variability at this locus plays in the risk for primary dystonia. © 2006 Movement Disorder Society [source]

Management of Nevus Sebaceous and the Risk of Basal Cell Carcinoma: An 18-Year Review

PEDIATRIC DERMATOLOGY, Issue 6 2009
Heather Rosen M.D., M.P.H.
It may undergo malignant transformation to basal cell carcinoma (BCC). However the incidence and lifetime risk of malignant transformation is unknown. We performed an 18-year review of all NS excisions at our institution, to report the number of cases of BCC and other neoplasms within excised NS. The aim is to inform physicians who must weigh the risks in recommending excision of a NS in a pediatric patient population with the risk of malignancy. After a database query for years 1990,2008, charts were reviewed and data were extracted on demographics and surgical history relating to NS. Thirty-one NS with abnormal findings were reviewed microscopically by a dermatopathologist. There were 651 NS distinct lesions among 631 patients and 690 excisions. Twenty-one intralesional diagnoses were found in 18 patients. Five patients (0.8%) had BCC (mean age 12.5 yrs, range 9.7,17.4 yrs). Seven (1.1%) had syringocystadenoma papilliferum (SP) (mean age 8.8 yrs, range 1.7,16.9 yrs), a lesion that may undergo malignant transformation. Malignant transformation of NS can occur in childhood or adolescence. We believe all NS should be excised, however timing of excision can be flexible. Our data do not support age cutoffs or morphologic changes to determine optimal excision time. In conjunction with the treating physician, the parent and patient may weigh the small risk of malignant transformation of NS against the morbidity associated with excision and anesthesia. [source]

The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009
Tamar H. Taddei
Mutations in GBA1 gene that encodes lysosomal glucocerebrosidase result in Type 1 Gaucher Disease (GD), the commonest lysosomal storage disorder; the most prevalent disease mutation is N370S. We investigated the heterogeneity and natural course of N370S GD in 403 patients. Demographic, clinical, and genetic characteristics of GD at presentation were examined in a cross-sectional study. In addition, the relative risk (RR) of cancer in patients compared with age-, sex-, and ethnic-group adjusted national rates of cancer was determined. Of the 403 patients, 54% of patients were homozygous (N370S/N370S) and 46% were compound heterozygous for the N370S mutation (N370S/other). The majority of N370S/N370S patients displayed a phenotype characterized by late onset, predominantly skeletal disease, whereas the majority of N370S/other patients displayed early onset, predominantly visceral/hematologic disease, P < 0.0001. There was a striking increase in lifetime risk of multiple myeloma in the entire cohort (RR 25, 95% CI 9.17,54.40), mostly confined to N370S homozygous patients. The risk of other hematologic malignancies (RR 3.45, 95% CI 1.49,6.79), and overall cancer risk (RR 1.80, 95% CI 1.32,2.40) was increased. Homozygous N370S GD leads to adult-onset progressive skeletal disease with relative sparing of the viscera, a strikingly high risk of multiple myeloma, and an increased risk of other cancers. High incidence of gammopathy suggests an important role of the adaptive immune system in the development of GD. Adult patients with GD should be monitored for skeletal disease and cancers including multiple myeloma. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]

,Normal for Now' or ,At Future Risk': A Double Standard for Selecting Young and Older Living Kidney Donors

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010
R. W. Steiner
Transplant centers medically evaluate potential living kidney donors in part to determine their baseline remaining lifetime risk for end stage renal disease (ESRD). If baseline risk is increased by the presence of a risk factor for ESRD, donation is often refused. However, as only about 13% of ESRD occurs in the general population by age 44, a normal medical evaluation cannot be expected to significantly reduce the 7% lifetime risk for a ,normal' 25-year-old black donor or the 2,3% risk for a similar white donor. About half of newly diagnosed ESRD in the United States occurs by age 65, and about half of that is from diabetic nephropathy, which takes about 25 years to develop. Therefore, the remaining baseline lifetime risk for ESRD is significantly lower in the normal, nondiabetic 55-year-old donor candidate. Some older donors with an isolated medical abnormality such as mild hypertension will be at lower or about the same overall baseline lifetime risk for ESRD as are young ,normal' donor candidates. Transplant centers use a ,normal for now' standard for accepting young donors, in place of the long-term risk estimates that must guide selection of all donors. [source]

Biologic markers in endometrial cancer treatment

APMIS, Issue 10 2009
INGEBORG B ENGELSEN
With a lifetime risk among women of 2,3%, endometrial cancer is the most common pelvic gynecologic malignancy in industrialized countries. Approximately 75% of cases are diagnosed at an early stage with a tumor confined to the uterine corpus. Although most patients are cured by surgery alone, about 15,20% with no signs of locally advanced or metastatic disease at primary treatment recurs, with limited responsiveness to systemic therapy. The most common basis for determining the risk of recurrent disease has been classification of endometrial cancers into two subtypes. Type I, associated with a good prognosis, accounts for the majority of cases and is associated with a low-stage, low-grade and endometrioid histology. In contrast, type II, associated with a poor prognosis, is characterized by a high-stage, high-grade and non-endometrioid histology. However, the prognostic value of this distinction is limited, as up to 20% of type I endometrial cancers recur, while half of type II cancers do not. We review the current literature on epidemiology, etiology, pathology, molecular alterations, staging, treatment and prognostic factors in endometrial cancer. Ongoing molecular-based clinical trials and newly reported molecular alterations with a potential for development of new targeted therapy are discussed. [source]

Profile of Cognitive Impairment in Parkinson's Disease

BRAIN PATHOLOGY, Issue 3 2010
G. Stennis Watson
Abstract Cognitive impairment (CI) is a common nonmotor complication of Parkinson's disease (PD), and is associated with significant disability for patients and burden for caregivers. Similar to motor symptoms, the characteristics of CI in PD can be quite variable, both in terms of what cognitive domains are impaired, and the timing of onset and rate of progression. This review will examine the profile of cognitive domain impairments observed in PD, with a focus on early CI (without dementia). We will also discuss possible relationships between specific cognitive domain impairments in PD and pathological processes such as Lewy-related pathology and Alzheimer's disease. It is our hypothesis that the specific characteristics of CI observed in individual PD patients provide clues to the underlying pathological processes, and that understanding the biological basis of this clinical phenomenon will assist in directing disease-specific treatments. Given the high lifetime risk for CI in PD, it is imperative that we improve our understanding and treatments for this common and disabling problem in PD. [source]

Ophthalmic lymphoma: epidemiology and pathogenesis

ACTA OPHTHALMOLOGICA, Issue thesis1 2009
Lene Dissing Sjö
Abstract With a lifetime risk of 1% and 700 new cases per year, Non-Hodgkin lymphoma (NHL) is the seventh most frequent type of cancer in Denmark. The incidence of NHL has increased considerably in Western countries over the last decades; consequently, NHL is an increasing clinical problem. Ophthalmic lymphoma, (lymphoma localized in the ocular region, i.e. eyelid, conjunctiva, lacrimal sac, lacrimal gland, orbit, or intraocularly) is relatively uncommon, accounting for 5%,10% of all extranodal lymphomas. It is, however, the most common orbital malignancy. The purpose of this thesis was to review specimens from all Danish patients with a diagnosis of ophthalmic lymphoma during the period 1980,2005, in order to determine the distribution of lymphoma subtypes, and the incidence- and time trends in incidence for ophthalmic lymphoma. Furthermore, an extended analysis of the most frequent subtype, extranodal marginal zone lymphoma (MALT lymphoma), was done to analyse clinical factors and cytogenetic changes with influence on prognosis. A total of 228 Danish patients with a biopsy-reviewed verified diagnosis of ocular adnexal-, orbital-, or intraocular lymphoma were identified. We found that more than 50% of orbital- and ocular adnexal lymphomas were of the MALT lymphoma subtype, whereas diffuse large B-cell lymphoma (DLBCL) predominated intraocularly (Sjo et al. 2008a). Furthermore, lymphoma arising in the lacrimal sac was surprisingly predominantly DLBCL (Sjo et al. 2006). Incidence rates were highly dependent on patient age. There was an increase in incidence rates for the whole population from 1980 to 2005, corresponding to an annual average increase of 3.4% (Sjo et al. 2008a). MALT lymphoma arising in the ocular region was found in 116 patients (Sjo et al. 2008b). One third of patients had a relapse or progression of disease after initial therapy and relapses were frequently found at extra-ocular sites. Overall survival, however, was not significantly poorer for patients with relapse. Furthermore, we found that the frequency of translocations involving the MALT1- and IGH-gene loci is low in ocular region MALT lymphoma (2 of 42, 5%), but may predict increased risk of relapse (Sjo et al. 2008b). In conclusion the incidence of ophthalmic lymphoma is increasing at a high rate in Denmark. Ophthalmic lymphoma consists primarily of MALT lymphoma. The molecular pathogenesis of MALT lymphoma arising in the ocular region rarely involves translocations in the MALT1- and IGH-gene loci. [source]

Prevention and management of infections in patients without a spleen

CLINICAL MICROBIOLOGY AND INFECTION, Issue 12 2001
R. N. Davidson
Patients who lack a functioning spleen become vulnerable to sepsis caused by bacteria and, occasionally, protozoa. The risk is higher in children and in those who have had immunosuppressive treatment, and the risk remains lifelong. Overwhelming post-splenectomy infection (OPSI) occurs at an estimated incidence of 0.23,0.42% per year, with a lifetime risk of 5%. Episodes of OPSI are emergencies, requiring immediate parental antibiotics and intensive care; intravenous immunoglobulins may be useful. OPSI carries a mortality of 38,69%. Streptococcus pneumoniae is the commonest infecting organism, accounting for 50,90% of isolates from blood cultures in reported series; it is particularly common in children with sickle cell disease. Less commonly, the infecting organisms are other bacteria, Babesia or Ehrlichia. OPSI may be, to some extent, preventable by several interventions. These are surgical conservation of the spleen; immunization against S. pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis; prophylactic antibiotics; stand-by antibiotics; patient information sheets; and a medical alert bracelet. Asplenic patients living in malaria-endemic areas require optimal prophylaxis. The initial step in prevention of OPSI is the creation of an asplenia register, as many patients are not covered by these simple measures. [source]

Evidence From Data Searches and Life-Table Analyses for Gender-Related Differences in Absolute Risk of Hip Fracture After Colles' or Spine Fracture: Colles' Fracture as an Early and Sensitive Marker of Skeletal Fragility in White Men,