Comparing 3T and 1.5T MRI for mapping hippocampal atrophy in the Alzheimer's Disease Neuroimaging Initiative.

BACKGROUND AND PURPOSE: Prior MR imaging studies, primarily at 1.5T, established hippocampal atrophy as a biomarker for Alzheimer disease. 3T MR imaging offers a higher contrast and signal-to-noise ratio, yet distortions and intensity uniformity are harder to control. We applied our automated hippocampal segmentation technique to 1.5T and 3T MR imaging data, to determine whether hippocampal atrophy detection was enhanced at 3T. MATERIALS AND METHODS: We analyzed baseline MR imaging data from 166 subjects from the Alzheimer's Disease Neuroimaging Initiative-1 (37 with Alzheimer disease, 76 with mild cognitive impairment, and 53 healthy controls) scanned at 1.5T and 3T. Using multiple linear regression, we analyzed the effect of clinical diagnosis on hippocampal radial distance, while adjusting for sex. 3D statistical maps were adjusted for multiple comparisons by using permutation-based statistics at a threshold of P < .01. RESULTS: Bilaterally significant radial distance differences in the areas corresponding to the cornu ammonis 1, cornu ammonis 2, and subiculum were detected for Alzheimer disease versus healthy controls and mild cognitive impairment versus healthy controls at 1.5T and more profoundly at 3T. Comparison of Alzheimer disease with mild cognitive impairment did not reveal significant differences at either field strength. Subjects who converted from mild cognitive impairment to Alzheimer disease within 3 years of the baseline scan versus nonconverters showed significant differences in the area corresponding to cornu ammonis 1 of the right hippocampus at 3T but not at 1.5T. CONCLUSIONS: While hippocampal atrophy patterns in diagnostic comparisons were similar at 1.5T and 3T, 3T showed a superior signal-to-noise ratio and detected atrophy with greater effect size compared with 1.5T.

Uncomplicated diverticular disease is not a common cause of colonic symptoms.

BACKGROUND: Colonic diverticular disease is common among older individuals whereas colonic symptoms, such as those of irritable bowel syndrome, are frequent in the general population. AIM: To determine among patients in secondary care, if uncomplicated diverticular disease is a common cause of colonic symptoms. METHODS: Patients aged ≥50 years attending gastroenterology out-patient clinics or scheduled for colonoscopy or barium enema in a secondary care hospital were invited to take part. Those with structural gastrointestinal diseases were excluded. Participants completed a locally validated Rome II questionnaire on colonic symptoms. Patients with diverticular disease were compared with those without. RESULTS: Seven hundred and eighty four patients with no structural pathology other than diverticular disease or benign colonic polyps completed the study. A total of 744 patients underwent colonoscopy, 40 barium enema. Of these, 281 patients had diverticular disease. Among patients with and without diverticular disease, the frequency of abdominal pain, diarrhoea, constipation and irritable bowel syndrome were 123 (44%) and 226 (46%), 44 (16%) and 80 (17%), 38 (14%) and 80 (17%) and 66 (25%) and 119 (25%), respectively (N.S.). CONCLUSION: Uncomplicated colonic diverticular disease is not a common cause of colonic symptoms among patients in secondary care.

Bariatric surgery in the field of gynecological oncology.

Obesity has become a foremost health problem. More than half of US adults are overweight or obese. This has been due to sedentary lifestyles, increased intake of refined carbohydrates, and fat-rich diets. Obese women are particularly susceptible to a variety of health risks including cancer, especially cancers of the breast, endometrium, and colon. Bariatric surgery appears to be a viable option for the treatment of severe obesity. As the role of surgery in the management of this condition becomes increasingly frequent, it is important for gynecological oncologists to recognize the potential for gynecological malignancies in this patient population.

The Martius flap neovagina revisited.

The Martius bulbocavernosus flap has been used frequently in the repair of various vaginal fistulas. It can also be a useful source for the construction of a neovagina if used in the appropriate patient. We present a case of a patient who underwent a total pelvic exenteration for recurrent cervical cancer. For her neovagina, a novel variation of the Martius flap was constructed. In carefully selected patients, this can be a useful option for neovagina reconstruction.

The bisphosphonate acute phase response: rapid and copious production of proinflammatory cytokines by peripheral blood gd T cells in response to aminobisphosphonates is inhibited by statins.

The bisphosphonates are a novel class of drug that have been registered for various clinical applications worldwide. Bisphosphonates, and in particular the aminobisphosphonates (nBPs), are known to have a number of side-effects including a rise in body temperature and accompanying flu-like symptoms that resemble a typical acute phase response. The mechanism for this response has been partially elucidated and appears to be associated with the release of tumour necrosis factor (TNF)alpha and interleukin (IL)6, although the effector cells that release these cytokines and the mechanism of action remain enigmatic. Here, we show that the nBP-induced acute phase response differs from the typical acute phase response in that CD14+ cells such as monocytes and macrophages are not the primary cytokine producing cells. We show that by inhibiting the mevalonate pathway, nBPs induce rapid and copious production of TNFalpha and IL6 by peripheral blood gammadelta T cells. Prior treatment with statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, blocks nBP-induced production of these proinflammatory cytokines by gammadelta T cells and may offer a means of avoiding the associated acute phase response. In addition, our findings provide a further mechanism for the anti-inflammatory effects attributed to inhibitors of HMG CoA reductase.

Recognition of nonpeptide antigens by human V gamma 9V delta 2 T cells requires contact with cells of human origin.

SUMMARY It is becoming apparent that gamma delta T cells form an important part of the adaptive immune response. However, the ligands recognized by gamma delta T cell receptors (TCRs) and the exact biological function of the cells that express this receptor remain unclear. Numerous studies have shown that the dominant human peripheral blood subset of gamma delta T cells, which express a V gamma 9V delta 2 TCR, can activate in response to low molecular weight nonpeptidic molecules. Some of these components have been purified from bacteria or parasites. We examined the activation of polyclonal gamma delta T cell lines, clones with V gamma 9V delta 2 and V gamma 9V delta 1 TCRs, and gamma delta T cells directly ex vivo in response to multiple phosphate, alkylamine and aminobisphosphonate (nBP) antigens and purified protein derivative from Mycobacterium tuberculosis (PPD). V gamma 9V delta 2 T cells were able to respond to multiple small organic molecules of highly variable structure whereas cells expressing a similar V gamma 9 chain paired with a V delta 1 chain failed to recognize these antigens. Thus, the TCR delta chain appears to make an important contribution to the recognition of these antigens. The kinetics of responses to alkylphosphate and alkylamine antigens differ from those of responses to the nBP pamidronate. These different classes of antigen are believed to have differed mechanisms of action. Such differences explain why nBPs can be pulsed onto antigen presenting cells (APCs) and still retain their ability to activate gamma delta T cells while alkylphosphate and alkylamine antigens cannot. We also demonstrate that a substantial proportion of the cells that produce IFN gamma directly ex vivo in response to PPD are gamma delta T cells and that gamma delta T cell activation requires contact with cells of human origin.

Correlation of immunohistochemical molecular staging of bladder biopsies and radical cystectomy specimens.

PURPOSE: To determine the relationship of p53, retinoblastoma (RB), and p16 expression between precystectomy transurethral resection bladder (TURB) biopsy and matched cystectomy specimens; and to determine the value of p53 immunoreactivity for predicting progression and survival in patients undergoing radical cystectomy. METHODS AND MATERIALS: We performed p53 immunohistochemical staining on matched archival TURB and cystectomy specimens taken from 40 patients. Twenty-seven and 26 of these patients were also evaluated for RB and p16 expression, respectively. RESULTS: Twenty-eight (70%) of the TURB and 22 (55%) of the cystectomy specimens stained positive for p53. RB and p16 protein expression were altered in 19 (70%) and 19 (73%) of the TURB specimens, respectively, and 19 (70%) and 19 (73%) of the cystectomy specimens, respectively. There was a strong correlation between p53, RB, and p16 expression and TURB and cystectomy specimens (all p < 0.001). In preoperative and postoperative multivariate analyses, biopsy p53 and cystectomy p53 were independently associated with disease progression (p = 0.049 and p = 0.034, respectively) and bladder cancer-related death (p = 0.044 and p = 0.037, respectively). CONCLUSION: p53, RB, and p16 expression patterns on TURB specimens correlate with cystectomy specimens. p53 immunoreactivity is an independent predictor of disease progression and bladder cancer survival. These data support the potential of prognostic staging using immunohistochemical analysis on bladder biopsy specimens prior to neoadjuvant or definitive therapy.

Regulation of leptin and leptin receptor in baboon pregnancy: effects of advancing gestation and fetectomy.

Leptin, a product of both adipose tissue and the placental syncytiotrophoblast and a potential regulator of primate conceptus development, increases in the maternal circulation with advancing gestation. This increase may be potentiated by estrogens, which also increase as pregnancy progresses. In the present study adipose tissue was collected from nonpregnant (n = 5) baboons (Papio sp) and in baboons during early (days 58-62; n = 5), mid (days 98--102; n = 5), and late (days 158-162; n = 5) pregnancy (term, approximately 184 days). Additionally, placental estrogen production was inhibited in pregnant baboons by the removal of fetal androgen precursors via fetectomy at midgestation, with tissues collected from fetectomized (n = 5) baboons approximately 60 days later. Leptin, estrogens, and androgens were quantitated in maternal serum by RIA. Leptin (LEP) and leptin receptor (LEP-R(L) and LEP-R(S) isoforms) messenger ribonucleic acids (mRNAs) were quantitated by competitive RT-PCR, and leptin concentrations were determined by RIA in maternal adipose and placental villous tissues. Although LEP transcript abundance in adipose tissues was unchanged as a result of pregnancy or with advancing gestation, the leptin protein level was higher (P < 0.02) in pregnant baboons in early gestation than in nonpregnant baboons and increased with gestational age (P < 0.04). Maternal serum estrogens (estradiol and estrone) and androgens (androstenedione and testosterone) were lower (P < 0.0001) in fetectomized baboons than in intact controls. Serum leptin concentrations were unchanged by fetectomy, but the abundance of LEP mRNA transcripts was lower (P < 0.003) in sc adipose tissue and 3-fold higher (P < 0.05) in placenta. Similarly, the leptin protein level declined (P < 0.05) in sc adipose tissue and increased (P < 0.05) in placenta in fetectomized baboons. Although LEP-R(L) mRNA levels were unchanged after fetectomy, placental LEP-R(S) transcript abundance was lower (P < 0.04) than in pregnancy-intact baboons matched for gestational age. Results suggest that both adipose tissue and the placenta may contribute to maternal hyperleptinemia during normal primate pregnancy. Furthermore, the withdrawal of placental steroids results in the enhanced placental leptin production that is commensurate with a decline in production by sc adipose tissue.

Effects of estrogen on leptin gene promoter activation in MCF-7 breast cancer and JEG-3 choriocarcinoma cells: selective regulation via estrogen receptors alpha and beta.

Leptin is a potential regulator of conceptus development. We have previously suggested that in primate pregnancy, leptin biosynthesis is regulated by estrogen in a tissue-specific manner. Therefore, the objective of the current study was to determine the mechanism of estrogen action on LEP promoter activation in divergent cell types. The effects of estrogen were investigated in estrogen receptor (ER)-positive MCF-7 breast cancer cells and in ER-negative JEG-3 choriocarcinoma cells. Cells were transfected with a leptin-luciferase or an estrogen responsive element (ERE)-luciferase reporter construct, in conjunction with ERalpha, ERbeta, or empty vector expression plasmids. Cells were treated with estradiol and/or the specific estrogen antagonists, ICI-182,780 or 4-hydroxytamoxifen. In MCF-7 cells, estradiol stimulated (P<0.05) ERE-luciferase activity and was inhibited by ICI-182,780, but did not stimulate leptin-luciferase activity. However, leptin-luciferase was stimulated by estradiol (P<0.05) and inhibited by antiestrogens in JEG-3 cells that were co-transfected with ERalpha. Both antiestrogens stimulated leptin-luciferase activity (P<0.05) in JEG-3 cells co-transfected with ERbeta. Results suggested that LEP promoter activation may depend upon co-activators present in leptin-producing cells and may be inhibited by repressors present in non-leptin producing cells. Divergent effects of estrogen may be owed to differences in the type of ER (alpha or beta) expressed in target tissues.

E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder.

OBJECTIVES: The clinical course of carcinoma in situ (CIS) of the bladder is highly variable. Our objective in this study was to describe E-cadherin expression patterns in CIS with and without papillary disease and to determine whether altered E-cadherin expression is associated with disease progression and survival in patients with CIS of the bladder. METHODS: Tumor specimens from 53 patients who had CIS in the absence of muscle-invasive carcinoma on bladder biopsy were identified. Formalin-fixed paraffin sections were processed using a hot citric acid antigen retrieval method, followed by immunostaining with anti-E-cadherin monoclonal antibody. Expression patterns were evaluated in a blinded fashion and scored as normal and abnormal, which included absent and various degrees of heterogeneous immunostaining. Outcomes analyzed were recurrence, progression, and survival. RESULTS: Loss of normal membrane E-cadherin immunoreactivity was found in 17 patients (32%). At a median follow-up of 131 months, abnormal E-cadherin expression was significantly associated with disease recurrence (P = 0.0087), disease progression (P = 0.0003), and bladder cancer-specific survival (P = 0.0285). In multivariate analyses, E-cadherin expression was independently associated with disease recurrence (P = 0.019, 95% confidence interval [CI] 1.342 to 5.940), disease progression (P = 0.002, 95% CI 2.049 to 17.989), and bladder cancer-specific survival (P = 0.025, 95% CI 1.179 to 10.432). CONCLUSIONS: Loss of E-cadherin expression in patients CIS with and without papillary disease of the bladder predicts disease recurrence, disease progression, and bladder cancer-specific death. CIS with and without papillary disease associated with abnormal E-cadherin expression may represent a biologically more aggressive cancer, requiring early definitive therapy. This hypothesis should be evaluated in larger studies and prospective clinical trials.

Leptin receptor transcripts are constitutively expressed in placenta and adipose tissue with advancing baboon pregnancy.

The baboon (Papio sp.) is an accepted nonhuman primate model for the study of the endocrinology of human pregnancy. To further characterize this model with regard to leptin function, messenger RNA transcripts for both long (Ob-RL) and short (Ob-RS) leptin receptor isoforms were identified in maternal tissues at various stages of gestation. Thus, placental villous, subcutaneous and omental adipose tissues were collected upon cesarean delivery at early (Days 60-62), mid (Days 98-102) and late (Days 159-164) pregnancy (term approximately 184 days). Additionally, amniochorion, decidua, and corpus luteum were collected in late gestation. Expression of Ob-RL and Ob-RS transcripts was determined in relation to constitutively expressed glyceraldehyde-3-phosphate dehydrogenase via reverse transcriptase-polymerase chain reaction, and transcripts were localized within specific placental cell types by in situ hybridization. Ob-RL and Ob-RS transcripts were present in amniochorion, decidua, and corpus luteum at term and appeared constitutively expressed throughout gestation in placenta and adipose tissues. Ob-RS was expressed in greater (P < 0.02) abundance than Ob-RL in all tissues. Within the placenta, receptor isoforms were localized predominantly to the syncytiotrophoblast. The expression of leptin receptor transcripts in maternal adipose tissues, as well as in the syncytiotrophoblast, amniochorion, decidua, and corpus luteum, suggests the potential for autocrine/paracrine roles for the polypeptide in the endocrinology of primate pregnancy. These are the first such observations in a nonhuman primate and support the use of the baboon as a model for the study of leptin in human pregnancy.

Serum leptin concentrations and expression of leptin transcripts in placental trophoblast with advancing baboon pregnancy.

Leptin is a polypeptide hormone originally thought to be produced exclusively by adipocytes. Recently, however, both leptin messenger ribonucleic acid (mRNA) and leptin protein were identified in human placental trophoblast cells, suggesting a potential role in primate pregnancy. In the present study, venous blood samples were collected at 5-day intervals during gestation from baboons (Papio sp), an established model for the study of human pregnancy, as well as from nonpregnant baboons, and leptin concentrations were determined by RIA. Additionally, placental villous tissue was collected upon cesarean delivery at early (days 60-62; n = 5), mid (days 98-102; n = 5), and late (days 159-167; n = 5) gestation (term = approximately 184 days), and leptin mRNA was quantitated by competitive RT-PCR. Finally, in situ hybridization was employed to localize transcripts to specific placental cell types. Results determined that maternal leptin levels (mean +/- SEM), which were dramatically greater (P<0.01) than those in nonpregnant cycling baboons (1.4+/-0.1 ng/mL), increased (P<0.005) with gestational age from 63.6+/-10.4 ng/mL on day 60 of gestation to 157.8+/-16.1 near term. Levels declined to those found in cycling baboons by 15 days postdelivery. In contrast to maternal leptin concentrations, placental leptin mRNA decreased (P<0.02) with advancing pregnancy, as transcript abundance declined approximately 8-fold from early to late gestation. Maternal peripheral leptin concentrations were positively correlated (r = 0.66; P<0.001) whereas placental leptin mRNA levels were negatively correlated (r = -0.64; P<0.01) with gestational age. Expression of leptin mRNA transcripts, as evidenced by RT-PCR in villous tissue, was localized principally within syncytiotrophoblast by in situ hybridization. In summary, changes in maternal peripheral leptin concentrations and placental leptin mRNA abundance that occur commensurate with advancing gestational age may imply evolving roles for the polypeptide with advancing primate pregnancy. In this capacity, localization of leptin transcripts within the baboon syncytiotrophoblast suggests the potential for autocrine or paracrine interactions within this endocrinologically active tissue. Finally, both the similarities in leptin ontogeny in baboon and human pregnancy and the singular enhancement of maternal leptin levels inherent throughout baboon gestation emphasize the potential of this nonhuman primate model for the study of leptin action in the maternal-fetoplacental unit.

Longer distance commuting as a substitute for migration in Britain: a review of trends, issues and implications.

"Drawing on analyses of commuting data from secondary sources as well as on selected results from a research project on long-distance commuting in Britain, this article investigates the extent to which, and why, households may choose to substitute longer distance commuting for migration. Reasons for long-distance weekly commuting, and associated advantages and disadvantages from individual, household and employer perspectives, are outlined. The evidence points to increasing complexity in home and working lives, with important implications for housing, transport and human resource management policies, as well as for family life."

Special needs children in the public schools: perceptions of school nurses and school teachers.

Schools are faced with the challenges presented by special needs children (SNC) because the law requires that they must provide educational opportunities to all children--those who have no handicapping conditions as well as those who do, no matter how severe those conditions. The need exists for adequately prepared health care professionals in the school setting. Using a convenience sample of school teachers and school nurses, this investigation focused on the perceptions of school teachers and nurses regarding the challenges and demands of having these children in the public school. Two surveys were conducted to study those perceptions. Quantitative and qualitative data analyses showed that the needs of both groups of providers--school nurses and school teachers--can be summed up in three categories: information dissemination, communication, and resource integration. Infrastructure development involves the establishment of an effective information management system, effective use of such a system in establishing communications between all participants, and adequate administrative support to facilitate the development of the school providers' sense of competence in the care of SNC. A well-planned and adequately supported program goes a long way toward changing people's attitudes toward the inclusion of SNC in the classroom.

Ethnic minority groups in regional and local labour markets in Britain: a review of data sources and associated issues.

"This paper outlines the context of, and discusses the need for, local information on the demographic patterns and labour market experience of ethnic minority groups in many parts of Britain. The specific focus is on the identification and assessment of the strengths and weaknesses of particular data sources providing spatially disaggregated information on the economic position of ethnic minority groups."

Ultrasonography in the management of developmental dysplasia of the hip (DDH).

Real time ultrasonography, according to the method of Graf, was performed on 113 infant hips because of abnormal physical findings (ranging from hip clicks to frank dislocation). Three parameters were measured on the standard coronal images: alpha and beta angles of Graf and the d/D ratio of Morin. Results indicated that the presence of hip clicks (88 hips) in general is a benign condition and not associated with abnormal anatomy. Hips that were reduced at birth but dislocatable (Barlow hip) showed no significantly abnormal acetabular anatomy. Hips that were dislocated at rest but were reducible (Ortolani hip) showed definite abnormal acetabular anatomy and femoral head coverage. Ultrasonography is beneficial in the management of developmental dysplasia of the hip (DDH); it confirms the clinical findings and eliminates radiation exposure to the infant's pelvis, especially in the first 4-6 months of life when standard radiography is not always reliable in diagnosing DDH.

The geography of dual career households: a research agenda and selected evidence from secondary data sources for Britain.

"Amongst the key dimensions of population and labour market change in most parts of western Europe and other similar economies in the 1990s are low fertility rates, rising numbers of smaller households, increasing female participation rates, growth in higher level non-manual occupations and the spread of flexible employment patterns. This paper explores how these trends have led to an increase in the number and significance of one particular subgroup: dual career households. An overview from available secondary sources of the geography and socio-economic characteristics of such households in Britain is presented, and directions for possible future research on dual career households are outlined."

A comparison of alternative measures of unemployment.

PIP: Local unemployment rates are often used as economic and social indicators at the subregional scale. Recently, however, there has been growing debate among social scientists, economists, and planners over the scope, coverage, and usefulness of unemployment counts and rates. This paper compares and contrasts unemployment data from the Employment Department claimant count, the Census of Population, and the Labor Force Survey with the central goal of comparing the census and claimant-based counts for different subgroups of the population disaggregated by age and gender at a range of spatial scales. Analysis reveals that in some cases there are substantial variations in unemployment counts and rates derived from different data sources. These findings suggest the merit of using alternative parallel measures of unemployment designed for a specific purpose. To effectively apply this approach necessitates a better understanding on the part of users of the strengths and weaknesses of alternative sources in order that the most appropriate measure is selected.^ieng

Middle ultraviolet spectroscopy of suppressant-flame interactions.

By minimization of stray light, it is possible to use the middle ultraviolet to gain useful information on flame-suppressant mechanisms.