Endocrine controls of eating: CCK, leptin, and ghrelin

The peripheral physiological and central nervous mechanisms contributing to the control of eating present formidable challenges to experimental analysis. One of the most productive approaches to these challenges has been endocrinological. This review introduces the endocrine control of eating by considering three hormonal signals that have been hypothesized to control hunger or satiation, cholecystokinin CCK, leptin, and ghrelin. The roles of these molecules in humans and in rodents are considered against a set of criteria established in classical endocrinology for establishing physiological endocrine action. It is concluded that according to these criteria, CCK's satiating action in humans is the best-established physiological endocrine action. In contrast, support for endocrine actions of leptin in satiation and of ghrelin in hunger is incomplete, and areas urgently requiring further research are identified. Finally, a review of work on these three hormones suggests the utility of a new conceptual scheme for understanding the endocrine control of eating. This scheme distinguishes between endocrine, in which the stimuli for hormonal secretion and the effect of secretion on eating are tightly coupled, and endocrine effects, in which one or both of these links is uncoupled. The implications of this concept for research design and interpretation of data are discussed. A vast literature links endocrine systems to the control of eating behavior [Geary, N. Hunger and satiation. In: Martini, L., ed. Encyclopedia of endocrine diseases. San Diego, CA: Academic Press, 2004, in press.]. This is fortunate for ingestive science. Endocrinology is a well-developed discipline with an impressive armamentarium of intellectual and technical tools. In contrast, ingestive science, i.e., the study of eating, drinking, and drug use, is at a more rudimentary stage of development. My general thesis here is that the adaptation and application of some of the well-accepted intellectual tools of endocrinology is likely to accelerate progress in ingestive science. The organization of the review is threefold. First, the treatment of endocrine controls of eating is selective. Just three hormones, CCK, leptin, and ghrelin, are considered. It is not clear that these are the three most important endocrine controls of eating, but they are each certainly interesting candidates, and comparisons among them are instructive. Second, I argue for the utility of the application of classical endocrine criteria for the identification of physiological effects of hormones, as adapted to eating behavior. This is done by introducing these criteria, considering each hormone's status with respect to them, and identifying the areas where relevant evidence is currently available or is lacking. Third, I argue for the utility of making explicit the distinction between endocrine actions, in which the stimuli for hormonal secretion and the effect of secretion on eating are tightly coupled, and endocrine actions, in which these links are uncoupled. This concept is assembled inductively in the course of the review.     

Breast neoplasms detected only with ultrasonography: incidental finding or clinical evidence?

INTRODUCTION: Mammography is the only technique of proven efficacy in the early diagnosis of breast cancer, even though its sensitivity is much lower in breasts that are dense or with a high parenchymal-stromal component. In the past malignant breast nodules detected at US in patients with negative mammographic and physical findings were considered incidental findings, but more recent papers report increasing numbers of breast cancers detected only at US. PURPOSE: We investigated the yield of US performed as a diagnostic complement in asymptomatic women with mammographic findings that were either negative or poorly readable because of dense breast. MATERIAL AND METHODS: We examined 13 women 37 to 55 years old (mean 47): 9 of them were asymptomatic and 4 had poorly specific physical findings. The patients underwent physical examination, mammography, US, microhistologic biopsy with 14G needles under US guidance and surgery. RESULTS: Fourteen breast lesions 7.0-15 mm in diameter were detected only by US. Mammography (2 or 3 standard views) was negative in all cases. The lesions detected only by US (10% of all carcinomas) were typified with US-guided needle biopsy and finally confirmed surgically. DISCUSSION AND CONCLUSIONS: Though obtained in a small series, our results seem to suggest that US should be included in the diagnostic work-up, especially of women with dense breast. Also, any hypoechoic lesion detected at breast US in clinically asymptomatic women with negative mammographic findings should be further investigated with US, needle aspiration or core biopsy to make the final diagnosis.     

Mortality risk factors in chronic haemodialysis patients with infective endocarditis.

BACKGROUND: It is well documented that infective endocarditis (IE) is strongly associated with morbidity and mortality in haemodialysis (HD) patients. Less clear are the mortality risk factors for IE, particularly in an urban African-American dialysis population. METHODS: IE patients were identified from the medical records for the period from January 1999 to February 2004 and confirmed by Duke criteria. The patients were classified as 'survivors' and 'non-survivors' depending on in-hospital mortality, and risk factors for IE mortality were determined by comparing the two cohorts. Survivors were followed as out-patients with death as the endpoint. RESULTS: A total of 52 patients with 54 episodes of IE were identified. A catheter was the HD access in 40 patients (74%). Mitral valve (50%) was the commonest valve involved, and Gram-positive infections accounted for 87% of IE. In-hospital mortality was high (37%) and valve replacement was required for 13 IE episodes (24%). On logistic regression analyses, mitral valve disease [P = 0.002; odds ratio (OR) = 15.04; 95% confidence interval (CI) = 2.70-83.61] and septic embolism (P = 0.0099; OR = 9.56; 95% CI = 1.72-53.21) were significantly associated with in-hospital mortality. Using the Cox proportional hazards model, mitral valve involvement (P = 0.0008; hazard ratio 4.05; 95% CI = 1.78-9.21) and IE related to drug-resistant organisms such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus sp. (P = 0.016; hazard ratio 2.43; 95% CI = 1.18-5.00) were associated with poor outcome after hospital discharge. CONCLUSIONS: IE was associated with high mortality in our predominantly African-American dialysis population, when the mitral valve was involved, or septic emboli occurred and if MRSA or VRE were the causal organisms.     

Brachyury downstream notochord differentiation in the ascidian embryo

The ascidian tadpole represents the most simplified chordate body plan. It contains a notochord composed of just 40 cells, but as in vertebrates Brachyury is essential for notochord differentiation. Here, we show that the misexpression of the Brachyury gene (Ci-Bra) of Ciona intestinalis is sufficient to transform endoderm into notochord. Subtractive hybridization screens were conducted to identify potential Brachyury target genes that are induced upon Ci-Bra misexpression. Of 501 independent cDNA clones that were surveyed, 38 were specifically expressed in notochord cells. These potential Ci-Bra downstream genes appear to encode a broad spectrum of divergent proteins associated with notochord formation.     

Late appearance of acanthocytes during the course of chorea-acanthocytosis.

A case of chorea-acanthocytosis (CA) syndrome is described. The presence of acanthocytes has usually been considered an important diagnostic marker of CA. However, it is not specific and other neurological diseases have to be considered. In the present report we rule out other diagnostic possibilities and show that the acanthocytes in the peripheral blood smears can appear even later during the course of the disease.     

Further genetic evidence for three psoriasis-risk genes: ADAM33, CDKAL1, and PTPN22

Predisposition to psoriasis is known to be affected by genetic variation in HLA-C, IL12B, and IL23R, and although other psoriasis-associated variants have been identified, incontrovertible statistical evidence for these markers has not yet been obtained. To help resolve this issue, we tested 15 single-nucleotide polymorphisms (SNPs) from 7 putative psoriasis-risk genes in 1,448 psoriasis patients and 1,385 control subjects; 3 SNPs, rs597980 in ADAM33, rs6908425 in CDKAL1 and rs3789604 in PTPN22, were significant with the same risk allele as in prior reports (one-sided P<0.05, false discovery rate<0.15). These three markers were tested in a fourth sample set (599 cases and 299 controls); one marker, rs597980, replicated (one-sided P<0.05) and the other two had odds ratios with the same directionality as in the original sample sets. Mantel-Haenszel meta-analyses of all available case-control data, including those published by other groups, showed that these three markers were highly significant (rs597980: P=0.0057 (2,025 cases and 1,597 controls), rs6908425: P=1.57 x 10(-5) (3,206 cases and 4,529 controls), and rs3789604: P=3.45 x 10(-5) (2,823 cases and 4,066 controls)). These data increase the likelihood that ADAM33, CDKAL1, and PTPN22 are true psoriasis-risk genes.     

Subnormal head circumference in very low birth weight children: neonatal correlates and school-age consequences

BACKGROUND: Subnormal head circumference (HC) has been associated with poor neurologic and developmental outcomes. AIM: To examine the correlates and consequences of subnormal HC in a cohort of school age, very low birth weight (VLBW, <1,500 g) children. STUDY DESIGN AND OUTCOME MEASURES: We examined developmental outcomes at a mean age of 6.8 years in a cohort of 128 VLBW children born from 1982-1986 and 58 normal birth weight controls. The VLBW cohort included a regional sample of <750 g birth weight children and matched children with 750-1,499 g birth weight. Outcomes included an IQ equivalent, neuropsychological skills, academic achievement, adaptive behavior, and attention problems. HC was defined along a continuum and as subnormal vs. normal. Linear and logistic regressions were employed to determine the effects of HC on the outcomes after controlling for confounding variables. RESULTS: Thirty one VLBW children (24%) had subnormal HC vs. none of the controls. The VLBW children with subnormal HC differed significantly from the normal HC group in birth weight (748 g vs. 977 g, p<.001), SGA status (52% vs. 27%, p<.05), high neonatal risk (57% vs. 29%, p<.05), and neurosensory impairment (23% vs. 8%, p<.05). Even after taking these risk factors into account, subnormal HC was associated with poorer IQ equivalent, perceptual motor skills, academic achievement, and adaptive behavior. Results were similar after excluding the children with neurosensory impairment. CONCLUSIONS: Subnormal HC is associated with adverse developmental outcomes in VLBW children, independent of other risk factors. Interventions to improve antenatal and postnatal growth may contribute to better school-age outcomes.