We previously reported a syndrome of severe hyperinsulinemia and early-onset hypertension in three patients with dominant-negative mutations in the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-␥. We now report the results of further detailed pathophysiological evaluation of these subjects, the identification of affected prepubertal children within one of the original families, and the effects of thiazolidinedione therapy in two subjects. These studies 1) definitively demonstrate the presence of severe peripheral and hepatic insulin resistance in the affected subjects; 2) describe a stereotyped pattern of partial lipodystrophy associated with all the features of the metabolic syndrome and nonalcoholic steatohepatitis; 3) document abnormalities in the in vivo function of remaining adipose tissue, including the inability of subcutaneous abdominal adipose tissue to trap and store free fatty acids postprandially and the presence of very low circulating levels of adiponectin; 4) document the presence of severe hyperinsulinemia in prepubertal carriers of the proline-467-leucine (P467L) PPAR-␥ mutation; 5) provide the first direct evidence of cellular resistance to PPAR-␥ agonists in mononuclear cells derived from the patients; and 6) report on the metabolic response to thiazolidinedione therapy in two affected subjects. Although the condition is rare, the study of humans with dominant-negative mutations in PPAR-␥ can provide important insight into the roles of this nuclear receptor in human metabolism. Diabetes 52:910 -917, 2003

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A dynamic computed tomographic (CT) technique for separate quantification of arterial and portal components of liver perfusion with functional imaging was developed and used to study 24 livers. A single-location dynamic sequence was performed after intravenous administration of a 50-mL bolus of contrast medium. The time to maximum splenic enhancement was used to differentiate arterial and portal phases, and the maximal slopes of the liver time-density curve in each phase were used to calculate both arterial and portal perfusion. The arterial/total perfusion ratio was also calculated. The values of these parameters for individual pixels were used to create functional images. Arterial perfusion was increased in patients with metastases and cirrhosis. Portal perfusion was reduced in patients with cirrhosis. Functional images were successfully created in all but one case. The technique enables quantification and functional mapping of several perfusion parameters with a spatial resolution greater than that achieved with other imaging techniques.

necessary. A national waiting list policy that guarantees access according to agreed criteria, rather than simply guaranteeing maximum waiting times, could facilitate contracts between purchasers and providers on the basis of agreed criteria for the prioritisation of waiting lists. Points Breast screening has failed older women ED1TOR,-Gary Rubin, service director of the East Sussex Breast Screening Service, said that invitations to breast screening should not be extended to women aged 65 or over until more information is available on the success rate of the current screening programme and that a lack of staff would limit an immediate expansion.' Age Concern England's view is that the fundamental issue of the equity of the NHS breast screening service should not depend on further information. The question that needs to be answered is why the programme of breast screening invitations excludes the age group of women in whom the largest number of cancers might be detected. This reduces the potential effectiveness of the breast screening programme and, more importantly, denies older women an important step towards the early detection of breast cancer.The inequity of this situation will become increasingly difficult to reconcile as women aged 50-64 move through the breast screening programme and then ask, at age 65, why they cannot continue to receive invitations. The current system, in which women aged 65 or over can request a screening every three years, has proved a resounding failure, with around 97% of eligible women failing to be screened.Women should be informed that breast cancers do occur in older women and that it is a good precaution to report any breast symptoms promptly. A recent Gallup survey showed that 65% of older women thought that their age group was at little or no risk from breast cancer; 28% thought that there was no risk at all.Many older women do not seek advice about breast symptoms, believing they cannot develop the disease. In many cases, older women mention that the screening cut off age at 65 encourages this belief.In Thirty one women and 16 men presenting for routine computed tomography had their weight, height, and waist circumference measured; all but three men and three women also had their hip circumference measured. The subjects were aged 18-73, and the range of body mass index (kg/m2) was 20.148.5. The cross sectional areas of both intra-abdominal and subcutaneous fat were calculated from images taken immediately cranial to the iliac crests, as previously described.3Pearson product-moment correlations for the logarithms of selected anthropometric variables and ratios with estimates of total fat and the two fat compartments showed that the ratio of waist circumference to height had the highest correlation with intra-abdominal fat (r = 0.83, P<0.001). This was higher than the correlations of waist circumference (r = 0.75), body mass index (r = 0.69), and the ratio of waist to hip circumference (r = 0.54) with intra-abdominal fat.

Abstract-Arterial stiffening is an independent predictor of mortality and underlies the development of isolated systolic hypertension (ISH). A number of factors regulate stiffness, but arterial calcification is also likely to be important. We tested the hypotheses that aortic calcification is associated with aortic stiffness in healthy individuals and that patients with ISH exhibit exaggerated aortic calcification compared with controls. A total of 193 healthy, medication-free subjects (mean ageϮSD: 66Ϯ8 years) were recruited from the community, together with 15 patients with resistant ISH. Aortic pulse wave velocity (PWV) was measured noninvasively, and aortic calcium content was quantified from high-resolution, thoraco-lumbar computed tomography images using a volume scoring method. In healthy volunteers, calcification was positively and significantly associated with aortic PWV (rϭ0.6; PϽ0.0001) but was not related to augmentation index or brachial PWV.