Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.

BACKGROUND/OBJECTIVES: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. SUBJECTS/METHODS: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. RESULTS: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001). CONCLUSIONS: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance.

Impact of empiric antibiotics and chest radiograph on delays in the diagnosis of tuberculosis.

SETTING: Maryland Department of Health and Mental Hygiene, Division of Tuberculosis (TB) Control. OBJECTIVES: To assess the implications of antibiotic treatment of presumed community-acquired pneumonia (CAP) on delays in the diagnosis of TB, and to assess the frequency with which chest radiographs (CXRs) were utilized before a diagnosis of pneumonia or pulmonary TB was made. DESIGN: A nested case-control study within a prospective study conducted to assess factors associated with delays in the diagnosis of TB. RESULTS: Cases (n = 85; 54%) were patients who received antibiotics for non-TB diagnoses/indications prior to TB diagnosis, and controls (n = 73; 46%) were patients who had initially received TB therapy. Median health care delay for cases was 39 days vs. 15 days (P < 0.01) for controls. Median antibiotic delay was similar among all antibiotic classes. Of 54 patients who did not have a CXR at their first health care visit, 41 (79%) received empiric antibiotics, compared to 44/105 (42%) who had a CXR (P < 0.01). Only 31/54 (57%) patients initially diagnosed with CAP had a CXR at the time of diagnosis. CONCLUSION: More widespread use of CXR when diagnosing CAP should reduce delays in diagnosing TB, and the unnecessary use of antibiotics.

Central and peripheral glucocorticoid receptor function in abdominal obesity.

Abdominal obesity seems to be associated with a moderately deranged feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis where central glucocorticoid receptors (GR) are involved. Therefore, functions of central and peripheral GR were compared in this study. Furthermore, since trinucleotide repeats in early exons of steroid hormone receptor genes influence transcription, and therefore may influence receptor density, this was also studied. Ten middle-aged men, 5 with abdominal obesity and 5 controls, were studied. The suppression of dexamethasone (dex) on serum cortisol was used in dose-response tests to assess the function of central GR. Abdominal adipose tissue biopsies were incubated and exposed to cortisol in different concentrations, and the function of the peripheral GR assayed as induction of lipoprotein lipase (LPL) activity. Aberrant expansion of exonic trinucleotide repeats in the first coding exon of the GR gene was studied by sequencing of genomic DNA. Results showed that men with abdominal obesity showed less inhibition of serum cortisol by dex, particularly at lower concentrations, while in the controls cortisol secretion was inhibited in an apparent dose-response manner. LPL activity in adipose tissue was lower in abdominal obese men than in controls. However, the sensitivity to cortisol was not different between the groups. There was no evidence for expansion of trinucleotide repeats. These results suggest that the central GR and the peripheral GR in adipose tissue exhibit functional differences in abdominal obesity.

Assimilation of triglycerides in subcutaneous and intraabdominal adipose tissues in vivo in men: effects of testosterone.

To determine the effects of testosterone (T) on lipid assimilation in different adipose tissue depots, T (250 mg, im) was given to 17 middle-aged men 5 days before abdominal surgery. Twenty-four hours before surgery, 10 microCi labeled oleic acid in 80 g milk fat were administered orally. Lipid radioactivity was measured in adipose tissue biopsies from abdominal ac, omental, and retroperitoneal adipose tissues. Subcutaneous, visceral (omental plus mesenteric), and retroperitoneal adipose tissue masses were determined using computerized tomography scans at 22 levels. Sixteen men who were not treated with T served as controls. T administration was followed by an increase in serum concentrations from 17.7 +/- 1.1 to 32.6 +/- 1.8 nmol/L (P < 0.001) and a marked (> 50%) reduction compared with controls in lipid radioactivity in omental and retroperitoneal adipose tissues, but not in sc adipose tissue. In controls, sc, visceral, and retroperitoneal adipose tissues assimilated 59.2 g (73.4%), 16.9 g (20.9%), and 4.6 g (5.7%), respectively, of the orally administered fat. In the T-treated men, this was changed to 73.5 g (88.8%), 6.4 g (7.7%), and 2.9 g (3.5%), respectively. It was concluded that T inhibits triglyceride assimilation in intra-abdominal depots and apparently directs this lipid to sc fat in men.

Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens.

Studies on regional differences of adipose tissue metabolism have mainly been performed in vitro. To allow measurements of lipid uptake in vivo in man, radioactive label from [9,10-3H]oleic acid in 80 g orally administered milk fat was measured after 4 h in abdominal and femoral sc adipose tissues in 28 middle-aged, abdominally obese men. Radioactivity was measured in adipose tissue triglycerides extracted from needle biopsies. Lipoprotein lipase (LPL) activity was also measured. Uptake of label in triglycerides and LPL activity were higher (20% and 15%, respectively; P < 0.05) in the abdominal compared to the femoral adipose tissue region. The men were then randomly assigned to three groups, receiving testosterone (T), dihydrotestosterone, or placebo, for 9 months. After 2 months of treatment, the procedure of administration of label was repeated, this time using [U-14C]oleic acid as a marker. Measurements of radioactive label was then performed after 4 h and monthly up to 7 months. Supplementation with T was followed by an inhibited uptake of label in triglycerides (34%; P < 0.05), lower LPL activity (48%; P < 0.05), and a shorter t1/2 (30%; P < 0.05) in the abdominal adipose tissue region compared with the dihydrotestosterone and placebo groups. No significant effect of T on triglyceride uptake, LPL activity, or t1/2 was found in sc femoral adipose tissue. It was concluded that the turnover rate of depot triglycerides is more rapid in abdominal compared to femoral sc adipose tissue in men. Furthermore, T supplementation inhibits triglyceride uptake and LPL activity and causes a more rapid turnover of triglycerides only in the sc abdominal adipose tissue region. These results demonstrate the marked effects of T on adipose tissue metabolism in vivo and suggest that T is an important regulator of the proportion of depot fat mass in central and peripheral adipose tissue in men.

The role of the family and state in old-age support: the Swedish experience up to 1913.

This paper presents the Swedish experience of caring for the old prior to the welfare state, and focusses on the State's effort to place the responsibility for the aged on the children and kin. If old people were poor and without kin the congregation, e.g. the local community, were responsible for their care and support. The hospitals were built for other groups in society and only the poorhouses were open to the elderly. Pressure on the local community was strongly increased by demographic changes at the turn of the century and the Riksdag was able to unite in passing a law for a State-administered People's Pension 1913.

Maternal ethanol consumption: binding of L-glutamate to synaptic membranes from whole brain, cortices, and cerebella of offspring.

We examined the influence of chronic maternal ethanol consumption on the Na+- and Ca2+-independent binding of L-glutamate to synaptic plasma membranes from whole brain as well as from cortices and cerebella of developing offspring. The maximum specific binding (Bmax) of L-glutamate to the Na+- and Ca2+-independent binding sites in synaptic plasma membranes of brain peaked at 17 days of age in the offspring of both control and ethanol-fed rats, although at that age there were significantly fewer binding sites in the brains of the offspring of ethanol-fed rats. The regional localization of this deficit is not now known. However, it appears that one major glutamatergic region (the cortex) does not reflect the transient deficiency of L-glutamate sites in brain. In fact, the concentration of L-glutamate binding sites in cortical synaptic plasma membranes was significantly increased in the 20-day-old offspring of ethanol-fed rats. In contrast to the cortex, binding to cerebellar synaptic plasma membranes was comparable in 20-day-old offspring of control and ethanol-fed rats. Despite transient alterations in the concentrations of L-glutamate binding sites in brain and synaptic plasma membranes, the affinity of the sites for L-glutamate (Kd) was consistently normal in the 14- to 26-day-old offspring of ethanol-fed rats.

Angiography in acute gastrointestinal bleeding.

Angiography in patients with acute gastrointestinal bleeding is a necessary adjunct to fiberoptic endoscopy to identify the site of the bleeding, especially if it is from the small or large intestine. Clinically, a bleeding rate of 3 milliliters per minute is associated with perceptible extravasation of the contrast medium, venous bleeding excluded. Although celiac or mesenteric arteriography is preferred, abdominal aortography can be useful as the selective examination.