The relation between obesity and age in children with idiopathic intracranial hypertension (pseudotumor cerebri) has remained uncertain. The authors reviewed the records of 45 consecutive children with newly diagnosed idiopathic intracranial hypertension seen at two medical centers. Forty-three percent of patients aged 3 to 11 years were obese, whereas 81% of those in the 12- to 14-year age group and 91% of those in the 15- to 17-year age group met criteria for obesity (p = 0.01). Younger children with idiopathic intracranial hypertension are less likely to be obese than are older children or adults.

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The data indicate a relation between the serum concentration of iPLP and the presence of hypercalcemia in solid malignancies. The results support a role for PLP as a humoral mediator of hypercalcemia in most patients with solid tumors. Measurement of iPLP should be useful in the differential diagnosis of hypercalcemia.

The properties and regulation of insulin receptors on monolayers of cultured clonal osteoblastic rat osteosarcoma UMR-106 cells and human osteosarcoma U20S cells were studied. Confluent cultures of UMR-106 cells bound lactoperoxidase-labeled, HPLC-purified [125I]A-14-monoiodinated insulin in a reversible, saturable, and specific manner. Binding was related inversely to the incubation temperature. Prolonged period of steady-state binding was achieved at all temperatures studied. Competition curves demonstrated half-maximal inhibition of [125I]insulin binding at an unlabeled insulin concentration of about 1 nM. Scatchard analysis of the binding data was curvilinear, suggesting negative cooperativity, and revealed that UMR-106 osteoblasts contained about 87,000 receptor sites per cell according to a two-site model. Bound [125I]insulin dissociated from osteoblasts with a t1/2 of about 15 minutes at 22 degrees C. The dissociation curve was multiexponential, and the addition of native insulin accelerated the dissociation of intact but not degraded [125I]insulin. Preincubation with 125 nM insulin for 1 h induced 70% loss of binding sites and reduced total insulin bound by 30%. When monolayers were treated with the lysosomotropic agent chloroquine, a 40% increase in cell-associated radioactivity that could not be dissociable in fresh buffer was observed. The use of an energy depleter, sodium fluoride, completely inhibited the effects of chloroquine. Similar results were obtained for human osteosarcoma U20S cells except that the number of receptor sites was far less than that of UMR-106 cells. Insulin increased collagen synthesis at a half-maximal concentration of 1 nM. To conclude, cultured rat and human osteoblasts possess insulin receptors that exhibit kinetic properties and specificity similar to those of other insulin target cells. Receptor-bound insulin is internalized and degraded by a chloroquine-sensitive, energy-requiring reaction. Insulin receptor on bone cells modulates the synthesis of collagen and this role may be important in bone homeostasis.

Metastases to the adrenal glands are common in patients with malignancy but malignant disease presenting as Addisonian crisis is rare. The authors presented two patients with acute Addisonian crises due to metastatic infiltration of the adrenal glands. They were otherwise asymptomatic from the primary tumor. Computed tomographic scan showed bilateral adrenal enlargement and transcutaneous biopsy confirmed metastatic adenocarcinoma in the adrenals. Adequate glucocorticoid replacement improves quality of life and prolongs survival.

Total body and regional bone mineral density (BMD) levels were determined in 26 premenopausal women with Hashimoto's thyroiditis receiving long-term physiological doses of levothyroxine sodium replacement therapy. The BMD levels of each patient were compared with the mean of the BMD levels of age-matched normal controls. The mean levothyroxine sodium dose was 111 +/- 6 micrograms/d, and the mean duration of treatment was 7.5 +/- 5.3 years (range, 1 to 24 years). Dietary calcium intake was similar in both groups, as were serum thyroxine, triiodothyronine, free thyroxine index, and thyrotropin levels. Women receiving the levothyroxine treatment had normal total body BMD levels but had significantly lower BMD levels at the femoral neck (-5.7%), femoral trochanter (-7.0%), Ward's triangle (-10.6%), both arms (right, -7.8%; left, -8.9%), and pelvis (-4.9%). In contrast, lumbar spine BMD levels were similar in the two groups. There was no correlation between the total body or different regional BMD levels and the duration or dosage of levothyroxine treatment or thyroid function test results. However, the z score of the femoral neck of these patients showed a significant negative correlation with their serum free thyroxine index levels. We conclude that patients receiving physiological doses of levothyroxine may have decreased bone density. Thyroid functions in patients receiving long-term levothyroxine treatment should be closely monitored and bone densitometry should be performed in patients at risk for osteoporosis.

Abstract-1 In this paper, we will present an effective layout method for analog circuits. We consider symmetry constraint, common centroid constraint, device merging and device clustering during the placement step. Symmetric routing will then be performed. In order to have successful routing, we will perform analog-based routability-driven adjustment during the placement process, taking into account for analog circuits that wires are not preferred to be layout on top of active devices. All these concepts were put together in our tool. Experimental results show that we can generate quality analog layout within minutes of time that passes the design rule check, layout-schematic verification and the simulation results are comparable with those of manual design, while a manual design will take a designer a couple of days to generate.

To determine whether testosterone replacement therapy reverses the detrimental effects of hypogonadism on bone density, we measured the total body, lumbar spine and proximal femur bone mineral density (BMD) by dual-energy X-ray absorptiometry in 14 patients with Klinefelter's syndrome on long-term testosterone replacement therapy and compared the results with 14 age- and sex-matched normal controls. Seven of the patients were receiving oral testosterone undecanoate thrice daily (240 mg/day) and the others were having intramuscular testosterone enanthate injections once every 3 weeks (250 mg/injection). Their serum testosterone levels were maintained within the normal limits (10-40 nmol/l). We showed that patients on testosterone replacement had decreased amount of bone density in the left femoral neck when compared with the controls (p < 0.01). Similar decreases were also observed in the left Ward's triangle (p < 0.01) and in the left trochanter (p < 0.05). There were no significant differences in the total body and the lumbar spine measurements in these two groups of subjects. No correlation was found between the BMD values of femur and the duration of testosterone treatment in the patients with Klinefelter's syndrome. The type of testosterone treatment was also not associated with significant differences in BMD. In conclusion, sufficient testosterone replacement with currently available methods does not reverse the decrease in bone mass associated with hypogonadism in patients with Klinefelter's syndrome.