The neuroendocrine challenge paradigm in headache research

The neuroendocrine challenge paradigm provides a "window" on central neurotransmitter function in vivo. This strategy is based on the premise that the sensitivity of certain central receptors can be inferred from the magnitude of the hormonal response to specific pharmacologic probes. For example, the serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin and induces migraine-like headaches. We have previously reported that the headache and cortisol responses to m-CPP are highly correlated, which may implicate a disturbance in central serotonergic neurotransmission in the pathogenesis of migraine. As pharmacologic probes with greater specificity for 5HT receptor subtypes become available, we may be able to elucidate these mechanisms with greater precision. The neuroendocrine challenge methodology is also applicable to the study of other neurotransmitter systems and other headache disorders.     

Does bone measurement on the radius indicate skeletal status? Concise communication

Single-photon (I-125) absorptiometry was used to measure bone mineral content (BMC) of the distal third of the radius, and dual-photon absorptiometry (Gd-153) was used to measure total-body bone mineral (TBBM), as well as the BMC of major skeletal regions. Measurements were done in normal females, normal males, osteoporotic females, osteoporotic males, and renal patients. The BMC of the radius predicted TBBM well in normal subjects, but was less satisfactory in the patient groups. The spinal BMC was predicted with even lower accuracy from radius measurement. The error in predicting areal density (bone mass per unit projected skeletal area) of the lumbar and thoracic spine from the radius BMC divided by its width was smaller, but the regressions differed significantly among normals, osteoporotics, and renal patients. There was a preferential spinal osteopenia in the osteoporotic group and in about half of the renal patients. Bone measurements on the radius can indicate overall skeletal status in normal subjects and to a lesser degree in patients, but these radius measurements are inaccurate, even on the average, as an indicator of spinal state.     

Hepatocellular carcinoma: assessment of resectability by computed tomography and ultrasound

A retrospective review of the CT and ultrasound scans from examinations of 30 patients who had hepatocellular carcinoma (hepatoma) was undertaken with special emphasis placed on evaluation of hepatic distribution of tumor, vascular invasion, and extrahepatic spread. Although both CT and ultrasound detected hepatoma in 29 of 30 patients (96%), CT showed more extensive hepatic parenchymal involvement in eight of the patients. Vascular invasion was seen more frequently with ultrasound than with CT. Invasion into the main portal vein was seen by ultrasound in 11 of 30 patients (37%). Extrahepatic spread of tumor was much more frequently detected by CT and was present in 21 of 30 patients (70%). A reasoned approach to the diagnostic workup of hepatomas that will minimize invasive procedures and unnecessary surgery is presented.     

Effects of 1,25(OH)2D3 on bone tissue in the rabbit: Studies on fracture healing,disuse osteoporosis,and prednisone osteoporosis

Summary A closed tibial fracture, which was controlled by an intramedullary stainless steel pin, was created in 16 rabbits. Eight rabbits were treated with 75 ng of 1,25(OH)₂D₃ daily as subcutaneous (s.c.) injections. After three weeks, the fractured tibia resisted a force of 101,7±21.0 Newtons in the control group and 57.3±8.0 Newtons in animals given 1,25(OH)₂D₃ (m±SE,P<0.05). In another group of eight rabbits, the left hindleg was immobilized in a plastic splint. Four rabbits were given 75 ng of 1,25(OH)₂D₃/day s.c. and the effect of immobilization was studied on the calcaneus. Bone ash/cm³ of the calcaneus on the immobilized side was decreased by 11±2% in control rabbits and by 20±2% in the group treated with 1,25(OH)₂D₃ indicating a more advanced immobilization osteoporosis (m±SE,P<0.05), which was also demonstrated by studies of bone density. Eighteen rabbits were used in a study of the effects of 1,25(OH)₂D₃ on the development of prednisolone osteoporosis. The dose of prednisolone was 2.5 mg per day, given by the oral route. After four months, the density of the femur was 1.53±0.02 g/cm² in control rabbits and 1.42±0.01 in prednisolonetreated animals (P<0.01). In rabbits additionally given 1,25(OH)₂D₃, the mean value for bone density was further lowered (n.s.). It appears that 1,25(OH)₂D₃ exaggerates disuse osteoporosis and prednisolone osteoporosis and impairs fracture healing in rabbits. These results differ from what has been shown earlier with 1,25(OH)₂D₃ treatment in the rat.     

Bone mineral status measured by direct photon absorptiometry in institutionalized adults receiving long-term anticonvulsant therapy and multivitamin supplementation

The effects of long-term anticonvulsant drug therapy and multivitamin supplementation on bone mineral status were evaluated by direct photon absorptiometry in 53 adult residents of an institution for the mentally disturbed. Results demonstrated a similar amount of osteopenia for control subjects and those on anticonvulsant drugs. Average osteopenia was 8% for control subjects and 6% for subjects taking anticonvulsant drugs. Significant osteopenia was found in 25% of subjects taking anticonvulsant drugs and 20% of control subjects. Multivitamin supplementation had a beneficial effect on bone status in both subject groups. The use of anticonvulsant drugs had a significant effect on levels of alkaline phosphatase. Elevated alkaline phosphatase was found in 37% of subjects taking anticonvulsant drugs and 22% of control subjects. Hypocalcemia was found only in subjects taking anticonvulsant drugs (19%). Average calcium values were similar for both subject groups. Multivitamins were shown to have no significant effect on alkaline phosphatase or calcium values. Because both control subjects and those taking anticonvulsant drugs showed similar levels of osteopenia, factors other than anticonvulsant drug therapy appeared to adversely affect bone mineral status in this population. Conversely, multivitamin supplementation and the dietary control present in the institutionalized setting appear to have ameliorated the osteopenia commonly seen in anticonvulsant-treated populations without greatly modifying elevated alkaline phosphatase and hypocalcemia.     

Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis.

Patterns of bone loss in the axial and the appendicular skeleton were studied in 185 normal volunteers (105 women and 82 men; age range, 20--89 yr) and in 76 women and 9 men with vertebral fractures due to osteoporosis. Bone mineral density was measured in vivo at the lumbar spine (predominantly trabecular bone) by dual photon absorptiometry and at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry. In normal women, bone diminution from the vertebrae began in young adulthood and was linear. In the appendicular skeleton, bone diminution did not occur until age 50 yr, was accelerated from aged 51 to 65 yr, and then decelerated somewhat after age 65 yr. Overall bone diminution throughout life was 47% for the vertebrae, 30% for the midradius, and 39% for the distal radius. In normal men, vertebral and appendicular bone diminution with aging was minimal or insignificant. Mean bone mineral density was lower in patients with osteoporosis than in age- and sex-matched normal subjects at all three scanning sites, although spinal measurements discriminated best; however, there was considerable overlap. By age 65 yr, half of the normal women (and by age 85 yr, virtually all of them) had vertebral bone mineral density values below the 90th percentile of women with vertebral fractures and, thus, might be considered to have asymptomatic osteoporosis. For men, the degree of overlap was less. The data suggest that disproportionate loss of trabecular bone from the axial skeleton is a distinguishing characteristic of spinal osteoporosis.