Proximal femur bone geometry is appropriately adapted to lean mass in overweight children and adolescents

It is unclear if the bones of overweight children are appropriately adapted to increased loads. The objective of this study was to compare bone geometry in 40 overweight (body mass index [BMI] > 85th percentile) and 94 healthy weight (BMI < or = 85th percentile) subjects, ages 4-20 years. Dual energy X-ray absorptiometry (Hologic QDR 2000) scans were analyzed at the femoral shaft (FS) and narrow neck (NN) by the Hip Structure Analysis program. Subperiosteal width, cortical thickness and indices of bone axial and bending strength (bone cross-sectional area [CSA] and section modulus [Z]) were measured from bone mass profiles. Multivariate regression models were used to compare overweight and healthy weight subjects. Z was 11 (95% CI 5, 19) and 13 (7, 20) percent higher at the FS and NN, respectively, in overweight subjects (P < 0.001), adjusted for height, maturation and gender. At the NN, higher Z was due to greater subperiosteal width [4% (2, 7)] and bone CSA [10% (5, 16]) and at the FS, to higher bone CSA [10% (5, 16)] and thicker cortices [9% (3, 15)]. When lean mass was added to the models, bone variables did not differ between overweight and healthy weight subjects (P > 0.22), with the exception of NN subperiosteal width [3% (0, 6), P = 0.04]. Fat mass did not contribute significantly to any model. In summary, proximal femur bone geometric strength in overweight children was appropriately adapted to lean mass and height but greater weight in the form of fat mass did not have an independent effect on bone bending strength. These geometric adaptations are consistent with the mechanostat hypothesis that bone strength adapts primarily to muscle forces, not to static loads represented by body weight.     

Intrathecal minocycline attenuates peripheral inflammation-induced hyperalgesia by inhibiting p38 MAPK in spinal microglia

Activation of p38 mitogen-activated protein kinase (p38) in spinal microglia is implicated in spinal nociceptive processing. Minocycline, a tetracycline derivative, displays selective inhibition of microglial activation, a function that is distinct from its antibiotic activity. In the present study we examined antinociceptive effects of intrathecal (IT) administration of minocycline in experimental models of inflammation-evoked hyperalgesia in addition to the effect of minocycline on stimulation-induced activation of p38 in spinal microglia. Intrathecal minocycline produced a dose-dependent reduction of formalin-evoked second-phase flinching behaviour in rats, and prevented thermal hyperalgesia induced by carrageenan injection into the paw. In contrast, systemic delivery (intraperitoneally) of minocycline inhibited the first but not the second phase of formalin-induced flinching, and it had no effect on carrageenan-induced hyperalgesia. Centrally mediated hyperalgesia induced by IT delivery of N-methyl-d-aspartate was completely blocked by IT minocycline. An increase in phosphorylation (activation) of p38 (P-p38) was observed in the dorsal spinal cord after carrageenan paw injection, assessed by both Western blotting and immunohistochemistry. The increased P-p38 immunoreactivity was seen primarily in microglia but also in a small population of neurons. Minocycline, at the IT dose that blocked carrageenan-induced hyperalgesia, also attenuated the increased P-p38 in microglia. In addition, minocycline suppressed lipopolysaccharide-evoked P-p38 in cultured spinal microglial cells. Taken together, these findings show that minocycline given IT produces a potent and consistent antinociception in models of tissue injury and inflammation-evoked pain, and they provide strong support for the idea that this effect is mediated by direct inhibition of spinal microglia and subsequent activation of p38 in these cells.     

Radiographic assessment of resectability of locoregional disease in children with high-risk neuroblastoma during neoadjuvant chemotherapy

BACKGROUND: The optimal timing for attempting removal of the primary tumor and regional disease in patients with high-risk neuroblastoma is uncertain. The purpose of this study was to evaluate resectability of the primary tumor and regional disease, as determined radiographically, in children with high-risk neuroblastoma during neoadjuvant chemotherapy. PROCEDURE: Patients enrolled in our institutional high-risk neuroblastoma protocol were evaluated prospectively by CT scan and/or MRI to determine the resectability of their primary tumor and regional disease at diagnosis, after two cycles of experimental therapy and after standard induction therapy. Tumors were considered to be unresectable if there was significant involvement with major vascular structures or contiguous organs, or would likely require nephrectomy to remove the entire tumor. RESULTS: Twenty-four patients were referred prior to surgery for treatment of high-risk neuroblastoma. Seven of 24 (29%) patients were felt to be resectable at diagnosis, with an additional 9 patients becoming resectable after the initial experimental therapy. Thus, overall, 16 of 24 (67%) patients were felt to be resectable by the completion of the initial therapy. Only four additional patients of the remaining eight were considered resectable after the completion of standard induction therapy. CONCLUSIONS: Based on these data, we conclude that complete resection of the primary tumor and regional disease in children with high-risk neuroblastoma can be performed after an initial phase therapy in the majority of patients. Since earlier tumor removal may decrease the chance for the subsequent development of chemotherapy-resistant disease, we are recommending surgical resection as soon as the locoregional disease appears to be resectable.     

Host population persistence in the face of introduced vector-borne diseases: Hawaii amakihi and avian malaria

The past quarter century has seen an unprecedented increase in the number of new and emerging infectious diseases throughout the world, with serious implications for human and wildlife populations. We examined host persistence in the face of introduced vector-borne diseases in Hawaii, where introduced avian malaria and introduced vectors have had a negative impact on most populations of Hawaiian forest birds for nearly a century. We studied birds, parasites, and vectors in nine study areas from 0 to 1,800 m on Mauna Loa Volcano, Hawaii from January to October, 2002. Contrary to predictions of prior work, we found that Hawaii amakihi (Hemignathus virens), a native species susceptible to malaria, comprised from 24.5% to 51.9% of the avian community at three low-elevation forests (55-270 m). Amakihi were more abundant at low elevations than at disease-free high elevations, and were resident and breeding there. Infection rates were 24-40% by microscopy and 55-83% by serology, with most infected individuals experiencing low-intensity, chronic infections. Mosquito trapping and diagnostics provided strong evidence for year-round local transmission. Moreover, we present evidence that Hawaii amakihi have increased in low elevation habitats on southeastern Hawaii Island over the past decade. The recent emergent phenomenon of recovering amakihi populations at low elevations, despite extremely high prevalence of avian malaria, suggests that ecological or evolutionary processes acting on hosts or parasites have allowed this species to recolonize low-elevation habitats. A better understanding of the mechanisms allowing coexistence of hosts and parasites may ultimately lead to tools for mitigating disease impacts on wildlife and human populations.     

Dysregulation of dopamine signaling in the dorsal striatum inhibits feeding

Dopamine signaling is an important component of many goal-directed behaviors, such as feeding. Acute disruption of dopamine signaling using pharmacological agents tends to inhibit normal feeding behaviors in rodents. Likewise, genetically engineered dopamine-deficient (DD) mice are unable to initiate sufficient feeding and will starve by approximately 3 weeks of age if untreated. Adequate feeding by DD mice can be achieved by daily administration of L-3,4-dihydroxyphenylalanine (L-dopa), a precursor of dopamine, which can be taken up by dopaminergic neurons, converted to dopamine, and released in a regulated manner. In contrast, adequate feeding cannot be restored with apomorphine (APO), a mixed agonist that activates D1 and D2 receptors. Viral restoration of dopamine production in neurons that project to the dorsal striatum also restores feeding in DD mice. Administration of amphetamine (AMPH) or nomifensine (NOM), drugs which increase synaptic dopamine concentration, inhibits food intake in virally rescued DD mice (vrDD) as in control animals. These results indicate that the dysregulation of dopamine signaling in the dorsal striatum is sufficient to induce hypophagia and suggest that regulated release of dopamine in that brain region is essential for normal feeding and, probably, many other goal-directed behaviors.     

Destructive facial T-cell lymphoma: the difficulty in diagnosis of pyoderma-like processes

A 48-year-old woman presented with extensive facial ulceration of 1 year in duration. Based on the combination of the clinical appearance and a “nondiagnostic” biopsy taken elsewhere, the patient was started on oral prednisone at a dose of 40 mg/day, with a working diagnosis of pyoderma gangrenosum. According to the patient, the ulceration worsened over the 2 months whilst on prednisone and pain control was a major issue, controlled for the most part with oral oxycodone. One month prior to our evaluation of the patient, she was started on dapsone at 50 mg/day with no added benefit. Approximately 2 years prior to our evaluation, she developed raised, reddish, skin lesions on the abdomen and legs which recurred, but healed spontaneously each time after a few weeks. Her past medical history was remarkable for the remote use of intravenous drugs (which she had stopped for the past 20 years) and the past and continued use of alcohol on a daily basis. She had recently been tested elsewhere and was found to be positive for hepatitis C, but not human immunodeficiency virus (HIV). Examination revealed several ulcerations of the face and forehead, with an “apple jelly” coloration to the periphery and necrotic center. There was complete erosion of the nasal sidewall with apparent involvement of the septum ( Fig. 1 ). There were also scattered, smaller, nonulcerated, reddish to purplish lesions on the abdomen. Otolaryngologic examination revealed ulceration of the right ala and erosion of the nasal septum, but was otherwise unremarkable. No cervical or submental lymphadenopathy was noted.

Figure 1 Open in figure viewer PowerPoint Facial ulceration at the time of initial evaluation     

Measuring nutritional status in children with chronic kidney disease

Children with chronic kidney disease (CKD) are at risk of protein-energy malnutrition. Existing clinical practice guidelines recognize this and recommend specific methods to assess nutritional status in patients with CKD. This review summarizes the methods for nutritional assessment currently recommended in the United States for children with CKD and details the strengths and limitations of these techniques in the clinical setting. Dietary assessment, serum albumin, height, estimated dry weight, weight/height index, upper arm anthropometry, head circumference, and the protein equivalent of nitrogen appearance are reviewed. We also describe methods for body-composition assessment, such as dual-energy X-ray absorptiometry, bioelectrical impedance analysis (BIA), total body potassium, densitometry, and in vivo neutron activation analysis, pointing out some advantages and disadvantages of each. In CKD, fluid overload is the most important factor leading to misinterpretation of nutritional assessment measures. Abnormalities in the distribution of fat and lean tissue may also compromise the interpretation of some anthropometric measures. In addition, metabolic abnormalities may influence the results obtained by some techniques. Issues specific to evaluating nutritional status in the pediatric population are also discussed, including normalization of nutritional measures to body size and sexual maturity. We stress the importance of expressing body-composition measures relative to height in a population in whom short stature is highly prevalent.     

HIV education in a Siberian prison colony for drug dependent males

Aim  

To evaluate the effectiveness of an HIV peer training program conducted in a colony for drug dependent male prisoners in Siberia, Russia.