Body size and pubertal development explain ethnic differences in structural geometry at the femur in Asian, Hispanic, and white early adolescent girls living in the U.S.

UNLABELLED: Variation in structural geometry is present in adulthood, but when this variation arises and what influences this variation prior to adulthood remains poorly understood. Ethnicity is commonly the focus of research of skeletal integrity and appears to explain some of the variation in quantification of bone tissue. However, why ethnicity explains variation in skeletal integrity is unclear. METHODS: Here we examine predictors of bone cross sectional area (CSA) and section modulus (Z), measured using dual-energy X-ray absorptiometry (DXA) and the Advanced Hip Analysis (AHA) program at the narrow neck of the femur in adolescent (9-14 years) girls (n=479) living in the United States who were classified as Asian, Hispanic, or white if the subject was 75% of a given group based on parental reported ethnicity. Protocols for measuring height and weight follow standardized procedures. Total body lean mass (LM) and total body fat mass (FM) were quantified in kilograms using DXA. Total dietary and total dairy calcium intakes from the previous month were estimated by the use of an electronic semi-quantitative food frequency questionnaire (eFFQ). Physical activity was estimated for the previous year by a validated self-administered modifiable activity questionnaire for adolescents with energy expenditure calculated from the metabolic equivalent (MET) values from the Compendium of Physical Activities. Multiple regression models were developed to predict CSA and Z. RESULTS: Age, time from menarche, total body lean mass (LM), total body fat mass (FM), height, total calcium, and total dairy calcium all shared a significant (p<0.05), positive relationship with CSA. Age, time from menarche, LM, FM, and height shared significant (p<0.05), positive relationships with Z. For both CSA and Z, LM was the most important covariate. Physical activity was not a significant predictor of geometry at the femoral neck (p≥0.339), even after removing LM as a covariate. After adjusting for covariates, ethnicity was not a significant predictor in regression models for CSA and Z. CONCLUSION: Variability in bone geometry at the narrow neck of the femur is best explained by body size and pubertal maturation. After controlling for these covariates there were no differences in bone geometry between ethnic groups.

Comparison of therapeutic regimens in the amelioration of alterations in rat gastrointestinal mucosal DNA, RNA and protein induced by streptozotocin diabetes mellitus.

Type 1 diabetes mellitus is characterized by hyperglycemia, insulinopenia, and secondary neural, renal and vascular complications. Clinical manifestations in the gastrointestinal tract range from initial mild complications to more severe complications as the disease progresses, but as of yet, are poorly understood. The current study has two main foci 1) to monitor the alterations in gastrointestinal DNA, RNA and protein content induced by streptozotocin diabetes and 2) to use these parameters to monitor the efficacy of intensive insulin treatment versus pancreatic islet transplantation in the amelioration of the diabetes induced alterations. Female Wistar Furth rats were rendered diabetic by streptozotocin injection and measured for alterations in gastrointestinal DNA, RNA and protein content. Similarly, animals which had streptozotocin-induced diabetes were also treated by intensive insulin therapy or pancreatic islet transplant and monitored for alterations in gastrointestinal DNA, RNA and protein content. In general, diabetes induced increases in stomach, duodenal, jejunal and colonic macromolecular content. With few exceptions, treatment with either intensive insulin or pancreatic islet transplantation returned each variable measured back to control levels. In every case, pancreatic islet transplantation was comparable to intensive insulin therapy. In the short term the treatments are comparable, but long term analyses are needed to determine if the treatments offer any difference in their ability to prevent the long term complications related to diabetes mellitus.

Giant cell tumor of tendon sheath, tenosynovial giant cell tumor, and pigmented villonodular synovitis: defining the presentation, surgical therapy and recurrence.

Giant cell tumor of the tendon sheath (GCTTS), tenosynovial giant cell tumor (TGCT), and pigmented villo-nodular synovitis (PVNS) are the common names for a group of rare proliferative disorders that involve synovial joints and tendon sheaths. Considerable confusion exists about the surgical treatment and diagnosis of these disorders. This review evaluates the presentation, surgical therapy and recurrence of these three proliferative disorders. We retrospectively reviewed the clinical data from all cases of GCTTS, TGCT, and PVNS from 1985 to 1997. A total of 35 patients were identified: GCTTS (n=8), TGCT (n=1), and PVNS (n=26), there were 18 men and 17 women. The median age was 48 years (range 6-84 years). The most common site of involvement was the knee (15), followed by wrist (7), elbow (4), and hip (4). Seven patients had extra-articular involvement, and 19 were found incidentally at operations for other reasons. Among the 4 patients who developed recurrent disease, 2 had extra-articular disease at the time of their original diagnosis. None died, and none required major amputation. One patient was treated with adjuvant radiotherapy following resection of a recurrence. It is important to distinguish between focal and diffuse forms of synovial involvement. If focal, simple surgical excision is appropriate. If diffuse, complete synovectomy is indicated for disease confined to the joint, and resection of all gross disease is indicated for extra-articular disease. Radical resection with negative margins is not necessary in most instances. In rare aggressive cases, local recurrence may necessitate more extensive resection and radiation therapy.

Blunt carotid artery injuries: difficulties with the diagnosis prior to neurologic event.

OBJECTIVE: To evaluate the incidence, timing of diagnosis, clinical factors for adverse outcome, and role of anticoagulant, surgical therapy, or endovascular intervention for patients with blunt carotid artery injury (BCAI). METHODS: Retrospective review of the records of patients who sustained BCAI between 1987 and 1997. RESULTS: There were 18 men and 12 women, with an average age of 29 years. The diagnosis of BCAI was initially suspected in 15 patients after a major or new neurologic event, and in 15 patients after changes were shown by computed tomography. BCAI was confirmed by arteriography in 29 patients and by magnetic resonance angiography in 1 patient. Treatment consisted of antiplatelet therapy (n = 9), anticoagulation (n = 8), surgical repair (n = 6), observation (n = 4), and endovascular embolization (n = 3). With some type of treatment, 14 patients with no neurologic deficits remained stable; however, treatment improved the final neurologic outcome in 8 patients (20%). Three patients remained with severe deficits, and five patients died. CONCLUSION: The consequences of BCAI may be devastating. In our study, there were no reliable means to suspect this injury before neurologic symptoms or abnormalities show on computed tomographic scan. Although external signs are occasionally helpful, most patients have no pattern of injury to suggest BCAI. For patients whose findings after neurologic examination do not correlate with those on the computed tomographic scan, an immediate angiogram is indicated. Occasionally, a proximal injury can be surgically repaired, but in most patients, anticoagulation therapy appears to be the best treatment to avoid or improve neurologic deficits.

Bedside percutaneous endoscopic gastrostomy. A safe alternative for early nutritional support in critically ill trauma patients.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a good alternative that provides long-term nutritional support and is associated with minimal morbidity. METHODS: During a 24-month period, we studied 54 critically injured patients who underwent early PEG to provide enteral nutritional support. Patients were selected due to the inability to tolerate intake by mouth secondary to multiple associated injuries, especially to the central nervous system. RESULTS: All patients sustained multiple injuries with an average Injury Severity Score of 27. The mean Glasgow Coma Scale at the time of admission was 7 and at the time of the PEG was 10. Eleven patients (20%) had an intracranial pressure (ICP) device, and there was no significant increase in the mean ICP before, during, or after the procedure. In 63% of patients, tube feedings were interrupted for a variety of problems in the 72 h preceding the PEG, and in 70% of patients an average of five radiographs were obtained to document tube position. In 95% of patients, the nutritional goal was achieved within 48 h of PEG placement. There were one immediate and two delayed complications after PEG placement. There were two deaths, neither related to the PEG placement. CONCLUSIONS: Early PEG in critically injured patients is a safe and effective method of providing access to the GI tract for nutritional support. In patients with significant brain injuries, adequate sedation and the presence of an ICP monitor help to minimize secondary insults to the brain.

Development of ischemia/reperfusion tolerance in the rat small intestine. An epithelium-independent event.

In stable organ systems, such as the heart and kidneys, an oxidant stress induces an increase in endogenous antioxidant systems resulting in an increased resistance of the tissue to a subsequent oxidant challenge. The development of this oxidant tolerance requires 1.5-6 d. The aim of the present study was to determine whether oxidant tolerance can be induced in the small intestinal mucosa, a labile system whose epithelium turns over every 2-3 d. Ischemia/reperfusion-induced epithelial barrier dysfunction of the small intestinal mucosa was monitored in Sprague-Dawley rats whose intestines had been exposed to an ischemic insult 1, 24, or 72 h previously. At 24 h, but not 1 or 72 h after the initial ischemic insult, the mucosa was more resistant to ischemia/reperfusion-induced barrier dysfunction. The antioxidant status of the mucosa was enhanced at 24 h, but not at 1 or 72 h after the initial ischemic insult. This adaptation appears to be specific for oxidants, since an initial ischemic insult imposed 24 h earlier also protected against H2O2-induced, but not acid- or ethanol-induced, barrier dysfunction. Further studies indicated that the increase in antioxidant status of the mucosa observed 24 h after the initial ischemic insult was a result of adaptational changes in the lamina propria, rather than the epithelium. In vitro studies with isolated epithelial cells also indicated that epithelial cells do not develop oxidant tolerance. We conclude that the development of oxidant tolerance in the small intestinal mucosa does not involve an active participation of the epithelial lining.

Multiple promoter elements govern expression of the human ornithine decarboxylase gene in colon carcinoma cells.

Overexpression of the ornithine decarboxylase (ODC) gene may be important to the development and maintenance of colonic neoplasms, as well as tumors in general. In this study, we examined the promoter elements governing constitutive expression of the human ODC gene in HCT 116 human colon carcinoma cells and, for comparison, K562 human erythro-leukemia cells. It was determined by functional analysis that the promoter elements responsible reside within the 378 bp immediately upstream from the transcription start site. Within this sequence, there are at least three regions that modulate the efficiency of the ODC promoter cooperatively. Both DNA bandshift and footprint assays demonstrated all three regions to be rich in sites that bind to nuclear proteins isolated from HCT 116 and K562 cells; the protein binding pattern of non-transformed, diploid fibroblasts was found to be much less complex. Several of the protein binding sequences have little or no homology to common regulatory elements. We suggest that the constitutive activity of the ODC gene in HCT 116 colon carcinoma cells, and perhaps transformed cells in general, involves a complex interaction of multiple regulatory sequences and their associated nuclear proteins. Finally, the saturation of the promoter in these transformed cell lines suggests that high levels of protein binding in the ODC promoter may contribute to elevated constitutive expression of this gene.

Gastrointestinal luminal polyamines: cellular accumulation and enterohepatic circulation.

The concentration of polyamines contained in the lumen of the gut was quantified. The duodenum and jejunum of the rat contained 2-3 mM putrescine and 1-2 mM cadaverine, whereas in the ileum and colon the concentration of these polyamines was significantly less. In addition, the concentrations of spermine and spermidine in the intestinal lumen were low to undetectable. Putrescine in the lumen of the gut was over 90% free with only 10% or less bound to protein. The activity of the enzymes responsible for the synthesis of polyamines was also measured. In contrast to concentration, enzyme activity was found to be high in the ileum, cecum, and colon and nonexistent in the duodenal and jejunal lumen. This suggested the potential for enterohepatic circulation of polyamines that were synthesized by the colonic microflora and transported to the proximal gut via the portal circulation and biliary tree. Indeed, when [14C]putrescine was instilled into the lumen of the gut, it was secreted in pancreaticobiliary secretions. Upper and lower jejunum and colon all supported enterohepatic circulation of polyamines, whereas it was absent in the ileum. Polyamine accumulation in IEC-6 cells grown under in vitro conditions was also measured. Putrescine was transported under time- and temperature-dependent but sodium-independent conditions. The transporter displayed little selectivity for the various polyamines and compounds with related structures but did not recognize amino acids. The Michaelis constant for putrescine accumulation was 1.26 x 10(-6) M with a maximal velocity of the enzyme reaction of 5,184 pmol putrescine.mg protein-1.h-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Putrescine stimulates DNA synthesis in intestinal epithelial cells.

Experiments were designed to examine the effects of exogenously supplied putrescine on the synthesis of DNA, RNA, and protein in cultured epithelial cells (IEC-6). Putrescine increased aphidicolin-sensitive DNA synthesis at concentrations as low as 0.3 microM putrescine with maximal stimulation (267% control) at 10 microM. This response appeared to be an effect of increases in the intracellular concentration of putrescine as the intracellular levels of spermidine and spermine did not change over the time period examined. Furthermore, pulse-chase experiments revealed that putrescine that entered the cell was not metabolized to another polyamine or degraded. In addition, 10 microM putrescine enhanced both cycloheximide-sensitive lysine incorporation and actinomycin D-sensitive uridine incorporation, indexes of protein and RNA synthesis, respectively. Incorporation of both lysine and uridine was maximal 12 h after the addition of putrescine, whereas thymidine incorporation was still increasing at 24 h, the longest time point examined. These data suggest that putrescine synthesis and/or transport during mucosal proliferation is directly involved in the stimulation of epithelial DNA, RNA, and protein synthesis.

Microflora-derived polyamines modulate obstruction-induced colonic mucosal hypertrophy.

Experiments were designed to determine the role of microflora-derived intraluminal polyamines in the colonic mucosal response to obstruction. Sprague-Dawley rats were treated per os with 0.9% NaCl or a combination of nonabsorbable antibiotics prior to the placement of either a sham or complete colonic obstruction. Sixty-six hours after surgery, wet tissue weight, DNA, RNA, and protein content were all increased in the mucosa proximal to the obstruction in NaCl-treated animals; however, DNA content was the only parameter increased after antibiotics. This induction was a purely local effect as neither hyperplasia nor hypertrophy was observed in the ileum or colon distal to the obstruction. In the NaCl-treated animals, mucosal ornithine decarboxylase activity was not induced until 48 h postsurgery, yet mucosal spermidine concentrations were significantly higher as early as 24 h. Intraluminal bacterial lysine, ornithine, and arginine decarboxylase activities were induced by obstruction but were reduced by antibiotic treatment. [14C]putrescine uptake by intestinal epithelial cells (IEC-6) in culture was blocked by the antibiotics employed in this study, but [14C]-lysine transport was relatively unaffected. These data demonstrate that intraluminal polyamines modulate the trophic response of the colonic mucosa after colonic obstruction.