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Biomedical subjects

H James Norton

Publications and source records attributed to H James Norton.

At least 19 recordsLinked to original sources

The impact of oral disease and nonsurgical treatment on bacteremia in children.

BACKGROUND: The authors examine the role of dental disease and nonsurgical dental procedures in the incidence and duration of bacteremia in children. METHODS: The authors randomized a group of children to receive amoxicillin or a placebo before dental rehabilitation in an operating room setting. They collected eight blood draws at the following times: two minutes after intubation (draw 1); after dental restorations, pulp therapy and cleaning (draw 2); 10 minutes later (draw 3); and five draws during and after dental extractions (draws 4-8). The authors compared dental disease parameters and the type of dental procedures performed with the incidence and duration of bacteremia. RESULTS: The authors enrolled 100 children (aged 1-8 years) in the study. The incidence of bacteremia from draw 2 was 20 percent in the placebo group and 6 percent in the amoxicillin group (P = .07), and the incidence from draw 3 was 16 percent in the placebo group and zero percent in the amoxicillin group (P = .03). Subjects with higher gingival scores were more likely to have a bacteremia for draw 2 (P = .01). The authors found that subjects in the group with bacteremia for draw 3 had undergone more pulpotomies than did subjects in the group without bacteremia for draw 3 (3 +/- 2.5 standard deviation [SD] versus 1.5 +/- 1.6 SD, P = .04), while they found almost no differences for draw 2. CONCLUSIONS: This study suggests that gingival disease has an impact on bacteremia after dental restorations and prophylaxis. Although antibiotics have an impact, they do not eliminate bacteremia altogether.

Amoxicillin↗

Method of biopsy and incidence of positive margins in primary melanoma.

BACKGROUND: The staging of patients with primary melanoma is dependent on adequate sampling of the tumor thickness. Initial biopsies with a positive deep margin suggest inadequate sampling, potentially limiting accurate staging and affecting treatment decisions. METHODS: To determine the efficacy of shave biopsy to adequately sample the tumor, we retrospectively reviewed our pathology database for original pathology reports of primary melanomas accessioned between 01/01/04 and 6/30/05. The biopsies were evaluated by technique, the presence of tumor at the margins of the specimen, and specimen thickness. RESULTS: We identified 240 cases of primary melanoma; 223/240 were analyzable. The specimens were divided by biopsy technique (excisional, n = 51; punch, n = 44; and shave, n = 128). Shave and punch specimens had a significantly higher percentage of positive margins than excisional specimens (50, 68, and 16%, respectively; P < 0.0001). Shave specimens had a significantly higher percentage of positive deep margins than punch or excisional specimens (22, 7, and 2%, respectively; P = 0.0009). For melanomas <or=1 mm, shave specimens had a significantly higher percentage of positive deep margins than punch or excisional specimens (17, 0, and 0%, respectively; P = 0.0014). There was a significant difference in specimen thickness (P = 0.0005), with shave specimens being the thinnest. CONCLUSIONS: The presence of tumor at the lateral margin of punch biopsies is an expected result, since this method is often used to diagnose lesions with a large diameter. The presence of positive deep margins in 22% of shave biopsy specimens compromises the ability of this technique to properly stage patients.

Biopsy↗

Outcomes of adrenal cortical carcinoma in the United States.

BACKGROUND: Improvements in the sensitivity of radiographic imaging have lead to an increase in the number of adrenal masses diagnosed. The purpose of this study is to determine if technologic advancements have resulted in the diagnosis of earlier-staged adrenal cortical cancer (ACC) and to determine if the survival of patients with ACC has improved over the past 15 years. METHODS: Patients with ACC were identified in the Surveillance, Epidemiology, and End Results database between 1988 and 2002. Changes in demographics, stage, size, and treatment were analyzed by standard statistical testing. RESULTS: We identified 602 patients with a mean age of 53 years and an average tumor size of 11.8 cm. Two hundred thirty-eight (39.5%) patients presented with localized disease (stages I and II), and 311 (52%) patients presented with advanced disease (stages III and IV). The comparison of smaller lesions and number of patients were 5 to 6 cm in 24 (4%) patients, 4 to 5 cm in 27 (4.5%) patients, and <4 cm in 19 (3.1%) patients. Patients with masses less than 5 cm were statistically more likely to have localized disease (P <. 001). Age (P = .10), tumor size (P = .85), tumor stage (P = .45), and 5-year survival (P = .5) did not change over the 15-year study. CONCLUSIONS: Over the 15-year study, patients with ACC were not diagnosed at an earlier stage or with tumors smaller, and survival did not improve.

Adrenal Cortex Neoplasms↗

Emergency department sonographic measurement of optic nerve sheath diameter to detect findings of increased intracranial pressure in adult head injury patients.

STUDY OBJECTIVE: Our objective is to determine whether a bedside ultrasonographic measurement of optic nerve sheath diameter can accurately predict the computed tomographic (CT) findings of elevated intracranial pressure in adult head injury patients in the emergency department (ED). METHODS: We conducted a prospective, blinded observational study on adult ED patients with suspected intracranial injury with possible elevated intracranial pressure. Exclusion criteria were age younger than 18 years or obvious ocular trauma. Using a 7.5-MHz ultrasonographic probe on the closed eyelids, a single optic nerve sheath diameter was measured 3 mm behind the globe in each eye. A mean binocular optic nerve sheath diameter greater than 5.00 mm was considered abnormal. Cranial CT findings of shift, edema, or effacement suggestive of elevated intracranial pressure were used to evaluate optic nerve sheath diameter accuracy. RESULTS: Fifty-nine patients were enrolled in the study. Average age was 38 years, and median Glasgow Coma Scale score was 15 (interquartile 6 to 15). Eight patients with an optic nerve sheath diameter of 5.00 mm or more had CT findings that correlated with elevated intracranial pressure. The sensitivity for the ultrasonography in detecting elevated intracranial pressure was 100% (95% confidence interval [CI] 68% to 100%) and specificity was 63% (95% CI 50% to 76%). The sensitivity of ultrasonography for detection of any traumatic intracranial injury found by CT was 84% (95% CI 60% to 97%) and specificity was 73% (95% CI 59% to 86%). CONCLUSION: Bedside ED optic nerve sheath diameter ultrasonography has potential as a sensitive screening test for elevated intracranial pressure in adult head injury.

Adult↗

The effect of soft-tissue ultrasound on the management of cellulitis in the emergency department.

OBJECTIVES: To evaluate the effect of diagnostic soft-tissue ultrasound (US) on management of emergency department (ED) patients with clinical cellulitis. METHODS: This was a prospective observational study in an urban ED of adult patients with clinical soft-tissue infection without obvious abscess. The treating physician's pretest opinions regarding the need for further drainage procedures and the probability of subcutaneous fluid collection were determined. Emergency sonologists then performed US of the infected area, and the effect on management plan was recorded. RESULTS: Ultrasound changed the management of patients with cellulitis in 71/126 (56%) of cases. In the pretest group that was believed not to need further drainage, US changed the management in 39/82 (48%), with 33 receiving drainage and 6 receiving further diagnostics or consultation. In the pretest group in which further drainage was believed to be needed, US changed the management in 32/44 (73%), including 16 in whom drainage was eliminated and 16 who had further diagnostic interventions. US had a management effect in all pretest probabilities for fluid from 10% to 90%. CONCLUSIONS: Soft-tissue US changes physician management in approximately half of patients in the ED with clinical cellulitis. US may guide management of cellulitis by detection of occult abscess, prevention of invasive procedures, and guidance for further imaging or consultation.

Abscess↗

Emergency ultrasound evaluation of symptomatic nontraumatic pleural effusions.

OBJECTIVE: We hypothesized that thoracic ultrasound (ThorUS) performed by emergency physicians would be a rapid and effective management tool for the evaluation of nontraumatic pleural effusion (PleurEff). METHODS: This is a prospective observational study of symptomatic adults presenting to an urban ED with suspicion of PleurEff. ThorUS was performed bilaterally in the upright position. Measurements included treating physician's procedural time requirements, pre- and posttest likelihood of PleurEff, and management changes. RESULTS: There were 59 patients who were entered into the study. Investigating physician's actual time to perform ThorUS was 2.19 minutes. After ThorUS, 48 (81%) patients had an increase and 11 (19%) had a reduction in likelihood of PleurEff with average absolute change in likelihood of PleurEff of 34% (P < .02). ThorUS changed management in 41% of cases; thoracentesis occurred most frequently. CONCLUSION: ThorUS performed by emergency physicians is a rapid and effective management tool for the evaluation of nontraumatic PleurEff in symptomatic ED patients.

Adult↗

Surrogate markers for adverse outcomes in normotensive patients with pulmonary embolism.

BACKGROUND: Although echocardiography has proven utility in risk stratifying normotensive patients with pulmonary embolism, echocardiography is not always available. OBJECTIVE: Test if a novel panel consisting of pulse oximetry, 12-lead electrocardiography, and serum troponin T would have prognostic equivalence to echocardiography and to examine the prognostic performance of age, previous cardiopulmonary disease, D-dimer, brain natriuretic peptide, and percentage of pulmonary vascular occlusion on chest computed tomography. DESIGN: Prospective cohort study. PATIENTS AND SETTING: Normotensive (systolic blood pressure of >100 mm Hg) emergency department and hospital inpatients with diagnosed pulmonary embolism who underwent cardiologist-interpreted echocardiography and other measurements within 15 hrs of anticoagulation. MEASUREMENTS AND MAIN RESULTS: End points were in-hospital circulatory shock or intubation, or death, recurrent pulmonary embolism, or severe cardiopulmonary disability (defined as echocardiographic evidence of severe right ventricular dysfunction with New York Heart Association class III dyspnea or 6-min walk test of <330 m) at 6-month follow-up. The two-one-sided test tested the hypothesis of equivalence with one-tailed alpha = 0.05 and Delta = 5%. Of 200 patients enrolled, data were complete for 181 (88%); 51 of 181 patients (28%) had an adverse outcome, including in-hospital complication (n = 18), death (n = 11), recurrent pulmonary embolism (n = 2), or cardiopulmonary disability (n = 20). Right ventricular dysfunction on initial echocardiogram was 61% sensitive (95% confidence interval, 46-74%) and 57% specific (48-66%). The panel was 71% sensitive (56-83%) and 62% specific (53-71%). The two-one-sided procedure demonstrated superiority of the panel to echocardiography for both sensitivity and noninferiority for specificity. No other biomarker demonstrated equivalence, noninferiority, or superiority for sensitivity and specificity. CONCLUSION: Normotensive patients with pulmonary embolism have a high rate of severe adverse outcomes during 6-month follow-up. A panel of three widely available tests can be used to risk stratify patients with pulmonary embolism when formal echocardiography is not available.

Age Factors↗

Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: a noninferiority trial.

BACKGROUND: Two relatively small previous studies comparing once-daily amoxicillin with conventional therapy for group A streptococcal (GAS) pharyngitis reported similar rates of bacteriologic success for each treatment group. The purpose of this study was to further evaluate once-daily amoxicillin for GAS pharyngitis in a larger study. METHODS: In a single pediatric practice, from October through May for 2 consecutive years (2001-2003), we recruited children 3 to 18 years of age who had symptoms and signs suggestive of GAS pharyngitis. Patients with a positive rapid test for GAS were stratified by weight (<40 kg or >or=40 kg) and then randomly assigned to receive once-daily (750 mg or 1000 mg) or twice-daily (2 doses of 375 mg or 500 mg) amoxicillin for 10 days. We determined bacteriologic failure rates for GAS in the pharynx from subsequent swabs taken at 14 to 21 (visit 2) and 28 to 35 (visit 3) days after treatment initiation. We conducted a randomized, controlled, investigator-blinded, noninferiority trial to evaluate whether amoxicillin given once daily would have a bacteriologic failure rate no worse than that of amoxicillin given twice daily within a prespecified margin of 10%. GAS isolates were characterized to distinguish bacteriologic failures from new acquisitions. Adverse events were described and adherence was evaluated by review of returned daily logs and dosage bottles. RESULTS: Of 2139 potential study patients during the 2-year period, we enrolled 652 patients, 326 into each treatment group. Children in the 2 groups were comparable with respect to all demographic and clinical characteristics except that children <40 kg more often presented with rash in each treatment group. At visit 2, failure rates were 20.1% (59 of 294) for the once-daily group and 15.5% (46 of 296) for the twice-daily group (difference, 4.53%; 90% confidence interval [CI], -0.6 to 9.7). At visit 3, failure rates were 2.8% (6 of 216) for the once-daily group and 7.1% (16 of 225) for the twice-daily group (difference, -4.33; 90% CI, -7.7 to -1.0). Gastrointestinal and other adverse events occurred in the once-daily treatment group with a frequency comparable to that in the twice-daily treatment group. Presumed allergic reactions occurred in 0.9% (6 of 635). More than 95% (516 of 541) of patients complied with 10 days of therapy with no significant differences between groups. CONCLUSIONS: We conclude that amoxicillin given once daily is not inferior to amoxicillin given twice daily. Gastrointestinal and other events did not occur significantly more often in the once-daily treatment group. From the data in this large, investigator-blinded, controlled study, once-daily amoxicillin appears to be a suitable regimen for treatment of GAS pharyngitis.

Adolescent↗

Accuracy of trauma ultrasound in major pelvic injury.

BACKGROUND: Trauma ultrasound (US) utilizing the focused assessment with sonography in trauma (FAST) is often performed to detect traumatic free peritoneal fluid (FPF). Yet its accuracy is unclear in certain trauma subgroups such as those with major pelvic fractures whose emergent diagnostic and therapeutic needs are unique. We hypothesized that in patients with major pelvic injury (MPI) trauma ultrasound would perform with lower accuracy than has previously been reported. METHODS: Retrospective analysis of adult trauma patients with pelvic fractures seen at an urban Level I emergency department and trauma center. Patients were identified from the institutional trauma registry and ultrasound database from 1999 to 2003. All patients aged >16 years with MPI (Tile classification A2, all type B and C pelvic fractures, and type C acetabular fractures determined by a blinded orthopedic traumatologist) and who had a trauma US performed during the initial emergency department evaluation were included. All ultrasounds were performed by emergency physicians or surgeons using the four-quadrant FAST evaluation. Results of US were compared with one of three reference standards: abdominal/pelvic computed tomography, diagnostic peritoneal tap, or exploratory laparotomy. Two-by-two tables were constructed for diagnostic indices. RESULTS: In all, 96 patients were eligible; 9 were excluded for indeterminate ultrasound results. Of the remaining 87 patients, the pelvic fracture types were distributed as follows: 9% type A2, 72% type B, 16% type C, and 3% type C acetabular fractures. Overall US sensitivity for detection of FPF was 80.8%, specificity was 86.9%, positive predictive value was 72.4%, and negative predictive value was 91.4%. Categorization of sensitivity according to pelvic ring fracture type is as follows: type A2 fractures: sensitivity and specificity, 75.0%; type B fractures: sensitivity, 73.3%, specificity, 85.1%; and type C fractures (pelvis and acetabulum): sensitivity and specificity, 100%. Of the true-positive US results, blood was the FPF in 16 of 21 (76%) and urine from intraperitoneal bladder rupture in 4 in 21 (19%) patients. CONCLUSION: US in the initial evaluation of traumatic peritoneal fluid in major pelvic injury patients has lower sensitivity and specificity than previously reported for blunt trauma patients. Additionally, uroperitoneum comprises a substantial proportion of traumatic free peritoneal fluid in patients with MPI.

Adult↗

Odontogenic signs and symptoms as predictors of odontogenic infection: a clinical trial.

BACKGROUND: The authors conducted a study to determine if odontogenic signs and symptoms in the emergency department predicted the development of overt odontogenic infection at a follow-up dental visit. METHODS: One hundred ninety-five patients with odontalgia, but without overt signs of infection, were enrolled in a prospective, double-blind, randomized clinical trial. Data included dental diagnosis, pain characteristics, presence of caries and restorations, presence and size of periapical radiolucencies and other diagnostic test results. RESULTS: Thirteen of 134 subjects for whom data were available had signs of infection at the follow-up visit. Subjects in the follow-up infected (FU-I) group had larger baseline radiolucencies than did subjects in the follow-up noninfected (FU-NI) group, and restorations were more prevalent for involved teeth in the FU-I group than in the FU-NI group. CONCLUSIONS: A relationship exists between radiolucency size and the presence of amalgam restorations in patients who develop clinical signs of infection. Penicillin did not appear to influence this progression. CLINICAL IMPLICATIONS: Antibiotics are not effective in preventing the development of odontogenic infection when definitive dental therapy cannot be provided for acute pain in the absence of clinical signs of infection. Although the overall risk of developing infection is low, early treatment is indicated for teeth with larger periapical radiolucencies, amalgam restorations or both.

Abscess↗

Vertebral endplate architecture and vascularization: application of micro-computerized tomography, a vascular tracer, and immunocytochemistry in analyses of disc degeneration in the aging sand rat.

STUDY DESIGN: Lower lumbar vertebral endplates from young and old sand rats were assessed in an Institutional Animal Care and Use Committee approved study for architectural endplate features using micro-computerized tomography (CT) 3-dimensional (3D) models and vascularization studies by an in vivo vascular tracer or immunocytochemical identification of blood vessels. OBJECTIVE: To assess endplate porosity and vascularization using microCT architectural analysis, an in vivo vascular tracer, and immunocytochemical identification of blood vessels in the endplate. SUMMARY OF THE BACKGROUND DATA: The vertebral endplates, also called cartilage endplates, form the superior and inferior, or cranial and caudal, boundaries of the disc. In the human being and sand rat, the cartilaginous endplate undergoes calcification with aging and is replaced by bone. Endplate sclerosis has long been thought to play a role in disc degeneration by decreasing nutrient availability to the disc, but this is still poorly understood. Previous work has identified increasing bone mineral density with aging and disc degeneration in the sand rat model. METHODS: microCT models of the lower lumbar endplates of vertebrae at L5-6 and L6-7 were constructed from 6 younger (mean age 11 months) and 21 older (mean age 25.6 months) sand rats. Architectural features were scored on a semiquantitative scale for smoothness of the endplate face, irregularities on the endplate margin, and endplate thickness. There were 2 smaller sets of animals (n = 18) evaluated for endplate vascularity following in vivo injection of a fluorescent vascular tracer or by the use of immunocytochemistry to identify blood vessels. RESULTS: microCT revealed a solid bony surface to the endplate, which was not penetrated by vasculature; with aging/disc degeneration, there was roughening and pitting of the plate surface, and the development of irregular margins. In L5-6 and L6-7, sites of prominent disc degeneration evident on radiographs, the proportion of abnormalities in surface smoothness, margin irregularity, and endplate thickening were all statistically significant in both younger and older animals (P < or = 0.0027). More severe changes were evident in the caudal versus cranial endplate surfaces. Histologic study of vascular tracer showed that there was no penetration of the disc by vascular supply from the endplate; this was verified by immunocytochemical identification of blood vessels. The canal system within the endplate was a complex 3D interconnected network. CONCLUSIONS: Findings show that disc degeneration in the sand rat occurs concomitantly with marked architectural bony changes on the endplate face, including loss of smoothness and development of irregular bony margins. Vascular connections were not present between the endplate and disc; this was verified with microCT studies, in vivo vascular tracers, and traditional immunocytochemistry. The canal system within the imaged endplate was revealed to consist of a complex 3D interconnected network.

Aging↗

Normal intraabdominal pressure in healthy adults.

BACKGROUND: Intraabdominal pressure (IAP) has been considered responsible for adverse effects in trauma and other abdominal catastrophes as well as in formation and recurrence of hernias. To date, little information is available concerning IAP in normal persons. Our purpose in this study was to measure the normal range of IAP in healthy, nonobese adults and correlate these measurements with sex and body mass index (BMI). METHODS: After Institutional Review Board approval, 20 healthy young adults (< or =30 years old) with no prior history of abdominal surgery were enrolled. Pressure readings were obtained through a transurethral bladder (Foley) catheter. Each subject performed 13 different tasks including standing, sitting, bending at the waist, bending at the knees, performing abdominal crunches, jumping, climbing stairs, bench-pressing 25 pounds, arm curling 10 pounds, and performing a Valsalva and coughing while sitting and also while standing. Data were analyzed by Student's t-test and Pearson's correlation coefficients. RESULTS: Intraabdominal pressure was measured in 10 male and 10 female subjects. The mean age of the study group was 22.7 years (range, 18-30 years), and BMI averaged 24.6 kg/m(2) (range, 18.4-31.9 kg/m(2)). Mean IAP for sitting and standing were 16.7 and 20 mm Hg. Coughing and jumping generated the highest IAP (107.6 and 171 mm Hg, respectively). Lifting 10-pound weights and bending at the knees did not generate excessive levels of pressure with the maximum average of 25.5 mm Hg. The mean pressures were not different when comparing males and females during each maneuver. There was a significant correlation between higher BMI and increased IAP in 5 of 13 exercises. CONCLUSION: Normal IAP correlates with BMI but does not vary based on sex. The highest intraabdominal pressures in healthy patients are generated during coughing and jumping. Based on our observations, patients with higher BMI and chronic cough appear to generate significant elevation in IAP. Thus, this group of patients may potentially be at increased risk for abdominal wall hernia formation following surgery.

Abdomen↗

Targeted deletion of the SPARC gene accelerates disc degeneration in the aging mouse.

SPARC (secreted protein, acidic, and rich in cysteine) is a matricellular protein that is present in the intervertebral disc; in man, levels of SPARC decrease with aging and degeneration. In this study, we asked whether targeted deletion of SPARC in the mouse influenced disc morphology. SPARC-null and wild-type (WT) mice were studied at 0.3-21 months of age. Radiologic examination of spines from 2-month-old SPARC-null mice revealed wedging, endplate calcification, and sclerosis, features absent in age-matched WT spines. Discs from 3-month-old SPARC-null mice had a greater number of annulus cells than those of WT animals (1884.6 +/- 397.9 [mean +/- SD] vs 1500.2 +/- 188.2, p=0.031). By 19 months discs from SPARC-null mice contained fewer cells than WT counterparts (1383.6 +/- 363.3 vs 1466.8 +/- 148.0, p=0.033). Histology of midsagittal spines showed herniations of lower lumbar discs of SPARC-null mice ages 14-19 months; in contrast, no herniations were seen in WT age-matched animals. Ultrastructural studies showed uniform collagen fibril diameters in the WT annulus, whereas in SPARC-null disc fibrils were of variable size with irregular margins. Consistent with the connective tissue deficits observed in other tissues of SPARC-null mice, our findings support a fundamental role for SPARC in the production, assembly, or maintenance of the disc extracellular matrix.

Aging↗

The SOX9 transcription factor in the human disc: decreased immunolocalization with age and disc degeneration.

STUDY DESIGN: Human intervertebral disc anulus tissue was obtained in a prospective study of immunolocalization of SOX9, a protein that plays a role in chondrogenesis and Type II collagen expression. The Human Subjects Institutional Review Board approved experimental studies. Discs were obtained from surgical specimens and from control donors. OBJECTIVES: To determine whether SOX9 could be detected in discs of Thompson Grades I-IV using immunohistochemistry and to quantify the percentage of cells with SOX9 expression. SUMMARY OF BACKGROUND DATA: SOX9 is involved with cell-specific activation of COL2A1 in chondrocytes. Recent studies have used adenoviral delivery vectors expressing SOX9 to infect a chondroblastic cell line and human disc cells; SOX9 and Type II collagen production increased. The AdSOX9 virus has also been injected directly into rabbit discs in which disc architecture was preserved for 5 weeks. Despite current interest in SOX9 for gene therapy, there have been few studies of SOX9 in normal or degenerated discs. METHODS: Discs from 12 normal donors and 25 surgical subjects 15-76 years old were examined for SOX9 immunolocalization. Eight Thompson Grade I discs, 7 Grade II discs, 10 Grade III discs, and 12 Grade IV discs were studied. RESULTS: In Thompson Grade I discs, SOX9 was uniformly localized throughout the anulus and in some cells of the nucleus. However, in discs from adult donors, anulus cells were present that showed no SOX9 localization, although neighboring cells might be positive. Mean percent localization was 74% for Grade II discs, 69% for Grade III, and 71.6% for Grade IV. Cervical sites showed significantly greater localization than lumbar sites. CONCLUSIONS: Findings showed a uniform expression of SOX9 in the newborn healthy anulus. With aging and disc degeneration, some anulus cells no longer express this transcription product. These observations suggest that the loss of expression of SOX9 in some disc cells may play a role indisc aging and disc degeneration by resulting in decreased expression and production of Type II collagen.

Adolescent↗

Optic nerve sheath diameter does not change with patient position.

OBJECTIVES: Optic nerve sheath diameter (ONSD) has been proposed as a marker for increased intracranial pressure. Trendelenburg's position is often used in hypotensive patients and reverse Trendelenburg's position (30 degrees head up) is often used in head injury patients. We asked if there would be any change in OSND in healthy human adults between the supine, Trendelenburg's, and reverse Trendelenburg's positions. METHODS: Prospective case-control blinded study using consenting healthy adults. Three separate investigators measured the ONSD in each eye of 10 separate volunteers in the supine, Trendelenburg's, and reverse Trendelenburg's positions with 30 degrees angulation from the horizontal. Data were analyzed using the paired t test. RESULTS: In the supine position, the mean ONSD was 4.6 +/- 0.71 (SD) mm in the right eye and 4.5 +/- 0.56 (SD) mm in the left eye. In Trendelenburg's position, the mean ONSD was 4.4 +/- 0.72 (SD) mm in the right eye and 4.7 +/- 0.53 (SD) mm in the left eye. In reverse Trendelenburg's position, the mean ONSD was 4.4 +/- 0.49 (SD) mm in the right eye and 4.8 +/- 0.76 (SD) mm in the left eye. There was no significant difference in OSND between positions for either eye by analysis of variance. Interobserver agreement was +/-1 mm in at least 90% of the subjects regardless of position. CONCLUSION: Optic nerve sheath diameter measurement by ultrasound does not significantly change with Trendelenburg's or reverse Trendelenburg's position in comparison with the supine position in healthy individuals.

Adult↗

Dietary magnesium reduction to 25% of nutrient requirement disrupts bone and mineral metabolism in the rat.

Low dietary magnesium (Mg) may be a risk factor for osteoporosis. In animals, severe Mg deficiency (0.04% of nutrient requirement [NR]) results in bone loss. We have also found that a more moderate dietary Mg restriction (10% of NR) also resulted in loss of bone. We now report the effect of Mg intake of 25% NR on bone and mineral metabolism in the rat. Serum Mg, Ca, PTH, 1,25(OH)2-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were measured at 2, 4, and 6 months in control and Mg-deficient animals. Femurs and tibias were collected for mineral content, micro-computerized tomography, histomorphometry, and immunocytochemical localization. Profound Mg deficiency developed as assessed by marked hypomagnesemia and 27% reduction in bone Mg content. Serum calcium was not significantly different between groups. Mg depletion resulted in a significantly lower serum PTH concentrations. Serum 1,25(OH)2-vitamin D was also significantly lower. No difference was noted in markers of bone turnover. Histomorphometry and micro-computerized tomography demonstrated decreased bone volume and trabecular thickness. No difference was observed for osteoclast or osteoblast number. Inflammatory cytokines may contribute to bone loss. We found that immunocytochemical localization of TNFalpha in osteoclasts was increased 138-150%. This increase in TNFalpha may be due to increased substance P as it was found to be elevated from 179% to 432%. These data demonstrate that Mg intake of 25% NR in the rat causes lower bone mass which may be related to increased release of substance P and TNFalpha.

Animals↗

Evaluation of adhesion formation and host tissue response to intra-abdominal polytetrafluoroethylene mesh and composite prosthetic mesh.

BACKGROUND: The purpose of this study was to measure the extent of adhesion formation to ePTFE mesh (DualMesh, W.L. Gore & Associates, Inc, Flagstaff, AZ) and two composite prosthetic materials, ePTFE and polypropylene (Bard Composix, C.R. Bard, Inc, Murray Hill, NJ) and hyaluronic acid/carboxymethylcellulose and polypropylene (Sepramesh, Genzyme Corp, Cambridge, MA) after their intra-abdominal placement on an intact peritoneum, simulating laparoscopic ventral hernia repair, and to evaluate host tissue response to the prosthetic biomaterials. MATERIALS AND METHODS: Through a midline laparotomy, a 2 x 2 cm piece of mesh (n = 60) was sewn to an intact peritoneum on each side of a midline incision in 30 New Zealand white rabbits. Mesh adhesions were scored using a modified Diamond scale (0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 >50%) at 1, 3, 9, and 16 weeks by serial microlaparoscopy (2 mm). All laparoscopic evaluations were videotaped for blinded scoring by three surgeons. Host tissue response was graded (1-4) for inflammation, tissue ingrowth, and mesothelialization. The predominant cell type (polymorphonuclear leukocytes versus foreign body giant cell) was recorded. Statistical differences (P value <0.05*) were measured using a two-tailed t test and Kruskal-Wallis test. RESULTS: The mean adhesion score was significantly (P < 0.001) less for ePTFE mesh at 1, 3, 9, and 16 weeks compared with the two composite prosthetic materials. There were no differences in the mean adhesion scores between the two biosurgical composite meshes at any of the time intervals. There were no differences in the mean score for inflammation, tissue ingrowth and mesothelialization between any of the prosthetic biomaterials. The predominant cell type on all histological evaluations was polymorphonuclear leukocytes. CONCLUSIONS: Placing ePTFE mesh (DualMesh) intra-abdominal against an intact peritoneum results in significantly fewer adhesions than the composite prosthetic meshes during a 4-month follow-up. The host tissue response is equivalent for the three prosthetic biomaterials. The long-term consequences of increased adhesion formation to the composite meshes and the ultimate biocompatibility of the nonabsorbable and absorbable barriers on the polypropylene mesh are to be determined.

Abdomen↗

Colony formation and matrix production by human anulus cells: modulation in three-dimensional culture.

STUDY DESIGN: Human intervertebral disc cells from the anulus were tested in a study of colony formation and extracellular matrix (ECM) production during long-term three-dimensional culture with exposure to selected cytokines. Experimental studies were approved by the authors' Human Subjects Institutional Review Board. OBJECTIVES: To quantitatively evaluate colony formation and qualitatively assess ECM production (using immunohistochemistry and in situ hybridization) in cells derived from Thompson Grades I to V discs and tested in culture with cytokines and nutrient supplementation. SUMMARY OF THE BACKGROUND DATA: Human intervertebral disc cells offer special in vitro challenges because of the slow-growing nature of these cells and their need for specialized three-dimensional in vitro conditions, which permit the expression and production of proteoglycans and Type II collagen, two ECM products that are important for disc cell biology. METHODS: Discs from 9 human subjects (2 control donors and 7 surgical patients, Thompson Grades I-V), mean age 35.8 years, were used to obtain anulus cells to be tested in three-dimensional agarose culture. Tests of specialized growth conditions included treatment with ITS (insulin-transferrin-sodium selenite supplement), insulin-like growth factor I (IGF-I), and transforming growth factor-beta1 (TGF-beta1). Cultures were evaluated after 14 to 36 days of culture for % colony formation and cell numbers/colony; immunocytochemistry, in situ hybridization, and quantitative histology were used to evaluate colony formation and ECM production. RESULTS: : Data showed that compared with the average 17.5% colony formation observed in controls, ITS, TGF-beta1 and ITS with IGF-I significantly increased colony formation (28.4%, 30.4%, and 30.4%, respectively, P < or = 0.04). Even cells derived from Thompson Grade V disc showed responsiveness to cytokines and improved production of ECM in vitro. CONCLUSIONS: : Findings indicated that cells derived from discs with advanced degeneration were still responsive to cytokines and could be modulated to produce Type II collagen and proteoglycans in three-dimensional culture by the addition of enriched media and selected cytokines. Such findings are important since they advance our understanding of how to modulate disc cell behavior in vitro, and may have application to potential future biologic therapies for disc degeneration.

Adult↗