Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.     

A graded forceps crush spinal cord injury model in mice

Given the rising availability and use of genetically modified animals in basic science research, it has become increasingly important to develop clinically relevant models for spinal cord injury (SCI) for use in mice. We developed a graded forceps crush model of SCI in mice that uses three different forceps with spacers of 0.25, 0.4, and 0.55 mm, to produce severe, moderate, and mild injuries, respectively. Briefly, each mouse was subjected to laminectomy of T5-T7, 15-second spinal cord crush using one of those forceps, behavioral assessments, and post-mortem neuroanatomical analyses. There were significant differences among the three injury severity groups on behavioral measures (Basso Mouse Score, footprint, and ladder analyses), demonstrating an increase in neurological deficits for groups with greater injury severity. Quantitative analysis of the lesion demonstrated that as injury severity increased, lesion size and GFAP negative area increased, and spared tissue, spinal cord cross-sectional area, spared grey matter and spared white matter decreased. These measures strongly correlated with the behavioral outcomes. Similar to other studies of SCI in mice, we report a dense laminin and fibronectin positive extracellular matrix in the lesion sites of injured mice, but unlike those previous studies, we also report the presence of numerous p75 positive Schwann cells in and around the lesion epicenter. These results provide evidence that the graded forceps crush model is an attractive alternative for the study of SCI and related therapeutic interventions. Because of its demonstrated consistency, ease of use, low cost, and clinical relevance, this graded forceps crush is an attractive alternative to the other mouse models of SCI currently available.     

Serum amylase and lipase elevation is associated with intracranial events

Serum amylase and lipase elevation has been observed in trauma patients and patients with traumatic intracranial bleeding. However, the causes of this elevation have not been clearly elucidated. A further question remains as to whether other intracranial events are associated with such enzyme elevation as well. We retrospectively reviewed 75 patients consecutively admitted to Cook County Hospital Neurosurgical Intensive Care Unit over a 3-month period for trauma, infection, tumor, or other space-occupying lesions with an unstable condition or neurological deficit. Eleven patients (15%) had elevated amylase and lipase levels. The patients were divided into two groups: Group I (n = 64) had normal and Group II (n = 11) had raised amylase and lipase levels [amylase 402 +/- 444 U/L with normal < or = 125 U/L and lipase 474 +/- 313 U/L with normal < or = 55 U/L]. All Group II patients suffered an intracranial event. Twenty-four Group I (38%) and 10 Group II (91%) patients required craniotomy (P < 0.01). No patients had clinical or radiographic evidence of pancreatitis. In summary, intracranial events are associated with serum amylase and lipase elevation probably through centrally activated pathways. Because of the lack of diagnostic value, routine pancreatic enzyme monitoring should not be performed in this patient population.     

Combined interleukin 1 and tumour necrosis factor α blockade in rat crescentic anti-glomerular basement membrane glomerulonephritis

SUMMARY: Studies in experimental models have established that blockade of either interleukin 1 (IL‐1) or tumour necrosis factor α (TNF‐α) is effective in suppressing crescentic glomerulonephritis. However, it is not known whether simultaneous blockade of both cytokines will provide additional disease suppression compared with that produced by single cytokine blockade. We have addressed this question in a study of accelerated crescentic anti‐glomerular basement membrane (GBM) glomerulonephritis in the rat. Groups of six animals were treated with an IL‐1 receptor antagonist (IL‐1ra), TNF‐α‐binding protein (TNFbp), IL‐1ra + TNFbp (combined) or saline (control) from the time of anti‐GBM serum injection until being killed, 10 days later. Saline‐treated animals developed crescentic glomerulonephritis with tubulointerstitial damage, heavy proteinuria and renal impairment. Compared with saline, treatment with either IL‐1ra or TNFbp alone resulted in significant suppression of crescent formation (3.0% and 3.3%, respectively, vs. 21.0%; both P < 0.001 vs. control), tubulointerstitial leucocytic infiltration (262 ± 31 and 282 ± 32 cells/mm² vs. 481 ± 71 cells/mm²; both P < 0.001 vs. control) and proteinuria (167 ± 44 and 164 ± 23 mg/24 h vs. 279 ± 36 mg/24 h; both P < 0.001 vs. control) and prevented the loss of renal function. Combined IL‐1ra and TNFbp treatment resulted in a virtually identical degree of disease suppression as individual cytokine blockade in terms of crescent formation (2.7%), interstitial leucocytic infiltration (274 ± 45 cells/mm²), proteinuria (190 ± 18 mg/24 h) and renal function preservation. In conclusion, this study has demonstrated that blockade of either IL‐1 or TNF‐α alone substantial suppresses experimental crescentic glomerulonephritis to a similar extent to that achieved by simultaneous blockade of both cytokines. These findings provide a rationale for the use of cytokine monotherapy, rather than multiple cytokine blockade, in the treatment of human crescentic glomerulonephritis.     

Does the two-week rule pathway improve the diagnosis of soft tissue sarcoma? A retrospective review of referral patterns and outcomes over five years in a regional sarcoma centre

INTRODUCTION

The NHS Cancer Plan was introduced in 2000 and included guidelines for the rapid assessment and referral of cases of suspected malignancy. We wished to assess the efficiency and appropriateness of patients referred under the Department of Health''s general practitioner referral guidelines implemented for sarcomas in December 2000.

PATIENTS AND METHODS

A retrospective case-note review was performed of all patients referred to our regional soft tissue sarcoma unit between 1 January 2004 and 31 December 2008. Patients referred under the two-week guidelines and all patients referred routinely were analysed. The main outcome measures were the total number of patients referred on the basis of the two-week guidelines and the proportion they constitute of all referrals. The referring criteria were noted and compared to the observed criteria recorded. The final histo-logical diagnosis of patients referred on the basis of the two-week guidelines are documented.

RESULTS

A total of 2746 referrals for suspected sarcoma were made from January 2004 to December 2008. Of these, 154 referrals were made under the two-week rule of which 102 were referred purely on the clinical criteria for suspected soft tissue sarcoma. The remaining patients were referred after non-urgent special investigations indicated the possibility of sarcoma. Twelve patients referred under the two-week rule were proved to have sarcoma, nine after specific investigations including imaging or histological diagnosis. Of the 102 patients referred on clinical suspicion of a sarcoma, two patients had proven soft tissue sarcomas and one patient a cutaneous sarcoma. Between 2004 and 2008, the number of 2-week referrals rose 25-fold but accounted for an increase of less than 1% of the sarcomas treated in this unit.

CONCLUSIONS

The numbers of all referrals for suspected sarcoma are increasing; however, the rate of increase of 2-week referrals is increasing faster than routine referrals and will exceed it in 2012 if current trends continue. There has not been a commensurate rise in the detection of sarcoma or, more specifically, diagnosis of the deep sarcomas associated with worse prognosis. Current clinical guidelines have essentially had no impact on the early diagnosis and treatment of soft tissue sarcoma, and may negatively impact on the treatment of patients with proven sarcoma by delaying treatment within a regional centre because of redirection of a large number of patients with benign abnormalities to such centres.     

Fat mass is an important predictor of parathyroid hormone levels in postmenopausal women

Previously, we reported that people with elevated parathyroid hormone (PTH) levels due to primary hyperparathyroidism have increased body weight compared to eucalcemic controls. We sought to determine whether the same relationship between PTH and body weight exists in eucalcemic healthy postmenopausal women, and to investigate the relationships between components of body weight, PTH, vitamin D metabolites, and metabolic indices. We performed a cross-sectional analysis of 116 healthy community-dwelling postmenopausal women. Pearson correlation analysis was used to test for univariate linear relationships between variables, and stepwise multiple regression analysis to assess for multivariate relationships. We found that PTH was significantly positively correlated with body weight, regional and total fat mass, and percent body fat, and negatively correlated with activity levels, 25 hydroxyvitamin D (25OHD), dietary calcium intake, and serum phosphate. On multivariate analysis, PTH was positively related to percent body fat (P = 0.020; partial r2 = 0.10) and negatively related to dietary calcium intake (P = 0.041; partial r2 = 0.03) and serum phosphate (P = 0.026; partial r2 = 0.04). Adjusting for vitamin D insufficiency or 25OHD levels did not affect the relationship between PTH and fat mass. For 25OHD, there were significant positive correlations with lumbar spine BMD and serum albumin, and significant negative correlations with PTH, total fat mass, trunk fat, and pelvic fat. On multivariate analysis, 25OHD was positively related to serum albumin (P = 0.008; partial r2 = 0.07) and negatively related to pelvic fat mass (P = 0.014; partial r2 = 0.05). Adjusting for PTH levels did not change the relationship between 25OHD and pelvic fat mass. We conclude that fat mass is a significant independent determinant of serum PTH levels, and that this relationship is independent of the inverse relationship between 25OHD and fat mass. This association between fat mass and PTH might contribute to the association between primary hyperparathyroidism and increased body weight.     

Pyloroplasty divides vagus nerve fibers to the greater curvature of the stomach. An axonal tracing study.

Recent studies have demonstrated the location in the dorsal motor nucleus of the vagus nerve (dmnX) of nerve cells that project preganglionic efferent vagus nerve fibers to the greater curvature of the stomach. Although it is clear that these fibers are contained within the vagus nerve trunks, the intra-abdominal pathways of these fibers are unknown. When a neurotracer was applied to the right gastroepiploic pedicle, nerve cells in the bilateral dmnX were labeled. If a preliminary anterior or posterior pyloroplasty was performed before the application of the neurotracer, cellular labeling was seen on the right or left side of the dmnX, respectively. Furthermore, division of the anterior Latarjet nerve eliminated labeling in cells of the left dmnX. This study demonstrates that the preganglionic vagus nerve fibers within the right gastroepiploic pedicle traverse an intramural course across the pylorus and are contained in the Latarjet nerve.     

Ligation as definitive management of injury to the superior mesenteric vein

Ligation of the injured superior mesenteric vein in patients with multisystem trauma has been regarded as a hazardous procedure with a narrow spectrum of indications. We present three patients who underwent ligation of their superior mesenteric veins. A collective review of 33 superior mesenteric vein ligations and 75 superior mesenteric venorrhaphies indicated that ligation of this vein is indeed a valid option when a simple repair cannot easily be performed.     

Evaluating the use of a scanning laser-derived oedema index to grade diabetic retinopathy and maculopathy

PURPOSE: To evaluate the Heidelburg Retina Tomograph II (HRTII) retinal module as a tool for grading severity of retinopathy in a diabetic retinal screening and treatment service. METHODS: Seventy-seven consecutive patients with type 2 diabetes underwent scanning laser tomography using the HRTII. Scan data were analysed using the proprietary macular module software and oedema indices calculated for each of nine topographic macular zones. Two consultant ophthalmologists, masked to the result of the HRTII scans, graded each subject for severity of retinopathy and presence of macular oedema. The oedema indices were analysed statistically to determine whether these correlated with severity of retinopathy and presence of macular oedema. RESULTS: There is an increased oedema index in severe non-proliferative diabetic retinopathy in the outer temporal zone compared with lesser grades of diabetic retinopathy (P = 0.001). In patients with clinically detectable macular oedema, the oedema index from the 500-microm-diameter central zone was significantly higher than those without (P = 0.03). CONCLUSION: The scanning laser-derived oedema index differentiated between moderate and severe non-proliferative diabetic retinopathy in this series and detected diabetic macular oedema. Further development of this technology may provide an important tool to supplement retinal photographic surveillance in eye clinics overwhelmed by an increasing prevalence of type 2 diabetes.     

Field evaluation of the Welch Allyn SureSight vision screener: incorporating the vision in preschoolers study recommendations.

INTRODUCTION: The prospective Vision in Preschoolers (VIP) study evaluated 11 methods of screening and proposed referral criteria for the Welch Allyn SureSight(trade mark) Vision Screener with 90% and 94% specificity. The SureSight had a higher sensitivity than most other screening techniques when these criteria were applied. We evaluated the usefulness of these criteria in a field study of healthy preschool children. METHODS: The SureSight software was altered to recommend referral using the VIP referral criteria with 90% specificity. Lions Club volunteers screened preschool children throughout Tennessee. Referred children underwent comprehensive eye examinations with cycloplegic refraction. Examination failure criteria were based upon published standards. Reanalysis using the 94% specificity criteria was then performed. Outcomes included referral rate and positive predictive value. RESULTS: The SureSight was used to screen 4,733 children, and screening was successful in 99.7% of children. The referral rate using the 90% specificity criteria was 12.2%. Most children (73%) were referred for suspected astigmatism. The positive predictive value was 30%. Using the 94% specificity criteria from the VIP study decreased the referral rate to 7.9% and substantially decreased over referral for suspected astigmatism; however, several anisometropes went undetected. Higher specificity was achieved by raising astigmatism referral criteria to 2.2 diopters while leaving the anisometropia criteria unchanged. CONCLUSIONS: The SureSight can be used successfully for preschool screening in the field provided that criteria with high specificity are incorporated into the instrument's software program. Higher rates of positive predictive value can be achieved without jeopardizing sensitivity by raising astigmatism referral criteria to 2.2 diopters.