Accelerated rehabilitation following thumb ulnar collateral ligament repair with suture tape augmentation: A case series of professional basketball players.

STUDY DESIGN: Case series. INTRODUCTION: Rehabilitation protocols following thumb metacarpophalangeal (MCP) ulnar collateral ligament (UCL) repair typically do not allow for return to sport until 12 weeks post-surgery. The potential for accelerated rehabilitation following thumb MCP UCL repair with suture tape augmentation has yet to be explored. PURPOSE OF THE STUDY: To describe the accelerated rehabilitation following thumb MCP UCL repair with the suture tape augmentation in professional basketball players. METHODS: Three professional basketball players underwent thumb MCP UCL repair with suture tape augmentation. The athletes followed an accelerated rehabilitation program post-surgery that began with range-of-motion exercises at 2-3 days, proximal strengthening at 7-10 days, grip/pinch strengthening at 1-2 weeks, followed by progressive sport specific intervention with a custom orthosis. RESULTS: At 5-6 weeks post-surgery, active thumb MCP range of motion returned to 83%-100%, grip strength to 81%-100%, and tripod pinch strength to 73%-78% of the contralateral side. All athletes successfully returned to sport within 5-6 weeks post-surgery. DISCUSSION/CONCLUSION: This is the first clinical application of an accelerated rehabilitation protocol in athletes following thumb MCP UCL repair. In this series, professional basketball players were able to return to sport in half the routine recovery time. Further prospective studies re-thinking current rehabilitation protocols are warranted.

Fluorescent Tracers for In Vivo Imaging of Lymphatic Targets.

The lymphatic system continues to gain importance in a range of conditions, and therefore, imaging of lymphatic vessels is becoming more widespread for research, diagnosis, and treatment. Fluorescent lymphatic imaging offers advantages over other methods in that it is affordable, has higher resolution, and does not require radiation exposure. However, because the lymphatic system is a one-way drainage system, the successful delivery of fluorescent tracers to lymphatic vessels represents a unique challenge. Each fluorescent tracer used for lymphatic imaging has distinct characteristics, including size, shape, charge, weight, conjugates, excitation/emission wavelength, stability, and quantum yield. These characteristics in combination with the properties of the target tissue affect the uptake of the dye into lymphatic vessels and the fluorescence quality. Here, we review the characteristics of visible wavelength and near-infrared fluorescent tracers used for in vivo lymphatic imaging and describe the various techniques used to specifically target them to lymphatic vessels for high-quality lymphatic imaging in both clinical and pre-clinical applications. We also discuss potential areas of future research to improve the lymphatic fluorescent tracer design.

Increasing the quantitative bandwidth of NMR measurements.

The frequency range of quantitative NMR is increased from tens to hundreds of kHz by a new pulse sequence, CHORUS. It uses chirp pulses to excite uniformly over very large bandwidths, yielding accurate integrals even for nuclei such as (19)F that have very wide spectra.

Abnormal connexin expression in human chronic wounds.

BACKGROUND: Regulated alteration of connexin expression has been shown to be integral to acute wound repair. Downregulation of the gap-junction protein connexin 43 at the wound edge has been correlated with keratinocyte and fibroblast migration, while abnormal overexpression of connexin 43 significantly perturbs healing, as shown in the streptozotocin diabetic rodent impaired healing model. OBJECTIVES: To examine the protein expression levels of connexin 43, in addition to connexins 26 and 30, in a variety of human chronic wounds. METHODS: Wound-edge punch biopsies and a matched control from the arm were taken from a cohort of patients with venous leg, diabetic foot or pressure ulcers. Wound connexin expression in each patient was compared with that in a matched, nonwounded arm punch. Tissue was sectioned, stained and imaged by confocal microscopy using identical parameters per patient to permit quantification. RESULTS: Epidermal connexin 43, connexin 26 and connexin 30, and dermal connexin 43 were discovered to be strikingly upregulated in every ulcer from all three wound types, pointing to connexin upregulation as a common feature between chronic wounds. CONCLUSIONS: This result supports efforts to target connexin 43 to promote cell migration and wound healing in chronic ulcers.

Optimal positioning of the DVR plate in distal radius fractures: a cadaveric examination of a referencing technique.

INTRODUCTION: Volar locking plates have revolutionised the treatment of distal radius fractures but complications are not uncommon. We present a cadaveric study and a technical tip to assist in the accurate and reproducible placement of one such plate. STUDY: We placed 25-g needles in the distal radioulnar joint and radiocarpal joint and measured the distance from these needles to a DVR plate in its optimal position. This distance measured 5mm, corresponding to the width of the depth gauge handle. Placing this next to needles in these joints can help pre-plan the most distal and ulnar extent of the plate allowing for reproducible optimal positioning of the DVR plate. TECHNIQUE: The technique developed uses the existing kit and is simple and easy to build into one's existing fixation technique.

Pharmacological characterization of rat amylin receptors: implications for the identification of amylin receptor subtypes.

BACKGROUND AND PURPOSE: Amylin (Amy) is an important glucoregulatory peptide and AMY receptors are clinical targets for diabetes and obesity. Human (h) AMY receptor subtypes are complexes of the calcitonin (CT) receptor with receptor activity-modifying proteins (RAMPs); their rodent counterparts have not been characterized. To allow identification of the most clinically relevant receptor subtype, the elucidation of rat (r) AMY receptor pharmacology is necessary. EXPERIMENTAL APPROACH: Receptors were transiently transfected into COS-7 cells and cAMP responses measured in response to different agonists, with or without antagonists. Competition binding experiments were performed to determine rAmy affinity. KEY RESULTS: rCT was the most potent agonist of rCT((a)) receptors, whereas rAmy was most potent at rAMY(1(a)) and rAMY(3(a)) receptors. rAmy bound to these receptors with high affinity. Rat α-calcitonin gene-related peptide (CGRP) was equipotent to rAmy at both AMY receptors. Rat adrenomedullin (AM) and rAM2/intermedin activated all three receptors but were most effective at rAMY(3(a)) . AC187, AC413 and sCT(8-32) were potent antagonists at all three receptors. rαCGRP(8-37) displayed selectivity for rAMY receptors over rCT((a)) receptors. rAMY(8-37) was a weak antagonist but was more effective at rAMY(1(a)) than rAMY(3(a)) . CONCLUSIONS AND IMPLICATIONS: AMY receptors were generated by co-expression of rCT((a)) with rRAMP1 or 3, forming rAMY(1(a)) and rAMY(3(a)) receptors, respectively. CGRP was more potent at rAMY than at hAMY receptors. No antagonist tested was able to differentiate the rAMY receptor subtypes. The data emphasize the need for and provide a useful resource for developing new CT or AMY receptor ligands as pharmacological tools or potential clinical candidates.

Copper(II)-selective chelation improves function and antioxidant defences in cardiovascular tissues of rats as a model of diabetes: comparisons between triethylenetetramine and three less copper-selective transition-metal-targeted treatments.

AIMS/HYPOTHESIS: Treatment with the Cu(II)-selective chelator triethylenetetramine (TETA) improves cardiovascular disease in human patients, and cardiac and vascular/renal disease in rats used as a model of diabetes. Here we tested two hypotheses: first, that TETA elicits greater improvement in organ function than less Cu-selective transition-metal-targeted treatments; second, that the therapeutic actions of TETA are consistent with mediation through suppression of oxidative stress. METHODS: Rats were made diabetic with streptozotocin (55 mg/kg, i. v.) and treated from 8 weeks after disease induction for the following 8 weeks with effective dosages of oral TETA, or one of three less Cu-selective transition-metal-targeted treatments: D-penicillamine, deferiprone or Zn acetate. Treatment effects were measured in ex vivo cardiac and aortic tissues, plasma and urine. RESULTS: Diabetes damaged both cardiac and renal/vascular function by impairing the ability of cardiac output to respond physiologically to rising afterload, and by significantly elevating the urinary albumin/creatinine ratio. Diabetes also lowered total antioxidant potential and heparan sulphate levels in cardiac and arterial tissues, and serum ferroxidase activity, whereas it elevated urinary heparan sulphate excretion. TETA treatment rectified or partially rectified all these defects, whereas the other three experimental treatments were ineffectual. By contrast, none of the four drug treatments lowered diabetes-mediated elevations of plasma glucose or lipid concentrations. CONCLUSIONS/INTERPRETATION: TETA may limit the cardiac and renal/vascular damage inflicted by diabetes through its actions to reinforce antioxidant defence mechanisms, probably acting through selective chelation of 'loosely-bound'/chelatable Cu(II). It may also improve heparan sulphate homeostasis and bolster antioxidant defence by increasing vascular extracellular superoxide dismutase activity. Urinary albumin/creatinine ratio might prove useful for monitoring TETA treatment.

Systematic review and meta-analysis of enteral nutrition formulations in acute pancreatitis.

BACKGROUND: Although the benefits of enteral nutrition in acute pancreatitis are well established, the optimal composition of enteral feeding is largely unknown. The aim of the study was to compare the tolerance and safety of enteral nutrition formulations in patients with acute pancreatitis. METHODS: Electronic databases (Scopus, MEDLINE, Cochrane Controlled Clinical Trials Register) and the proceedings of major pancreatology conferences were searched. RESULTS: Twenty randomized controlled trials, including 1070 patients, met the inclusion criteria. None of the following was associated with a significant difference in feeding intolerance: the use of (semi)elemental versus polymeric formulation (relative risk (RR) 0.62 (95 per cent confidence interval (c.i.) 0.10 to 3.97); P = 0.611); supplementation of enteral nutrition with probiotics (RR 0.69 (95 per cent c.i. 0.43 to 1.09); P = 0.110); or immunonutrition (RR 1.60 (95 per cent c.i. 0.31 to 8.29); P = 0.583). The risk of infectious complications and death did not differ significantly in any of the comparisons. CONCLUSION: The use of polymeric, compared with (semi)elemental, formulation does not lead to a significantly higher risk of feeding intolerance, infectious complications or death in patients with acute pancreatitis. Neither the supplementation of enteral nutrition with probiotics nor the use of immunonutrition significantly improves the clinical outcomes.

Systematic review of oxidative stress associated with pneumoperitoneum.

BACKGROUND: There have been several reports of ischaemic complications after routine laparoscopy. The aim of this review was to investigate the relationship between this oxidative stress and pneumoperitoneum. METHODS: Medline, Medline in-process, The Cochrane Library, PubMed and EMBASE were searched for papers on oxidative stress and pneumoperitoneum, from 1947 to March 2008 with no language restriction or restriction on trial design. Papers that did not investigate pneumoperitoneum as a causative factor, or did not report outcome measures related to oxidative stress, were excluded. RESULTS: A total of 73 relevant papers were identified: 36 animal studies, 21 human clinical trials, nine case reports, five review articles and two comments. Pneumoperitoneum causes a reduction in splanchnic blood flow, resulting in biochemical evidence of oxidative stress in a pressure- and time-dependent manner. There is evidence that the use of carbon dioxide for insufflation is contributory. Several measures proposed to minimize the oxidative stress have shown promise in animal studies, but few have been evaluated in the clinical setting. CONCLUSION: There is an increasing body of evidence, mainly from animal studies, that pneumoperitoneum decreases splanchnic perfusion with resulting oxidative stress. It is now appropriate to investigate the clinical significance of pneumoperitoneum-associated oxidative stress.

A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study.

AIMS/HYPOTHESIS: Cu(II)-selective chelation with trientine ameliorates cardiovascular and renal disease in a model of diabetes in rats. Here, we tested the hypothesis that Cu(II)-selective chelation might improve left ventricular hypertrophy (LVH) in type 2 diabetic patients. METHODS: We performed a 12 month randomised placebo-controlled study of the effects of treatment with the Cu(II)-selective chelator trientine (triethylenetetramine dihydrochloride, 600 mg given orally twice daily) on LVH in diabetic patients (n = 15/group at baseline) in an outpatient setting wherein participants, caregivers and those assessing outcomes were blinded to group assignment. Using MRI, we measured left ventricular variables at baseline, and at months 6 and 12. The change from baseline in left ventricular mass indexed to body surface area (LVM(bsa)) was the primary endpoint variable. RESULTS: Diabetic patients had LVH with preserved ejection fraction at baseline. Trientine treatment decreased LVM(bsa) by 5.0 +/- 7.2 g/m(2) (mean +/- SD) at month 6 (when 14 trientine-treated and 14 placebo-treated participants were analysed; p = 0.0056 compared with placebo) and by 10.6 +/- 7.6 g/m(2) at month 12 (when nine trientine-treated and 13 placebo-treated participants were analysed; p = 0.0088), whereas LVM(bsa) was unchanged by placebo treatment. In a multiple-regression model that explained ~75% of variation (R (2) = 0.748, p = 0.001), cumulative urinary Cu excretion over 12 months was positively associated with trientine-evoked decreases in LVM(bsa). CONCLUSIONS/INTERPRETATION: Cu(II)-selective chelation merits further exploration as a potential pharmacotherapy for diabetic heart disease. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12609000053224 FUNDING: The Endocore Research Trust; Lottery Health New Zealand; the Maurice and Phyllis Paykel Trust; the Foundation of Research, Science and Technology (New Zealand); the Health Research Council of New Zealand; the Ministry of Education (New Zealand) through the Maurice Wilkins Centre for Molecular Biodiscovery; and the Protemix Corporation.

A copper(II)-selective chelator ameliorates diabetes-evoked renal fibrosis and albuminuria, and suppresses pathogenic TGF-beta activation in the kidneys of rats used as a model of diabetes.

AIMS/HYPOTHESIS: The selective Cu(II) chelator triethylenetetramine (TETA) extracts systemic Cu(II) into the urine of diabetic humans and rats as a model of diabetes, and in the process also normalises hallmarks of diabetic heart disease. However, the role of Cu and its response to TETA in animals with diabetic nephropathy were previously unknown. Here, we report the effects of TETA treatment on Cu and other essential elements, as well as on indices of renal injury and known pathogenic molecular processes, in kidneys from a rat model of diabetes. METHODS: Rats at 8 weeks after streptozotocin-induction of diabetes were treated with oral TETA (34 mg/day in drinking water) for a further 8 weeks and then compared with untreated diabetic control animals. RESULTS: Renal tissue Cu was substantively elevated by diabetes and normalised by TETA, which also suppressed whole-kidney and glomerular hypertrophy without lowering blood glucose. The urinary albumin: creatinine ratio was significantly elevated in the rat model of diabetes but lowered by TETA. Total collagen was also elevated in diabetic kidneys and significantly improved by TETA. Furthermore, renal cortex levels of TGF-beta1, MAD homologue (SMAD) 4, phosphorylated SMAD2, fibronectin-1, collagen-III, collagen-IV, plasminogen activator inhibitor-1 and semicarbazide-sensitive amine oxidase all tended to be elevated in diabetes and normalised by TETA. CONCLUSIONS/INTERPRETATION: Dysregulation of renal Cu homeostasis may be a key event eliciting development of diabetic nephropathy. Selective Cu(II) chelation can protect against pathogenic mechanisms that lead to or cause diabetic nephropathy and might be clinically useful in the treatment of early-stage diabetic kidney disease.

Dealing with lead in Broken Hill--trends in blood lead levels in young children 1991-2003.

The objective of the study was to investigate trends in blood lead concentrations in preschool children between 1991 and 2003, as part of the evaluation strategy of a public health lead management program in Broken Hill, Australia. Since 1991, all Broken Hill children aged 1-4 years have been offered at least annual blood lead screening as part of a community-wide lead management program. Recruitment of children was promoted throughout the period using local media and distribution of promotional material from health care centres and preschool, childcare, and educational facilities around the city. Venous blood samples were collected using standard procedures and analyses were subjected to internal and external quality control programs. Because the frequency distribution of blood lead levels are skewed, geometric rather than arithmetic means were used for comparative purposes. Trend analysis was based on age and sex standardised mean blood lead levels. The number of 1- to 4-year-old children screened ranged between 496 and 948 in any one year and response rates varied between 39% and 73%. The age-sex standardised mean blood lead level decreased from 16.3 microg/dL to 7.1 microg/dL between 1991 and 2003. Overall, blood lead levels declined by 56% over 13 years. These reductions were consistently observed irrespective of age or where a child lived in the town. The rate of decline has slowed since 1997. We conclude that substantial progress has been made in dealing with the lead problem in Broken Hill children, although the rate of decline of blood lead levels has slowed. Continued public health action is still needed to bring the proportion of young children with significantly elevated blood lead levels (>15 microg/dL) down from the 2003 figure of 12% to the NHMRC community-based target for lead in young Australians of 5%.

Insulin resistance in the Zucker diabetic fatty rat: a metabolic characterisation of obese and lean phenotypes.

The Zucker diabetic fatty (ZDF) rat is a commonly used animal model of type 2 diabetes yet complete descriptions of insulin resistance in this model are limited. We present a full characterisation of in vivo insulin resistance in obese (fa/fa) animals compared to lean (+/?) littermates. Anaesthetised, ten-week old, obese ZDF rats and their lean littermates underwent a hyperinsulinaemic euglycaemic glucose clamp. Compared with lean littermates, obese ZDF rats required an 89% lower glucose infusion rate to maintain euglycaemia and showed a 35% decrease in peripheral glucose disposal. Insulin-stimulated glucose uptake (R(g')) in obese animals was also significantly less in all skeletal muscles studied. R(g') in cardiac and white adipose tissue was not different between the two groups. Total glycogen content in skeletal and cardiac muscle was significantly less in obese animals, while total glycogen content in the liver was significantly greater than in lean littermates. Glycogen synthesis was also decreased in skeletal muscle of obese animals. Compared with lean animals, total triglyceride content was significantly greater in skeletal muscle, heart and liver of obese ZDF rats. Obese animals also showed significantly increased glucose incorporation into lipid in all of these tissues, indicating an increase in lipogenesis. Collectively, these results provide an integrated characterisation of in vivo insulin resistance in obese ZDF rats and a direct comparison with lean littermates.

Preptin derived from proinsulin-like growth factor II (proIGF-II) is secreted from pancreatic islet beta-cells and enhances insulin secretion.

Pancreatic islet beta-cells secrete the hormones insulin, amylin and pancreastatin. To search for further beta-cell hormones, we purified peptides from secretory granules isolated from cultured murine beta TC6-F7 beta-cells. We identified a 34-amino-acid peptide (3948 Da), corresponding to Asp(69)-Leu(102) of the proinsulin-like growth factor II E-peptide, which we have termed 'preptin'. Preptin, is present in islet beta-cells and undergoes glucose-mediated co-secretion with insulin. Synthetic preptin increases insulin secretion from glucose-stimulated beta TC6-F7 cells in a concentration-dependent and saturable manner. Preptin infusion into the isolated, perfused rat pancreas increases the second phase of glucose-mediated insulin secretion by 30%, while anti-preptin immunoglobulin infusion decreases the first and second phases of insulin secretion by 29 and 26% respectively. These findings suggest that preptin is a physiological amplifier of glucose-mediated insulin secretion.

Plasma amylin concentration is related to the severity of intestinal ischemic injury in rats.

BACKGROUND: Previous work has demonstrated that intestinal ischemia increases plasma amylin concentration. This study examined the relationship between the degree of intestinal ischemia injury and plasma amylin in an experimental rat model. METHODS: Wistar rats were divided into a control group (n = 6); a sham-operated group (n = 9); and 3 intestinal ischemia-reperfusion groups (n = 8 in each), which underwent clamping of the superior mesenteric artery for either 15, 30, or 45 minutes followed by 15 minutes of reperfusion. Samples were then collected for intestinal histology and measurement of amylin, insulin, and glucose. RESULTS: There was a positive correlation between the histologic score of the intestinal injury and the measured plasma amylin concentration (R = 0.48, P =.007). The median plasma concentration of amylin was 62 pmol/L (range, 42-97 pmol/L) in the 30-minute intestinal ischemia group and 58 pmol/L (42-86 pmol/L) in the 45-minute intestinal ischemia group. Both these groups were increased compared with the sham-operated group (29 pmol/L; range, 22-57 pmol/L; P <.001 and P <.005, respectively) and the control group (28 pmol/L; range, 26-42 pmol/L; P <.001 and P <.0005, respectively). The median plasma concentration of insulin in the 30-minute intestinal ischemia group was 4230 pmol/L (range, 1360-5770 pmol/L), which was increased compared with both the control group (950 pmol/L; range, 550-1510 pmol/L; P <.005) and the sham-operated group (720 pmol/L; range, 280-4180 pmol/L; P<.005). There were no differences between any of the other groups either for glucose, insulin, or amylin. CONCLUSIONS: Plasma amylin concentration is related to the severity of intestinal ischemic injury.

A method using laser Doppler flowmetry to study intestinal and pancreatic perfusion during an acute intestinal ischaemic injury in rats with pancreatitis.

Intestinal ischaemia is implicated in the pathogenesis of severe acute pancreatitis, a disorder characterized by acinar necrosis. To study the relationship between pancreatic and intestinal microvascular perfusion during 40 min of intestinal ischaemia and 30 min of reperfusion in rodents with acute pancreatitis, a model utilizing laser Doppler flowmetry was developed. It is reported here together with practical solutions for (1) a modified method of vessel cannulation; (2) a novel method for the temperature-controlled optical coupling between laser Doppler probes and rodent tissues, and (3) a simple technique of inducing intestinal ischaemia-reperfusion while continuously monitoring the microvascular perfusion in both pancreas and intestine. The utility of the model is demonstrated in a pilot study that showed that the pancreatic perfusion fell acutely to 58% (p = 0.029) of baseline during the intestinal reperfusion phase. This reduced perfusion continued for 30 min despite recovery of both the intestinal perfusion and the mean arterial blood pressure to baseline levels.

Intestinal ischaemia-reperfusion increases plasma amylin concentration in rats.

Intestinal ischaemia-reperfusion and hyperamylinaemia are both associated with severe acute pancreatitis. The aim of this study was to examine the relationship between intestinal-ischaemia reperfusion and plasma amylin in an experimental model. Wistar rats (n = 24, 400-450 g) were divided into three groups: (1) a sham (S)-operated group (n = 7) that underwent laparotomy and isolation (without clamping) of the superior mesenteric artery, (2) an ischaemia-reperfusion (IR) group (n = 7) that had clamping of the superior mesenteric artery for 60 min followed by 15 min reperfusion, and (3) a control (C) group (n = 10) that underwent no surgery. Amylin was significantly elevated in the IR group (median 39 pM, range 30-44) compared with the S group (19 pM, range 15-45; Mann-Whitney U, p < 0.05) and the C group (24 pM, range 15-55; p < 0. 01). Insulin was significantly elevated in the IR group (2,060 pM, range 1,000-4,650) compared with the S group (558 pM, range 424-2, 020; p < 0.01). There was a significant positive correlation between amylin and insulin (R = 0.82, F = 46.6, p < 0.0001), but not between amylin and glucose or insulin and glucose. Intestinal histology was consistent with an ischaemia-reperfusion injury, whereas pancreatic histology was normal. The unique finding that plasma amylin concentration is increased with intestinal ischaemia-reperfusion injury warrants further investigation.

Acylation of 1-palmitoyl-sn-glycerophosphocholine by chick brain microsomes is unaffected by fatty acid binding protein.

Rates of incorporation of exogenously supplied fatty acids into 1-palmitoyl-sn-glycerophosphocholine were measured using the microsomal fraction from brains of 14-15 day old chick embryos. The substrate preferences for reacylation were: 18: 2(n-6) = 20: 4(n-6) > or = 20: 5(n-3) = 18: 3(n-3) > or = 18: 1(n-9) > or = 22: 6(n-3) > or = 18: 0. The normalized rate with 18: 0 was significantly lower than all other rates except for 22: 6(n-3), and the acylation rate with 22: 6(n-3) was significantly lower than with 18: 2(n-6) and 20: 5(n-3). With the addition of fatty acid binding protein partially purified from brain cytosol, a decrease (not significant) in the rate of incorporation was observed; the substrate preference was unchanged. In the presence of FABP, normalized rates with 18: 2(n-6) were significantly higher than with 18: 0, 18: 1(n-9), or 22: 6(n-3); rates with 20: 4(n-6) were significantly higher than those with 22: 6(n-3). Preliminary data on the acylation of 1-palmitoyl-sn-glycerophosphoethanolamine showed lower rates of incorporation than for the choline analogue and no clear substrate preference, but a similar lack of effect of fatty acid binding protein. These results do not support the proposed function of fatty acid binding protein in the establishment of a phospholipid composition rich in polyunsaturated fatty acids. The results are consistent, however, with the role of the reacylation reaction in the continual turnover of particular substrates [18: 2(n-6) and 20: 4(n-6)] used to generate second messengers.