Biomedical subjects

D R Gill

Publications and source records attributed to D R Gill.

At least 19 recordsLinked to original sources

PubMed2006

Long-term persistence of gene expression from adeno-associated virus serotype 5 in the mouse airways.

Recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) have been used to deliver transgenes to the airways in a variety of pre-clinical and clinical studies. Gene transfer in these studies has been severely restricted by the basolateral localization of rAAV2 receptors. Here, we studied vectors constructed from the AAV5 genome and capsid, which utilize N-linked sialic acid-containing receptors found on the apical surface of airway epithelial cells. We investigated gene transfer efficacy and duration of transgene expression following delivery of rAAV5/5 vectors to the mouse respiratory tract. Robust, dose-dependent transgene expression was observed in the epithelium lining the nose for at least 32 weeks, and for at least 52 weeks in the lung. Importantly, in the lung, transgene expression mediated by rAAV5/5 was 40-fold greater than by rAAV2/2 vectors. A distinct cellular preference for rAAV5/5-mediated transduction was observed, with transgene expression being predominantly restricted to sustentacular cells of the olfactory epithelium in the nose and alveolar type II cells in the lung. Administration of rAAV5/5 vectors to both the nose and lungs led to the rapid development of rAAV5/5-neutralizing antibodies, suggesting that repeated administration may be severely hampered by host immune responses.

Animals↗

PubMed2006

Optimising non-viral gene delivery in a tumour spheroid model.

BACKGROUND: Our current understanding of how the unique tumour microenvironment influences the efficacy of gene delivery is limited. The current investigation systematically examines the efficiency of several non-viral gene transfer agents to transfect multicellular tumour spheroids (MCTS), an in vitro model that displays a faithful three-dimensional (3D) representation of solid tumour tissue. METHODS: Using a luciferase reporter assay, gene transfer to MCTS was optimised for 22 kDa linear and 25 kDa branched polyethyleneimine (PEI), the cationic lipids Lipofectamine(trade mark) and DCChol : DOPE, and the physical approach of tissue electroporation. Confocal microscopy was used to take optical tissue slices to identify the tissue localisation of green fluorescent protein (GFP) reporter gene expression and the distribution of fluorescently labelled complexes. A MCTS model of quiescent tumour regions was used to establish the influence of cellular proliferation status on gene transfer efficiency. RESULTS: Of the polyplexes tested, 22 kDa linear PEI provided optimal gene delivery, with gene expression peaking at 46 h. Despite being the optimal vector tested, PEI-mediated transfection was limited to cells at the MCTS periphery. Using fluorescent PEI, it was found that complexes could only penetrate the outer 3-5 proliferating cell layers of the MCTS, sparing the deeper quiescent cells. Gene delivery in an MCTS model comprised entirely of quiescent cells demonstrated that in addition to being inaccessible to the vector, quiescent tumour regions are inherently less susceptible to PEI-mediated transfection than proliferating regions. This 'resistance' to transfection observed in quiescent cells was overcome through the use of electroporation. Despite the improved efficacy of electroporation in quiescent tissue, the gene expression was still confined to the outer regions of MCTS. The results suggest that limited access to central regions of an MCTS remain a significant barrier to gene delivery. CONCLUSIONS: This data provides new insights into tumour-specific factors affecting non-viral gene transfer and highlights the difficulties in delivering genes to avascular tumour regions. The MCTS model is a useful system for the initial screening of future gene therapy strategies for solid tumours.

Cell Line, Tumor↗

PubMed2005

Measurement of the Michel parameter rho in muon decay.

The TWIST Collaboration has measured the Michel parameter rho in normal muon decay, mu(+)--> e(+)nu(e)nu (mu). In the standard model, rho = 3/4. Deviations from this value imply mixing of left- and right-handed muon and electron couplings. We find rho=0.750 80+/-0.000 32(stat) +/- 0.000 97(syst) +/- 0.000 23, where the last uncertainty represents the dependence of rho on the Michel parameter eta. This result sets new limits on the W(L)-W(R) mixing angle in left-right symmetric models.

Journal Article↗

PubMed2005

Keratinocyte growth factor therapy in murine oleic acid-induced acute lung injury.

Alveolar type II (ATII) cell proliferation and differentiation are important mechanisms in repair following injury to the alveolar epithelium. KGF is a potent ATII cell mitogen, which has been demonstrated to be protective in a number of animal models of lung injury. We have assessed the effect of recombinant human KGF (rhKGF) and liposome-mediated KGF gene delivery in vivo and evaluated the potential of KGF as a therapy for acute lung injury in mice. rhKGF was administered intratracheally in male BALB/c mice to assess dose response and time course of proliferation. SP-B immunohistochemistry demonstrated significant increases in ATII cell numbers at all rhKGF doses compared with control animals and peaked 2 days following administration of 10 mg/kg rhKGF. Protein therapy in general is very expensive, and gene therapy has been suggested as a cheaper alternative for many protein replacement therapies. We evaluated the effect of topical and systemic liposome-mediated KGF-gene delivery on ATII cell proliferation. SP-B immunohistochemistry showed only modest increases in ATII cell numbers following gene delivery, and these approaches were therefore not believed to be capable of reaching therapeutic levels. The effect of rhKGF was evaluated in a murine model of OA-induced lung injury. This model was found to be associated with significant alveolar damage leading to severe impairment of gas exchange and lung compliance. Pretreatment with rhKGF 2 days before intravenous OA challenge resulted in significant improvements in PO2, PCO2, and lung compliance. This study suggests the feasibility of KGF as a therapy for acute lung injury.

Acute Disease↗

PubMed2005

Detection of plasmid DNA vectors following gene transfer to the murine airways.

Non-viral gene therapy is being considered as a treatment for cystic fibrosis. In clinical studies and in studies using the mouse airways as a model, current formulations result in only transient transgene expression. A number of reasons for this have been proposed including the loss of plasmid DNA from cells. The aim of these studies was to investigate why transgene expression from non-viral vectors is transient in the mouse lung. Plasmid DNA encoding the luciferase reporter gene was complexed with the cationic lipid GL67 and delivered to the mouse airways. The persistence of plasmid DNA in the mouse lungs was investigated using quantitative PCR and Southern hybridization. Results showed that intact plasmid DNA persisted in the mouse lung in the absence of any detectable luciferase activity. The de novo methylation of plasmid DNA in vivo was investigated as a potential cause of this transient gene expression but results suggested that plasmid DNA does not become de novo methylated in the mouse lung. Therefore processes other than the loss of plasmid DNA from the lung or the de novo methylation of plasmid DNA vectors must be responsible for the transient transgene expression.

Adenoviridae↗

PubMed2005

Vitamin E supplementation of newly arrived feedlot calves.

Seven hundred fifteen crossbred (primarily British) calves purchased in southern Oklahoma and northern Texas auction barns were received at the Willard Sparks Beef Research Center, Stillwater, OK, and used to study effects of duration (days) of vitamin E feeding during a 42-d receiving period on animal performance, health, and serum cholesterol and vitamin E concentrations. Upon arrival, calves were blocked by load (seven loads), sorted by BW (light, n = 4 pens per load; and heavy, n = 4 pens per load), and assigned randomly to one of four dietary treatments (n = 2 pens per load; 14 pens per treatment). Experimental diets were formulated to provide 2,000 IU.calf(-1).d(-1) of supplemental vitamin E (dl-alpha-tocopherol acetate) for 0 (CON), 7 (E7), 14 (E14), or 28 (E28) d. Vitamin E was delivered in a pelleted supplement that was added to the basal diet in decreasing concentrations as DMI increased (2.0 kg of DMI = 6%; 4.0 kg of DMI = 4%; and 6.0 kg of DMI = 2%). Serum samples were collected on d 0, 14, 28, and 42 for determination of cholesterol, alpha-tocopherol (d 0, 28, and 42), and antibody (IgG) concentrations. Duration of vitamin E supplementation did not affect ADG (0.98 kg/d; P = 0.56) or G:F (0.189; P = 0.87). Serum cholesterol concentrations decreased (day effect; P < 0.001) for all treatments from d 0 (average = 127 mg/100 mL) to 14 (average = 62 mg/100 mL). Serum alpha-tocopherol decreased (day effect; P < 0.001) from d 0 (5.2 microg/mL) to 28 (1.8 microg/mL); however, on d 28, a greater (P < 0.001) serum alpha-tocopherol concentration was observed for E28 (3.4 microg/mL) calves than for CON (1.1 microg/mL), E7 (1.2 microg/mL), or E14 (1.5 microg/mL) calves. Respiratory disease was diagnosed in 64.6% of calves in this study. Medical costs were less (P = 0.08) for calves fed vitamin E for 28 d (4.88 dollars/calf) than for calves fed the control diet (6.29 dollars/calf). Carcass characteristics were not affected (P = 0.19 to 0.88) by dietary treatments. Supplemental vitamin E formulated for 2,000 IU.calf(-1).d(-1) had little influence on performance and overall health status of calves under our experimental conditions; however, the increased serum concentrations of alpha-tocopherol when vitamin E was fed for 28 d suggests that any potential effects of vitamin E on health status might be time-dependent.

Animal Feed↗

PubMed2004

The development of gene therapy for diseases of the lung.

The development of a successful gene therapy has many stages, including preclinical testing in animal models and proof of principle clinical studies. A variety of diseases affect the lung, which are candidates for gene therapy; this review will mainly focus on the diseases that have attracted the most attention and have therefore yielded the most progress, namely lung cancer and the monogenic disorder cystic fibrosis. Knowledge gained from clinical studies could eventually be applied to more complex lung conditions such as acute respiratory distress syndrome and asthma. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.

Animals↗

PubMed2004

Effects of dietary energy and starch concentrations for newly received feedlot calves: I. Growth performance and health.

Crossbred calves (n = 572; initial BW = 186 +/- 27 kg) purchased from northern Texas, Arkansas, and southeast Oklahoma auction markets were delivered to the Willard Sparks Beef Research Center, Stillwater, OK, and used to study the effects of dietary energy and starch concentrations on performance and health of newly received feedlot calves during a 42-d receiving period. On arrival, calves were assigned randomly to one of two dietary energy levels (0.85 or 1.07 Mcal NEg/kg DM) and one of two dietary starch levels (34 or 48% of ME from starch) in a 2 x 2 factorial arrangement of treatments. Cattle were weighed and serum samples were collected on d 0, 7, 14, 28, and 42. Individual animal records of morbidity were kept for all cases of respiratory and other disease. Nasal swabs were collected from each morbid animal and cultured for upper-respiratory pathogens. There were no energy x starch level interactions for performance or health response variables. Daily gain (1.14 kg/d) and gain efficiency (ADG:DMI = 0.179) were not affected by increasing dietary energy or starch concentrations. Calves fed low-energy diets consumed (P < 0.05) more DM. No difference (P = 0.54) was detected in morbidity for calves fed high-energy (62.4% calves treated) compared with low-energy (65.8% calves treated) diets; however, calves fed the high-starch diets had numerically (P = 0.11) greater morbidity than calves fed low-starch diets (68.8 vs. 59.4% calves treated, respectively). There were no energy or starch effects on Mannheimia haemolytica or Pasteurella multocida antibody titers; however, day effects (P < 0.02) occurred. On d 7, 14, and 28, calves had antibody titers for P. multocida that were greater (P < 0.05) than titers on d 0. In addition, calves had greater antibody titers to M. haemolytica on d 7 and 14 than on d 0. Nasal swabs revealed that calves fed the high-energy diets tended (P = 0.06) to have a lower percentage of morbid calves with P. multocida during the first antimicrobial treatment and a lower percentage of Haemophilus somnus isolates during the first (P = 0.01) and second (P = 0.06) antimicrobial treatments than calves fed the low-energy diets. Although animal performance was not influenced, the present data suggest that feeding the high-energy diet decreased the percentage of P. multocida and H. somnus pathogens in calves that received one or more antimicrobial treatments.

Animal Feed↗

PubMed2004

Effects of dietary energy and starch concentrations for newly received feedlot calves: II. Acute-phase protein response.

Two hundred forty five market-stressed bull and steer calves (205 +/- 14 kg) were received in January and September 2001 to determine the response of acute-phase proteins to dietary energy and starch concentrations and to determine whether acute-phase proteins could be used as a diagnostic or prognostic tool for calves affected by bovine respiratory disease. On arrival, calves were randomly assigned to one of two dietary energy levels (0.85 or 1.07 Mcal of NEg/kg of DM) and one of two dietary starch levels (34 or 48% of dietary ME from starch; n = 5 pens/treatment). All calves were weighed, and plasma and serum samples were collected from a subset of animals (n = 6 calves/pen; 30 calves/treatment) on d 0, 7, 14, 28, and 42 of the receiving period. This subset of calves (n = 120) was used for all subsequent analyses. Concentrations of fibrinogen (Fb), haptoglobin (Hp), and serum amyloid-A (SaA) were determined. In addition, samples were collected from the subset of calves when they received medical treatment and 7 d following treatment to measure serum concentrations of Hp and SaA. Serum concentrations of Fb, Hp, and SaA did not differ among dietary treatments, but decreased (P < 0.03) as day of the receiving period increased. Fibrinogen (P < 0.001) and the ratio of Fb:total blood protein were greater (P < 0.003) in calves treated multiple times than in calves never treated or treated once for bovine respiratory disease. In addition, on d 0 and 7, Hp concentration increased (antimicrobial treatment x day interaction, P < 0.03) as the number of antimicrobial treatments increased, and was greater on d 14 and 28 in calves treated multiple times than in calves never treated or treated once. Haptoglobin concentration was greater (P < 0.05) in calves on medical treatment days compared with recovery days (7 d after medical treatment). Although diet seemed to have little effect on acute-phase protein response, these results suggest that haptoglobin may be useful as a diagnostic tool to make management decisions regarding treatment protocols for calves with bovine respiratory disease.

Acute-Phase Proteins↗

PubMed2002

Optimisation of real-time quantitative RT-PCR for the evaluation of non-viral mediated gene transfer to the airways.

Naked plasmid DNA and DNA/liposome complexes are currently being considered as gene therapy treatments for cystic fibrosis (CF) pulmonary disease. Current methods of gene delivery to the airways result only in transient correction of the CF ion transport defect, and disease treatment is likely to require repeated administrations of vector. However, it is unclear if repeat administration will be tolerated by CF individuals. Technologies including TaqMan (Applied Biosystems) real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) can be used to determine the efficacy of gene transfer formulations. TaqMan RT-PCR assays were designed and optimised to detect plasmid vector-derived and endogenous gene expression. Subsequently, these assays were used to quantify vector-derived mRNA after delivery of naked DNA and DNA/liposome formulations expressing human and murine cystic fibrosis transmembrane conductance regulator (CFTR) to the mouse airways. Vector-derived mRNA was detected in samples following the delivery of naked DNA or DNA/liposomes to the mouse airways, and no reduction in vector-derived mRNA was observed upon repeat administration, a finding that is consistent with the murine and human CFTR being tolerated by the mouse. Although it remains to be seen if CF patients can tolerate long-term expression of wild-type CFTR, these data demonstrate that TaqMan RT-PCR is an effective tool to accurately quantify transgene expression in the airways.

Animals↗

PubMed2002

Effects of restricted versus conventional dietary adaptation on feedlot performance, carcass characteristics, site and extent of digestion, digesta kinetics, and ruminal metabolism.

Three experiments were conducted to determine effects of restricting intake of the final finishing diet as a means of dietary adaptation compared with diets increasing in grain over a period of 20 to 22 d on overall cattle performance, carcass characteristics, digestibility, digesta kinetics, and ruminal metabolism. In Exp. 1, 84 Angus x Hereford yearling steers (initial BW = 418 +/- 29.0 kg) were fed for 70 d. Restricting intake during adaptation had no effect (P > 0.10) on overall ADG:DMI, but decreased (P < 0.05) DMI compared with ad libitum access to adaptation diets, which resulted from differences during the initial 28 d of the experiment. In Exp. 2, 150 mixed crossbred steer calves (initial BW = 289 +/- 22.9 kg) were fed for an average of 173 d. Restricting intake decreased (P < 0.01) overall daily gain (1.51 vs 1.65 kg/d) and DMI (8.68 vs 9.15 kg/d) compared with ad libitum fed steers; however, ADG:DMI was not influenced (P > 0.10) by adaptation method. Experiment three used eight ruminally and duodenally fistulated steers (initial BW = 336 +/- 20 kg) in a completely random design. Total tract digestibility, digesta kinetics and ruminal metabolism were determined. Restricting intake reduced (P < 0.10) daily DMI variation from d 1 through 7, 8 through 14, and 22 through 28 compared with ad libitum feeding of three adaptation diets. Restricted steers had reduced (adaptation method x period interaction, P < 0.05) intakes and fecal excretions of ADF and greater OM digestibilities on d 4 through 7, 11 through 14, and 18 through 21. Digesta kinetics and ruminal metabolism were generally not affected (P > 0.10) by adaptation method. Our results suggest that restricted-feeding of the final diet as a means of dietary adaptation can be used in finishing cattle with few problems from acidosis or related intake variation. In light-weight steers (Exp. 2), disruptions in intake during the adaptation period might have resulted in restriction for an extended period, which decreased (P < 0.01) hot carcass weight compared with calves fed ad libitum. Effects of limit feeding during the initial 28 d of the feeding period on site and extent of digestion, digesta kinetics, and ruminal metabolism were minimal, supporting few differences in performance across the finishing period for yearling cattle.

Adaptation, Physiological↗

PubMed2001

Increased persistence of lung gene expression using plasmids containing the ubiquitin C or elongation factor 1alpha promoter.

For effective gene therapy of chronic disease, persistent transgene expression at therapeutic levels is required. Clinical studies of airway gene transfer in patients with cystic fibrosis (CF) have resulted in short-lived transgene expression. We used intra-nasal dosing of naked plasmid DNA to the murine lung as a model for investigating the duration of airway gene transfer from a series of reporter expression plasmids. Transgene expression was transient when mediated by the viral promoters CMV, RSV and SV40, falling to less than 10% of peak expression after 2 weeks, although the presence of the adenoviral E4ORF3 gene in cis, resulted in extended duration of reporter activity from the CMV promoter. Transient expression from these promoters was not due to loss of the vector as determined by quantitative TaqMan PCR analysis. However, use of the promoters from the human polybiquitin C (UbC) and the elongation factor 1alpha (EF1alpha) genes resulted in persistent gene expression in the mouse lung. The UbC promoter directed high-level reporter activity which was maintained for up to 8 weeks and was still detectable 6 months after a single administration. Such persistent airway transgene expression from a nonviral vector without the concomitant expression of a potential antigen has not been reported previously. Thus, despite the persistence of vector DNA in vivo, attenuation of promoter function may lead to silencing of transgene expression and careful selection of promoter sequences is recommended for in vivo gene transfer.

Administration, Inhalation↗

PubMed2001

Effects of supplemental vitamin D3 on feed intake, carcass characteristics, tenderness, and muscle properties of beef steers.

Research was conducted to determine the effects of supplemental dietary vitamin D3 on DMI, carcass traits, Warner Bratzler shear (WBS) force, calpastatin activity, plasma minerals, pH (0, 3, 12, and 24 h after slaughter), water-holding capacity (WHC), and sensory characteristics of three muscles. Pre-slaughter vitamin D3 treatments included no supplemental vitamin D3, 6 x 106 IU (MIU) of vitamin D3 for 4 d, or 6 MIU of vitamin D3 for 6 d. Cattle were slaughtered and carcasses were chilled for 48 h before removal of steaks from the longissimus, gluteus medius, and biceps femoris muscles. Steaks were aged at 2 degrees C for 7, 14, or 21 d before cooking to a final internal temperature of 70 degrees C for WBS and sensory panel analysis. Dry matter intake was lower for steers supplemented with vitamin D3 for 4 or 6 d. Live and carcass weights were lower (P < 0.05) in steers supplemented with vitamin D3. Supplementing 6 MIU/6 d of vitamin D3 decreased (P < 0.05) WBS values of gluteus steaks (pooled over aging times). Longissimus steaks from steers supplemented with vitamin D3 for 6 d had lower (P < 0.05) WBS force values than these steaks from control steers or steers fed vitamin D3 for 4 d at 7 d postmortem. Biceps femoris steaks from steers receiving vitamin D3 for 4 d had higher WBS values than steaks from control steers at 14 and 21 d postmortem. Feeding vitamin D3 at 6 MIU for 6 d decreased (P < 0.05) the percentage of steaks that had WBS values > or = 3.86 kg for all steaks. Feeding vitamin D3 had no effect on palatability traits evaluated by trained panelists. Blood Ca concentrations were greater (P < 0.05) when vitamin D3 was fed and with increased vitamin D3 feeding time. Feeding vitamin D3 for 6 d (vs 4 d) delayed pH decline for all muscle types after 0, 3, and 12 h postmortem. Water-holding capacity was increased (P > 0.02) after 0 h, 24 h, and 21 d postmortem when vitamin D3 was fed and was greater at 0 and 24 h if vitamin D3 was fed for 6 d rather than 4 d. These data suggest that supplementing 6 MIU of vitamin D3 will decrease DMI and improve beef tenderness through increased blood plasma Ca concentrations and WHC.

Animals↗

PubMed2000

Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis.

The major cause of mortality in patients with cystic fibrosis (CF) is lung disease. Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene product in the airways is a potential treatment. Clinical studies in which the CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in modest, transient gene expression. It seems likely that repeated administration of the gene transfer vector will be required for long-term gene expression. We have undertaken a double-blinded study in which multiple doses of a DNA/liposome formulation were delivered to the nasal epithelium of CF patients. Ten subjects received plasmid DNA expressing the CFTR cDNA complexed with DC-Chol/DOPE cationic liposomes, whilst two subjects received placebo. Each subject received three doses, administered 4 weeks apart. There was no evidence of inflammation, toxicity or an immune response towards the DNA/liposomes or the expressed CFTR. Nasal epithelial cells were collected 4 days after each dose for a series of efficacy assays including quantitation of vector-specific DNA and mRNA, immunohistochemistry of CFTR protein, bacterial adherence, and detection of halide efflux ex vivo. Airway ion transport was also assessed in vivo by repeated nasal potential difference (PD) measurements. On average, six of the treated subjects were positive for CFTR gene transfer after each dose. All subjects positive for CFTR function were also positive for plasmid DNA, plasmid-derived mRNA and CFTR protein. The efficacy measures suggest that unlike high doses of recombinant adenoviral vectors, DNA/liposomes can be successfully re-administered without apparent loss of efficacy.

Adolescent↗

PubMed1999

The spiral compression plate for proximal humeral shaft nonunion: a case report and description of a new technique.

We present a case of humeral nonunion managed with a dynamic compression plate (DCP) contoured in a spiral fashion to preserve the deltoid muscle insertion. A forty-one-year-old woman sustained a closed proximal third humeral shaft fracture with an associated supraclavicular brachial plexus injury. She presented five months later with an atrophic nonunion of the proximal humeral shaft, inferior subluxation of the humeral head, and a resolving brachial plexopathy. Autogenous cancellous bone grafting and open reduction and internal fixation with a narrow DCP was performed. The deltoid muscle insertion was preserved by contouring the plate to fix the proximal humerus laterally over the greater tuberosity and anteriorly over the mid-humeral shaft. During the postoperative period, the humeral head reduced spontaneously. Five months after surgery, the fracture healed, and an excellent clinical result was achieved. We recommend the use of the spiral DCP for proximal shaft fractures and nonunions when preservation of the deltoid insertion is desirable.

Adult↗

PubMed1999

Ipsilateral total shoulder and elbow arthroplasties in patients who have rheumatoid arthritis.

BACKGROUND: The data on seventeen patients with rheumatoid arthritis who had been managed with ipsilateral total shoulder and elbow arthroplasties were analyzed to determine whether the operative technique, the presence of total shoulder and total elbow prostheses in the same upper extremity, or complications of the arthroplasties affected the result in each joint or the overall functional outcome of the upper extremity. METHODS: Seventeen patients with rheumatoid arthritis who were managed with a total of eighteen ipsilateral total shoulder and elbow arthroplasties were evaluated. The most recent physical examination was at an average of six years and six months (range, two years and one month to fourteen years) postoperatively. Radiographs, including 40-degree oblique and axillary radiographs of the shoulder as well as anteroposterior and lateral radiographs of the elbow, were made at an average of six years and eleven months (range, two years and two months to twenty-two years and eleven months) postoperatively. The radiographs of the shoulder were examined for loosening of the glenoid component, glenohumeral subluxation, and radiolucency at the bone-cement or bone-implant interface. The functional results of the total shoulder arthroplasties were evaluated with use of the rating systems of Neer et al. and Cofield. The Mayo elbow-performance score was used to evaluate elbow function. A rating system was also developed to assess the overall function of the upper extremity, including pain and motion of both the elbow and the shoulder. With this system, the overall function of the upper extremity was rated as excellent, good, fair, or poor. RESULTS: Evaluation of the shoulders revealed substantial relief of pain and an increase in active elevation. On radiographic evaluation, eight glenoid and five humeral components were considered to be loose. There were no reoperations. According to the rating system of Neer et al., eight shoulders had a satisfactory result and eight had an unsatisfactory result with limited active abduction. Limited-goals rehabilitation was successful after one shoulder arthroplasty and unsuccessful after another. There were two type-B periprosthetic humeral fractures. There was also substantial relief of pain in the elbows as well as an increase in the extension-flexion arc; the pronation-supination arc was sufficient for tasks of daily living. There was no radiographic loosening. Two elbows had an avulsion of the triceps, and two had aseptic loosening (one of which also had a worn bushing); all four needed a reoperation. One other elbow had persistent ulnar neuritis. The average interval between the arthroplasties was two years and eight months when the shoulder was replaced first and three years and five months when the elbow was replaced first. The interval between the joint replacements and the sequence of the joint replacements were not found to influence the outcome. Function of the extremity was improved by replacement of either the shoulder or the elbow alone; however, it improved significantly only when both joints were replaced (p = 0.03). According to combined clinical outcomes scores, there were nine excellent outcomes, four good outcomes, four fair outcomes, and one poor outcome after ipsilateral total shoulder and elbow arthroplasties. CONCLUSIONS: When there is severe arthritis of both the shoulder and the elbow, consideration should be given to replacing both joints in order to obtain optimum functional and clinical outcomes. The possibility of fracture of the humeral shaft necessitates an alteration of the technique for ipsilateral total shoulder and elbow arthroplasties.

Adult↗

PubMed1999

Vitamin D3 supplementation of beef steers increases longissimus tenderness.

The objectives of these experiments were to determine 1) the effectiveness of supplemental vitamin D3 (VITD) on altering plasma and muscle calcium levels, 2) whether VITD supplementation improves Warner-Bratzler shear force (WBS) values of steaks from feedlot beef steers, and 3) the tenderness response curve of longissimus steaks from steers supplemented with VITD. In Exp. 1, 20 crossbred steers were assigned randomly to one of four treatment diets consisting of either 0, 2.5, 5.0, or 7.5 x 106 IU of VITD per day for 10 d. Blood samples were obtained daily during this supplementation period and 5 d thereafter (d 11 to 15). Between d 6 and 13, a linear increase (P < .01) in ionized plasma calcium concentrations was observed in steers supplemented with VITD. Compared to unsupplemented steers, serum calcium concentrations of the steers receiving 7.5 x 106 IU of VITD per day were increased 8 to 48%. In Exp. 2, longissimus samples from crossbred steers (n = 118) that were supplemented with either 0 or 5 x 106 IU of VITD per day for 7 d were obtained and aged for 7, 14, or 21 d. Following the initial 7-d postmortem aging period, VITD supplementation lowered (P < .01) WBS (.58 kg) and increased sensory tenderness rating (.6 units) compared to cuts originating from unsupplemented steers. In Exp. 3, 44 steers were supplemented with either 0 or 7.5 x 106 IU of VITD per day for 10 d immediately prior to slaughter. Results indicated that plasma and longissimus calcium concentration were higher (P < .05) for steers that received supplemental VITD. Compared with unsupplemented cuts, VITD supplementation improved WBS of cuts aged for either 7 or 14 d (P = .02 and P = .07, respectively). Sensory panelists rated samples from VITD supplemented steers as more tender than their unsupplemented counterparts. Activation of calpain proteases could be responsible for the observed tenderization due to the supplementation of VITD.

Animal Feed↗

PubMed1999

Effect of anabolic implants on beef intramuscular lipid content.

Sixty ribeye steaks were used to determine the effects of anabolic implants on i.m. lipid composition of beef steers. Steaks were obtained from carcasses (346 kg) of steers assigned to four treatment groups (C = nonimplanted control; ET = 28 mg of estradiol benzoate plus 200 mg of trenbolone acetate on d 0; ET/ET = ET on d 0 and d 61; and S/ET = 20 mg of estradiol benzoate plus 200 mg of progesterone on d 0 and ET on d 61) and fed a high-concentrate diet for 127 d. Total fatty acid content of the longissimus was less (P < .05) for implanted steers. Implanting increased (P < .05) stearic and linolenic acid percentages and reduced (P < .05) oleic acid percentage but did not alter (P > .05) percentages of other fatty acids. These changes translated into increased (P < .05) percentages of saturated fatty acids and reduced (P < .05) monounsaturated fatty acids in the longissimus of implanted steers. However, on a per-steak weight basis, implanting did not alter (P > .05) the amounts of any of the individual fatty acids, but it increased (P < .05) the total cholesterol amount. Implanting with an estrogenic compound first reduced (P < .05) the percentage and total amounts of linoleic and polyunsaturated fatty acids. On a percentage basis, implanting alters fatty acid amounts; however, when the increase in ribeye size with implanting is accounted for and fatty acids are evaluated on a per-steak basis, these differences are not significant.

Animals↗