Corticosteroid injection of the arthritic hip: what is the indication?

Forty-four patients who had image-guided corticosteroid injection of the hip were reviewed as part of a service improvement project to ascertain the medium term benefit of the procedure. Injections were indicated for treatment of hip pain or as part of a diagnostic work up to differentiate hip from back pain. At 42-month review, 39 patients fulfilled the criteria for the study. Of those having therapeutic injections, 70% had gone on to hip replacement, while only 20% of those having diagnostic injections had done so. These results suggest that, for patients who are fit for surgery, hip replacement should be the intervention of choice as corticosteroid injection does not substantially delay the need for surgery. Where there is doubt about the source of pain, there seems to be a clear role for diagnostic injection.

Arm versus forearm tourniquet for carpal tunnel decompression - Which is better? A randomized controlled trial.

UNLABELLED: Tourniquet pain is a common source of complaint for patients undergoing carpal tunnel decompression and practice varies as to the tourniquet position used. There is little evidence to suggest benefit of one position over another. Our aim was to compare patient and surgeon experience of forearm and arm tourniquets. Following a power calculation, 100 patients undergoing open carpal tunnel decompression under local anaesthetic were randomized to either an arm or a forearm tourniquet. Measurements of blood pressure, heart rate and pain were taken at 2.5 min intervals. The operating surgeon also provided a visual analogue scale rating for the extent of bloodless field achieved and for any obstruction caused by the tourniquet. There was no statistically significant inter-group difference in patient pain or physiological response, tourniquet time, bloodless field or length of procedure. The degree of obstruction caused by the tourniquet was significantly higher in the forearm group. LEVEL OF EVIDENCE: I. Prospective Randomized Controlled Trial.

The Kenya orthopaedic project: surgical outcomes of a travelling multidisciplinary team.

We report the results of six trauma and orthopaedic projects to Kenya in the last three years. The aims are to deliver both a trauma service and teaching within two hospitals; one a district hospital near Mount Kenya in Nanyuki, the other the largest public hospital in Kenya in Mombasa. The Kenya Orthopaedic Project team consists of a wide range of multidisciplinary professionals that allows the experience to be shared across those specialties. A follow-up clinic is held three months after each mission to review the patients. To our knowledge there are no reported outcomes in the literature for similar projects. A total of 211 operations have been performed and 400 patients seen during the projects. Most cases were fractures of the lower limb; we have been able to follow up 163 patients (77%) who underwent surgical treatment. We reflect on the results so far and discuss potential improvements for future missions.

Patient-reported outcomes after Silastic replacement of the trapezium for osteoarthritis.

This retrospective study evaluated 69 Swanson trapezium replacements performed between 1990 and 2009 for trapeziometacarpal osteoarthritis in 58 patients. Pain and function were assessed using the Michigan Hand Questionnaire and the Disability of the Arm, Shoulder and Hand questionnaire. Patients had a mean age of 62 years at the time of surgery, with a mean time of 7.7 years (range 9 months to 19 years) from surgery to follow-up interview. There was no association between outcome scores and the length of follow-up, suggesting that the results are maintained over time (Spearman's rank correlation test < ±0.2). Scores for activities of daily living and work-related activities were higher when surgery was on the dominant hand (p < 0.05). Silicone trapezium replacement remains a good option for patients with painful trapeziometacarpal osteoarthritis that has not responded to nonoperative management.

Intraoperative and early postoperative gastric intramucosal pH predicts morbidity and mortality after major abdominal surgery.

The present study was undertaken to investigate the correlation between the intraoperative and postoperative gastric intramucosal pH (pHi) with important perioperative variables and to explore any potential relationship of the measured pHi with the patients' postoperative course. A prospective study was carried out in a group of 48 patients who underwent major abdominal operations over an 8-month period at St. John Hospital and Medical Center. An automated air tonometer was used for gastric pHi monitoring. Twenty-eight elective and 20 emergency abdominal operations were performed in 23 men and 25 women. Twenty-six patients (54%) required postoperative hospitalization in the Intensive Care Unit (ICU). Seventeen patients (35%) developed early postoperative complications. The non-ICU and ICU mortality rates were 4.5 and 19.2 per cent respectively. The mean intraoperative pHi (pHiOR) and postoperative pHi (pHiPO) ranged between 7.03 and 7.58 (7.38+/-0.12) and 6.89 and 7.56 (7.35+/-0.12) respectively (mean +/- standard deviation). There was a significant decrease of the gastric pHi at the first hour intraoperatively compared with the pHi after induction to anesthesia (7.44 vs 7.38+/-0.14, P < 0.001). Patients who underwent emergent abdominal procedures were characterized by lower pHiOR and pHiPO values (7.43+/-0.08 vs 7.30+/-0.13 and 7.39+/-0.84 vs 7.30+/-0.15, P < 0.001 and P < 0.05). Similarly patients who required surgical ICU admission had significantly lower pHiOR and pHiPO measurements (7.3+/-0.12 and 7.28+/-0.12) compared with the rest (7.46+/-0.06 and 7.43+/-0.06; P < 0.001). Overall, lower pHiOR and pHiPO values were associated with the occurrence of postoperative complications (P < 0.001), the postoperative mortality (P < 0.001), the requirement for postoperative mechanical ventilator (P < 0.001) and its duration (P < 0.001), longer ICU stay (P < 0.001), and prolonged hospitalization (P < 0.05). Evidence of intraoperative and early postoperative gastric mucosal ischemia (pHiOR and pHiPO < or = 7.32) was observed in 12 (25%) and 15 (31%) patients respectively. The incidence of postoperative complications and the mortality rate were higher in this group of patients (P < 0.001). At a cutoff point of 7.32 gastric pHiOR gave a sensitivity of 69 per cent and specificity of 97 per cent for predicting postoperative complications as well as a sensitivity and specificity of 67 per cent and 81 per cent for predicting death. Intraoperative and early postoperative gastric pHi is a reliable predictor of patient outcome after major abdominal operations. Splanchnic ischemia may play an important role in determining early complications and survival; therapy guided by the gastric pHi might improve outcome.

Laparoscopic versus conventional live donor nephrectomy: experience in a community transplant program.

Fifty-nine consecutive patients underwent live donor nephrectomy for transplantation. Twenty-nine patients (Group I) had open kidney procurement, and 30 patients (Group II) had laparoscopic procurement. The mean operative time in Group I was 2:30 hours (range 1:55-2:59), whereas in Group II it was 3:01 hours (1:54-5:21). All kidneys functioned immediately after transplantation. The average warm ischemia time was not calculated in Group I; it was 3.9 minutes (2-15) in Group II. Intraoperative complications occurred in two patients in Group II. One patient had bleeding from an accessory renal artery. The second patient had a tear in the splenic capsule. No ureteral complications occurred in either group. Postoperatively one patient in Group I developed incisional hernia, one developed pneumothorax, and two developed atelectasis. In Group II one patient developed pancreatitis, one developed flank ecchymosis, and two had suprapubic wound hematomas. Using the laparoscopic approach the hospital stay decreased from 4.1 to 1.27 days (69%) (P < 0.001) and return to work decreased from 28.4 to 14.8 days (49%) (P < 0.01). Live donation increased by 67 per cent. We conclude that the laparoscopic procurement of kidneys for transplantation compares well with the open method. It offers several advantages that may increase the living donor pool.

Molecular evolution: dynamic combinatorial libraries, autocatalytic networks and the quest for molecular function.

The principles of Darwinian evolution have been explored in molecular systems such as autocatalytic networks and dynamic combinatorial libraries. Molecular evolution in such systems manifests itself as ligand or receptor amplification by selection. Research efforts exploring these concepts may provide a mechanism for the identification of novel catalysts, molecular receptors and bioactive molecules.

Electrospray ionisation Fourier-transform ion cyclotron resonance mass spectrometry of dynamic combinatorial libraries.

The use of electrospray ionisation Fourier-transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS/MS) for the analysis of dynamic combinatorial libraries (DCLs) of pseudo-peptide macrocyclic hydrazone oligomers is presented. The design of library building blocks results in mixtures of compounds with greater diversity than libraries generated by conventional combinatorial chemistry and so presents increased demands for analysis. The extended capabilities of the FTICR technique, specifically selective ion trapping, sensitivity, high resolution and mass accuracy over a broad mass range, are compatible with these increased demands and, most importantly, without the need for chromatography. Preliminary studies on the sequencing of cyclic oligomers and confirmation of the presence of sequence isomers are presented. These studies highlight the potential of FTICR-MS as a superior technique for the analysis of combinatorially generated compounds.

Orally effective CVS-1123 prevents coronary artery thrombosis in the conscious dog.

BACKGROUND: We examined the oral efficacy of a direct thrombin inhibitor, CVS-1123 [(CH3CH2CH2)(2)-CH-CO-Asp (OCH3)-Pro-Arg-CHO; MW, 575]. The object was to determine whether thrombin inhibition could reduce the incidence of occlusive coronary artery thrombosis in response to arterial wall injury. METHODS AND RESULTS: Arterial wall injury was induced in conscious dogs by a 150-muA anodal current applied to the intimal surface of the circumflex coronary artery 30 minutes after oral CVS-1123 (20 mg/kg every 8 hours for three doses; n = 11) or placebo containing diluent (n = 10). Dogs were monitored for 8 hours and at 24 hours. The coronary artery remained patent for 24 hours in 8 of 11 CVS-1123-treated dogs. All dogs (n = 10) in the placebo group developed a sustained, occlusive arterial thrombus. Two hours after the initial oral dose, the plasma CVS-1123 concentration was 13 +/- 1 microgram/mL, reaching a maximum of 15 +/- 1 micrograms/mL after the second dose and 4.4 +/- 0.5 micrograms/mL at 24 hours. Ex vivo platelet aggregation to gamma-thrombin was inhibited and activated partial thromboplastin time was increased after treatment with CVS-1123 (P < .05). CONCLUSIONS: The direct thrombin inhibitor CVS-1123 is effective after oral administration in reducing the incidence of primary thrombus formation in an experimental model of arterial wall injury. Thrombin-specific inhibitors, such as CVS-1123, may be alternative antithrombotic agents in clinical settings in which heparin-associated thrombosis is a complicating factor or when long-term anticoagulation is required.

A uniform isopeptide-linked multiubiquitin chain is sufficient to target substrate for degradation in ubiquitin-mediated proteolysis.

The proteolytic targeting function of ubiquitin was investigated by a combination of site-specific mutagenesis and covalent modification. Lys48 was replaced by a cysteine via mutagenesis of a synthetic ubiquitin gene to generate the mutant Ub-C48. The single cysteine residue in Ub-C48 can be converted into a lysine analog by modification with the sulfhydryl-specific reagent, aminoethyl-8 (N-(iodoethyl)trifluoroacetamide). The resulting protein, Ub-(S-aminoethyl)C48, is equivalent to a wild type ubiquitin except for the substitution of a sulfur atom at the gamma carbon of Lys48. We have tested the ability of these two modified ubiquitins to target the degradation of an engineered beta-galactosidase substrate protein in ubiquitin-depleted reticulocyte lysates. Ub-C48 was unable to stimulate the degradation of this protein substrate although a monoubiquitinated beta-galactosidase was formed. In contrast, Ub-(S-aminoethyl)C48 appears to be as effective as wild type ubiquitin in targeting this substrate protein's degradation as well as the formation of multiply ubiquitinated beta-galactosidase intermediates. In conjunction with the cysteine substitution and modification, we have also examined the effects of blocking the amino groups in ubiquitin with reductive methylation. The methylation of either Lys48 in ubiquitin or its S-aminoethylcysteine counterpart abolished its proteolytic function while the blockage of the remaining six lysines in Ub-(S-aminoethyl)C48 did not alter its competence. Thus, of the seven lysine residues in ubiquitin, only Lys48 is essential. These results established unambiguously that a uniform multiubiquitin chain with ubiquitin-ubiquitin linkage solely at Lys48 is sufficient to target the degradation of a substrate protein in ubiquitin-mediated proteolysis.

Boron-containing antibacterial agents: effects on growth and morphology of bacteria under various culture conditions.

The effects of a number of synthetic antibacterial agents of the borinic acid and diazaborine types on the growth of enteric bacteria were examined. In minimal medium aerobic growth was immediately slowed; slow nonexponential growth continued for an extended period, and the cells remained viable. The effect was also seen in anaerobic cultures and was not antagonized by a number of common nutrients, vitamins, or growth factors. The response was modified by the addition of casein hydrolysate to the medium. This seemed to be a nutritional effect dependent principally on lysine and leucine. The modified response consisted of a period of abnormal growth lasting for at least one doubling time after the addition of the antibacterial agent. The turbidity at first increased more rapidly than that of the controls and was approximately equal to that of the controls after 30 min. However, the increase in bacterial mass (dry weight) was only 0.75 of the amount predicted by the change in turbidity. The viable count increased in proportion to the turbidity. Changes in the cell envelope were revealed by electron microscopy and by an alteration in the response of cells to lytic agents. After the period of abnormal growth cultures entered a premature stationary phase.

Studies on immune responses to parasite antigens in mice. I. Ascaris suum larvae numbers and antiphosphorylcholine responses in infected mice of various strains and in hypothymic nu/nu mice.

In terms of day 7 lung larvae numbers, mice vary markedly in their suscepibility to a first infection with the nematode worms, Ascaris suum, and the highly susceptible strain, C57Bl, is resistant to second infection. Time course studies suggested that the period of residence in the liver or migration to, or into, the lungs are stages of the life cycle in which natural or acquired resistance of the host is expressed. The traits, susceptibility and resistance to first infection, were under polygenic control and no linkage of susceptibility to the major histocompatibility complex of C57Bl mice (H-2b) was observed. Acquired resistance (to second infection) has not been dissected because of our inability to show adoptive transfer of resistance to naive recipeints. Studies in hypothymic BALB/c. nu/nu mice indicate that natural resistance (to first infection) is not affected by a lack of T cells. The T cell dependence of acquired resistance in C57Bl mice remains in doubt although in the relatively resistant strain BALB/c, hypothymic nu/nu mice after second infection contain as many larvae in their lungs and liver as are present after first infection. An eosinophilia is observed in infected intact mice but not in infected T cell-deficient mice. Partially T cell-dependent serum antibodies and plaque-forming cells to phosphorylcholine (PC) were present in mice infected with A. suum but no evidence was obtained that this anti-PC antibody response was in any way protective for the host. The cell membrane-acitive properties of PC and related molecules suggest that PC-containing parasite antigens may be tolerogens for certain of the B cells with specificity for parasite antigens. A state of partial tolerance involving high affinity antibody production may be one means whereby parasites survive in natural or unnatural hosts.