Clinical outcomes and patient satisfaction following total hip and knee arthroplasty in patients with inherited bleeding disorders: A 20-year single-surgeon cohort.

INTRODUCTION: Persons with haemophilia and other inherited bleeding disorders are prone to disabling joint arthropathy frequently requiring arthroplasty for end-stage joint disease. Higher complication rates and more modest post-operative functional outcomes have previously been described. AIM: To evaluate the clinical outcomes and patient satisfaction of persons with inherited bleeding disorders (predominantly haemophilia) undergoing total hip and knee replacement. METHODS: Retrospective, single-centre cohort study with longitudinal assessment of patients with inherited bleeding disorders who underwent total hip and knee replacement over a 20-year period. Eligible patients were clinically assessed with Harris Hip Score (HHS), Knee Society Score (KSS), pain visual analogue scale (VAS) and a patient satisfaction questionnaire. RESULTS: Thirty-one patients (48 joints) met the inclusion criteria. Mean age at surgery was 49.3 years (SD: 13.1, range 21-75 years) with a mean follow-up of 9.33 years (1.7-19.3). The majority (26/31) of patients had haemophilia A, predominantly severe haemophilia A (22/26). Reported pain levels were low, and patient satisfaction was high. Joint-specific outcome scores were "good" to "excellent" in 67% of total hip replacement patients and 92% of total knee replacement patients. A low complication rate was observed, with 2 patients requiring revision surgery and 4 patients requiring re-operation without implant revision. CONCLUSION: Arthroplasty is a reliable procedure in patients with inherited bleeding disorders with end-stage hip or knee arthropathy. The overall complexity of this group is highlighted, and the need for multidisciplinary care is emphasised.

Australian multicentre study of current real-world prophylaxis practice in severe and moderate haemophilia A and B.

INTRODUCTION: With the emergence of novel treatment products for haemophilia and an increasing focus on the benefits of pharmacokinetic driven individualized prophylaxis, robust national data with regard to current patterns of factor consumption and adherence are required. AIM: To characterize current Australian practice with regard to use of prophylactic clotting factor infusions in patients with moderate or severe haemophilia A (HA) and haemophilia B (HB). METHODS: This was a retrospective, non-interventional study utilizing Australian Bleeding Disorder Registry (ABDR) data collected over a 12 month period. Registered and consented patients with moderate or severe HA or HB without inhibitors were included. RESULTS: A total of 718 HA (551 severe, 167 moderate) and 166 HB (87 severe, 79 moderate) patients were included. Regular prophylaxis was prescribed in 453 patients (82%) with severe HA, 42 patients (25%) with moderate HA, 66 patients (75%) with severe HB and 11 patients (14%) with moderate HB. Near universal prophylaxis was achieved in the paediatric subgroup. The mean weekly dose of factor VIII in severe HA was 84 international units/kg/wk (IU/kg/wk) vs 71 IU/kg/wk of factor IX in severe HB. Most patients on prophylaxis were treated ≥3 times/wk (HA) or 2 times/wk (HB). Non-adherence peaked in the 20-29 year age group. Older individuals on regular prophylaxis used more factor than was expected for their prescribed regimen. CONCLUSION: Prophylaxis rates in severe haemophilia are comparable with other developed nations. The benefit of a national registry is demonstrable. Furthermore research into the underlying reasons for non-compliance in young adults with haemophilia is required.

Assessment and validation of a defined fluid restriction protocol in the use of subcutaneous desmopressin for children with inherited bleeding disorders.

INTRODUCTION: Despite the availability of subcutaneous desmopressin (1-deamino-8-d-arginine vasopressin, SC-DDAVP) as a haemostatic agent for children with mild bleeding disorders, few publications specifically address the safety or efficacy of this mode of administration. AIM: Our aim was to assess whether a defined fluid restriction protocol was effective in preventing hyponatremia in children receiving perioperative SC-DDAVP, and to document adequate biological and clinical response in this setting. METHODS: We retrospectively analysed a cohort of children with mild bleeding disorders prescribed SC-DDAVP over a 5-year period following institution of a 'two-thirds maintenance' fluid restriction protocol. RESULTS: Sixty-nine patients received SC-DDAVP following this protocol, including 15 with mild haemophilia A, 49 with von Willebrand disease (VWD) and five with platelet storage pool disorder. In patients who underwent formal preoperative assessment a complete or partial response was observed in 28/29 with type 1 VWD and 14/15 with mild haemophilia A. Perioperative SC-DDAVP provided excellent haemostasis in all patients, with no requirement for factor concentrate or blood products. Mild asymptomatic hyponatremia was detected in seven children who received multiple doses of DDAVP (lowest sodium 129 mmol L(-1) ); however, adherence to the prescribed fluid restriction protocol was questionable in six of these cases. Symptomatic hyponatremia was not observed. CONCLUSION: Subcutaneous desmopressin was well-tolerated, with no serious side-effects observed, and good biological responses in preoperative trials. A two-thirds maintenance fluid regimen was effective at preventing symptomatic hyponatremia in our cohort, and is now the standard protocol for fluid restriction post-DDAVP administration in our centre.

Oncogenic Ras differentially regulates metabolism and anoikis in extracellular matrix-detached cells.

In order for cancer cells to survive during metastasis, they must overcome anoikis, a caspase-dependent cell death process triggered by extracellular matrix (ECM) detachment, and rectify detachment-induced metabolic defects that compromise cell survival. However, the precise signals used by cancer cells to facilitate their survival during metastasis remain poorly understood. We have discovered that oncogenic Ras facilitates the survival of ECM-detached cancer cells by using distinct effector pathways to regulate metabolism and block anoikis. Surprisingly, we find that while Ras-mediated phosphatidylinositol (3)-kinase signaling is critical for rectifying ECM-detachment-induced metabolic deficiencies, the critical downstream effector is serum and glucocorticoid-regulated kinase-1 (SGK-1) rather than Akt. Our data also indicate that oncogenic Ras blocks anoikis by diminishing expression of the phosphatase PHLPP1 (PH Domain and Leucine-Rich Repeat Protein Phosphatase 1), which promotes anoikis through the activation of p38 MAPK. Thus, our study represents a novel paradigm whereby oncogene-initiated signal transduction can promote the survival of ECM-detached cells through divergent downstream effectors.

Selective thermal emission from patterned steel.

Patterned metal films have been shown to possess unique optical properties resulting from the excitation of surface plasmon polaritons at the patterned metal surface. Here we demonstrate spectrally selective thermal emission from patterned steel substrates. The materials and processes used in this work were chosen for their potential scalability to large-area and low cost production of metal films with distinct and designable thermal signatures. The samples studied were characterized by reflection and emission spectroscopy, and a factor of 2.6 emission enhancement is demonstrated for the design wavelength. These results are compared to numerical simulations.

The clinical characterisation of systemic lupus erythematosus in a Far North Queensland Indigenous kindred.

The aetiology of systemic lupus erythematosus (SLE) is thought to involve both genetic and environmental factors. In other complex diseases, analysis of large multi-case families has resulted in insights into biological mechanisms. We have sought to characterise the members of an extended Indigenous family, five of whom have been diagnosed with SLE. Pedigree members were evaluated using the Lupus Screening Questionnaire, clinical interviews and medical records. Participants contributed blood and urine samples for laboratory analysis. A Mendelian pattern of inheritance was not observed. The five affected members (all female) shared two American College of Rheumatology criteria (positive ANA and arthritis) but showed a wide variety of other SLE manifestations. Disease onset, severity and progression were discordant. Including the five individuals with SLE, 15 blood relatives and two non-consanguineous spouses had autoimmune manifestations. Autoimmune haemolytic anaemia (one case), idiopathic thrombocytopenic purpura (ITP) (one case) and hypothyroidism (two cases) were observed in non-SLE affected individuals. Anti-nuclear antibodies were present in 12 blood relatives and one non-consanguineous spouse. Infections (especially of the skin) were observed to be common in the kindred. The lack of clear Mendelian inheritance or phenotypic concordance makes a rare monogenic explanation for SLE unlikely in this family. The finding of familial autoimmunity associated with SLE further supports the hypothesis that a common genetic pathway can precipitate autoimmunity, with further genes and possible environmental factors interacting to produce the eventual phenotype. Future genetic linkage studies may reveal a rare 'autoimmune gene' variant in this kindred.

Universal infant hearing screening by automated auditory brainstem response measurement.

BACKGROUND: Our purpose was to identify infants with a bilateral, permanent, handicapping hearing loss and to provide them with amplification before age 6 months. METHODOLOGY: The study population consisted of 10,372 infants born during a 5-year period. Universal hearing screening by automated auditory brainstem response was done in the nursery. Infants who failed the screening test were followed up diagnostically. Infants who were not tested in the nursery were followed up as outpatients. Hearing aids were recommended for those infants who had bilateral hearing loss. RESULTS: Successful screening in the nursery was achieved for 96% of infants. The failure rate was 4%. The incidence of bilateral loss requiring amplification was 1.4/1000. The false-positive rate was 3.5% after the initial screening and .2% when a two-stage screening procedure was used. The incidence of congenital bilateral hearing loss in the well population was 1/1000, and in the neonatal intensive care unit population, 5/1000. The cost of screening was $17 per infant, and the cost to identify each true bilateral hearing loss was $17,750. Amplification was recommended for 15 infants; well infants who used hearing aids before age 6 months achieved age-appropriate speech and language development. CONCLUSIONS: Mild, moderate, and severe bilateral, persistent hearing loss can be identified in the nursery by automated auditory brainstem response measurement to provide amplification before age 6 months and thus optimize speech and language development.

Isolation of nuclei for chromatin analysis in fission yeast.

The methods available for analysis of the chromatin of Schizosaccharomyces pombe are time consuming (>8 h) and/or result in some degradation of the chromatin. Here we report an optimised method for the preparation of spheroplasts and the isolation of nuclei which takes <25 min and is suitable for analysis of chromatin structure by micrococcal nuclease, restriction endonuclease or by immunoprecipitation.

Effects of structured cooperative contact on changing negative attitudes toward stigmatized social groups.

The contact hypothesis predicts that cooperative interaction with members of a disliked group results in increased liking for those members and generalizes to more positive attitudes toward the group. The authors sought to provide evidence consistent with the hypothesis that contact affects attitude in part by eliciting a more positive portrait of the typical group member. Undergraduates participated in a 1-hr dyadic learning session (scripted cooperative learning, jigsaw cooperative learning, or individual study) with a confederate portrayed as a former mental patient. Students initially expected the confederate to display traits similar to those of a typical former mental patient. After the sessions, initially prejudiced students in the 2 cooperative conditions described the typical mental patient more positively and adopted more positive attitudes and wider latitudes of acceptance toward the group. Connections between intergroup attitudes and impression formation are discussed.

Methodological variables affecting phonational frequency range in adults.

This study examined the effects of selected elicitation variables on phonational frequency (Fo) range in normal adults. Twenty men and 20 women responded to five audiotaped tone conditions: (a) discrete steps, (b) slow steps, (c) fast steps, (d) slow glissando, and (e) fast glissando. These stimuli were devised to elicit each person's maximal and minimal Fo. All elicitation conditions evoked a significantly higher maximal Fo and a significantly larger Fo range (in both hertz and semitones) than did the discrete-steps condition. Fast steps produced a significantly higher minimal Fo than did fast glissando. Both slow glissando and fast glissando yielded a significantly larger Fo range in semitones than did fast steps. Finally, the women demonstrated a significantly larger Fo range (in hertz but not semitones) than did the men.

Factors influencing fundamental frequency range estimates in children.

Selected elicitation conditions were manipulated to determine their effect on fundamental frequency (Fo) range estimates in children. Forty normal children each responded to five autiotaped tone conditions: (a) discrete steps, (b) slow steps, (c) fast steps, (d) slow glissando, and (e) fast glissando. These tonal stimuli were devised to elicit each child's maximal and minimal Fo. The traditional discrete-steps condition was associated with a lower maximal Fo, higher minimal Fo, and a more restricted Fo range than all other conditions.

Spinal fusion for chronic low back pain.

Results of spinal fusion for chronic low back pain in 46 patients are analyzed, and the authors set forth the clinical circumstances in which the procedure may relieve this common complaint.

Undiagnosed bleeding states and medical treatment.

Relatively little attention has been placed in mild hemophilia in the orthopedic literature even though there are probably an equal number of patients with mild as compared to classic manifestations. Mild hemophilia and similar related conditions frequently are undiagnosed and may represent major problems and if associated with surgery, catastrophic results. Patients with milder bleeding diatheses may not have a diagnosis made until late in life. Mild hemophilia and hemophiloid conditions are defined and typical findings are given. Other causes of intra or postoperative hemorrhagic states are mentioned. Three case reports of mild Factor VIII and Factor XI deficiency, undiagnosed prior to the author's medical treatment, are presented. Knowledge of the typical historical findings, diagnostic methods, and proper treatment of patients seeking medical treatment with mild hemophilia, hemophiloid and similar conditions explaining hemorrhage following trauma and intra and postoperatively will help to prevent undesirable results as well as severe complications.

Immature stages of Trichonema spp as a cause of diarrhoea in adult horses in spring.

Several incidents of diarrhoea and loss of weight occurred in adult horses during the spring of 1976. Detailed investigation of one typical case suggested that maturation of inhibited larvae of Trichonema spp was responsible.

Vascular and adjacent soft tissue injuries associated with fractures of the pelvis.

One hundred fifty-one patients with fractures of the pelvis and associated injuries have been reviewed. Patients who have these injuries are likely to have uncontrollable, fatal hemorrhage. Of this group, nine died, 11 had exploratory laparotomies, ten had bladder injuries, and two had rectal damage. Blood gas determinations, arterial catheterization, and pulmonary wedge pressure determinations are valuable in making and early diagnosis of pathologic changes resulting from internal hemorrhage.