Severe anaemia: implications for functional recovery during rehabilitation

Purpose : This case report examines the hospital course and functional recovery of a geriatric patient with severe anaemia undergoing rehabilitation following total hip replacement. It serves to highlight the need for further study of the impact of anaemia on recovery in the rehabilitation setting as well as the importance of developing clinical guidelines for the appropriate medical management of anaemia in this patient population. Method : Single case report. Results : The course of recovery during rehabilitation in a geriatric patient with sever post-operative anaemia was notably different from other geriatric patients undergoing rehabilitation following total hip replacement. The patient demonstrated a markedly reduced tolerance for therapies and prolonged length of stay, but did not experience cardiopulmonary complications during intensive rehabilitation. Her hematocrit responded nicely to treatment with human recombinant erythropoietin. Despite a prolonged recovery period, the patient ultimately progressed well and achieved a good functional outcome. Conclusions : The impact of anaemia on functional recovery in the acute inpatient rehabilitation setting as well as the theoretical risk of increased morbidity and mortality during prescribed therapeutic exercise has not been closely examined in the literature. Further study is indicated to examine the implications for anaemia on functional recovery and cardiopulmonary complications during rehabilitation. General guidelines should be developed for the management of anaemia in the rehabilitation setting.     

Studies of human polyclonal and monoclonal antibodies binding to lupus autoantigens and cross-reactive antigens

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune rheumatic disease serologically characterized by production of a variety of autoantibodies. Antibodies to double-stranded (ds) DNA are considered to be a diagnostic marker in SLE and their presence often correlates with active disease. The murine R4A anti-dsDNA antibody was found to cross-react with a peptide, D/EWD/EYS/G (R4A peptide), identified by analysing decapeptides selected from a peptide library. The R4A peptide inhibited binding of antibody to dsDNA and antibody deposition in kidneys in vivo. In other previous work, mice immunized with the peptide in a decapeptide form bound to a polylysine backbone, multiple antigenic peptide, were found to develop both anti-DNA and anticardiolipin antibodies. METHODS: To determine if human anti-DNA antibodies bind R4A peptide, we investigated the binding of monoclonal and polyclonal anti-dsDNA and anticardiolipin antibodies to the R4A peptide from patients with SLE. RESULTS: DNA binding by four immunoglobulin (Ig) G and two IgM human monoclonal anti-DNA antibodies was inhibited by the R4A peptide. While monomeric peptide was unable to inhibit affinity-purified polyclonal anti-DNA antibodies, serum anti-DNA reactivity was inhibited by an octameric form of the peptide in 10 SLE patients. CONCLUSIONS: Human anti-DNA reactivity includes the same fine specificity as that present in murine anti-DNA reactivity. Peptide binding might be a useful surrogate marker for SLE.     

Macrolides: A Canadian Infectious Disease Society position paper

Since the introduction of erythromycin in 1965, no new compounds from the macrolide antimicrobial class were licensed in Canada until the 1990s. Clarithromycin and azithromycin, since their introduction, have become important agents for treating a number of common and uncommon infectious diseases. They have become prime agents in the treatment of respiratory tract infections, and have revolutionized the management of both genital chlamydial infections, by the use of single-dose therapy with azithromycin, and nontuberculous mycobacterial infections, by the use of clarithromycin. The improvement of clarithromycin and azithromycin over the gastrointestinal intolerability of erythromycin has led to supplanting the use of the latter for many primary care physicians. Unfortunately, the use of these agents has also increased the likelihood for misuse and has raised concerns about a resultant increase in the rates of macrolide resistance in many important pathogens, such as Streptococcus pneumoniae. This paper reviews the pharmacology and evidence for the current indications for use of these newer agents, and provides recommendations for appropriate use.Key Words: Azithromycin, Clarithromycin, Erythromycin, Macrolides, Review, Therapeutic useErythromycin A is a naturally occurring, microbiologically active compound of the macrolide class of antibiotics. Chemical modification of erythromycin A''s 14-membered lactone ring has led to the formation of semisynthetic derivatives with not only improved bioavailability and tolerability, but also expanded spectrums of microbiological activity and improved pharmacokinetic profiles. Such modifications produced clarithromycin, classified as a macrolide because it retains the central 14-membered lactone ring (1,2), and azithromycin, classified as an azalide due to its 15-membered aglycone ring (1). The latter two compounds are the newest agents in the macrolide class licensed for use in Canada. Roxithromycin and dirithromycin are available in other countries.These compounds are clinically active against Gram-positive and Gram-negative cocci, and Gram-negative bacilli (primarily Haemophilus influenzae, Legionella species, Moraxella catarrhalis, Campylobacter jejuni, Bordatella pertussis and Helicobacter pylori). Azalides such as azithromycin have exhibited superior activity against Gram-negative pathogens and are generally less active against Gram-positive pathogens. Intracellular pathogens such as Chlamydia species, Mycoplasma species, Ureaplasma species, Borrelia species and nontuberculous mycobacteria species show varying susceptibilities. On the basis of their microbial activity, both the macrolides and azalides have been shown to be clinically useful in the treatment of uncomplicated skin and soft tissue infections, upper and lower respiratory tract infections, sexually transmitted Chlamydia trachomatis infection and peptic ulcer disease. Additionally, the improved pharmacokinetic profiles and acid stability exhibited by the newer agents may lead to enhanced patient adherence through less frequent dosing and improved bioavailability in the presence of food.     

Alternative referent standards for cardiac normality. Implications for diagnostic testing

The radionuclide ventriculographic exercise response was evaluated in three patient populations representing alternative referent standards for cardiac normality: patients with normal coronary arteriograms, healthy volunteers, and uncatheterized patients with a low probability of coronary artery disease. Disease probability was determined by Bayesian analysis of age, sex, symptoms, and the results of cardiac fluoroscopy, exercise electrocardiography, or thallium scintigraphy. A wide range of ventriculographic responses was noted in the 62 catheterized normal patients; 21 (34%) had an abnormal ejection fraction response and 22 (35%) had an abnormal wall motion response. In contrast, the ejection fraction and wall motion responses were normal in the 9 volunteers. In 90 patients (18 catheterized and 72 uncatheterized) who had low disease probability (less than 1%), abnormal responses were rare; the ejection fraction response was abnormal in only 7% and the wall motion response was abnormal in 8%. Thus, these three populations are not equivalent referent standards of normality. Volunteers and patients with low disease probability provide too strict a standard, and their use can overestimate test specificity; catheterized normal patients, on the other hand, provide too lenient a standard, and their use can underestimate test specificity.     

Ethanol reduces bone formation and may cause osteoporosis

INTRODUCTION: The etiology of ethanol-associated osteopenia is not fully understood. In order to define the role of ethanol in the pathogenesis of hepatic osteodystrophy, we compared two groups of alcoholic patients with histologically established alcoholic liver disease. PATIENTS AND METHODS: Twenty-eight patients currently drinking ethanol ("drinkers") and 12 claiming not to have consumed any ethanol for at least six months ("abstainers") were enrolled in the study. In addition, 35 non-alcoholic control subjects without clinical or biochemical evidence of liver disease were also studied. Bone mineral density and various biochemical and hormonal values were measured in each subject; iliac crest biopsies were taken under local anesthesia in the patients and under general anesthesia in the control subjects. RESULTS: Forearm bone mineral densities, spinal bone mineral densities, and iliac crest cancellous bone areas were significantly lower in the alcoholic patients compared with control subjects (p less than 0.01 for all measurements), but these values did not differ between the drinkers and the abstainers. The drinkers, however, had significantly less osteoblastic activity than the abstainers, as assessed by dynamic bone histomorphometry (p less than 0.001). Serum bone Gla-protein concentrations were higher in the abstainers than in the drinkers (p less than 0.001). No differences were seen relating to histologic parameters of bone resorption, although the alcoholic patients who had lower serum free testosterone concentrations than the control subjects also had higher urinary hydroxyproline excretion rates. CONCLUSION: These data suggest that ethanol may be responsible for osteoblastic dysfunction resulting in diminished bone formation and reduced bone mineralization.     

Colonization of the uterus by the oral protozoan Entamoeba gingivalis.

Pap smears occasionally reveal protozoa of the genus Entamoeba in the uterus of intrauterine device (IUD) users, but definitive identification of the species involved has not been possible. Using riboprinting, a technique that compares ribosomal RNA gene sequences, we present evidence that the organism is Entamoeba gingivalis, an inhabitant of the mouth. Colonization most likely occurs via orogenital contact and requires the presence of an IUD and a concomitant bacterial infection.     

TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons

Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. Tlr3^–/– mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-β secretion and ISG mRNA in induced pluripotent stem cell–derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-β immunity.