Drugs and blood transfusions: dogma- or evidence-based practice?

There is a lack of consensus on the safety of the coadministration of drugs and red blood cells (RBCs). A systematic review was undertaken to establish the evidence base for this question and assess how the evidence may be translated into present clinical day practice. Comprehensive searches of MEDLINE, EMBASE, CINAHL, the Cochrane Library and hand searching of transfusion journals, guidelines and websites identified 12 relevant papers: 11 in-vitro experiments and 1 case report. Data on incidences of haemolysis and agglutination following coadministration were extracted and analysed. Overall findings suggest that iron chelators (two papers), antimicrobials (three papers) and lower doses of opioids (three papers) are safe to coadminister with RBCs. Haemolysis was observed with higher doses of opioids (three papers). Transposition of these findings to clinical practice is limited because of the lack of clinical applicability of in-vitro experiments and diversity in how, and what, clinical outcome measures were used. Further evidence from true clinical settings would be required to inform clinical practice on the efficacy and safety of the coadministration of drugs and RBCs.

Nurse-led 24-h hotline for patients with chronic obstructive pulmonary disease reduces hospital use and is safe.

BACKGROUND: Despite recent advances in the management of patients with chronic obstructive pulmonary disease (COPD), interventions to reduce hospitalization have had only modest success. The aim of this study was to report the outcomes of a novel, nurse-led 24-h telephone support line (hotline) for patients with COPD. METHODS: Observational study of patients' use of hotline between September 2002 and November 2004. All patients with COPD referred to a Respiratory Ambulatory Care programme over this period (n = 458) were given access to the hotline. The number and time of calls to the hotline, outcomes of hotline calls and safety of hotline, were assessed. The characteristics of hotline callers and non-callers were compared using an unpaired Student's t-test for normally distributed variables, a chi(2) test for categorical variables and a Mann-Whitney test for non-normally distributed variables. RESULTS: Over the period studied, 675 calls were made to the hotline by 118 patients and 56% of calls were made after hours. For 78 calls (12%), advice and interventions given by hotline staff averted potential 000 calls by patients/carers. Specific advice about interventions for acute exacerbations of COPD (AECOPD) was given in a further 117 calls (17%). Callers had more severe COPD than non-callers (worse lung function, lower exercise capacity and higher prescription of home oxygen, all P < 0.05). No adverse events related to use of the hotline were documented. CONCLUSION: A nurse-led 24-h hotline for patients with COPD is safe, is used by patients and carers and, when used, reduces hospital presentations with AECOPD.

"Facial" and standard concentric needle electrodes are not interchangeable.

Motor unit action potentials (MUAPs) were recorded using a standard concentric needle (SCN), a "facial" concentric needle (FCN) and a monopolar needle (MN) in the biceps brachii and first dorsal interosseous manus muscles of 7 normal subjects. For each muscle, the MUAP durations were similar for all electrodes. However, the FCN electrode more frequently registered high-amplitude MUAPs compared to the SCN electrode. Hence, the FCN and SCN needles should not be considered interchangeable in assessment of EMG signal amplitude. Although, the pattern of changes in amplitude and duration on FCN and MN recordings is similar, the electrodes have different uptake areas.

Preventing alcohol-related harm in college students: Alcohol-related Harm Prevention program effects on hypothesized mediating variables.

The Alcohol-related Harm Prevention (AHP) program is a normative education and skill-acquisition program designed to reduce serious, long-term alcohol-related harm in college students. Without admonishing students not to drink, which is likely to fail in many student populations, the AHP program attempts to give students the necessary perceptions, motivation and skills to intervene within their peer group, and to make proactive harm-avoidance plans with friends prior to social occasions that involve using alcohol. The AHP program is a two-session, in-class intervention that corrects misperceived norms regarding levels of alcohol use, caring about friends, acceptability of risky behaviors and willingness to intervene. The program also makes use of interactive discussions with students and a graded, peer interview assignment to identify and promote harm-prevention strategies. The AHP program was implemented during fall 1999 at a large northeastern university. The program was received very well by students and showed significant effects on the proximal outcomes hypothesized to mediate more distal health-relevant outcomes.

Selected CD34 blood cell allografts for older patients: low transplant-related mortality, graft failure and acute GvHD.

BACKGROUND: Early transplant mortality is related to acute GvHD, which this study in older patients (40 to 60 years) decreased by reducing the graft T-cell number while maintaining a high CD34 cell number--by positive CD34 cell selection. Potential increased risk of relapse is addressed by giving donor leucocyte infusion (DLI) post-transplant. METHODS: CD34 cells selected by Isolex devices from leukophereses obtained from Filgrastim-treated matched sibling donors were transplanted and DLI given later if there was no GvHD. RESULTS: Selection of CD34 cells achieved a median of 5.2 million cells/kg, with minimum target for transplantation achieved in 17 of 21 donors. Median CD3 cell number was 0.24 million/kg. Engraftment was rapid and graft failure rare. Transplant-related mortality was low (6% at 3 months). Acute GvHD of >or=Grade 2 occurred in only two patients (12.5%). DLI were given to only six patients who had resolved Grade 1 or no GvHD. Eight of the 17 patients relapsed, including three of the six who had DLI. Extensive chronic GvHD developed in six of 12 evaluable patients, two of these had received DLI. Seven of the 17 patients (41%) are alive at median follow-up of 56 months. CONCLUSION: CD34 selection allows transplantation of high numbers of CD34 cells with low CD3 cell count, reducing early mortality in patients 40-60 years old because of rapid hemopoietic reconstitution and low acute GvHD incidence. Administration of DLI was often precluded by low-grade acute GvHD.

The TB structural genomics consortium: a resource for Mycobacterium tuberculosis biology.

The TB Structural Genomics Consortium is an organization devoted to encouraging, coordinating, and facilitating the determination and analysis of structures of proteins from Mycobacterium tuberculosis. The Consortium members hope to work together with other M. tuberculosis researchers to identify M. tuberculosis proteins for which structural information could provide important biological information, to analyze and interpret structures of M. tuberculosis proteins, and to work collaboratively to test ideas about M. tuberculosis protein function that are suggested by structure or related to structural information. This review describes the TB Structural Genomics Consortium and some of the proteins for which the Consortium is in the progress of determining three-dimensional structures.

Bone density adjacent to press-fit acetabular components. A prospective analysis with quantitative computed tomography.

BACKGROUND: The status of periprosthetic bone stock is an important concern when revision total hip arthroplasty is undertaken. Remodeling of periprosthetic femoral bone after total hip arthroplasty has been studied extensively, and the phenomenon of femoral stress-shielding has been well characterized. Finite element analysis and computer-simulated remodeling theory have predicted that retroacetabular bone-mineral density decreases after total hip arthroplasty; however, remodeling of periprosthetic pelvic bone in this setting has yet to be well defined. This study was conducted to evaluate the short-term natural history of periacetabular bone-mineral density following primary total hip arthroplasty. METHODS: Periacetabular bone-mineral density was studied prospectively in a group of twenty-six patients who underwent primary hybrid total hip arthroplasty for the treatment of advanced osteoarthritis. Density within the central part of the ilium (directly cephalad to a press-fit acetabular component) was assessed with serial quantitative computed tomography. Baseline density was measured within the first five days following the total hip arthroplasty. Ipsilateral density measurements were repeated at an average of 1.28 years postoperatively. Density values at corresponding levels of the contralateral ilium were obtained at both time-points in all patients to serve as internal controls. RESULTS: Bone-mineral density decreased significantly (p< or =0.001) between the two time-points on the side of the operation. The mean absolute magnitude of the interval density reduction (75 mg/cc) was greatest immediately adjacent to the implant (p<0.001), but it was also significantly reduced (by 35 mg/cc) at a distance of 10 mm cephalad to the implant (p = 0.001). Relative declines in mean density ranged from 33% to 20% of the baseline values. No focal bone resorption (osteolysis) was detected at the time of this short-term follow-up study. With the numbers available, no significant interval alteration in bone-mineral density was found on the untreated (internal control) side (p> or =0.07). CONCLUSIONS: We suggest that the observed decline in bone-mineral density represents a remodeling response to an altered stress pattern within the pelvis that was induced by the presence of the acetabular implant. This finding corroborates the predictions of finite element analysis and computer-simulated remodeling theory. It remains to be seen whether this trend of atrophy of retroacetabular bone stock will continue with longer follow-up or will ultimately affect the long-term stability of press-fit acetabular components.

Correlates of quantitative ultrasound in the Women's Healthy Lifestyle Project.

Quantitative ultrasound (QUS) assessment of bone is a strong predictor of hip fractures and is currently an FDA-approved tool to identify women at risk of osteoporosis. However, few studies have investigated the lifestyle and genetic correlates of QUS in women. This study investigated the cross-sectional associates of several lifestyle, demographic and genetic factors with calcaneal QUS parameters (broadband ultrasound attenuation (BUA) and speed of sound (SOS)) in 393 women aged 45-53 years. Leisure-time and historical physical activity, dietary calcium and protein, body composition, vitamin D receptor genotypes, menopause status, other health behaviors, calcaneal QUS parameters and bone mineral density (BMD) were assessed at a single clinic visit. Lean mass, recent physical activity and African-American race were the strongest correlates of SOS whereas dietary protein, calcium and recent physical activity were the strongest correlates of BUA. These predictors explained 13% and 6% of the variance in SOS and BUA, respectively. Smoking, alcohol intake, education, hormone replacement therapy, calcium and vitamin D supplements, historical physical activity and vitamin D receptor genotypes were not significantly associated with BUA or SOS. Lean body mass and premenopausal status were the strongest correlates of lumbar BMD whereas lean body mass, physical activity, African-American race and body mass index were significantly related to femoral neck BMD. Physical activity remained predictive of SOS after controlling for lumbar BMD. The spectrum and magnitude of risk factors for SOS and BUA, including lean body mass, physical activity, race, protein and calcium intake, parallel previously observed predictors of BMD.

Electrodiagnostic examination of the supinator--a more dorsal approach: a brief report.

Examination of the supinator muscle of the forearm may be useful in suspected lesions of the 5th and 6th cervical nerve roots, the upper trunk of the brachial plexus, or the radial nerve. It is critical in localizing the level of involvement in a patient with possible posterior interosseous nerve injury. The traditional techniques in the electrodiagnostic examination of this muscle have approached the muscle from the volar aspect, just radial to the insertion of the biceps tendon, medial to the brachioradialis, through the extensor carpi radialis longus/brevis, between the radial wrist extensors and extensor digitorum communis, or through the extensor digitorum communis. These approaches have the inherent risk of piercing vessels and/or nerves. After reviewing the pertinent anatomy in standard textbooks, magnetic resonance imaging, and a cadaver, we developed a more dorsal approach in the examination of the supinator. Examination of 20 patients by staff, fellows, and residents at our institution resulted in consistent, accurate needle placement, with no complications. We describe a more dorsal approach in the examination of the supinator muscle in the forearm.

Prolonged release and c-kit expression of haemopoietic precursor cells mobilized by stem cell factor and granulocyte colony stimulating factor.

Mobilization of haemopoietic precursor cells into the circulation by the combination of cytokines, stem cell factor (SCF) and G-CSF in previously untreated patients with carcinoma of the breast resulted in increased yield of collected peripheral blood precursor cells (PBPC). This mobilization of PBPC by SCF with G-CSF lasted several days after ceasing the cytokines in comparison to the rapid fall of PBPC after ceasing G-CSF. Possible mechanisms for this increased and prolonged mobilization were investigated. Immunological phenotyping with CD38, Thy-1 and MDR-1 of the CD34-positive mobilized PBPC detected no difference in maturity compared to PBPC mobilized by G-CSF alone. However, the down-regulation of c-kit, which is associated with the mechanism of mobilization, was much greater in the PBPC mobilized by SCF and G-CSF. The potential clinical implication of increased and prolonged mobilization is increased yield, allowing transplantation of heavily pre-treated patients, transplantation with PBPC from a single apheresis, or PBSC support for multiple courses of high-dose therapy from one mobilization procedure.

Crystallization, x-ray diffraction and preliminary structure analysis of Mycobacterium tuberculosis chaperonin 10.

The Mycobacterium tuberculosis chaperonin 10 (Mtcpn10) has been crystallized by the sitting-drop vapour-diffusion method. The crystals belong to the monoclinic space group P21, with unit-cell parameters a = 76.5, b = 87.9, c = 124.4 A, beta = 106.8 degrees. X-ray diffraction data were collected to 2.8 A. The self-rotation function and the molecular-replacement solution show that the asymmetric unit contains a dimer of heptamers related by twofold non-crystallographic symmetry. The two heptamers interact through interleaving flexible loops in a similar fashion to M. leprae and Gp31 cpn10. In addition to its role in protein folding, Mtcpn10 has unique effects on the growth of host cells and is a major immunogen in tuberculosis infections. The structure determination will permit the analysis of the amino acids identified as important for the protein-folding and cell-signalling activity of Mtcpn10.

Physiological effects of technique and rolling resistance in uphill roller skiing.

OBJECTIVE: The double pole technique (DP) has been shown to be more economical than the V1 skate technique (V1 ) on flat terrain. The objective of the present study was to compare these two techniques during uphill roller skiing. In addition, the physiological effects of changing roller ski rolling resistance was examined for V1. METHODS: Five female and five male competitive cross-country skiers roller skied 4-min bouts on a 5.2% incline while physiological measurements were made. RESULTS: Oxygen uptake (VO2) values averaged 8% greater (P = 0.0004) with V1, whereas rating of perceived exertion (RPE) and blood lactate concentrations were higher (P < or = 0.002) with DP. Doubling the dynamic friction coefficient of the roller skis, which increased external power output by 16-17%, resulted in VO2 values with V1 that averaged 13% higher (P = 0.0006). This magnitude of change in roller ski rolling resistance did not cause a statistical change in the relationship of VO2 with RPE. CONCLUSIONS: These findings suggest that 1) grade has little effect on relative economies of DP and V1, possibly because of a lower effectiveness of force application with V1 when going uphill, and 2) large differences in roller ski rolling resistance should have no effect on the cardiovascular training adaptations that result from uphill roller skiing with V1.

Pelvic floor function/dysfunction and electrodiagnostic evaluation.

The pelvic floor provides support for the bladder, rectum, and genital systems, as well as proper positioning and orientation of the urethral and anal sphincters. Impairment may result in prolapse, urinary and fecal incontinence, and sexual dysfunction. The impact is enormous in terms of personal, social, and financial burden. Pertinent anatomy is presented, followed by an overview of available electrodiagnostic techniques and a description of pudendal nerve conduction studies, sacral reflex testing and selected electromyographic techniques. Clinical applications are discussed throughout the text and the need for further research is addressed.

Mycobacterium tuberculosis chaperonin 10 stimulates bone resorption: a potential contributory factor in Pott's disease.

Pott's disease (spinal tuberculosis), a condition characterized by massive resorption of the spinal vertebrae, is one of the most striking pathologies resulting from local infection with Mycobacterium tuberculosis (Mt; Boachie-Adjei, O., and R.G. Squillante. 1996. Orthop. Clin. North Am. 27:95-103). The pathogenesis of Pott's disease is not established. Here we report for the first time that a protein, identified by a monoclonal antibody to be the Mt heat shock protein (Baird, P.N., L.M. Hall, and A.R.M. Coates. 1989. J. Gen. Microbiol. 135:931-939) chaperonin (cpn) 10, is responsible for the osteolytic activity of this bacterium. Recombinant Mt cpn10 is a potent stimulator of bone resorption in bone explant cultures and induces osteoclast recruitment, while inhibiting the proliferation of an osteoblast bone-forming cell line. Furthermore, we have found that synthetic peptides corresponding to sequences within the flexible loop and sequence 65-70 of Mt cpn10 may comprise a single conformational unit which encompasses its potent bone-resorbing activity. Our findings suggest that Mt cpn10 may be a valuable pharmacological target for the clinical therapy of vertebral tuberculosis and possibly other bone diseases.

Guidelines for the investigation of invasive fungal infections in haematological malignancy and solid organ transplantation. British Society for Medical Mycology.

Invasive fungal infections are increasing in incidence and now affect as many as 50% of neutropenic/bone marrow transplant patients and 5 to 20% of solid organ transplant recipients. Unfortunately, many of the diagnostic tests available have a low sensitivity. The guidelines presented here have been produced by a working party of the British Society for Medical Mycology in an attempt to optimise the use of these tests. The yield of fungi from blood cultures can be increased by ensuring that at least 20 ml of blood are taken for aerobic culture, by using more than one method of blood culture, and by employing terminal subculture if continuous monitoring systems are used with a five-day incubation protocol. Skin lesions in febrile neutropenic patients should be biopsied and cultured for fungi. The detection of galactomannan in blood or urine is of value in diagnosing invasive aspergillosis only if tests are performed at least twice weekly in high-risk patients. Antigen detection tests for invasive candidiasis are less valuable. Computed tomography scanning is particularly valuable in diagnosing invasive pulmonary fungal infection when the chest radiograph is negative or shows only minimal changes. Bronchoalveolar lavage is most useful in patients with diffuse changes on computed tomography scan. The major advances in the diagnosis of invasive fungal infection in patients with haematological malignancy or solid organ transplantation have been in the use of imaging techniques, rather than in the development of new mycological methods in the routine laboratory.

The epidemiology of quantitative ultrasound: a review of the relationships with bone mass, osteoporosis and fracture risk.

Quantitative ultrasound (QUS) is a simple, inexpensive and non-invasive measure of bone which has been used in research settings for the prediction of osteoporosis. This review summarizes the current status of the epidemiology of QUS analysis, including its relationship with bone mineral density (BMD), risk of osteoporotic fracture and risk factors for osteoporosis. Although only moderately correlated with BMD, QUS appears to be as strong a predictor of osteoporotic fracture as BMD and may predict fracture independent of BMD. Risk factors for low QUS, including age, menopause, body composition and physical inactivity, seem to parallel those of low BMD. More longitudinal research is needed to confirm the clinical utility of QUS and more experimental and population-based studies are needed to determine whether the etiology of low QUS values is different from that of low bone mass.

Secondary amenorrhea due to hydrocephalus treated with endoscopic ventriculocisternostomy. Case report.

The authors present a case of secondary amenorrhea in a 32-year-old woman found to have noncommunicating hydrocephalus due to aqueductal stenosis. Although the presentation of hydrocephalus with amenorrhea has been previously reported, this association remains rare. After treatment via endoscopic third ventriculocisternostomy, the patient resumed normal menstruation and all hormonal abnormalities have resolved except hypothyroidism. A review of the literature on the etiology of endocrinological disturbances in patients with hydrocephalus is presented.

Peripheral blood stem cells mobilized from patients with acute myeloid leukaemia have different platelet repopulating abilities compared with those mobilized from patients with other diseases.

Peripheral blood stem cell (PBSC) transplantation gives rapid recovery of neutrophils and platelets and sustained haemopoiesis. However in patients with acute myeloid leukaemia (AML) platelet recovery has a distinctive rapid rise and then secondary fall between 3 to 8 weeks post-transplant. This study compares platelet and neutrophil recovery after PBSC transplantation in 15 patients with AML and 29 patients with other diseases consecutively transplanted in a single unit. PBSC were collected during recovery from consolidation chemotherapy in AML patients and after cyclophosphamide or cytokine administration in the other patient groups. Mononuclear cell numbers collected were similar but CFU-GM numbers were greater from the AML patients. A significant secondary fall occurred only in the platelet count and only in AML patients. Long-term recovery of the platelet count was the same in AML as in the other patients. In AML patients, the fall was the same in the long term remitters as in those who eventually relapsed. Previous studies have not, demonstrated a difference in type of precursors mobilized by differing methods, but have not included AML patients. Megakaryocyte precursors were assayed in this study and showed no consistent differences in number between patient groups however pre-progenitor assays are not yet established especially in the megakaryocytic lineage. The possible explanation for this secondary fall in AML patients is discussed.

Chemically synthesised human immunodeficiency virus P7 nucleocapsid protein can self-assemble into particles and binds to a specific site on the tRNA(Lys,3) primer.

The zinc-bound form of the human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein, p7, aggregates into particles visible by electron microscopy. The HIV primer tRNA(Lys,3) forms similar high molecular weight complexes with p7 that are also detected by gel mobility shift assays. RNA oligonucleotides of the three stem-loop structures in tRNA(Lys,3) were assayed for the competitive inhibition of p7-tRNA(Lys,3) binding by the intensities of free tRNA(Lys,3) bands on native gels. This reveals that the p7 binds specifically to the central domain of tRNA(Lys,3) where the D and T psi C loops come together, but not the anticodon stem-loop.

Fungal infections: a survey of laboratory services for diagnosis and treatment.

A questionnaire on the services provided and the methods used for the diagnosis of fungal infections and for the support of antifungal chemotherapy was sent to members of the British Society for Medical Mycology (BSMM) and the British Society for Antimicrobial Chemotherapy (BSAC). Ninety-five responses from general microbiology laboratories in the United Kingdom were analysed, and we compared services provided by laboratories that serve a transplant unit with those offered by other laboratories. We estimate that about 150 cases of cryptococcosis, 500 to 600 of candidaemia, and 300 to 400 of invasive aspergillosis are identified by laboratories in the United Kingdom (UK) each year. The clinical laboratories are aware of the importance of fungal infection, but rely heavily on reference services. In some laboratories, however, the degree of investigation of specimens and the procedures in use are inadequate for diagnosing systemic mycoses and determining the susceptibility of isolates to antifungal agents. The balance between reference and local services requires attention and external quality assurance needs to be applied effectively. In addition, effective methods for the diagnosis of systemic mycoses, and reliable and practicable methods for determining the susceptibility of isolates to antifungal agents, are needed urgently.