Femoral head avascular necrosis: correlation of MR imaging, radiographic staging, radionuclide imaging, and clinical findings

To better correlate the appearance of avascular necrosis (AVN) of the femoral head on magnetic resonance (MR) images with the stage of disease, MR images of 56 proved AVN lesions were compared with staging from corresponding radiographs (n = 56), Tc-99m scans (n = 41), and grade of symptoms (n = 28). Fractures complicating AVN were seen in 28 (50%) of 56 radiographs (radiographic stages III-V). With long repetition (TR) and echo delay (TE) times, a characteristic "double line sign" consisting of high signal intensity inside a low-intensity peripheral rim was seen in 45 lesions (80%). The central region within the rim was isointense with marrow fat on both short and long TR and TE images in 20 (71%) of 28 lesions uncomplicated by fracture (stages I-II) but in only four (14%) of 28 stage III-V lesions (P less than .001). Symptoms were least severe in lesions isointense with fat and most severe in lesions with low-signal central regions at short and long TRs and TEs. The peripheral double line sign on long TR/TE images may add specificity to the diagnosis of AVN by MR imaging. A chronologic pattern of central MR signal features is presented which may allow staging of AVN by MR imaging.     

Prognostic role of troponin and natriuretic peptides as biomarkers for deterioration of left ventricular ejection fraction after chemotherapy

Cardiotoxicity due to anthracyclines, trastuzumab and other potential cardiotoxic drugs is still a problem of modern chemotherapy. For years researchers have tried to find biological markers that can predict changes in the heart. The most thoroughly tested markers are troponin and natriuretic peptides. Some studies have proven that these markers can indeed be useful. In studies which have shown the predictive role of troponin I the assessment of this marker was performed very frequently. It is not possible to carry out such serial measurements in many centers because of typical 1-day hospital stay times. The predictive role of natriuretic peptides still needs further investigation. This review considers the newest research from recent years.     

Lack of transmission of neutrophil and platelet antibodies by intravenous immunoglobulin in bone marrow transplant patients

BACKGROUND: Several studies have demonstrated that the administration of intravenous immunoglobulin (IVIG) may be followed by the transient appearance of positive red cell antibody screens, positive direct antiglobulin tests, and, occasionally, frank hemolysis. However, little information is available regarding the possibility that IVIG could transmit neutrophil and/or platelet antibodies. STUDY DESIGN AND METHODS: Serum samples were obtained both immediately before and immediately after the administration of 12 separate lots of commercially available IVIG to bone marrow transplant patients. RESULTS: None of the patients were shown by standard granulocyte immunofluorescence testing to have acquired neutrophil antibodies. Four of the 12 postinfusion sera were positive for platelet antibodies in standard platelet suspension immunofluorescence testing, but in all four instances the corresponding preinfusion serum was positive as well. CONCLUSION: The risk of acquiring neutrophil and/or platelet antibodies after the administration of commercially available IVIG appears to be low.     

DIAPHRAGMATIC PARALYSIS IN MOTOR NEURONE DISEASE: USE OF NON-INVASIVE INVESTIGATIVE AND THERAPEUTIC TECHNIQUES

SUMMARY Two cases of bilateral diaphragmatic weakness are described in which the condition was the presenting feature of motor neurone disease. Inspiratory muscle strength was assessed by a non-invasive technique involving measurements of pressures generated within the mouth. One patient with severe inspiratory muscle weakness is being treated with domiciliary nasal ventilation and has returned to a good-quality life. The other patient with less severe weakness has thus far required no ventilatory support.     

The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture

OBJECTIVES: To evaluate the effects of MK-0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals. DESIGN: Placebo-controlled, randomized, double-blind trial. SETTING: Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers. PARTICIPANTS: One hundred sixty-one hip-fracture patients were enrolled. Entry criteria included consenting hip-fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity. INTERVENTION: Random assignment to 6 months of daily treatment with MK-0677 or placebo. Patients were followed for an additional 6 months after completion of therapy. MEASUREMENTS: Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP-NH), the ability to live independently, and insulin-like growth factor I (IGF-I) levels. RESULTS: MK-0677 treatment increased serum IGF-I levels by 84% (95% confidence interval (CI)=63-107), compared with an increase of 17% (95% CI=8-28) on placebo. There were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score. Although MK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant. CONCLUSION: Although MK-0677 treatment increased serum IGF-I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip-fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.     

The role of MAP kinase kinase in interleukin-3 stimulation of proliferation

Expression of a dominant interfering mutant of MAP kinase kinase (MAPKK) inhibits interleukin-3 (IL-3) activation of MAP kinase in the murine bone marrow-derived cell line BAF3. This results in an increase in the level of IL-3 required to stimulate cell proliferation and suppress apoptosis. When apoptosis is constitutively inhibited by coexpression of bcl-2, the dominant interfering MAPKK inhibits IL-3 driven cell cycle progression. Thus, MAPKK function is necessary for optimal IL-3 inhibition of apoptosis and optimal IL-3 stimulation of entry into S phase. Expression of a constitutively activated mutant of MAPKK does not replace IL-3, but renders cells able to proliferate in a density-dependent manner. Cell contact is required to allow cell proliferation; such contact can be supplied by cells without activated MAPKK.     

Circulating glycosaminoglycan anticoagulants associated with suramin treatment

A complex coagulopathy appeared in three women receiving suramin as treatment for metastatic adrenocortical carcinoma. Although hepatocellular dysfunction accounted for some of the abnormality, a unique feature of the coagulopathy was the presence of an inhibitor of the thrombin clotting time. The potency of this circulating anticoagulant increased markedly during exacerbations of hepatic injury. The anticoagulant was removed from plasma samples from two of the patients by passage over a column of diethylaminoethyl (DEAE)- Sephacel. It eluted from the DEAE at salt concentrations that removed "high-charge" glycosaminoglycans. Elimination of the purified anticoagulant activity in vitro required a combination of heparitinase and chondroitinase ABC, suggesting that the activity was mediated by both heparan sulfate and dermatan sulfate. Suramin is hypothesized to inhibit enzymes that normally degrade glycosaminoglycans, resulting in accumulation of these substances, which are released from the liver into the circulation during periods of hepatic injury.