Treatment of aplastic anaemia with antilymphocyte globulin and cyclosporin

Improved survival of patients with aplastic anaemia (AA) has been reported over the last 20 years with immunosuppressive (IS) therapy using antilymphocyte globulin (ALG), and more recently cyclosporin (CSA). The antibody specificities of ALG have now been more clearly defined and are not only T cell directed but also include activities against B cells, NK cells and monocytes. Consequently, the effectiveness of ALG in AA may involve several different mechanisms, and may also help to explain the delayed response that occurs in AA. CSA increases the response rate to ALG in the first 3-6 months, but does not result in improved survival compared with ALG alone. Better supportive care has undoubtedly contributed to the improved survival of patients with time. Almost half the patients who do not respond to a first course of ALG can achieve a later response with a second course of ALG. Relapse occurs in 30% of patients, but up to 50% will respond again with a second course of ALG. Evaluation of the expression of (1) phosphatidylinositol-glycan (PIG)-anchored proteins on haemopoietic cells and (2) gamma-IFN in bone marrow mononuclear cells, may help to predict which patients are more likely to respond to IS therapy. Long term follow up of patients is required to assess the predictive value of X-inactivation DNA studies and PIG-protein expression for later clonal evolution.     

Cardiac single-photon emission tomography with a 90 degrees dual-head system

Dual-head single-photon emission tomography (SPET) systems which permit a 90 degrees orientation of the heads provide a twofold increase in sensitivity for 180 degrees SPET compared with single-head systems. Since such systems have additional mechanical and electrical alignment and stability requirements, clinical equivalency for myocardial perfusion SPET must be demonstrated. Accordingly, we studied 26 subjects who underwent exercise thallium scintigraphy consecutively with both single-head and dual-head systems. Image acquisition was similar, except that the dual-head study took one-half the time. Image reconstruction was identical. Images were interpreted in a blinded fashion, and rated for technical quality. All 26 studies were equivalently interpreted for the presence or absence of perfusion defects. Fourteen of the studies were judged to be technically equivalent; seven were judged to be slightly better with the single-head system; three were judged to be slightly better with the dual-head system; and two were judged to be definitely better with the dual-head system. We conclude that dual-head 90 degrees systems provide equivalent clinical performance in half the acquisition time.     

Extended reproductive roles of the fruitless gene in Drosophila melanogaster revealed by behavioral analysis of new fru mutants

The fruitless mutants fru3 and fru4 were assessed for sex-specific reproductive-behavioral phenotypes and compared to the previously reported fru mutants. Among the several behavioral anomalies exhibited by males expressing these relatively new mutations, some are unique. fru3 and fru4 males are less stimulated to court females than fru1 and fru2. No courtship pulse song is generated by either fru3 or fru4 males, even though they perform brief wing extensions. fru3 and fru4 males display significantly less chaining behavior than do fru1 males. The hierarchy of courtship responses by fru males directed toward females vs. males, when presented with both sexes simultaneously, is that fru1 males perform vigorous and indiscriminant courtship directed at either sex; fru4 males are similarly indiscriminant, but courtship levels were lower than fru1; fru2 males prefer females; fru3 males show a courtship bias toward males. fru3 and fru4 males essentially lack the Muscle of Lawrence (MOL). On several reproductive criteria, there was no difference between fru-variant females and fru+. The increases in phenotypic severity measured for the new mutants are discussed in the context of the emerging molecular genetics of fru and with regard to the gene's position within the sex-determination pathway.     

Evolution of the local calcium content around irradiated beta-tricalcium phosphate ceramic implants: in vivo study in the rabbit

To evaluate whether dissolved calcium from tricalcium phosphate implants contributes to osseous wound healing in bone defects, the authors used nuclear radioactivated materials. Six months after irradiation, the calcium was still radioactive. Samples of the material were prepared and placed in rabbit condyles for 1, 3 and 9 months. Over time the condyles were retrieved and treated for histology or radiocounting. Measurements of the radioactivity of the slices and histomorphometry of the implants and surrounding tissues were performed. The authors observed that the radioactivity decreased regularly. Connective tissue had penetrated the pores and totally invaded the implants, first at the periphery of the implants, then inside the pores. Comparison of the results of radioactivity and histomorphometry suggest that part of the calcium from the implants was re-used specifically in the new osseous tissue.     

The link between drug use and heart valve disease

We report MRI and angiographic findings of an unusual giant arachnoid granulation in the left sigmoid sinus in a boy with headache. Its signal intensity was lower than that of cerebral cortex on T1-weighted images and higher on T2 weighting, mimicking dural sinus thrombosis.     

An efficient method for gene disruption in Neurospora crassa

The frequency with which transforming DNA undergoes homologous recombination at a chromosomal site can be quite low in some fungal systems. In such cases, strategies for gene disruption or gene replacement must either select against ectopic integration events or provide easy screening to identify homologous site, double-crossover insertion events. A protocol is presented for efficient isolation of Neurospora crassa strains carrying a definitive null allele in a target gene. The protocol relies on the presence of a selectable marker flanking a disrupted plasmid-borne copy of the gene, and in the case presented led to a seven-fold enrichment for putative homologous site replacement events. In addition, a polymerase chain reaction assay is utilized for rapid identification of homologous recombinants among the remaining candidates. This protocol was used to identify 3 isolates, out of 129 primary transformants, which have a disruption in the Neurospora ccg-1 gene. The method should be applicable to a variety of fungal systems in which two selectable markers can be expressed, including those in which homologous recombination rates are too low to allow easy identification of homologous site insertions by the more traditional molecular method of Southern analysis. In addition to disrupting target genes for the purpose of generating null mutations, this method is useful for the targeting of reporter gene fusions to a native chromosomal site for the purpose of studying gene regulation.     

Acute childhood pyelonephritis: predictive value of positive sonographic findings in regard to later parenchymal scarring

RATIONALE AND OBJECTIVES: The authors evaluated the importance of positive sonographic findings in acute childhood pyelonephritis. MATERIALS AND METHODS: A total of 290 children (91 boys, 199 girls, aged 4 days to 15 years [median, 394 days]) with clinically suspected acute pyelonephritis underwent initial renal gray-scale ultrasound (US) and dimercaptosuccinate scintigraphic examination within 3 days of onset. A total of 173 patients underwent color or energy US examination. One hundred fifteen children with normal scintigraphic or pathologic findings (other than acute pyelonephritis) were excluded from further study; 170 patients with abnormal scintigraphic findings underwent follow-up scintigraphic scanning 60-90 days later. RESULTS: When pathologic structures other than acute pyelonephritis were not considered, the diagnostic value of gray-scale US was poor, with a sensitivity of 45.5%, a specificity of 86.6%, a positive predictive value of 88.8%, and a negative predictive value of only 40.6%. In regard to future renal scarring, gray-scale US had a positive predictive value of 67.7%, a negative predictive value of 40%, and a likelihood ratio of 1.16. Abnormal Doppler findings helped predict future scarring with a positive predictive value of 85.7%, a negative predictive value of 37.2%, a very low sensitivity of 26.9%, a high specificity of 90.6%, and a likelihood ratio of 2.87. CONCLUSION: Positive US Doppler findings in children with clinically suspected acute pyelonephritis indicate the need for immediate treatment. A positive initial gray-scale US examination does not predict future renal scarring, but a positive Doppler examination indicates a high probability of scarring. Negative gray-scale or Doppler US does not exclude a diagnosis of acute pyelonephritis and it cannot predict an absence of future scarring.     

Interrelationships of clinical outcome, length of resection, and energy cost of walking after prosthetic knee replacement following resection of a malignant tumor of the distal aspect of the femur

An automated method for analysis of in vivo proton magnetic resonance (MR) spectra and reconstruction of metabolite distributions from MR spectroscopic imaging (MRSI) data is described. A parametric spectral model using acquisition specific, a priori information is combined with a wavelet-based, nonparametric characterization of baseline signals. For image reconstruction, the initial fit estimates were additionally modified according to a priori spatial constraints. The automated fitting procedure was applied to four different examples of MRS data obtained at 1.5 T and 4.1 T. For analysis of major metabolites at medium TE values, the method was shown to perform reliably even in the presence of large baseline signals and relatively poor signal-to-noise ratios typical of in vivo proton MRSI. Identification of additional metabolites was also demonstrated for short TE data. Automated formation of metabolite images will greatly facilitate and expand the clinical applications of MR spectroscopic imaging.