9 tips to help prevent derm biopsy mistakes.

The authors--with expertise in dermatology and pathology--provide pointers that can help you improve your approach to skin biopsy.

Solitary necrobiotic xanthogranuloma of an upper extremity in association with multiple myeloma.

Necrobiotic xanthogranuloma (NXG) is an uncommon granulomatous disorder of unknown pathogenesis that often presents with yellowish plaques in a periorbital distribution. While a majority of cases are associated with an underlying paraproteinemia of the IgG kappa type, a much smaller number are found to be associated with an underlying multiple myeloma. We present a case of a 78-year-old male with an isolated lesion of NXG on his right upper extremity. Following his diagnosis of NXG, further investigation for underlying systemic disorders with serum immunofixation revealed a monoclonal IgG kappa immunoglobulin with an M-spike of 1.2 g/dL. A PET-CT demonstrated bone destruction in the left proximal fifth rib, left scapula, the anterior lumbar I (L1) vertebrae, the left lumbar III (L3) vertebrae posterior elements and possibly left sacrum. A bone marrow biopsy revealed 18 % plasma cells. With these findings he was diagnosed with stage I multiple myeloma. Though clinically unimpressive and atypical in location for NXG, early biopsy and diagnosis of this solitary lesion led to the discovery of his hematopoietic disorder.

Maternal adverse effects with different loading infusion rates of antenatal magnesium sulphate for preterm fetal neuroprotection: the IRIS randomised trial.

OBJECTIVE: To evaluate a slower (compared with a standard) infusion rate of the loading dose of magnesium sulphate for preterm fetal neuroprotection as a strategy to reduce maternal adverse effects. DESIGN: Randomised controlled trial. SETTING: South Australian maternity hospital. POPULATION: Fifty-one women at <30 weeks of gestation, where birth was planned or expected within 24 hours. METHODS: Women received a loading infusion of 4 g of magnesium sulphate over either 60 or 20 minutes (followed by maintenance of 1 g/hour until birth, or for up to 24 hours). MAIN OUTCOME MEASURES: Any maternal adverse effects associated with the infusion. RESULTS: Overall, 71% of women experienced adverse effects during the first hour of their infusion; the difference between groups was not significant [15/25 (60%) 60-minute loading; 21/26 (81%) 20-minute loading; risk ratio (RR) 0.74; 95% confidence interval (95% CI) 0.51-1.08]. Although no serious maternal complications occurred, adverse effects led to three women ceasing the loading treatment (1/25 in the 60-minute loading group; 2/26 in the 20-minute loading group; RR 0.52; 95% CI 0.05-5.38). Women in the 60-minute loading group experienced significantly less warmth and flushing at 20 minutes into the infusion (7/25 in the 60-minute loading group; 15/26 in the 20-minute loading group; RR 0.49; 95% CI 0.24-0.99). No other differences between groups for maternally reported and clinical adverse effects were shown. CONCLUSIONS: A slower rate of administering the loading dose of magnesium sulphate did not reduce the occurrence of maternal adverse effects overall. Flushing and warmth at 20 minutes into the infusion was reduced with a slower infusion.

Rho1 regulates Drosophila adherens junctions independently of p120ctn.

During animal development, adherens junctions (AJs) maintain epithelial cell adhesion and coordinate changes in cell shape by linking the actin cytoskeletons of adjacent cells. Identifying AJ regulators and their mechanisms of action are key to understanding the cellular basis of morphogenesis. Previous studies linked both p120catenin and the small GTPase Rho to AJ regulation and revealed that p120 may negatively regulate Rho. Here we examine the roles of these candidate AJ regulators during Drosophila development. We found that although p120 is not essential for development, it contributes to morphogenesis efficiency, clarifying its role as a redundant AJ regulator. Rho has a dynamic localization pattern throughout ovarian and embryonic development. It preferentially accumulates basally or basolaterally in several tissues, but does not preferentially accumulate in AJs. Further, Rho1 localization is not obviously altered by loss of p120 or by reduction of core AJ proteins. Genetic and cell biological tests suggest that p120 is not a major dose-sensitive regulator of Rho1. However, Rho1 itself appears to be a regulator of AJs. Loss of Rho1 results in ectopic accumulation of cytoplasmic DE-cadherin, but ectopic cadherin does not accumulate with its partner Armadillo. These data suggest Rho1 regulates AJs during morphogenesis, but this regulation is p120 independent.

The wild-type circadian period of Neurospora is encoded in the residual network of the null frq mutants.

We model theoretically the response of the widely studied circadian oscillator of Neurospora crassa to inactivation of the frq gene. The resulting organism has been termed "arrhythmic" under constant conditions. Under entrainment to periodic temperature cycles Roenneberg, Merrow and coworkers have shown that the phase angle at which spore formation occurs depends on the entrainment period, curiously even in the null frq mutants (frq9 and frq10). We show that such a response does not imply the presence of a self-sustained free-running oscillator. We derive a simple candidate model (a damped harmonic oscillator) for the null frq mutants that successfully reproduces the observed phase angle response. An endogenous period of 21 h for the damped harmonic oscillator coincides with the endogenous period of wild-type Neurospora. This suggests that the (noise driven) "residual system" present in the mutants may have a significant timekeeping role in the wild-type organism. Our model (with no change of parameters) was then used to investigate spore formation patterns under constant conditions and reproduces the corresponding experimental data of Aronson et al. (Proc. Natl. Acad. Sci. USA 91 (1994) 7683.)

Analysis of peptides synthesized in the presence of SAz-1 montmorillonite and Cu(2+) exchanged hectorite.

We have investigated the synthesis of oligopeptides containing glycine and tyrosine in the presence of the clay minerals montmorillonite (non-exchanged, SAz-1) and Cu(2+) exchanged hectorite. In both cases, homopolymers of the two amino acids are formed, as are mixed peptides. In the case of Cu(2+) hectorite, mixed oligopeptides up to trimers are detected in small amounts. For montmorillonite, heterogeneous oligopeptides up to hexamers are detected. Our experiments indicate montmorillonite is more effective in promoting oligopeptide formation than Cu(2+) hectorite. Analysis of the oligopeptide sequences formed on the montmorillonite surfaces indicates preferential synthesis of certain Gly-Tyr sequences over others.

The interaction of biological molecules with clay minerals: a scanning force microscopy study.

We have used the technique of scanning force microscopy (SFM) to investigate the reaction of both amino acids and activated nucleotides in the presence of the clay mineral Cu(II)-exchanged hectorite. Using simulated prebiotic heating and wetting cycles, we have shown that the clay mineral acts to adsorb, concentrate, and subsequently catalyze the polymerization of these biological monomers into short peptides and oligonucleotides. The presence of the Cu(II) cations within the clay intergallery regions, and at surface step edges and cracks, is crucial for the observed reactions to occur. Clay minerals such as hectorite may have thus played an important role in the evolution of biologically viable molecules on the prebiotic earth.

Preventing neural tube defects. Survey of preconceptional use of folic acid.

OBJECTIVE: To determine the proportion of women who take daily folic acid supplements in the month before conception and to identify factors associated with supplement use. DESIGN: Cross-sectional survey by self-administered questionnaire. SETTING: Tertiary care teaching hospital in Hamilton, Ont. PARTICIPANTS: Four hundred eighty-four (43%) of 1132 women who delivered normal babies between November 1997 and March 1998. MAIN OUTCOME MEASURES: Reports of daily vitamin supplement use in the month before pregnancy and after pregnancy, and having heard or read about the need to take folic acid before pregnancy; sources of information about folic acid; factors associated with preconceptional vitamin use. RESULTS: Thirty-four percent of respondents reported taking vitamins before conception (use ranged from 21% for those with unplanned pregnancies to 40% for those with planned pregnancies); 80% after conception. Of all respondents, 63% were aware of the need for preconceptional folic acid. Key information sources were family doctors and the mass media: the media were more important before conception, doctors after. Being older (30 years or more), having post-secondary education, and having a planned pregnancy were associated with knowing about the benefits of folic acid; knowledge, regular exercise, perceived good health, and planned pregnancy were associated with preconceptional use of vitamins. CONCLUSIONS: Even in this sample of well educated, English-speaking women, only one third took vitamin supplements before conception, which indicates that current educational efforts do not reach most women early enough. A coordinated, multi-pronged strategy that targets and involves physicians and capitalizes on opportunities to work with schools, public health outlets, and the media is needed.

Evaluation of use of a new chromogenic agar in detection of urinary tract pathogens.

CHROMagar Orientation, a new chromogenic medium, was evaluated for the detection and differentiation of gram-positive and gram-negative pathogenic microorganisms in 900 urine samples from hospitalized patients. Performance characteristics of the medium were evaluated in comparison to those of 5% sheep blood and MacConkey agars by direct inoculation of the urine samples on the three media. Four gram-negative and two gram-positive strains as well as one yeast control strain from the American Type Culture Collection were used to ensure quality control. CHROMagar Orientation succeeded in detecting all the urine pathogens that were detected by the reference media, including gram-negative bacilli, staphylococci, streptococci, and yeasts. Colony color and morphology on CHROMagar Orientation accurately differentiated Escherichia coli, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, and Acinetobacter spp. Owing to the similarity in the pigmentation produced by Klebsiella, Enterobacter, and Citrobacter isolates, the medium failed to distinguish among them; however, these isolates were easily recognized as coliforms because of their metallic blue coloration. Staphylococci were clearly perceptible: S. aureus and S. epidermidis grow in regular-size colonies that range from opaque white to yellowish, and S. saprophyticus produces opaque pink colonies. All streptococcus strains, including those from groups B and C, were detected. They grow as undifferentiated flat dry diffused colonies, and additional tests were required for identification. Enterococci were easily discriminated by their strong turquoise pigmentation and their typical growth on the agar's surface. Yeast grow in typical creamy wet convex colonies. The accuracy of antibiotic susceptibility determinations according to standard methods was also tested by picking isolates directly from CHROMagar Orientation. The results showed excellent correlation with those obtained with microorganisms picked from reference media. Owing to the ease in differentiating mixed flora on CHROMagar Orientation, antimicrobic susceptibility tests were performed directly from primary isolates in all cases without the need for subcultures.

Electrophoretic karyotype for Dictyostelium discoideum.

This paper reports on the separation of the Dictyostelium discoideum chromosomes by pulse-field electrophoresis and the correlation of the electrophoretic pattern with linkage groups established by classical genetic methods. In two commonly used laboratory strains, five chromosome-sized DNA molecules have been identified. Although the majority of the molecular probes used in this study can be unambiguously assigned to established linkage groups, the electrophoretic karyotype differs between the closely related strains AX3k and NC4, suggesting that chromosomal fragmentation may have occurred during their maintenance and growth. The largest chromosome identified in this study is approximately 9 million base pairs. To achieve resolution with molecules of this size, programmed voltage gradients were used in addition to programmed pulse times.

Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat.

The human immunodeficiency virus (HIV-1)-encoded trans-activator (tat) increases HIV gene expression and replication. Previously, we demonstrated that tat facilitates elongation of transcription through the HIV-1 long terminal repeat (LTR) and that short transcripts corresponding to prematurely terminated RNA are released and accumulate in the absence of tat. Here, using a transient expression assay, we tested clustered and compensatory mutations, as well as 3' deletions, in the trans-acting responsive region (tar) and observed that the primary sequence in the loop and secondary structure in the stem of the stem-loop in tar are required for trans-activation by tat. Insertions in the 5' region of tar revealed that tar must be near the site of HIV-1 initiation of transcription for trans-activation by tat. Deletions (3') and an insertion in tar demonstrated that an intact stem-loop is required for the recovery of prematurely terminated transcripts. Short and full-length transcripts were observed also with HIV type 2 (HIV-2) in the absence and presence of tat, respectively. We conclude that an intact stem-loop in tar is essential for trans-activation by tat and that initiation of transcription by HIV-1 promoter factors and elongation of transcription by tat are coupled.