Incompletely excised lentigo maligna melanoma is associated with unpredictable residual disease: clinical features and the emerging role of reflectance confocal microscopy.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) poses a treatment and surgical challenge given unpredictable subclinical extension resulting in incomplete excision. OBJECTIVES: To describe the demographic, clinical and pathologic characteristics of incompletely excised LM/LMM. To evaluate the potential role of reflectance confocal microscopy (RCM). PATIENTS AND METHODS: A retrospective review of a melanoma database at a tertiary cancer centre for patients referred with 'incompletely excised LM/LMM' or 'incompletely excised melanoma' between October 2006 and July 2017. We recorded clinical and pathological data and surgical margins needed to clear the residual LM/LMM. The second part consisted of a prospective cohort of patients in which RCM was performed when presenting with incompletely excised LM/LMM. RESULTS: We included a total of 67 patients (retrospective + prospective cohort); mean age was 64.9 (standard deviation: 11.3) years and 52.2% were males. For the retrospective cohort (n = 53), the mean scar size was 3.4 cm. The average initial margins excised prior to presentation were 4.8 mm (range 3-7 mm). The average additional margin needed to clear the residual, incompletely excised LM/LMM was 7.8 mm. For the prospective cohort (n = 14), there were no differences in age, gender or size when compared to the retrospective cohort. RCM had a diagnostic accuracy of 78.6%, a sensitivity of 90.9%, a specificity of 33.3% and a positive predictive value of 83.3% for the detection of incompletely excised LM/LMM. CONCLUSIONS: Incompletely excised LM/LMM is a poorly characterized clinical-pathological scenario that may require considerable extra margins for microscopic clearance. RCM may emerge as a valuable tool for the evaluation of patients with incompletely excised LM/LMM.

Decreased susceptibility to azithromycin and erythromycin mediated by a novel mtr(R) promoter mutation in Neisseria gonorrhoeae.

During a screen of Neisseria gonorrhoeae clinical isolates obtained in Uruguay for susceptibility to azithromycin, we noticed that approximately 10% of the strains examined displayed decreased susceptibility to azithromycin and erythromycin due to the mtr(CDE)-encoded efflux pump system, but remained susceptible to Triton X-100. We now report that the mtr(R) promoter region of one of these isolates contains a dinucleotide insertion (TT) that mediates this resistance phenotype.

Rapid, efficient detection and drug susceptibility testing of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures. The Tuberculosis Working Group in Peru.

Inexpensive, rapid, and reliable methods of detecting infection by and drug susceptibility of Mycobacterium tuberculosis (MTB) are crucial to the control of tuberculosis. The novel microscopic observation broth-drug susceptibility assay (MODS) detects early growth of MTB in liquid medium, allowing more timely diagnosis and drug susceptibility testing. Sputum samples from hospitalized patients in Peru were analyzed by using stains, culture, and PCR. Sensitivity of MODS (92%) compared favorably with the most sensitive of the other culture methods (93%). Sputum samples positive for tuberculosis were tested for susceptibility to isoniazid and rifampin with the microwell alamar blue assay (MABA) and MODS. In 89% of cases, there was concordance between MODS and MABA. Of the diagnostic and susceptibility testing methods used, MODS yielded results most rapidly (median, 9.0 and 9.5 days, respectively). MODS is a rapid, inexpensive, sensitive, and specific method for MTB detection and susceptibility testing; it is particularly appropriate for use in developing countries burdened by significant infection rates and increasing numbers of multiple-drug-resistant cases.

Decreased azithromycin susceptibility of Neisseria gonorrhoeae due to mtrR mutations.

Single-dose azithromycin therapy has recently been used in Uruguay for the treatment of uncomplicated gonococcal infections. As part of an active surveillance study to monitor the emergence of antibiotic resistance in gonococcal isolates, we examined the levels of azithromycin susceptibility in 51 consecutive isolates obtained from males with uncomplicated gonococcal urethritis. Isolates with decreased susceptibility to azithromycin (MICs, 0.25 to 0.5 microg/ml) were common, and these isolates often displayed cross-resistance to hydrophobic antimicrobial agents (erythromycin and Triton X-100). Resistance to erythromycin and Triton X-100 is frequently due to overexpression of the mtrCDE-encoded efflux pump mediated by mutations in the mtrR gene, which encodes a transcriptional repressor that modulates expression of the mtrCDE operon. Accordingly, we questioned whether clinical isolates that express decreased azithromycin susceptibility harbor mtrR mutations. Promoter mutations that would decrease the level of expression of mtrR as well as a missense mutation at codon 45 in the mtrR-coding region that would result in a radical amino acid replacement within the DNA-binding motif of MtrR were found in these strains. When these mutations were transferred into azithromycin-susceptible strain FA19 by transformation, the susceptibility of gonococci to azithromycin was decreased by nearly 10-fold. The mtrCDE-encoded efflux pump system was responsible for this property since insertional inactivation of the mtrC gene resulted in enhanced susceptibility of gonococci to azithromycin. We conclude that the mtrCDE-encoded efflux pump can recognize azithromycin and that the emergence of gonococcal strains with decreased susceptibility to azithromycin can, in part, be explained by mtrR mutations.

Very long chain acyl coenzyme A dehydrogenase deficiency in a 5-month-old Korean boy: identification of a novel mutation.

A 5-month-old Korean boy who presented with lethargy and cardiomyopathy was diagnosed with very long chain acyl coenzyme A dehydrogenase (VLCAD) deficiency by organic acid, fatty acid, acylcarnitine, and molecular genetic analysis. The patient was a compound heterozygote for mutations in the VLCAD gene. One allele contains a 3-bp deletion in exon 6, deleting glutamic acid in codon 130 (E130del ); this allele is of paternal origin. The patient's maternally derived allele is a novel mutation, C1843T in exon 20, which creates a premature termination codon (R615stop ). Although molecular genetic characterization of VLCAD deficiency is limited to a few patients, heterogeneity of mutations is already apparent. However, the E130del is a relatively frequent mutant allele, which has been noted in 2 previously identified patients. The 2 mutant alleles in our patient appear to be responsible for his severe and fatal clinical manifestations.

Effects of enhanced O3 and CO2 enrichment on plant characteristics in wheat and corn.

The effects of CO(2) enrichment and O(3) induced stress on wheat (Triticum aestivum L.) and corn (Zea mays L.) were studied in field experiments using open-top chambers to simulate the atmospheric concentrations of these two gases that are predicted to occur during the coming century. The experiments were conducted at Beltsville, MD, during 1991 (wheat and corn) and 1992 (wheat). Crops were grown under charcoal filtered (CF) air or ambient air + 40 nl liter(-1) O(3) (7 h per day, 5 days per week) having ambient CO(2) concentration (350 microl liter(-1) CO(2)) or + 150 microl liter(-1) CO(2) (12 h per day.). Averaged over O(3) treatments, the CO(2)-enriched environment had a positive effect on wheat grain yield (26% in 1991 and 15% in 1992) and dry biomass (15% in 1991 and 9% in 1992). Averaged over CO(2) treatments, high O(3) exposure had a negative impact on wheat grain yield (-15% in 1991 and -11% in 1992) and dry biomass (-11% in 1991 and -9% in 1992). Averaged over CO(2) treatments, high O(3) exposure decreased corn grain yield by 9%. No significant interactive effects were observed for either crop. The results indicated that CO(2) enrichment had a beneficial effect in wheat (C(3) crop) but not in corn (C(4) crop). It is likely that the O(3)-induced stress will be diminished under increased atmospheric CO(2) concentrations; however, maximal benefits in crop production in wheat in response to CO(2) enrichment will not be materialized under concomitant increases in tropospheric O(3) concentration.