Computerized system to enhance the clinical diagnosis of pigmented cutaneous malignancies

BACKGROUND: An increase in the incidence of cutaneous malignant melanoma in recent years has not been accompanied by satisfactory progress in diagnostic methods. This study was carried out to evaluate a specially designed computerized image analysis system, called Derma Vision, to aid in the differentiation between malignant and benign cutaneous pigmented lesions. METHODS: Seventy-one lesions were photographed with a digital camera and the data were analyzed by the Derma Vision system. The system assessed the variation of hues in each image, calculated the mean standard deviation of the hues, and produced a value that expressed the range of hues in the lesion. The lesions were then excised and examined histologically. The computer-assisted clinical diagnosis was correlated with the histologic diagnosis to determine the accuracy of the former. RESULTS: Derma Vision predicted the malignant character of a lesion with 92% precision, compared with 87% accuracy based only on the clinical features. CONCLUSIONS: This simple, inexpensive device can boost the accuracy of clinical diagnosis and provide a useful tool to the physician faced increasingly with having to determine whether pigmented lesions are malignant or benign.     

The Q359K/T360K mutation causes cystic fibrosis in Georgian Jews

Background

The Q359K/T360K mutation, described in Jewish CF patients of Georgian decent, is of questionable clinical significance.

Targeted drug-carrying bacteriophages as antibacterial nanomedicines

While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of approximately 20,000 compared to the free drug.     

Comorbidity of fibromyalgia and psychiatric disorders

There are mounting data supporting comorbidity of fibromyalgia syndrome (FMS) and psychiatric conditions. These include depression, panic disorders, anxiety, and post-traumatic stress disorder (PTSD). The nature of the relationship between depression and FMS is not fully understood, and it was hypothesized that chronic pain causes depression, or vice versa, and that chronic pain syndromes are variants of depression. A link between PTSD symptoms and FMS has been reported, and both conditions share similar symptomatology and pathogenetic mechanisms. Assessment of comorbid psychiatric disorders in FMS patients has clinical implications because treatment in these patients should focus both on physical and emotional dimensions of dysfunction.     

Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia

Preeclampsia is a hypertensive disorder of pregnancy in which patients develop profound sensitivity to vasopressors, such as angiotensin II, and is associated with substantial morbidity for the mother and fetus. Enhanced vasoconstrictor sensitivity and elevations in soluble fms-like tyrosine kinase 1 (sFLT1), a circulating antiangiogenic protein, precede clinical signs and symptoms of preeclampsia. Here, we report that overexpression of sFlt1 in pregnant mice induced angiotensin II sensitivity and hypertension by impairing endothelial nitric oxide synthase (eNOS) phosphorylation and promoting oxidative stress in the vasculature. Administration of the NOS inhibitor l-NAME to pregnant mice recapitulated the angiotensin sensitivity and oxidative stress observed with sFlt1 overexpression. Sildenafil, an FDA-approved phosphodiesterase 5 inhibitor that enhances NO signaling, reversed sFlt1-induced hypertension and angiotensin II sensitivity in the preeclampsia mouse model. Sildenafil treatment also improved uterine blood flow, decreased uterine vascular resistance, and improved fetal weights in comparison with untreated sFlt1-expressing mice. Finally, sFLT1 protein expression inversely correlated with reductions in eNOS phosphorylation in placental tissue of human preeclampsia patients. These data support the concept that endothelial dysfunction due to high circulating sFLT1 may be the primary event leading to enhanced vasoconstrictor sensitivity that is characteristic of preeclampsia and suggest that targeting sFLT1-induced pathways may be an avenue for treating preeclampsia and improving fetal outcomes.     

Plasma homocysteine level and functional outcome of patients with ischemic stroke

OBJECTIVE: To investigate the possible relationships between total plasma homocysteine level (tHcy) and functional outcome of stroke patients as evaluated by the FIM instrument. DESIGN: Retrospective chart analysis. SETTING: Inpatient stroke rehabilitation ward of a university-affiliated referral hospital. PARTICIPANTS: Consecutive patients (N=113) presenting with acute ischemic stroke. Patients were divided into 2 groups according to their tHcy levels (< or = 15 micromol/L, >15 micromol/L) and into 3 groups according to their FIM scores (low, < or =40; moderate, 41-80; high, >80). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The tHcy level was determined shortly after stroke onset by a high performance liquid chromatography method with fluorescence detection. Functional outcome was measured by the FIM instrument at admission and discharge. The tHcy level and FIM scores were obtained for all patients. Data outcomes were analyzed by t tests, 1-way analysis of variance, Mann-Whitney U, and Fisher exact tests, as well as by the 2 ordered polytomous logistic regression model. RESULTS: The 2 tHcy groups were similar in demographic, stroke, and comorbidity characteristics, differing only by higher frequency of hypertension in those with a tHcy greater than 15 micromol/L (51.7% vs 80.8%, respectively, P=.01). Compared with patients who had tHcy levels at 15 micromol/L or lower and were discharged from rehabilitation being in the highest FIM score group (>80), higher tHcy levels were not associated with a discharge FIM score of less than 40 (odds ratio [OR]=.77; 95% confidence interval [CI], 0.13-4.65; P=.77) or with a better functional outcome FIM score between 40 and 80 (OR=3.71; 95% CI, 0.73-18.99; P=.11). CONCLUSIONS: Our findings suggest that determination of tHcy level does not correlate with functional outcome in patients presenting for rehabilitation after acute ischemic stroke.     

The handwriting performance of children with NF1

The objective of this study was to analyze the process and product of handwriting among children with Neurofibromatosis Type 1 (NF1) in comparison to those of Typically Developing (TD) children. Children with NF1 are at risk for some cognitive deficits, a wide range of deficits in perceptual skills and, motor and visual-motor integration skills which may interfere with handwriting competency, which is an essential ingredient for success at school. Participants were 30 NF1 children and 30 age and gender matched TD children, between the ages 8 and 16.08. The handwriting performance of children with NF1 was evaluated with the Beery–Buktenica Developmental Test of Visual-Motor Integration (VMI), for copying text and free style writing tasks, using: (1) Computerized Penmanship Evaluation Tool (ComPET) to assess mechanical aspects of the writing process. (2) The Hebrew Handwriting Evaluation (HHE) to examine product legibility. (3) The Six-Trait Writing Model to judge the quality of the written product. Significant differences between the NF1 children and the control group were found in the process and product measures. Significant correlations were found between the VMI, the ComPET, the HHE and the Six-Trait Writing Model variables for both groups. We suggest a possible relationship between executive dysfunction and poor performance in handwriting.