Combined pharmacophore and 3D-QSAR study on a series of Staphylococcus aureus Sortase A inhibitors

Methicillin resistant Staphylococcus aureus has become a major health concern and it requires new therapeutic agents. Staphylococcus aureus Sortase A enzyme contributes in adherence of bacteria with the cell wall of host cell; consequently, inhibition of S. aureus Sortase A by small molecules could be employed as potential antibacterial agents against methicillin resistant S. aureus. Current study focused on the identification of 3D pharmacophoric features within a series of rhodanine, pyridazinone, and pyrazolethione analogs as S. aureus Sortase A inhibitors. Pharmacophore model was constructed employing representative molecules using Genetic Algorithm with Linear Assignment of Hypermolecular Alignment of Database. The identified pharmacophoric points were then utilized to create alignment hypothesis for three-dimensional quantitative structure-activity relationships. Outcome of comparative molecular field analysis and comparative molecular similarity indices analysis experiments were in good agreement (comparative molecular field analysis: q(2) = 0.562 and r(2) = 0.995, comparative molecular similarity indices analysis: q(2) = 0.549 and r(2) = 0.978) and capable of explaining the variance in biological activities coherently with respect to the structural features of compounds. The results were also found in concurrence with the outcome of pharmacophoric features.     

Juvenile myasthenia gravis

Juvenile myasthenia gravis shares a similar pathophysiologic origin with adult myasthenia gravis, but there are important differences, mostly relating to epidemiology, presentation, and therapeutic decision making. Gender ratios and the proportion of seropositive patients differ in the pre‐ and postpubertal age groups. The diagnostic evaluation is similar to that in adults, although special techniques are sometimes necessary to perform single‐fiber electromyography in younger patients. Therapeutic decisions in affected children and adolescents are complicated by the greater long‐term consequences of using steroids, and thus other interventions, such as intravenous immunoglobulin (IVIg) and plasmapheresis, may play a greater therapeutic role in this population than in adults. Steroid‐sparing agents may contribute to the management of refractory cases, but they should be used with caution due to the risk of malignancy. Muscle Nerve, 2008     

Is Patients’ Preferred Involvement in Health Decisions Related to Outcomes for Patients with HIV?

BACKGROUND Previous studies suggest that patients who are more involved in their medical care have better outcomes. OBJECTIVES We sought to compare health care processes and outcomes for patients with HIV based on their preferred level of involvement in health decisions. DESIGN Cross-sectional analysis of audio computer-assisted interviews with patients at an urban HIV clinic. PATIENTS One thousand and twenty-seven patients awaiting an appointment with their primary care provider. MEASURES Patients were asked how they preferred to be involved in decisions (doctor makes most or all decisions, doctor and patient share decisions, patient makes all decisions). We also asked patients to rate the quality of communication with their HIV provider, and their self-reported receipt of and adherence to HAART. RESULTS Overall, 23% patients preferred that their doctor make all or most decisions, 63% preferred to share decisions with their doctor, and 13% preferred to make all final decisions alone. Compared to patients who prefer to share decisions with their HIV provider, patients who prefer that their provider make all/most decisions were significantly less likely to adhere to HAART (OR [odds ratio] 0.57, 95% CI 0.38–0.86) and patients who preferred to make decisions alone were significantly less likely to receive HAART or to have undetectable HIV RNA in unadjusted analyses (OR 0.52, 95% CI 0.31–0.87 for receipt of HAART; OR 0.64, 95% CI 0.44–0.95 for undetectable HIV RNA). After controlling for potentially confounding patient characteristics and differences in patient ratings of communication quality, patients who preferred that their provider make all/most decisions remained significantly less likely to adhere to HAART (OR 0.58, 95% CI 0.38–0.89); however, the associations with receipt of HAART and undetectable HIV RNA were no longer significant (OR 0.60, 95% CI 0.34–1.05 for receipt of HAART; OR 0.80, 95% C.I 0.53–1.20 for undetectable HIV RNA). CONCLUSIONS Although previous research suggests that more patient involvement in health care decisions is better, this benefit may be reduced when the patient wants to make decisions alone. Future research should explore the extent to which this preference is modifiable so as to improve outcomes.     

Internal fixation in compound type III fractures presenting after golden period

Objective:

Patients often reach the hospital late after passage of golden hours (initial 6 hours) after sustaining high-velocity injuries. The decision of internal fixation in Gustilo''s Type IIIA and IIIB fractures becomes a formidable challenge in patients reaching late. The purpose of the present study was to find out if internal fixation could be safely undertaken in these patients.

Materials and Methods:

Sixty-three patients, having 70 compound fractures (46 Type IIIA and 24 IIIB), which were internally fixed after 6h but within 24h after injury, were included in the present analysis. Follow-up ranged from 18 to 48 months with mean of 28 months.

Result:

Overall infection rate noted was (n = 11) 15.71% (8.7% in IIIA, and 29.16% in IIIB). The difference in deep infection rate between Type IIIA and Type IIIB was found to be statistically significant (P value < 0.01). Nonunion was seen in five fractures. Functional evaluation using Katenjian''s criteria, showed 62.85% (44 fractures of 70) good to excellent results.

Conclusion:

Satisfactory results may be obtained in Gustilo''s Type IIIA and IIIB fractures even if fixed after the golden period, provided strict protocol such as aggressive debridement, prophylactic antibiotic coverage, early soft tissue reconstruction and timely bone grafting is followed. The primary coverage of the wound is discouraged.     

Expression of human neutrophil proteins in acne vulgaris

Background In acne vulgaris patients, the presence of a dysregulation of the production of innate and specific antimicrobial peptides has been postulated. Objective This study aims to determine whether human neutrophil proteins (HNP) 1–3 are expressed in acne patients. Materials and methods HNP 1–3 expression was investigated in 35 acne patients treated with isotretinoin and in 25 healthy subjects. At the beginning of the study, two skin biopsies were taken from acne patients; one biopsy was taken from an established pustule and one from uninvolved skin, and the biopsies were repeated after treatment. Only one biopsy was obtained from controls. Results The statistical analysis showed that pustular lesions of acne patients had significantly higher levels of perivascular and interstitial HNP 1–3 expression when compared with the biopsy of uninvolved skin of these patients (P = 0.003, P = 0.001, respectively) and with that of healthy controls (P = 0.007, P = 0.014, respectively). Isotretinoin treatment achieved a decrease in the perivascular and interstitial HNP 1–3 expression of pustular lesions (P = 0.01, P = 0.001, respectively). Conclusion Our current study demonstrates the novel observation that a recently identified antimicrobial peptide, HNP 1–3, is expressed in neutrophils of acne inflammation but not in uninvolved skin of these patients. These results suggest that HNP 1–3 may contribute to the development of inflammatory lesions of acne.     

Pyoderma gangrenosum or leukaemia cutis?

We report a case of atypical bullous pyoderma gangrenosum associated with acute myeloid leukaemia in which we found atypical myeloid cells within the skin lesion. Although there have been many reported cases of leukaemia-associated pyoderma gangrenosum, the finding of myeloblasts in the skin has rarely been described.