Antitumor activity of novel <Emphasis Type="Italic">N</Emphasis>-sulfonylpyrimidine derivatives on the growth of anaplastic mammary carcinoma in vivo

Purpose: The purpose of this study was to investigate in vivo antitumor activity of newly synthesized N-sulfonylpyrimidine derivatives 1-(p-toluenesulfonyl)cytosine (4H), 1-(p-toluenesulfonyl)cytosine hydrochloride (4H×HCl) and zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K). Materials and methods: In order to do that we have used mouse anaplastic mammary carcinoma (AMCa). Tumor cells (10⁶) in a volume of 0.02 ml were transplanted into the thigh of the right hind leg of CBA mice. All compounds were dissolved in distilled water immediately before injecting to animals. Results: Antitumor effect of these compounds depends on drug doses and time interval between tumor transplantation and drug application. Further the efficacy of these compounds depends on number of drug injections, i. e. whether drug was given in single or in multiple doses. Multiple doses of 400 mg/kg of 1-(p-toluenesulfonyl)cytosine (4H) showed good antitumor effect when applied on day 1, 3, 5, 7 and 9 after tumor transplantation. Still good but slightly lower antitumor effect was also achieved when that compound was given in a single dose (1,200 mg/kg) on day 1 after tumor transplantation. The longest period of tumor growth time was obtained after application of 1-(p-toluenesulfonyl)cytosine hydrochloride (4H×HCl) given as a single dose (300 mg/kg) on day 1 or on day 6 after tumor implantation. However, antitumor effect of zinc(II) complex of 1-(p-toluenesulfonyl)cytosine (4K) was very strong when 300 mg/kg was given on day 1 or day 6, while this effect was slightly lower when drug (200 mg/kg/inj) was given on day 1, 3, 5, 7 and 9 or on day 6, 8, 10, 12 and 14. Conclusion: In this work it has been found that N-1-sulfonylcytosine derivatives have strong antitumor activity against mouse mammary carcinoma which is a good reason for further research of these compounds both in experimental and preclinical studies.     

Safety and Efficacy of Intravenous Colistin in Neonates With Culture Proven Sepsis

Background:

Although it is well described among adults, intravenous colistin use and its associated toxicities in newborns are poorly understood.

Objectives:

We present our experience of efficacy and safety of intravenous colistin in the treatment of sepsis in term and preterm neonates.

Patients and Methods:

The records of neonates who received colistin between January 2013 and February 2014 were retrospectively reviewed. All neonates with culture proven nosocomial infections due to multidrug resistant organisms and treated continuously with colistin for more than 72 hours were included in the study.

Results:

Patients were evaluated for clinical and microbiological response to the drug and its and side effects. Twelve newborn infants with mean 31.8 ± 3.5 weeks gestational age and median 1482 (810 - 3200) gram birth weight were included. 11/12 (91.7%) patients showed microbiological clearance with intravenous colistin. One patient who had recurrent cerebrospinal fluid positive culture was treated with intraventricular colistin. The major side effects observed was hyponatremia and hypokalemia in 2 (16.6%) patients, all infants required magnesium supplementation.

Conclusions:

Intravenous colistin administration appears to be safe and efficacious for multidrug-resistant gram-negative infections in neonates, including preterm infants. However, we believe that large prospective controlled studies are needed to confirm its efficacy and safety in neonates.     

Feelings,thoughts and experiences of nurses working in a mental health clinic about individuals with suicidal behaviors and suicide attempts

Background

It is of the utmost importance to determine the views of nurses about patients with suicidal behavior and who attempt suicide so that they can help such individuals.

A critical assessment of early warning score records in 168,000 patients

The national early warning score (NEWS) is recommended to detect deterioration in hospitalised patients. In 2013, a NEWS-based system was introduced in a hospital service with over 250,000 annual admissions, generating large amounts of NEWS data. The quality of such data has not been described. We critically assessed NEWS data recorded over 12 months. This observational study included NEWS records from adult inpatients hospitalized in the Capital Region of Denmark during 2014. Physiological variables and the use of supplementary oxygen (NEWS variables) were recorded. We identified implausible records and assessed the distributions of NEWS variable values. Of 2,835,331 NEWS records, 271,103 (10%) were incomplete with one or more variable missing and 0.2% of records containing implausible values. Digit preferences were identified for respiratory rate, supplementation oxygen flow, pulse rate, and systolic blood pressure. There was an accumulation of pulse rate records below 91 beats per minute. Among complete NEWS records, 64% had NEWS?≥?1; 29% had NEWS?≥?3; and 8% had NEWS?≥?6. In a large set of NEWS data, 10% of the records were incomplete. In a system where data were manually entered into an electronic medical record, digit preferences and the accumulation of pulse rate records below 91 beats per minute, which is the limit for NEWS point generation, showed that staff practice influenced the recorded values. This indicates a potential limitation of transferability of research results obtained in such systems to fully automated systems.     

State-of-the art review: Noncompaction cardiomyopathy in pediatric patients

Heart Failure Reviews - Noncompaction cardiomyopathy (NCCM) is a disease characterized by hypertrabeculation, commonly hypothesized due to an arrest in compaction during fetal development. In 2006,...     

Catheter-based Treatment of In-stent Restenosis: A Review

Stenting is a safe and efficient method for treatment of ischaemic heart disease. Nevertheless, it gives rise to some additional problems, especially in-stent restenosis. Several techniques including balloon angioplasty, restenting, rotaablation, excimer laser angioplasty, directional coronary atherectomy, cutting balloon angioplasty, brachitherapy and radioactive stents have been performed to treat in-stent restenosis. Balloon angioplasty is preferred in focal lesions (<10 mm). Restenting can be used only in selective cases. The clinical results of debulking techniques associated with balloon angioplasty in patients with long lesions are better especially in diabetic patients. In addition to these procedures, coronary bypass surgery in patients in-stent restenosis with multivessel disease seems to yield to best outcomes. On the other hand, current smoking, diabetes mellitus, unstable angina pectoris, and time to reintervention and in-stent restenosis in saphenous vein lesions are important negative predictors for re-restenosis. The main goal of the treatment of in-stent restenosis is the prevention of the restenosis. Unless this problem is solved the newer techniques will develop, and they will also carry on the newer problems.     

Fgf20 governs formation of primary and secondary dermal condensations in developing hair follicles

In hair follicle development, a placode-derived signal is believed to induce formation of the dermal condensation, an essential component of ectodermal organs. However, the identity of this signal is unknown. Furthermore, although induction and patterning of hair follicles are intimately linked, it is not known whether the mesenchymal condensation is necessary for inducing the initial epithelial pattern. Here, we show that fibroblast growth factor 20 (Fgf20) is expressed in hair placodes and is induced by and functions downstream from epithelial ectodysplasin (Eda)/Edar and Wnt/β-Catenin signaling to initiate formation of the underlying dermal condensation. Fgf20 governs formation of primary and secondary dermal condensations in developing hair follicles and subsequent formation of guard, awl, and auchene hairs. Although primary dermal condensations are absent in Fgf20 mutant mice, a regular array of hair placodes is formed, demonstrating that the epithelial patterning process is independent of known histological and molecular markers of underlying mesenchymal patterns during the initial stages of hair follicle development.