Propranolol-hydralazine combination in essential hypertension

The efficacy of a propranolol-hydralazine combination tablet was compared with that of each of its two components in the twice-daily treatment of mild to moderate essential hypertension (diastolic blood pressure: 100 to 125 mmHg). After a three-week, single-blind, placebo period, a 9- to 18-week, single-blind, dose-finding phase with the combination was performed. The daily doses of propranolol/hydralazine were 40 mg/25 mg, 80 mg/25 mg, 80 mg/50 mg, 120 mg/50 mg, 160 mg/50 mg, and 160 mg/100 mg. Of 83 patients, 73 (88%) had decreases in diastolic blood pressure equal to or greater than 10 mmHg. Thirty-eight (46%) patients had a diastolic blood pressure equal to or less than 90 mmHg while taking 80 mg propranolol/50 mg hydralazine or less given BID. Mean systolic and diastolic pressures were reduced by 16.8 mmHg (10.9%) and 17.6 mmHg (16.7%), respectively (P less than 0.001). A ten-week, double-blind, parallel-treatment phase followed in which patients were randomly assigned to the combination tablet or to propranolol or hydralazine. There were significantly larger increases in mean systolic (P less than 0.01) and mean diastolic (P less than 0.03) blood pressure when the components were taken alone than with the combination from the mean of the last three weekly dose-finding visits to the mean of the last four biweekly parallel-treatment visits. The changes in systolic/diastolic blood pressures were: hydralazine (n = 30), 14.43/8.62 mmHg; propranolol (n = 24), 9.87/6.09 mmHg; and the combination (n = 27), 1.47/1.53 mmHg. During the parallel-treatment phase, the proportions of patients with new complaints were: hydralazine, 16/31 (52%); propranolol, 10/25 (40%); and the combination, 11/27 (41%). In the hydralazine group, three patients had cardiovascular events (severe tachycardia, mild palpitations, and skipped heart beats) and two patients had mild anxiety; no such occurrences were noted in the propranolol or combination group. The mean change (increase) in heart rate from the end of dose-finding to the end of the double-blind period was significantly larger for patients taking hydralazine than for patients taking propranolol or the combination. Mean changes for these groups were: hydralazine, 12.4 beats/min; propranolol, 2.9 beats/min; and the combination, 1.8 beats/min (P = 0.0001). This study found the combination of propranolol plus hydralazine to be safe and more effective than either component.     

Lead (Pb2+) sorptive removal using chitosan-modified biochar: batch and fixed-bed studies

Chitosan-Modified fast pyrolysis BioChar (CMBC) was used to remove Pb²⁺ from water. CMBC was made by mixing pine wood biochar with a 2% aqueous acetic acid chitosan (85% deacylated chitin) solution followed by treatment with NaOH. The characterizations of both CMBC and Non-Modified BioChar (NMBC) were done using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), scanning electron microscopy (SEM), surface area measurements (S_BET), elemental analysis, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and ζ-potential measurements. Elemental analysis indicated that chitosan accounts for about 25% weight of the CMBC. The Langmuir maximum adsorption capacity of CMBC at pH 5 was 134 mg g⁻¹versus 48.2 mg g⁻¹ for NMBC at 318 K. CMBC column adsorption studies resulted in a capacity of 5.8 mg g⁻¹ (Pb²⁺ conc. 150 mg L⁻¹; pH 5; column dia 1.0 cm; column length 20 cm; bed height 5.0 cm; flow rate 2.5 mL min⁻¹). CMBC removed more Pb²⁺ than NMBC suggesting that modification with chitosan generates amine groups on the biochar surface which enhance Pb²⁺ adsorption. The modes of Pb²⁺ adsorption on CMBC were studied by comparing DRIFTS and X-ray photoelectron spectroscopy spectra before and after Pb²⁺ adsorption.

Batch and fixed-bed column studies for the removal of lead (Pb²⁺) from aqueous solution by chitosan-modified pinewood biochar.     

Human factors in decision making in major trauma in Camp Bastion,Afghanistan

Introduction

The concentration of major trauma experience at Camp Bastion has allowed continuous improvements to occur in the patient pathway from the point of wounding to surgical treatment. These changes have involved clinical management as well as alterations to the physical layout of the hospital, training and decision making. Consideration of the human factors has been a major part of these improvements.

Methods

We describe the Camp Bastion patient pathway with the communication template that focused decision making at various key moments during damage control resuscitation and damage control surgery (DCR–DCS). This system identifies four key stages: ‘command huddle’, ‘snap brief’, ‘sit-reps’ (situation reports) and ‘sign-out/debrief’. The attitude of staff to communication and decision making is also evaluated.

Results

Twenty cases admitted to Camp Bastion with battlefield injuries were studied from 6 September to 6 October 2012. Qualitative responses from 115 members of staff were collected. All patients were haemodynamically shocked with a median pH of 7.25 (range: 6.83–7.40) and a median of 18 units of mixed red cells and plasma were transfused. In 89% of instances, theatre staff were aware of what was required of them at the beginning of the case, 86% felt there were regular updates and 93% understood what was required of them as the case progressed.

Conclusions

The evolution of the hospital at Camp Bastion has been a unique learning experience in the field of major trauma. The Defence Medical Services have responded with continuous innovation to optimise DCR–DCS for seriously injured patients. Together with the improvements in clinical care, a communication and decision making matrix was developed. Staff evaluation showed a high degree of satisfaction with the quality of communication.     

Correction of coronal plane deformities around the knee using a tension band plate in children younger than 10 years

Background:

Guided growth through temporary hemiepiphysiodesis has gained acceptance as the preferred primary treatment in treating pediatric lower limb deformities as it is minimally invasive with a lesser morbidity than the traditional osteotomy. The tension band plate is the most recent development in implants used for temporary hemiepiphysiodesis. Our aim was to determine its safety and efficacy in correcting coronal plane deformities around the knee in children younger than 10 years.

Materials and Methods:

A total of 24 children under the age of 10 were operated for coronal plane deformities around the knee with a single extra periosteal tension band plate and two nonlocking screws. All the children had a pathological deformity for which a detailed preoperative work-up was carried out to ascertain the cause of the deformity and rule out physiological ones. The average age at hemiepiphysiodesis was 5 years 3 months (range: 2 years to 9 years 1 month).

Results:

The plates were inserted for an average of 15.625 months (range: 7 months to 29 months). All the patients showed improvement in the mechanical axis. Two patients showed partial correction. Two cases of screw loosening were observed. In the genu valgum group, the tibiofemoral angle improved from a preoperative mean of 19.89° valgus (range: 10° valgus to 40° valgus) to 5.72° valgus (range: 2° varus to 10° valgus). In patients with genu varum the tibiofemoral angle improved from a mean of 28.27° varus (range: 13° varus to 41° varus) to 1.59° valgus (range: 0-8° valgus).

Conclusion:

Temporary hemiepiphysiodesis through the application of the tension band plate is an effective method to correct coronal plane deformities around the knee with minimal complications. Its ease and accuracy of insertion has extended the indication of temporary hemiepiphysiodesis to patients younger than 10 years and across a wide variety of diagnosis including pathological physis, which were traditionally out of the purview of guided growth.     

Genetic analyses of isolated high‐grade pancreatic intraepithelial neoplasia (HG‐PanIN) reveal paucity of alterations in TP53 and SMAD4

High‐grade pancreatic intraepithelial neoplasia (HG‐PanIN) is the major precursor of pancreatic ductal adenocarcinoma (PDAC) and is an ideal target for early detection. To characterize pure HG‐PanIN, we analysed 23 isolated HG‐PanIN lesions occurring in the absence of PDAC. Whole‐exome sequencing of five of these HG‐PanIN lesions revealed a median of 33 somatic mutations per lesion, with a total of 318 mutated genes. Targeted next‐generation sequencing of 17 HG‐PanIN lesions identified KRAS mutations in 94% of the lesions. CDKN2A alterations occurred in six HG‐PanIN lesions, and RNF43 alterations in five. Mutations in TP53, GNAS, ARID1A, PIK3CA, and TGFBR2 were limited to one or two HG‐PanINs. No non‐synonymous mutations in SMAD4 were detected. Immunohistochemistry for p53 and SMAD4 proteins in 18 HG‐PanINs confirmed the paucity of alterations in these genes, with aberrant p53 labelling noted only in three lesions, two of which were found to be wild type in sequencing analyses. Sixteen adjacent LG‐PanIN lesions from ten patients were also sequenced using targeted sequencing. LG‐PanIN harboured KRAS mutations in 94% of the lesions; mutations in CDKN2A, TP53, and SMAD4 were not identified. These results suggest that inactivation of TP53 and SMAD4 are late genetic alterations, predominantly occurring in invasive PDAC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Delineation of a novel pre-B cell component in plasma cell myeloma: immunochemical, immunophenotypic, genotypic, cytologic, cell culture, and kinetic features

A novel pre-B cell component in direct and cultured myeloma bone marrow material has been delineated by using immunochemistry and flow cytometry techniques. Our phenotypic studies suggest a novel hybrid expression of pre-B and plasma cell antigens with coexpression of cytoplasmic mu, common acute lymphoblastic leukemia antigen, terminal deoxynucleotidyl transferase, and plasma cell antigens (PCA-1 and PC- 1). This suggests that myeloma pre-B-like cells are aberrant malignant cells and not normal pre-B lymphocytic counterparts. With the advantage of a pure and stable source of these cells from M3 culture to allow molecular characterization, we performed one- and two-dimensional gel electrophoresis and Western blotting. We found that the cytoplasmic mu in myeloma pre-B-like cells has a molecular weight of 74,000 daltons and an isoelectric point of 6.3 and that it is strikingly homogeneous and discrete in size and charge compared with standard secretory mu, which suggests an aberrant, mutant, or monoclonal form of mu. Monoclonality was further evidenced by heavy- and light-chain immunoglobulin gene rearrangements demonstrated with JH and C kappa probes. We also established that this novel myeloma pre-B component is a major proliferative element as determined by double-labeling experiments with phenotype coupled to labeling/proliferative indexes. Our stimulatory studies indicate some capacity of these cells to mature on exposure to phorbol esters. These myeloma pre-B cells may represent the stem cell or self-renewal component in myeloma. Our establishment of these cells in long-term culture offers a considerable asset in studying the immature cells, which may be critical to the immortalization of myeloma.     

Sialylated O-glycans and L-selectin sequentially mediate myeloid cell rolling in vivo

Leukocyte rolling precedes firm adhesion and emigration in inflammatory cell recruitment. Both P-selectin, an endothelial lectin that binds to sialylated O-glycans containing sialyl-Lewisx (sLex) on the granulocyte surface, and leukocyte L-selectin have been shown to mediate leukocyte rolling in vivo. Here, we investigate rolling of isolated human neutrophils (PMN), HL-60 promyelocytes, and an L-selectin-transfected cell line (300.19-L) during trauma-induced inflammation in rat mesenteric venules. HL-60 cells, which express no L-selectin but abundant sLex, rolled effectively immediately after abdominal surgery. HL-60 cell rolling was almost completely abolished by pretreatment with sialidase or monoclonal antibody (MoAb) AM-3 recognizing sLex, and was reduced by about 80% by O-sialoglycoprotein-endopeptidase (OSGP). By contrast, 300.19-L cells rolled poorly immediately after surgery but rolled well between 40 and 120 minutes after surgery. Their rolling was completely inhibited by the blocking L-selectin MoAb LAM1-3, but not by a binding control MoAb. PMN express both L-selectin and clustered, sialylated glycoproteins including P-selectin glycoprotein ligand-1 (PSGL-1). PMN showed effective rolling at all times, which was abolished by sialidase or MoAb AM-3 pretreatment during the first 30 minutes after surgery, but not later, when PMN rolling was largely L- selectin-dependent. We conclude that in trauma-induced inflammation, a two-step mechanism accounts for most of myeloid cell rolling, which initially requires O-glycans and subsequently depends on L-selectin function.     

Restorative materials containing antimicrobial agents: is there evidence for their antimicrobial and anticaries effects? A systematic review

The aim of this systematic literature review was to investigate whether the incorporation of antimicrobial agents into dental restorative materials truly exerts an antimicrobial effect against common cariogenic bacteria (primary outcome), and whether the inclusion of antimicrobial agents is able to prevent caries around restorations (secondary outcome). MEDLINE, via PubMed, was searched for papers published between 1980 and 30 November 2014. A total of 1126 articles were retrieved. After inclusion/exclusion assessment, 147 full text articles were read and included in the review, comprising 130 in vitro, 1 in situ, and 4 in vivo studies, as well as 12 literature reviews. In about 78% of in vitro studies, and in all identified in situ and in vivo studies, a positive antimicrobial effect had been found. However, the anticaries effect had not been tested in any of the selected studies. It was concluded that there is indeed evidence that restorative dental materials containing antimicrobial agents exert an antimicrobial effect, both in laboratory and in clinical studies. However, no evidence has been found regarding the role of these agents in preventing or controlling dental caries, or in preventing caries around restorations.     

Complications of colostomy closure

A series of 126 colostomy closures was analyzed to evaluate factors contributing to morbidity. There were no deaths, but there was a 33 percent complication rate. Patients with penetrating abdominal trauma and foreign-body rectal perforations had fewer serious complications following colostomy closures than patients with diverticulitis or cancer. No significant difference was found in the anastomotic leak rate, length of surgery or length of hospitalization in patients with sutured or stapled anastomoses. Most patients in this series had end colostomies that required limited resection and anastomoses. Complication rates were comparable with previous series, which consisted predominantly of loop colostomy closures. The incidence of surgical complications was not related to the time interval between colostomy formation and closure. Timing of closure, however, significantly influenced the complication rate in two specific patient groups: patients with intraperitoneal colon perforation at the initial procedure when closure was performed within four weeks, and patients with surgical complications at the time of colostomy creation if they underwent closure within eight weeks. Early closures in patients still recovering from colostomy complications were associated with the highest incidence of anastomotic leak. Wound infections at stoma sites were decreased by leaving the skin open. The average hospitalization was 11.1 days for patients without complications, 15.5 days for those with wound infection, 18.5 days for patients with ileus, and 20.4 days for patients with anastomotic leaks. This study illustrates that the optimal time for colostomy closure must be determined on an individual basis. The morbidity can be minimized by delaying closure in specific groups of patients for one to two months. Delaying closure for an arbitrary time interval in all patients, however, is not warranted.