Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia

Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX.     

Graded responses of human neutrophils induced by serum-treated zymosan

A modified zymosan preparation was used to probe the interaction of particulate stimuli with human neutrophils (PMNs). After extraction with alkali and detergent, the zymosan particles retained their ability to be opsonized in serum and to stimulate PMNs. Serum-treated zymosan (STZ) induced dose-dependent superoxide (O2-) production and membrane potential depolarization in the range of 1 to 10 mg/mL of STZ. The rate and extent of secretion of lysozyme and beta-glucuronidase were also dose-dependent in the range of 1 to 10 mg/mL of STZ. Cytochemical studies using nitroblue tetrazolium, however, showed that 92% of PMNs were stimulated to produce O2- at 0.1 mg/mL of STZ. The dose response of O2- production induced by STZ is therefore due to increasing O2- production by individual PMNs and not to the stimulation of more PMNs to produce O2-. Evidence for O2- production was found only in the area of PMN-zymosan contact, suggesting a mechanism for the graded responses of PMNs treated with particulate stimuli. In order to determine the nature of the dose dependence of depolarization (a measure of PMN activation), PMNs equilibrated with the fluorescent probe 3,3'- dipentyloxacarbocyanine were analyzed by flow cytometry. The results demonstrate that STZ induces a dose-dependent depolarization of the membrane potential of individual PMNs. These results also demonstrate that increasing concentrations of STZ can induce increasing PMN responses even when all of the PMNs have been activated. These results are consistent with the hypothesis that receptor-mediated particulate stimulation of PMNs is a phenomenon that results in graded PMN responses.     

Alfentanil co-induction for laryngeal mask insertion

We assessed the effect of two different doses of alfentanil (5 and 10 micrograms.kg-1) on the conditions for laryngeal mask airway insertion in ASA 1 and 2 patients who received propofol for induction of anaesthesia. One hundred and fifty unpremedicated patients were randomly allocated to receive either propofol 2.5 mg.kg-1 only (Group P), alfentanil 5 micrograms.kg-1 and propofol 2.5 mg.kg-1 (Group A5), or alfentanil 10 micrograms.kg-1 and propofol 2.5 mg.kg-1 (Group A10). The addition of alfentanil to propofol resulted in a greater ease of insertion and a better quality of airway patency. Pretreatment with alfentanil also resulted in a significantly higher success rate during the first attempt at inserting the laryngeal mask airway compared with Group P (Group P 58%, Group A5 96%, Group A10 94%). Patients in Group P were apnoeic for a mean (+/- SD) time of 3.3(+/- 1.9) min, 4.71 (+/- 2.2) min in Group A5, and 7.32(+/- 4.3) min in Group A10. The use of alfentanil 10 micrograms.kg-1 with propofol, however, led to a significant decrease in mean arterial pressure and heart rate. We concluded that pretreatment with intravenous alfentanil 5 micrograms.kg-1 prior to propofol provides excellent conditions for insertion of laryngeal mask with minimal adverse haemodynamic changes.     

Quantitative Shear Wave Elastography as a Prognostic Implication of Papillary Thyroid Carcinoma (PTC): Elasticity Index Can Predict Extrathyroidal Extension (ETE)

Objective

To investigate whether the quantitative elasticity index of shear wave elastography (SWE) can predict extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) preoperatively.

Methods

A total of 208 patients with pathology confirmed PTC whom underwent SWE during preoperative staging US between April 2011 to June 2012 were included.SWE indices of E _mean, E _max, E _min of the index malignancy, the ratios between E _mean of the lesion and parenchyma (E _ratio-P), and muscle (E _ratio-M), and grayscale US findings, including ETE, multifocality, bilaterality, and central and lateral lymph node (LN) metastasis were evaluated. The correlations of SWE indices and grayscale US findings with pathologic prognostic factors of PTC were analyzed by Chi square or Fisher’s exact test, and multivariate regression analysis.

Results

ETE was associated with E _mean, E _max, E _min, and E _ratio-M (P = 0.005, 0.009, 0.016 and <0.001, respectively), multifocality was associated with E _mean, E _max, and E _min (P = 0.028, 0.007, and 0.004, respectively), and central LN metastasis was associated with E _ratio-M (P = 0.03). On multivariate analysis, E _mean and E _min were independent factors for predicting ETE (P = 0.032, 0.049, respectively).

Conclusions

Quantitative elasticity index of SWE could predict pathologic ETE, and SWE could be a complimentary method to grayscale US for preoperative prediction of prognostic factors of PTC.     

Men suffer more complications from diabetes than women despite similar glycaemic control and a better cardiovascular risk profile: the ADCM study 2008

BackgroundGender differences in glycaemic control and diabetes’ complications have been well studied overseas but not locally. Gender is one of the non-modifiable factors for the diabetes patient but it is an important factor for effective personalized diabetes care. This paper examined the gender differences in glycaemic control and diabetes’ complications.MethodsThis was a registry-based observational study from May–December 2008. An online standard case record form was available for site data providers to register their diabetes patients aged 18 years old and above annually. Demographic data, diabetes duration, treatment modalities, as well as various risk factors and diabetes complications were reported. Multivariate analysis was performed.ResultsA total of 20,646 diabetes patients were included. The majority (99.2%) had been diagnosed with type 2 diabetes mellitus (T2D); 42.8% of the sample were men; 57.1% were Malay. The mean age was 58.0 years (standard deviation (SD) = 11.49) with 77.6% of the sample being 50 years old and above. Despite similar diabetes control (HbA1c < 6.5%), females suffered more microvascular complications (estimated glomerular filtration rate (eGFR) <60 mls/min: X² = 753.54, P = <0.001) while men suffered more from macrovascular complications (ischaemic heart disease (X² = 57.61, P = <0.001) and stroke (X² = 13.87, P = <0.001)). Multivariate logistic regression analyses showed that T2D men were more likely to suffer from stroke (odds ratio (OR) = 1.21, 95% confidence interval (CI) = 0.89–1.64), ischaemic heart disease (OR = 1.55, CI = 1.35–1.78) and nephropathy (OR = 1.59, CI = 1.44–1.75).ConclusionWe observed that men suffered more diabetes-related complications despite similar glycaemic control and better risk factor control. This finding requires further verification from future studies.     

Post-marketing surveillance study of the safety and efficacy of sildenafil prescribed in primary care to erectile dysfunction patients

In order to investigate the safety and efficacy of sildenafil prescribed in primary care, a post-marketing surveillance study was undertaken. A total of 651 men with erectile dysfunction (ED) were enrolled from 31 family physicians in Korea from December 1999 to July 2002. Patients were regularly followed up to ascertain the safety and efficacy of sildenafil. Of the 651 patients enrolled, 572 (87.9%) returned for safety evaluation and efficacy assessment. In all, 458 (80.1%) of 572 patients reported improved erectile function with sildenafil. Hypertension, diabetes and low-dose sildenafil were associated with poor efficacy. A total of 71 adverse events were reported among 56 patients (8.6%), with the most frequent being hot flushes (5.6%), followed by headache (2.6%), palpitation (1.0%), anxiety (0.5%) and elevated ALT (0.5%). Only six patients (1.0%) discontinued sildenafil as a direct result of adverse events. These results suggest that sildenafil prescribed by primary care physicians was well tolerated and improved erectile function in patients with ED.     

Subtle lung cancers: impact of edge enhancement and gray scale reversal on detection with digitized chest radiographs

The authors studied the impact of edge enhancement and gray scale polarity reversal on the detection of subtle lung cancers. Three experienced readers reviewed 46 biopsy-proved subtle lung cancers and 46 normal controls on chest radiographs that had been digitized into a 1,024 X 1,536-pixel matrix 8 bits deep. Receiver-operating characteristics (ROC) analysis of 1,656 pooled observations indicated that performance was best with the unmodified images (ROC area = 0.83), degraded by moderate enhancement of medium frequencies (ROC area = 0.80), and markedly impaired by severe enhancement of low frequencies (ROC area = 0.69). Gray scale polarity reversal further degraded performance (unenhanced ROC area = 0.74; moderately enhanced ROC area = 0.76; severely enhanced ROC area = 0.76). The authors conclude that edge enhancement and gray scale polarity reversal can impair the detectability of subtle lung cancers on digitized radiographs of medium resolution.     

RPA facilitates rejoining of DNA double-strand breaks in an in vitro assay utilizing genomic DNA as substrate

PURPOSE: Replication protein-A (RPA) is a heterotrimeric single-stranded DNA-binding protein playing essential roles in many aspects of nucleic acid metabolism, including DNA replication, nucleotide excision repair and homologous recombination. Here, the role of RPA in the rejoining of radiation-induced DNA double-strand breaks (DSB) by non-homologous end-joining (NHEJ) was investigated. METHODS AND MATERIALS: A previously described in vitro assay for DSB rejoining was employed. The assay used 'naked' genomic DNA prepared from agarose-embedded G(1)-phase A549 cells as a substrate and extracts prepared from HeLa cells as a source of enzymes. Rejoining of DSB in this assay is absolutely dependent on cell extract and proceeds, under optimal reaction conditions, to an extent similar to that observed in intact cells. For experiments, extracts were supplemented with excess purified recombinant RPA. Alternatively, RPA was removed from the extracts either by fractionation or immunodepletion. RESULTS: Although the rejoining of DSB in vitro was not absolutely dependent on RPA, it proceeded faster and to higher levels of completion when recombinant protein was added to the extracts. Depletion of RPA from extracts reduced the rejoining half-times and addition of purified recombinant protein restored the kinetics of DSB rejoining. Extract fractionation indicated the operation of at least two pathways in DSB rejoining, only one of which was facilitated by RPA. CONCLUSIONS: The results suggest that in addition to its role in homologous recombination, RPA may also have a supportive role in some forms of non-homologous end-joining.     

Vancomycin pharmacokinetics in patients with severe burn injuries

Vancomycin is used in patients with severe burns and methicillin-resistant Staphylococcus aureus (MRSA) infection. This study investigated vancomycin pharmacokinetics in people with burns in comparison to people without burns and examined the factors contributing to pharmacokinetic variability. This was a retrospective, case-control study of hospitalised burns patients compared with a control patient cohort administered vancomycin without burn injury. Vancomycin pharmacokinetic parameters were determined using therapeutic drug monitoring data and a population pharmacokinetic modelling approach employing a two-compartment pharmacokinetic model. The impact of patient characteristics on vancomycin clearance was explored. Vancomycin clearance was significantly higher (p < 0.001) in burns patients (5.9 ± 3.1 L/h, n = 37) when compared to control patients (3.4 ± 1.8 L/h, n = 33), as was estimated creatinine clearance, which was correlated to drug clearance in burns patients (r² = 0.64). There was no significant change in volume of distribution between patient groups. The majority of patients received a dosing regimen of 1 g twice daily, resulting in significantly (p = 0.004) lower serum trough concentrations in patients with burns (median, 6.4 mg/L; range, 0.2–22.3 mg/L) than control (median, 9.2 mg/L; range, 4.0–29.8 mg/L). Higher clearance and lower serum vancomycin concentrations in people with severe burn may increase the risk of suboptimal bactericidal action and the development of resistance highlighting the need for dosage individualisation.