Clinical and radiographic effectiveness of mineral trioxide aggregate (MTA) partial pulpotomy with low power or high power diode laser irradiation in deciduous molars: a randomized clinical trial

Lasers in Medical Science - This study investigated the clinical and radiographic effectiveness of MTA partial pulpotomy with low power or high power diode laser irradiation in primary molars. In...     

Gaucher disease: different clinical manifestations associated with a rare mutation (R48W) in a Lebanese family

Gaucher disease (GD) is the most frequently encountered lysosomal storage disease, caused by autosomal recessive inborn defects in the glucocerebrosidase gene (GBA) at 1q21. The disease is most common in the Ashkenazi Jewish population. GD can present with a vast phenotypic heterogeneity, which can be predicted to some extent from the underlying mutation. In this report, we describe a Lebanese Arab family with multigenerational incidence of GD caused by a heterozygous genotype of a rare mutation, R48W, and a common one, L444P. Our patients' clinical course is described. We also review the English literature for patients with this rare mutation.     

应用诱导缓解及干细胞疗法治疗急性早幼粒细胞白血病的治疗策略特点

目的:全反式维甲酸、砷剂(三氧化二砷、复方黄黛片)、化疗治疗的联合应用明显提高了急性早幼粒细胞白血病的完全缓解率,缓解后治疗则进一步提高了长期生存率,但治疗方案及治疗时间仍存在争议,本文对此进行综述。资料来源:应用计算机检索Medline和CNKI 1992-01/2007-02期间的相关文献,检索词为"白血病、早幼粒细胞、急性、治疗、干细胞、移植,leukemia,promyelocytic,acute,therapy,stem cells,transplantation"。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:与急性早幼粒细胞治疗相关。排除标准:重复研究。资料提炼:共收集到361篇相关文献,41篇文献符合纳入标准,排除的320篇文献为内容陈旧或重复的文献。资料综合:临床分别采用全反式维甲酸、三氧化二砷、复方黄黛片或化疗治疗急性早幼粒细胞白血病,全反式维甲酸、三氧化二砷、复方黄黛片完全缓解率达60%～98%,联合化疗可提高具有高危因素患者的缓解率达90%。联合用药进行完全缓解后治疗可降低复发率,提高无病生存率,但治疗时间短者,其复发率较高,以采用长程治疗(时间大于6年)者5年无病生存率高达48%,而造血干细胞移植者5年无病生存率更可达100%。结论:全反式维甲酸或砷剂单独应用及其联合化疗治疗急性早幼粒细胞白血病均可获得较高的完全缓解率,全反式维甲酸或砷剂联合化疗和造血干细胞移植可进一步降低复发率,提高完全缓解率,以长程治疗和干细胞移植疗效较好。     

Internal podalic version for neglected shoulder presentation with fetal demise

In modern obstetrics, the role of internal podalic version (IPV) is limited to delivery of the second twin. A retrospective study was conducted to assess the efficacy of IPV in singleton neglected shoulder presentation with fetal demise. Women with live fetuses, previous CS or contracted pelvis were excluded. The procedure involved repositioning the prolapsed hand under anaesthetic followed by breech extraction. 12 women were identified over a 19 month period and all underwent successful IPV. One woman had a postpartum haemorrhage. We conclude that, in singleton pregnancies with a transverse lie, IPV has a role to play in the delivery of dead fetuses.     

Integrating circulating-free DNA (cfDNA) analysis into clinical practice: opportunities and challenges

In the current era of precision medicine, the identification of genomic alterations has revolutionised the management of patients with solid tumours. Recent advances in the detection and characterisation of circulating tumour DNA (ctDNA) have enabled the integration of liquid biopsy into clinical practice for molecular profiling. ctDNA has also emerged as a promising biomarker for prognostication, monitoring disease response, detection of minimal residual disease and early diagnosis. In this Review, we discuss current and future clinical applications of ctDNA primarily in non-small cell lung cancer in addition to other solid tumours.Subject terms: Cancer, Biomarkers     

Influence of two different resection techniques (conventional liver resection versus anterior approach) of liver metastases from colorectal cancer on hematogenous tumor cell dissemination – prospective randomized multicenter trial

Background

Preoperative radiotherapy of the pelvic abdomen presents with complications mostly affecting the small bowel. The aim of this study was to define the features of early radiation-induced injury on small bowel.

Methods

54 mice were divided into two groups (36 irradiated and 18 sham irradiated). Animals were placed on a special frame and (in the radiated group) the exteriorized segment of ileum was subjected to a single absorbed dose of 19 or 38 Gy radiation using 6 MV high energy photons. Specimens were collected for histology, immunohistochemistry (IHC) and ELISA analysis after 2, 24 and 48 hours. Venous blood was collected for systemic leucocyte count in a Burker chamber.

Results

Histology demonstrated progressive infiltration of inflammatory cells with cryptitis and increased apoptosis. MIP-2 (macrophage inflammatory protein) concentration was significantly increased in irradiated animals up to 48 hours. No significant differences were observed in IL-10 (interleukin) and TNF-α (tumour necrosis factor) levels. IHC with CD45 showed a significant increase at 2 hours of infiltrating leucocytes and lymphocytes after irradiation followed by progressive decrease with time. Caspase-3 expression increased significantly in a dose dependent trend in both irradiated groups up to 48 hours.

Conclusion

Acute small bowel injury caused by local irradiation is characterised by increased apoptosis of crypt epithelial cells and by lymphocyte infiltration of the underlying tissue. The severity of histological changes tends to be dose dependent and may affect the course of tissue damage.     

Optimal dose of pre-incision/post-incision gabapentin for pain relief following lumbar laminectomy: a randomized study

Background: Gabapentin has been introduced as an effective agent for post‐operative pain control. This study aimed to test the effects of pre‐ and post‐incision administration of different doses of gabapentin on post‐operative morphine requirement and pain following lumbar laminectomy. Methods: In this randomized clinical trial, 175 patients were allocated into seven groups of 25 patients each to receive placebo or gabapentin 600, 900 or 1200 mg pre‐ or post‐incision. Total patient‐controlled intravenous morphine consumption during the first 24 post‐operative hours, and the time to the first demand for morphine were recorded. Pain score at rest (visual analogue scale) was recorded every 30 min in the first 4 h and then every 2 h until 24 h post‐operatively. Side‐effects were observed. Results: In the first 12 h, morphine consumption was less, pain scores were lower and the time to the first demand for analgesia was longer in groups receiving gabapentin 900 or 1200 mg either pre‐ or post‐incision, compared with placebo and gabapentin 600 mg (P<0.001). There was no difference between gabapentin 900 and 1200 mg. Pain score, morphine consumption and time to the first demand for analgesia in equal pre‐ or post‐incision doses of gabapentin were not significantly different. No differences in the side‐effects were observed between groups. Conclusion: Gabapentin 900 or 1200 mg, administered either pre‐ or post‐incision, was found to be effective in pain management following lumbar laminectomy. Similar doses of gabapentin provide the same post‐operative analgesia whether administered pre‐ or post‐incision.     

Ca2+/calcineurin regulation of cloned vascular KATP channels: crosstalk with the protein kinase A pathway

Background and purpose:

Vascular ATP-sensitive potassium (K_ATP) channels are activated by cyclic AMP elevating vasodilators through protein kinase A (PKA). Direct channel phosphorylation is a critical mechanism, though the phosphatase opposing these effects is unknown. Previously, we reported that calcineurin, a Ca²⁺-dependent phosphatase, inhibits K_ATP channels, though neither the site nor the calcineurin isoform involved is established. Given that the type-2 regulatory (RII) subunit of PKA is a substrate for calcineurin we considered whether calcineurin regulates channel activity through interacting with PKA.

Experimental approach:

Whole-cell recordings were made in HEK-293 cells stably expressing the vascular K_ATP channel (K_IR6.1/SUR2B). The effect of intracellular Ca²⁺ and modulators of the calcineurin and PKA pathway on glibenclamide-sensitive currents were examined.

Key results:

Constitutively active calcineurin Aα but not Aβ significantly attenuated K_ATP currents activated by low intracellular Ca²⁺, whereas calcineurin inhibitors had the opposite effect. PKA inhibitors reduced basal K_ATP currents and responses to calcineurin inhibitors, consistent with the notion that some calcineurin action involves inhibition of PKA. However, raising intracellular Ca²⁺ (equivalent to increasing calcineurin activity), almost completely inhibited K_ATP channel activation induced by the catalytic subunit of PKA, whose enzymatic activity is independent of the RII subunit. In vitro phosphorylation experiments showed calcineurin could directly dephosphorylate a site in Kir6.1 that was previously phosphorylated by PKA.

Conclusions and implications:

Calcineurin Aα regulates K_IR6.1/SUR2B by inhibiting PKA-dependent phosphorylation of the channel as well as PKA itself. Such a mechanism is likely to directly oppose the action of vasodilators on the K_ATP channel.British Journal of Pharmacology (2009) 157, 554–564; doi:10.1111/j.1476-5381.2009.00221.x; published online 7 May 2009This article is commented on by Tammaro, pp. 551–553 of this issue and is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Does perioperative prostaglandin E1 affect survival of patients with esophageal cancer?

AIM: To detect the effect of intraoperative prostaglandin E1 (PGE1) infusion on survival of esophagectomized patients due to cancer.METHODS: In this preliminary study, a double blinded placebo based clinical trial was performed. Thirty patients with esophageal cancer scheduled for esophagectomy via the transthoracic approach were randomized by a block randomization method, in two equal groups: PGE1 group - infusion of PGE1 (20 ng/kg per minute) in the operating room and placebo group - saline 0.9% with the same volume and rate. The infusion began before induction of anesthesia and finished just before transfer to the intensive care unit. The patients, anesthetist, intensive care physicians, nurses and surgeons were blinded to both study groups. All the patients were anesthetized with the same method. For postoperative pain control, a thoracic epidural catheter was placed for all patients before induction of anesthesia. We followed up the patients until October 2010. Basic characteristics, duration of anesthesia, total surgery and thoracotomy time, preoperative hemoglobin, length of tumor, grade of histological differentiation, disease stage, number of lymph nodes in the resected mass, number of readmissions to hospital, total duration of readmission and survival rates were compared between the two groups. Some of the data originates from the historical data reported in our previous study. We report them for better realization of the follow up results.RESULTS: The patients’ characteristics and perioperative variables were compared between the two groups. There were no significant differences in age (P = 0.48), gender (P = 0.27), body mass index (P = 0.77), American Society of Anesthesiologists physical status more than I (P = 0.71), and smoking (P = 0.65). The PGE1 and placebo group were comparable in the following variables: duration of anesthesia (277 ± 50 vs 270 ± 67, P = 0.86), duration of thoracotomy (89 ± 35 vs 96 ± 19, P = 0.46), duration of operation (234 ± 37 vs 240 ± 66, P = 0.75), volume of blood loss during operation (520 ± 130 vs 630 ± 330, P = 0.34), and preoperative hemoglobin (14.4 ± 2 vs 14.7 ± 1.9, P = 0.62), respectively. No hemodynamic complications requiring an infusion of dopamine or cessation of the PGE1 infusion were encountered. Cancer variables were compared between the PGE1 and placebo group. Length of tumor (11.9 ± 3 vs 12.3 ± 3, P = 0.83), poor/undifferentiated grade of histological differentiation [3 (20%) vs 3 (20%), P = 0.78], disease stage III [5 (33.3%), 4 (26.7%), P = 0.72] and more than 3 lymph nodes in the resected mass [3 (20%) vs 2 (13.3%), P = 0.79] were similar in both groups. All the patients were discharged from hospital except one patient in the control group who died because of a post operative myocardial infarction. No life threatening postoperative complication occurred in any patient. The results of outcome and survival were the same in PGE1 and placebo group: number of readmissions (2.1 ± 1 vs 1.9 ± 1, P = 0.61), total duration of readmission (27 ± 12 vs 29 ± 12, P = 0.67), survival rate (10.1 ± 3.8 vs 9.6 ± 3.4, P = 0.71), overall survival rate after one year [8 (53.3%) vs 7 (47%), P = 0.72], overall survival rate after two years [3 (20%) vs 3 (20%), P = 0.99], and overall survival rate after three years [0 vs 1 (6.7%), P = 0.99], respectively.CONCLUSION: In conclusion, PGE1 did not shorten or lengthen the survival of patients with esophageal cancer. Larger studies are suggested.     

Adnexal and cul-de-sac abnormalities: transvaginal sonography

Sixty-seven patients selectively chosen from 354 undergoing conventional transabdominal (TA) sonography for evaluation of a clinically suspected adnexal mass subsequently underwent transvaginal (TV) sonography either because the TA sonograms were technically suboptimal or because it was not possible to characterize with certainty an abnormality identified with TA sonography. TV sonography added diagnostically useful information in 25 of 28 patients with cystic pathologic changes in the adnexa uteri. Eight of 12 patients with tuboovarian abscess and nonspecific adnexal masses visualized with TA sonography had tube-shaped fluid collections characteristic of pyosalpinx identified with TV sonography. TV sonography added diagnostically useful information in all seven patients with diseases of the cul-de-sac (rectouterine fossa) and allowed differentiation of adnexal from primary uterine disease in three patients with TA sonograms on which findings were equivocal. It also expedited the diagnosis of a tubal pregnancy in ten of 14 patients and was useful in the detection of adhesions and perforated intrauterine devices. These results indicate that adjunctive TV sonography can provide important diagnostic information.