[Establishment and validation of a predictive model for neurogenic urinary tract injury in children].

Objective: To establish a predictive model for upper urinary tract damage in children with neurogenic bladder and verify its efficacy. Methods: From January 2011 to December 2021, 143 children with NB in the Children's Hospital of Chongqing Medical University and 84 children with NB in the First Affiliated Hospital of Zhengzhou University were selected as the research objects. The former is set as the training set and the latter is set as the validation set, and the general parameters of the two are compared. The independent risk factors of upper urinary tract damage in children with NB were screened out by Lasso regression, and multivariate logistic regression analysis and a nomogram prediction model was established. The models were validated internally and externally on the training set and validation set, respectively, and the area under the receiver operating curve (ROC) was used to verify the accuracy of the model. Results: A total of 227 children with NB were included in this study, including 121 males and 106 females, aged (10.2±3.8) years. There was no significant difference in other parameters except age between the training set and validation set (all P>0.05); Lasso regression and multivariate logistic regression analysis showed that detrusor leakage point pressure (DLPP) ≥ 40 cmH2O (OR=4.76, 95%CI: 2.01-11.26, 1 cmH2O=0.098 kPa), overactive bladder (OAB) (OR=3.08, 95%CI: 1.34-7.04), bladder compliance (BC)<20 ml/cm H2O (OR=3.65, 95%CI: 1.41-9.47), history of previous urinary tract infection (OR=2.73, 95%CI: 1.09-6.81), and abdominal pressure/other voiding patterns (OR=2.86, 95%CI: 1.20-6.82) were risk factors for upper urinary tract damage in children with NB (all P<0.05). The above parameters were used to establish a nomogram model of upper urinary tract damage in children with NB. The internal and external validation results show that the AUC values for the training and validation sets were 0.84 (95%CI: 0.77-0.91) and 0.86 (95%CI: 0.79-0.94), respectively. Conclusion: The prediction model of upper urinary tract damage in children with NB constructed in this study has high discrimination, accuracy and clinical applicability, which can help clinicians identify high-risk patients and make individualized treatment design for these patients.

[Emulation pulmonary nodules localization model:a novel non-invasive localization technique in resection of pulmonary nodules].

Objective: To explore the accuracy and efficiency of a novel 3D-printed emulation localization model of small pulmonary nodules in lung surgery. Methods: From April 2020 to April 2021, a total of 66 patients were selected in the study, who underwent localization and resection of pulmonary nodules with video-assisted thoracoscopic surgery (VATS) guided by the 3D-printed emulation localization model at Department of Thoracic Surgery, West China Hospital of Sichuan University. There were 13 males and 53 females, aged from 25 to 79 (52.7±11.4) years. Of all patients, 24 (36.4%) had single pulmonary nodule, and 42 (63.6%) had synchronous multiple pulmonary nodules. The chest high-resolution CT image data were utilized for digital reconstruction and 3D printing to make a tailored life-size emulation pulmonary nodules localization model, which was used to navigate real-time intraoperative localization of nodules. Clinical data including operative parameters, localization information, resection types and pathological findings of nodules were analyzed. The pulmonary nodules that doctors planned to resect were categorized into two categories:major nodules and additional nodules, according to their presence of invasion and radiological risk factors. The accuracy of localization and resection efficiency of nodules were evaluated in accordance with the categories of the nodules respectively. Results: On the basis of preoperative evaluation, there were 71 major nodules with median maximal diameter of 0.9 (0.6-1.3) cm, and 77 additional nodules with median maximal diameter of 0.5 (0.4-0.7) cm. All patients underwent VATS surgery, 52 of them (78.8%) were treated with uniportal VATS and 14 (21.2%) with triportal VATS. Among the patients with single nodule, 18 segmentectomies and 6 wedge resections were performed; whereas among the patients with multiple nodules, 5 segmentectomies, 14 wedge resections, and 23 combined pulmonary resections (including 2 cases of lobectomy+segmentectomy, 7 cases of lobectomy+wedge resections, and 14 cases of segmentectomy+wedge resections) were achieved. The median operative time was 93 (45-240) min, and the median resection time for all nodules was 51.4 (6.7-147.0) min. All major nodules were successfully resected and visibly dissected after removal, and all additional nodules were successfully resected with 85.7%(66/77) nodules visibly dissected. The accuracy rate of localization of both types of nodules was 100%. All major nodules were malignant, and the malignancy rate of additional nodules was 21.2%(14/66). Conclusion: This novel 3D-printed emulation localization model of small pulmonary nodules proved to be a non-invasive, accurate and efficient technique. Not only that, it has a unique advantage in localization of synchronous multiple pulmonary nodules.

[A survey on the current development of thoracic surgery in tertiary hospitals of China].

Objective: To study the current development of thoracic surgery in China. Methods: Chinese Society for Thoracic and Cardiovascular Surgery and Chinese Association for Thoracic Surgeons jointly conducted a network survey to directors of thoracic surgery departments in the tertiary hospitals in China from November to December 2018. The contents of the survey included the basic information of the hospital and the status of thoracic surgery department in the hospital. Rank sum test was used to compare the data between different regional hospitals Results: A total of 636 tertiary hospitals participated in the survey. The total number of beds for thoracic surgery departments was 30 646, with M(Q(R)) of 40(20) (range: 3 to 393) for each hospital. The total number of thoracic surgeons was 6 747, with M(Q(R)) of 9(6) (range: 1 to 75) in each hospital. In 2015, a total of 312 425 operations were performed in the 636 hospitals, with M(Q(R)) of 268(484.5) (range: 4 to 8 320) for each hospital. The total number of lung cancer surgeries was 146 601 in 2015, with M(Q(R)) of 100(216) (range: 0 to 6 911) operations in each hospital. The total number of esophageal cancer operations was 67 076, with M(Q(R)) of 40(95) (range: 0 to 1 550) in each hospital. Minimal invasive thoracic surgery was performed in 94.3% (601/636) of the hospitals, with 86.6% (551/636) of hospitals carried out video-assisted thoracoscopic (VATS) lobectomy. Among the hospitals performing VATS lobectomy, 89.3% (492/551) of them started to perform the technique after 2006, and 93.1% (513/551) of them do single-direction thoracoscopic lobectomy. A total of 403 640 VATS lobectomies had been performed until 2015, including 163 682 cases of single-direction thoracoscopic lobectomy. In 2015, 73.74% (108 116/146 601) lung cancer operations and 37.44% (25 110/67 076) of esophageal cancer resections were performed by minimally invasive technique. The development level of hospitals among eastern, middle and Western China was different significantly on number of doctors, number of total operations, number of lung cancer surgeries, proportion of minimally invasive lung cancer surgery, number of esophageal cancer surgeries, and proportion of minimally invasive esophageal cancer surgery (χ(2)∶7.65 to 60.8, all P<0.05). Conclusions: The discipline of thoracic surgery, especially the minimally invasive thoracic surgery in China is now experiencing a rapid development. The proportion of minimally invasive lung cancer surgery is higher than that of in the developed countries. However, unbalanced development among different regions is still a great challenge in China.

[Strategies for the prevention and control of bleeding due to vascular injury in thoracoscopic lung surgery].

The technique of thoracoscopic lung surgery has gradually matured. Nowadays, thoracoscope is recommended as the most preferred approach for surgical treatment of early stage non-small cell lung cancer in different guidelines. However, there are still some cases of accidential major bleeding due to vascular injury during thoracoscopic lung surgery. The wall of the hilum vessels is relatively thin. These vessels often involve a great portion of the cardiac output blood flow. Once the injury happened, the emergent condition may be life-threatening due to massive blood loss. Therefore, this became an important factor which hindered the development of thoracoscopic lung surgery. In this review, details of the vascular injury in thoracoscopic lung surgery were summarized, including the incidence of vascular injury, commonly injured sites and reasons of the injuries. Among all the cases of thoracoscopic major pulmonary resection, 2.9% to 9.2% may suffer from vascular injury during the operation. The most commonly injuried sites are pulmonary artery and the branches, and this is also the most critical situation during thoracoscopic lung surgery. Hilum adhesion is the most important risk factor for vascular injury. On the one hand, the suction-compressing angiorrhaphy technique was developed for bleeding control and angioplasty. On the other hand, the strategies like pre-control of the pulmonary, cut the bronchus in advance, and fire the bronchus and pulmonary artery together may decrease the incidence of vascular injury in patients with risk factors.

[Clinical observation and related factors analysis of neonatal asphyxia complicated with retinal hemorrhage].

Objective: To observe and analyze related factors of neonatal asphyxia complicated with retinal hemorrhage. Methods: It was a retrospective case series. Seven hundred and twenty-one cases with neonatal asphyxia after 72 hours of birth were enrolled in this study. Fundus examination was performed on these newborns using the third generation wide-angle digital retina imaging system (RetCamⅢ), and the bleeding level was divided into level I, level Ⅱ and level Ⅲ. The conditions of the newborn and the mother during pregnancy were correlatively analyzed. The other factors were also analyzed including delivery mode, birth weight, gestational age, gender, grade of neonatal asphyxia, scalp hematoma, intracranial hemorrhage, fetal intrauterine distress, mother's age and antenatal complications. Single factor χ(2) test and multivariate logistic regression analysis were used to screen and judge risk factors causing retinal hemorrhage related to neonatal asphyxia. Results: In 721 cases of neonatal asphyxia, retinal hemorrhage was found in 204 newborns (28.29%). The hemorrhage was at level Ⅰ in 77 cases (37.75%) , at level Ⅱ in 38 cases (18.63%) and at level Ⅲ in 89 cases (43.63%) . Four cases also had vitreous hemorrhage. Asphyxia was mild in 673 infants (93.34%) and severe in 48 infants (6.66%). The difference in the degree of retinal hemorrhage between the patients with mild and severe asphyxia was significant (χ(2)=22.336, P=0.000). When asphyxia was aggravated, the degree of retinal hemorrhage increased. Relative factors analysis showed that delivery mode (χ(2)=158.643, P<0.05), gestational age (χ(2)=24.522, P<0.05), birth weight (χ(2)=11.916, P<0.05) and grade of neonatal asphyxia (χ(2)=19.809, P<0.05) had correlations with retinal hemorrhage. Logistic regression analysis indicated that grade of neonatal asphyxia and delivery mode were risk factors of retinal hemorrhage in neonatal asphyxia (OR=0.304, 0.085). Conclusion: The incidence of retinal hemorrhage in neonatal asphyxia was 28.29%. The degree of neonatal asphyxia and delivery mode may play roles in the occurrence of retinal hemorrhage in newborns with asphyxia. With aggravation of asphyxia, the degree of retinal hemorrhage may increase. (Chin J Ophthalmol, 2017, 53: 358-362).

Different sources of maternal selenium affect selenium retention, antioxidant status, and meat quality of 56-day-old offspring of broiler breeders.

The maternal effect of different Se source in offspring of young broiler breeders has been reported, but the lasting maternal effect of different sources of Se on offspring of breeders has received limited attention, so this study was conducted to investigate the effects of different maternal Se sources on Se retention, antioxidant status, and meat quality of 56-d-old offspring of broiler breeders. A total of two hundred forty 39-wk-old Lingnan Yellow broiler breeders were randomly distributed into 2 treatments, each of which was replicated 3 times with 40 birds per replicate, with a 14-d pretreatment and 56-d trial period. The treatments were fed a basal corn-soybean diet (0.04 mg∙kg⁻¹ Se) supplemented with 0.3 mg∙kg⁻¹ sodium selenite (SS) or selenomethionine (Se-Met). Fertile eggs were collected for incubation, after which 180 healthy chicks from each treatment were selected and randomly allocated into 3 replicates, with 60 birds per replicate. All the chicks were fed the same basal diet (0.04 mg∙kg⁻¹ Se) for 56 d. The Se concentrations in serum and tissues (liver, kidney, and breast muscle) of the 56-d-old offspring were significantly (P < 0.01) increased by maternal Se-Met intake compared with maternal SS intake. The antioxidant status of the 56-d-old offspring was greatly improved by maternal Se-Met supplementation in contrast with maternal SS supplementation, which was shown by increased glutathione peroxidase activity in serum and breast muscle (P < 0.01), glutathione concentration in serum (P < 0.05), and total antioxidant capability in pancreas (P < 0.01), as well as cytosolic glutathione peroxidase mRNA abundance in breast muscle, liver (P < 0.01), and pancreas (P < 0.05). The maternal Se-Met treatment was more effective in maintaining the shape of liver and pancreas cells, cell nuclei, chromatin, as well as cell membrane structure, and more organelles were observed in liver cells. The maternal Se-Met treatment had significant (P < 0.05) reduced the 48-h drip loss of 56-d-old offspring in comparison with maternal SS treatment. The results suggest that maternal Se-Met diet is superior to maternal SS diet in increasing Se retention and improving antioxidant status and meat quality of 56-d-old offspring.

Simultaneous operation of concomitant diseases in the esophagus and lung.

The aim of this study was to retrospectively review our experience of performing simultaneous operations on concomitant diseases in the esophagus and lungs. From January 1998 to July 2009, simultaneous operations were performed on 13 patients with concomitant esophageal and pulmonary diseases, using coordinated surgical approaches. Among the 13 patients, six had primary cancers in the esophagus and lungs, five had primary esophageal cancer accompanied by a benign pulmonary disease, one had benign diseases in both esophagus and lung, and one had primary esophageal cancer with metastasis to the left lower lung. All patients survived the operations. Two major complications occurred postoperatively. One complication was bronchopleural fistula and the other was intrathoracic gastric laceration. Both patients recovered after additional treatments. Simultaneous operation of concomitant diseases in the esophagus and lungs is feasible and safe in selected patients who have received careful preoperative assessment, well-designed surgical approach, and proper perioperative management.

Minimally invasive surgery for congenital diaphragmatic hernia: a meta-analysis.

OBJECTIVES: To compare the safety and efficacy of minimally invasive surgery (MIS) with traditional open surgical approach for congenital diaphragmatic hernia (CDH). METHODS: A literature search was performed using the PubMed database, Embase, and the Cochrane central register of controlled trials using a defined set of criteria. The outcomes, which include post-operative mortality, incidence of hernia recurrence, rates of patch use and complications, were analyzed. RESULTS: We investigated nine studies, which included 507 patients. All studies were non-randomized historical control trials. The MIS group had a significantly lower rate of post-operative death with a risk ratio of 0.26 [95% confidence interval (CI) 0.10-0.68; p = 0.006] but a greater incidence of hernia recurrence with a risk ratio of 3.42 (95% CI 1.98-5.88; p < 0.00001). Rates of prosthetic patch use were similar between the two groups. Fewer cases of surgical complications were found in the MIS group with a risk ratio of 0.66 (95% CI 0.47-0.94; p = 0.02). CONCLUSIONS: MIS for CDH repair is associated with lower post-operative mortality and morbidity compared with traditional open repair. Although rate of patch use appears to be comparable, the increased risk of CDH recurrence should not be ignored. The lack of well-controlled prospective trials still limits strong evaluations of the two surgical techniques.

HBV-induced ROS accumulation promotes hepatocarcinogenesis through Snail-mediated epigenetic silencing of SOCS3.

Interleukin-6 (IL-6) has been demonstrated to be involved in Hepatitis B virus (HBV)-associated hepatocarcinogenesis through activation of the STAT3 pathway. The sustained activation of the IL-6/STAT3 pathway is frequently associated with repression of SOCS3, which is both a target gene and a negative regulator of STAT3. However, the silencing mechanism of SOCS3 in hepatocellular carcinoma (HCC) remains to be elucidated. Here, we showed that the repression of SOCS3 and sustained activation of IL-6/STAT3 pathway in HBV-producing HCC cells were caused by HBV-induced mitochondrial ROS accumulation. Mechanistic studies revealed that ROS-mediated DNA methylation resulted in the silencing of SOCS3. Decreased SOCS3 expression significantly promoted the proliferation of HCC cells and growth of tumor xenografts in mice. Further studies revealed that HBV-induced ROS accumulation upregulated the expression of the transcription factor, Snail, which bound to the E-boxes of SOCS3 promoter and mediated the epigenetic silencing of SOCS3 in association with DNMT1 and HDAC1. In addition, we found that the expression of Snail and SOCS3 were inversely correlated in HBV-associated HCC patients, suggesting that SOCS3 and/or Snail could be used as prognostic markers in HCC pathogenesis. Taken together, our data show that HBV-induced mitochondrial ROS production represses SOCS3 expression through Snail-mediated epigenetic silencing, leading to the sustained activation of IL-6/STAT3 pathway and ultimately contributing to hepatocarcinogenesis.

Enhancement of radiosensitivity in human malignant glioma cells by hypericin in vitro.

Hypericin, an antidepressant and antiviral agent being evaluated in phase I and II trials for patients with HIV infection, is known to be a potent protein kinase C inhibitor. We have investigated its effects on cellular response to radiation via a tetrazolium-formazan cell growth rate assay using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and clonogenic assay in three human glioblastoma cell lines, U87-MG, A-172, and T98G, and a low-passage malignant glioma culture, 93-492. At a concentration of 5 microM, hypericin inhibited these cells slightly but caused significant radiosensitization (e.g., the cell survival rate after the radiation treatment was 50.2 and 26.0% in cells treated with 6 Gy and 6 Gy plus 5 microM hypericin in U87-MG cells, respectively; P = 0.0285). Hypericin also enhanced the radiosensitivity significantly in the low-passage glioma 93-492 cells. These findings suggest that hypericin represents a potential new agent in combination with radiation therapy of malignant gliomas.

Relationship between inward rectifier potassium current impairment and brain injury after cerebral ischemia/reperfusion.

Functional alterations of barium-sensitive potassium inward rectifier (KIR) current, which is involved in the vasodilation of middle cerebral arteries (MCA) in rat brain, have been described during brain ischemia/reperfusion (I/R). The authors investigate the effects of I/R on KIR current recorded in isolated myocytes from MCA of control rats and from contralateral and ipsilateral MCA of ischemic rats by the whole-cell patch-clamp technique, and the relationship between its alteration and the severity of brain injury. The vascular smooth muscle cells exhibited similar morphologic features in all conditions, and the KIR was present in the three groups of myocytes, exhibiting a characteristic inward rectification and a normal external potassium dependence. The KIR density was significantly reduced in cell of MCA ipsilateral to occlusion with a maximum at -135 mV, whereas there was no difference between control and contralateral cells. This alteration in KIR density in occluded MCA was significantly correlated with severity of brain injury and brain edema. These results suggest that the alteration of KIR density in MCA myocytes after I/R and the consecutive impaired dilation of MCA may contribute to aggravation of the brain injury.

Increase in endogenous brain superoxide dismutase as a potential mechanism of lipopolysaccharide-induced brain ischemic tolerance.

A low dose (0.5 mg/kg) of lipopolysaccharide (LPS), administered 72 hours before 60-minute middle cerebral artery occlusion, induced a delayed neuroprotection proven by the significant decrease (-35%) of brain infarct volume in comparison with control, whereas infarct volumes remained unchanged in rats treated 12, 24, or 168 hours before ischemia. This delayed neuroprotective effect of LPS was induced only with low doses (0.25 to 1 mg/kg), whereas this effect disappeared with a higher dose (2 mg/kg). The delayed neuroprotection of LPS was induced in the cortical part of the infarcted zone, not in the subcortical part. The beneficial effect of LPS on consequences of middle cerebral artery occlusion was suppressed by dexamethasone (3 mg/kg) and indomethacin (3 mg/ kg) administered 1 hour before LPS, whereas both drugs had no direct effect on infarct volume by themselves, suggesting that activation of inflammatory pathway is involved in the development of LPS-induced brain ischemic tolerance. Preadministration of cycloheximide, an inhibitor of protein synthesis, also blocked LPS-induced brain ischemic tolerance suggesting that a protein synthesis is also necessary as a mediating mechanism. Superoxide dismutase (SOD) could be one of the synthesized proteins because lipopolysaccharide increased SOD brain activity 72 hours, but not 12 hours, after its administration, which paralleled the development of brain ischemic tolerance. In contrast, catalase brain activity remained unchanged after LPS administration. The LPS-induced delayed increase in SOD brain content was suppressed by a previous administration of indomethacin. These data suggest that the delayed neuroprotective effect of low doses of LPS is mediated by an increased synthesis of brain SOD that could be triggered by activation of inflammatory pathway.

Conformal episcleral plaque therapy.

PURPOSE: Episcleral plaque therapy (EPT) with sealed 125I sources is widely used in the treatment of choroidal melanoma. In EPT, as elsewhere in radiotherapy, concern for normal tissue tolerance has frequently been a dose-limiting factor. The concept of conformal therapy, which seeks to improve dose homogeneity within the tumor and greatly reduce the dose to uninvolved structures may provide a solution to this problem. Radioactive sources are typically distributed uniformly over the surface of an episcleral plaque and are sometimes offset slightly from the scleral surface to reduce the dose to the sclera relative to the apex and prescribed therapeutic margin at the tumor base. Nevertheless, it is not uncommon for scleral dose to exceed the dose to the apex of intermediate to tall tumors by a factor of 4 or more. The availability of low-energy sealed sources such as 125I prompted the development of gold-backed plaques to shield noninvolved periocular tissues. The concept of shielding can be extended to include collimation of individual sources. The potential advantages of individual source collimation include reduced scleral dose, more homogeneous tumor dose, and superior shielding of adjacent normal structures such as the fovea as compared to previous plaque designs. METHODS AND MATERIALS: A three-dimensional treatment-planning system has been extended to design a plaque that incorporates individually collimated 125I sources. Thermoluminescent dosimetry (TLD) and radiochromic film were used to compare calculated dose-rate distributions with measured dose rates in an acrylic phantom. RESULTS: Calculations predict that source collimation in the form of a "slotted" gold plaque will achieve the purposes of the study. The collimating effect of the slots is demonstrated qualitatively using radiochromic film, and the accuracy of the calculation is demonstrated quantitatively with TLD. CONCLUSION: The episcleral plaque described in this report is simpler to assemble than previous plaque designs. It produces a more homogeneous dose distribution in the tumor, reduces scleral dose by up to 50% as compared to conventional designs, and significantly reduces radiation dose to uninvolved structures adjacent to the plaque.

Structure-activity relationships of N6-benzyladenosine-5'-uronamides as A3-selective adenosine agonists.

Adenosine analogues modified at the 5'-position as uronamides and/or as N6-benzyl derivatives were synthesized. These derivatives were examined for affinity in radioligand binding assays at the newly discovered rat brain A3 adenosine receptor and at rat brain A1 and A2a receptors. 5'-Uronamide substituents favored A3 selectivity in the order N-methyl > N-ethyl approximately unsubstituted carboxamide > N-cyclopropyl. 5'-(N-Methylcarboxamido)-N6-benzyladenosine was 37-56-fold more selective for A3 receptors. Potency at A3 receptors was enhanced upon substitution of the benzyl substituent with nitro and other groups. 5'-N-Methyluronamides and N6-(3-substituted-benzyl)adenosines are optimal for potency and selectivity at A3 receptors. A series of 3-(halobenzyl)-5'-N-ethyluronamide derivatives showed the order of potency at A1 and A2a receptors of I approximately Br > Cl > F. At A3 receptors the 3-F derivative was weaker than the other halo derivatives. 5'-N-Methyl-N6-(3-iodobenzyl)adenosine displayed a Ki value of 1.1 nM at A3 receptors and selectivity versus A1 and A2a receptors of 50-fold. A series of methoxybenzyl derivatives showed that a 4-methoxy group best favored A3 selectivity. A 4-sulfobenzyl derivative was a specific ligand at A3 receptors of moderate potency. An aryl amino derivative was prepared as a probe for radioiodination and receptor cross-linking.

Effect of lignocaine in myocardial contusion: an experiment on rabbit isolated heart.

1. The reported incidence of myocardial contusion after blunt chest trauma varies from 16 to 76%. Of these patients, about 6% present a severe, life threatening contusion. We used an isolated heart preparation to examine the effect of lignocaine on myocardial performance after contusion. 2. Thirty hearts obtained from male New Zealand rabbits were perfused at constant flow according to the Langendorff technique and were divided into four groups. The following parameters were measured at frequent intervals for 60 min: mean coronary perfusion pressure (CPP), left ventricular diastolic pressure (LVDP), developed pressure (DP), dP/dtmax, dP/dtmin. 3. Group 1 (n = 6) served as control, group 2 (n = 7) received lignocaine for 20 min (15 microM for the first 10 min and 30 microM for the following 10 min), group 3 (n = 9) had a contusion leading to a 30-50% decrease in dP/dtmax and group 4 (n = 8) had the contusion and the lignocaine infusion was started 10 min after the contusion and stopped after 30 min. Lignocaine concentration was measured in the effluent. 4. Lignocaine alone moderately decreased contractility in group 2. In group 3, after contusion, DP, dP/ dtmax, and dP/dtmin were markedly decreased during the 60 min recording period. In group 4, lignocaine infusion rapidly restored contractility. DP, dP/dtmax and dP/dtmin returned towards their basal values. This improvement of contractility remained stable, even after lignocaine infusion was discontinued. 5. In our rabbit isolated heart preparation, lignocaine at a low therapeutic concentration was able to restore contractility after contusion. These results need to be confirmed by other studies but this may lead to promising therapeutic intervention.

In vitro assessment of melphalan induced cytotoxicity and interstrand-DNA-cross-links in lymphocytes from patients with lymphoproliferative disorders.

The relationship between in vitro cytotoxicity and melphalan induced interstrand-DNA-cross-linking was studied in lymphocytes from healthy persons and from patients with a variety of lymphoproliferative disorders. Interstrand-DNA-cross-link formation, as measured by ethidium bromide fluorescence assay showed a highly significant correlation with in vitro cytotoxicity in normal lymphocytes an in those from patients with lymphoproliferative disorders. However, the melphalan concentration at which such cross-linking occurred, differed significantly when normal lymphocytes and those in patients with lymphoproliferative disorders were compared. The kinetics of interstrand-DNA-cross-link formation and removal following treatment with melphalan also differed, with lymphocytes from patients with lymphoproliferative disorders, particularly those having had prior alkylating agent exposure, showing a more rapid rate of disappearance of cross-links as compared to normal lymphocytes. These findings suggest an increased rate of DNA repair occurring in lymphocytes from patients with lymphoproliferative disorders. In a clinical correlation study in vitro melphalan resistance correlated with in vivo resistance to treatment with alkylating agent based chemotherapy. These results suggest a rapid and simple method for determining alkylator resistance in patients with lymphoproliferative disorders.

Serum ICAM-1 concentrations following conventional dose consolidation chemotherapy for acute myeloid leukemia and after high dose chemotherapy with autologous haematopoietic stem cell rescue.

Serum concentrations of soluble ICAM-1 (sICAM-1) were studied in patients with acute myeloid leukemia (AML) after conventional dose consolidation chemotherapy and in AML and in breast cancer patients following high dose chemotherapy with autologous haematopoietic stem cell transplantation. Investigations were carried out at 3 phases following treatment; during the chemotherapy induced neutropenic phase (neutrophil counts <0.5x109/l); during early recovery (neutrophil counts 0.5x109/l-1.0x109/l); and at recovery from neutropenia (neutrophil count 1.0x109/l-2.5x109/l). Results showed a significant elevation of serum levels of sICAM-1, above normal, in both groups of patients during the neutropenic phase. A further increase of sICAM-1 was found in conventional dose consolidation chemotherapy treated AML patients during the post-neutropenia recovery phases. By contrast, patients who were treated with high dose chemotherapy plus autologous haematopoietic stem cell transplantation showed a normalisation of sICAM-1 concentration during the post-neutropenic recovery phases. These findings suggest that recovery of neutrophil function do not coincide with recovery of neutrophil count following intensive chemotherapy while rapid recovery of neutrophil function occurred among patients who received autologous haematopoietic stem cell support.

Expression of CD11b/CD18 on neutrophils after consolidation chemotherapy for acute myeloid leukemia and after high dose chemotherapy with autologous haematopoietic stem cell transplantation.

Quantitative expression of neutrophil CD11b/CD18 following chemotherapy (either conventional dose consolidation chemotherapy or high dose chemotherapy with autologous stem cell transplantation) was investigated during the early recovery phase (neutrophil count 0. 5-1.0x109/l) and at full recovery (neutrophil count 1.0-2.5x109/l) following treatment. CD11b/18 expression was normal in stem cell transplantation supported patients during both early and full neutrophil recovery. By contrast CD11b/CD18 expression was markedly decreased in patients who received chemotherapy without stem cell support. These results suggest that recovery of neutrophil count may not always coincide with recovery of neutrophil function and that G-CSF stimulated peripheral stem cell transplantation enhances neutrophil function post chemotherapy.