The effect of vascular endothelial cell growth factor on survival of skin flap in rats

In order to study the effect of vascular endothelial cell growth factor (VEGF) on the survival of skin flap 30 SD rats were used. A randomized flap measuring 7.5 cm x 3.0 cm was created on the back of each SD rat. The treatment group (n = 10) received VEGF 40 ng/flap by subcutaneous injection with microinjector during and 24 hours after operation. The control groups received heparin 16 U/flap (n = 10) or normal saline 800 microliters/flap (n = 10). After operation, on the 3rd and 11th day, the survival rate of the skin flaps and the dermovascular density of each flap were investigated by histological and histo-morphometrical examination. The results showed that there was no significant difference in the survival rate between the treatment group and the controls on the 3rd day after operation, while on the 11th day, there was a significant difference between them, and the survival rate was much higher in the treatment group. Besides, dermovascular density was much more increased in the treatment group than that in the controls, especially in the distal 1/3 of the flap (P < 0.02). The conclusion was that VEGF could accelerate the vascularization of the flap and enhance the survival rate of the flap.     

The effect of the suture-induced delay phenomenon on skin flap survival and lipid peroxidation in rats

To assess the prognostic significance of a normal dobutamine-atropine stress echocardiogram in relation to the pretest probability of coronary artery disease (CAD), 200 consecutive patients (86 men and 114 women, mean [SD] age 59 [13] years) with a stable chest pain syndrome and a normal dobutamine-atropine stress echocardiogram were followed-up for 21 +/- 16 months. Outcome events were cardiac death, non-fatal myocardial infarction, and coronary revascularization procedures. Low (<10%), intermediate (10% to 80%), and high (>80%) pretest probabilities of CAD were present in 27 (14%), 108 (54%), and 65 (33%) patients, respectively. During follow-up, 2 patients (annual event rate 0.6%) had cardiac death, none had nonfatal myocardial infarction, and 4 patients (annual event rate 1.1%) underwent a coronary revascularization procedure. All patients with cardiac events had high pretest probabilities of CAD. Patients with cardiac death (but unproven significant CAD) had maximal tests without angina or ischemic electrocardiographic changes. In contrast, all patients with subsequent coronary revascularization had dobutamine-induced angina or ischemic electrocardiographic changes, and all except one study were submaximal. We conclude that patients with a stable chest pain syndrome and normal findings on dobutamine-atropine stress echocardiograms have an excellent cardiac prognosis. However, patients with typical angina, high pre-test probabilities of CAD, and stress-induced angina or ischemic electrocardiographic changes, and in particular those with submaximal stress, still appear to be at risk for functionally important CAD despite a normal dobutamine-atropine stress echocardiogram.     

Substructure in the cell survival response at low radiation dose: effect of different subpopulations

In order to obtain more accurate measurements of cell survival after low doses of radiation, we have used the cell sorter assay, in which a cell sorter is used to accurately count out the number of cells plated for colony formation. This method, combined with data averaging, permits measurements of survival with superior precision, which have revealed that there is substructure in the radiation response of asynchronously dividing Chinese hamster cells. The substructure, observed at doses of a few Gy, has features of a 2-component response, consistent with the presence of subpopulations of cells of different cell-cycle-related radiosensitivity. The absence of any substructure in the radiation response of homogeneous (tightly synchronized) cell populations lends strong support to this subpopulation explanation of the substructure. This assay has also been used on a variety of human tumour cell lines, most of which exhibited substructure similar to that of Chinese hamster cells. This paper outlines the application of the cell sorter assay to three different problems: (i) radiosensitizer mechanisms-etanidazole and RB 6145 are shown to enhance primarily the beta term and alpha term, respectively, of tumour cell kill, indicating that sensitizer efficacy may be tumour-specific and predictable from tumour response parameters; (ii) accurate measurement of Relative Biological Effectiveness (RBE) in a modulated clinical proton beam shows that the RBE is both dose- and depth-dependent; and (iii) measurements at lower doses clearly demonstrate a second order of substructure, termed the hypersensitive response, at doses < 1 Gy.     

The role of 80K/MARCKS, a specific substrate of protein kinase C, in cell growth and tumour progression

Since its discovery more than a decade ago [Wu et al., 1982; Rozengurt et al., 1983], the 80-87 kDa myristoylated alpha lanine-rich C-kinase substrate (80K/MARCKS) protein has attracted a great deal of attention from researchers interested in cell growth and tumour progression. However, despite its ubiquitous distribution, a definitive functional role for 80K/MARCKS has not been found. The purpose of this review is to describe the properties, distribution and regulation of 80K/MARCKS and to discuss some of the most recent findings, both from our laboratory and from others, that have suggested a functional role for this protein in modulating cell growth and tumour progression. Furthermore, I will present data from our laboratory that implicates 80K/MARCKS as a novel tumour suppressor in cells of melanocyte origin.     

Inactivation of ribonucleotide reductase in tumour cells and inhibition of tumour cell growth by p-alkoxyphenols

A significant correlation between the inactivation of the growth-regulating enzyme ribonucleotide reductase (RR) with the growth inhibition of four different tumour cell lines has been found for seven different p-alkoxyphenol derivatives with varying lengths of alkyl side chain. In Novikoff hepatoma and human leukaemia cells, inactivation of RR by p-alkoxyphenols was monitored by electron paramagnetic resonance (EPR) spectroscopy of the catalytically essential tyrosyl radical in the subunit R2 of RR. A significant inhibition of cellular growth of Novikoff hepatoma cells, human leukaemia cells and two human melanoma cell lines (MeWo and M5) by p-alkoxyphenols was also observed by growth inhibition assays. Inactivation of RR in whole tumour cells as well as inhibition of cellular growth of tumour cell lines by p-alkoxyphenols both show an increase in inhibition with increasing length of the alkyl side chain; the most effective inhibitors are p-isobutoxyphenol, p-butoxyphenol and p-propoxyphenol. The enzyme RR, and in particular the catalytically essential tyrosyl radical in the active site, is recognized as an important cellular target for growth inhibition of Novikoff hepatoma cells, human leukaemia cells and melanoma cells by p-alkoxyphenols. Thus, the most potent RR inhibitors-p-isobutoxyphenol, p-butoxyphenol and p-propoxyphenol-may be considered as future antiproliferative drugs for the systemic treatment of melanoma as well as leukaemia and possibly other malignancies.     

The promoting effect of tumour necrosis factor alpha in radiation-induced cell transformation

The aim of this study was to evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite, in the treatment of advanced transitional cell carcinoma of the urinary tract. 35 patients with unresectable or metastatic transitional cell carcinoma of the urinary tract previously treated with a platinum-based regimen were studied. Gemcitabine was administered at a dosage of 1200 mg/m2 as a 30-min intravenous infusion on days 1, 8 and 15, repeated every 28 days. 31 patients were evaluable for efficacy. 4 patients achieved a complete response (12.9%), 3 a partial response (9.6%) and 13 (42%) were stable for at least 4 weeks (overall response 22.5%; 95% confidence interval 8-37%). The median response duration was 11.8 months (range 3.6-17.7 + months) and median survival for all patients entered was 5 months (range 2-21 + months). 2 patients with complete response are still alive with no evidence of disease after 14 and 21 months. Gemcitabine also provided subjective symptomatic relief from pain, cystitis, dysuria, haematuria and peripheral oedema. Patients experienced little WHO grade 3-4 toxicity, with anaemia in 8 patients (23%), thrombocytopenia in 5 (14.2%), leucopenia in 4 (11.4%) and neutropenia in 7 (20%). WHO grade 3-4 hepatic toxicity occurred in 4 patients (11.4%) and transient elevations of transaminase was noted in 3 (8.6%). No patient had WHO grade 3-4 elevation of serum creatinine level. There was no WHO grade 4 symptomatic toxicity and no alopecia was noted. Transient influenza symptoms with gemcitabine occurred in 18 patients (51.4%) with 13 patients (37.1%) experiencing fever (2.9% WHO grade 3). In conclusion, gemcitabine is an new active agent for the treatment of transitional cell carcinoma of the urinary bladder with a mild toxicity profile; it warrants further investigation in combination with cisplatin in chemotherapy naive patients.     

Influence of ionizing radiation on proliferation, c-myc expression and the induction of apoptotic cell death in two breast tumour cell lines differing in p53 status

PURPOSE: To determine the capacity of ionizing radiation to inhibit proliferation, to suppress c-myc expression and to induce apoptotic cell death in the p53 wild-type MCF-7 cell line and the p53 mutated MDA-MB231 cell line. MATERIALS AND METHODS: Growth inhibition and cell killing were determined by cell number and trypan blue exclusion. Apoptosis was assessed through cell morphology and fluorescent end-labelling. c-myc expression was monitored by Northern blotting. RESULTS: Inhibition of cell proliferation by ionizing radiation was similar in both cell lines. MDA-MB231 cells accumulated in G2 while MCF-7 cells accumulated in both the G1 and G2 phases of the cell cycle after irradiation. There was no evidence of apoptosis in either cell line. In MCF-7 cells, growth inhibition correlated closely with an early dose-dependent suppression of c-myc expression; in MDA-MB231 cells, there was no correspondence between growth inhibition and a transient, dose-independent reduction in c-myc message. CONCLUSIONS: These findings suggest that in the absence of classical apoptotic cell death, radiosensitivity is not predictably related to the p53 status of the cell. While both p53 and c-myc may be linked to the DNA damage response pathway, neither p53 nor c-myc are essential for growth arrest in response to ionizing radiation.     

The growth response to tumour necrosis factor alpha of human gynaecological cancer cell lines

Academic computing initiatives rank high on the list of priorities of many dental schools. However, outcomes of academic computing initiatives have not been presented. The objectives of this program evaluation were to: 1) document a strategic initiative for academic computing over a five-year period; 2) assess outcomes; and 3) demonstrate how outcomes assessment changed strategic goals for the future. In 1992, Temple University School of Dentistry developed an academic computing plan. The plan proposed to develop the computer literacy of faculty, teach students the computer skills they need to be successful in their careers, and introduce computer-aided instruction as a new teaching tool. Before a new five-year plan was developed in 1997, the original plan's outcomes were summarily assessed. Assessment instruments included faculty and student surveys, budgets, inventory records, and utilization statistics. The school has reached two of three goals of the 1992 plan. Eighty percent of all full-time faculty have computers, are computer literate, and use computers for a variety of purposes. The school has implemented a comprehensive predoctoral dental informatics curriculum. However, the implementation of computer-aided instruction has not met expectations. Goals of the 1998-2003 plan include establishing an online learning infrastructure, improving student access, implementing computer-based oral health records, and further improving the computer literacy of faculty and students. Planning and supporting academic computing initiatives is a substantial challenge. Factors such as institutional culture, capital investment, ongoing support, and technological change influence plans and their success. While process and structure can be assessed relatively easily, measures for changed educational outcomes are still lacking.     

Experimental study of the effect of intra-abdominal pressure during laparoscopy on tumour growth and port site metastasis

BACKGROUND: The influence of raised intraperitoneal pressure during laparoscopy on tumour growth and port site metastasis is still unknown. METHODS: Tumour growth of colonic adenocarcinoma DHD/K12/TRb was measured after laparoscopy with carbon dioxide at different pressures (0, 5, 10 and 15 mmHg) in a rat model. Cell kinetics were determined after incubation with carbon dioxide (0, 5, 10 and 15 mmHg) in vitro (n=60). Additionally, tumour growth was measured subcutaneously and intraperitoneally 4 weeks after laparoscopy at different intraperitoneal pressures (5, 10 and 15 mmHg) (n=100). RESULTS: In vitro tumour growth decreased significantly after incubation with carbon dioxide at 10 and 15 mmHg compared with a pressure of 0 or 5 mmHg. In vivo, mean(s.d.) intraperitoneal tumour weight was significantly increased after laparoscopy at 5 mmHg (919(1085) mg) and at 10 mmHg (1274(1523) mg) (P< 0.05), but decreased again after laparoscopy with an intraperitoneal pressure of 15 mmHg (731(929) mg) compared with the control group (365(353) mg) (P=0.3). Mean(s.d.) subcutaneous tumour growth was promoted after laparoscopy at 5 mmHg (172(234) mg), at 10 mmHg (190(253) mg) and at 15 mmHg (178(194) mg) compared with controls (48(33) mg) (P < 0.05). CONCLUSION: In vitro, raised intraperitoneal pressure leads to suppression of tumour growth. In vivo, intraperitoneal tumour growth is suppressed only by higher pressure (15 mmHg). Subcutaneous tumour growth is stimulated by carbon dioxide independently of the intraperitoneal pressure.     

The effects of surgical and chemical delay procedures on the survival of arterialized venous flaps in rabbits

The aim of this study was to investigate the efficacy of a surgical delay procedure and a combined surgical and chemical delay procedure on the survival of arterialized venous flaps. Experimental groups included (1) a control group, (2) a surgical delay (4-day and 7-day delay) group, and (3) a combined surgical and chemical (doxazosin mesylate, nitroglycerine patch) delay group. These groups were further divided into subgroups (n = 10) depending on the delay period and the chemical agents. An arterialized venous flap was created on one ear of each rabbit. In the arterialized venous flap, arterial inflow was provided by anastomosis of the central auricular artery to the anterior branch of the central auricular vein and a venous outflow through the anterior marginal vein. In the control group, the arterialized venous flaps without any delay procedure showed complete necrosis of all flaps. In the surgical delay group, the mean percentage survival of arterialized venous flaps was 36.6 percent in the 4-day delay group and 59.7 percent in the 7-day delay group. In the combined surgical and chemical delay group, a 3-day chemical delay followed by a 4-day simultaneous surgical and chemical delay resulted in mean percentage survival of the arterialized venous flaps of 81.1 percent in the doxazosin mesylate group, 72.8 percent in the nitroglycerine patch group, and 92.9 percent in a combination group of doxazosin mesylate and nitroglycerine patch. A 3-day chemical delay followed by a 7-day simultaneous surgical and chemical delay resulted in mean percentage survival of the arterialized venous flaps of 94 percent in the doxazosin mesylate group, 90.2 percent in the nitroglycerine patch group, and 99 percent in a combination group of doxazosin mesylate and nitroglycerine patch. In conclusion, the surgical delay procedure increased the percentage survival of the arterialized venous flaps in proportion to the delay period. The combination group of surgical and chemical delay procedures had a significantly greater percentage survival than that of the surgical delay group (p < 0.001), and the delay period could be shortened.     

The effect of insulin-like growth factor-1 on cyclic change of tendon cell

BACKGROUND: Myoclonus is a possible side effect of opioid therapy, and have been described following systemic as well as spinal application. CASE REPORT: We report the case of a patient with metastatic carcinoma of the rectum who developed myoclonus following administration of high-dose epidural combined with iv morphine. This complication occurred with maximum daily doses of 300 mg epidurally and 80 mg intravenously and disappeared completely after dose reduction. Treatment trials are presented, the pathophysiology of the myoclonus is discussed. CONCLUSION: For treatment of opioid-induced myoclonus a dose reduction or a change of the opioid should be considered as well as symptomatic treatment with benzodiazepines or baclofen.     

Expression of interleukin-6 and its effect on the cell growth of gastric carcinoma cell lines

The expression and the effect of IL-6 were examined in human gastric carcinoma cell lines to determine whether IL-6 serves as a growth stimulator. The expression of IL-6 mRNA was detected in three (TMK-1, MKN-1, MKN-7) of 8 gastric carcinoma cell lines. All three cell lines secreted IL-6 into the culture fluid, in large amounts in the cases of MKN-1 and MKN-7 cells. Scatchard plot analysis of IL-6 binding revealed that MKN-1 and MKN-7 cells had both high- and low-affinity receptors. Cell growth of MKN-1 and MKN-7 cells was stimulated by IL-6, while anti-IL-6 antibody inhibited growth. The expression of IL-1 alpha mRNA by these three cell lines was induced by IL-6. IL-1 alpha increased the expression of mRNA for IL-6 by TMK-1 cells. These findings indicate that IL-6 induced by IL-1 alpha is an autocrine growth factor for some gastric carcinomas.     

The effect of lidocaine on growth of cells of head and neck squamous cell carcinoma

The relation between 21 absolute body dimensions as well as 20 anthropometric indices and the length as well as the regularity of the menstrual cycle have been investigated in 156 patients of the hormone ambulance of the I. Universit?ts-Frauenklinik in Vienna. It turned out, that the length as well as the regularity of the menstrual cycle significantly negatively with the amount of the subcutaneous fat tissue. With an increasing amount of adipose tissue, the cycle became shorter and more regular. The importance of the subcutaneous fat tissue as a secondary hormonal gland has been discussed as one cause for these significant connections. Regarding the length- and height dimensions and the menstrual cycle patterns, no statistically significantly relationship could be observed between these two trait system. This is also true for the relationship between body built and the bleeding duration.