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At least 127 records · Page 7Linked to original sources
PubMed2003

The effect of inhibiting topoisomerase I and II on the anti-apoptotic response associated with pro-inflammatory crystals of calcium pyrophosphate dihydrate in human neutrophils.

OBJECTIVE AND DESIGN: To investigate the ability of various topoisomerase I and II inhibitors to reverse the pro-survival effects of calcium pyrophosphate dihydrate (CPPD) crystals on human neutrophils, thereby identifying potential agents that may promote the resolution of neutrophil accumulation typical of crystal associated inflammatory diseases. MATERIALS AND METHODS: Freshly isolated human neutrophils incubated in the presence of CPPD crystals, with or without the pro-apoptotic cytokine TNF-alpha, were pre-incubated in the presence or absence of the topoisomerase I inhibitors camptothecin, nogalamycin or beta-lapachone, or topoisomerase II inhibitors etoposide, doxorubicin or mitoxantrone. Neutrophil respiratory burst was assessed via chemiluminescence, and two quantitative methods were used for the determination of neutrophil apoptosis; cytoplasmic histone-associated-DNA fragmentation assessment, and endogenous caspase 3 substrate (Ac-DEVD-AMC) cleavage. RESULTS: Beta-lapachone and mitoxantrone effectively repressed CPPD crystal associated respiratory burst, whereas the other topoisomerase inhibitors had no inhibitory or stimulatory effect. Camptothecin and all of the topoisomerase II inhibitors induced neutrophil apoptosis, even in the presence of the CPPD crystals that normally repress TNF-alpha-induced and spontaneous apoptosis. CONCLUSIONS: These results suggest that although topoisomerase II antagonists are distinctively effective agents at reversing the pro-survival effects of crystals on neutrophils, camptothecin was unique as a topoisomerase I inhibitor in that it was significantly more effective as a pro-apoptosis inducer than the topoisomerase II poisons without affecting normal neutrophil activation responses.

Apoptosis↗
PubMed2003

Prognostic value of postoperative detection of blood circulating tumor cells in patients with colorectal cancer operated on for cure.

OBJECTIVE: To assess whether postoperative detection of circulating tumor cells in peripheral blood influenced the prognosis of patients with colorectal cancer after radical surgery. SUMMARY BACKGROUND DATA: In a previous study, the authors demonstrated that baseline detection of blood circulating tumor cells does not have prognostic significance in patients with colorectal cancer. However, surgical procedures may increase tumor cell detachment and mobilization. METHODS: Sixty-six patients with histologically confirmed colorectal cancer operated on for cure were included in this study. Circulating tumor cells were detected by means of reverse transcriptase-polymerase chain reaction targeting to carcinoembryonic antigen messenger RNA in peripheral blood samples obtained 24 hours after surgery. Endpoints of the study were tumor recurrence, overall survival, and cancer-related survival. Univariate (Kaplan-Meier method) and multivariate (Cox regression model) analyses were performed. RESULTS: After a median follow-up of 36 months, 15 patients (23%) had tumor relapse and 14 had died (21%), 8 of them from a cancer-related cause. Cox regression analysis identified lymph node metastases and gender as independent predictors of tumor recurrence and cancer-related survival, whereas overall survival was dependent on the degree of differentiation of the primary tumor. More importantly, the presence of circulating tumor cells after surgery had no prognostic influence on tumor recurrence, overall survival, or cancer-related survival. CONCLUSIONS: Postoperative detection of blood circulating tumor cells had no prognostic significance in patients with colorectal cancer operated on for cure.

Aged↗
PubMed2005

Placenta growth factor expression is correlated with survival of patients with colorectal cancer.

BACKGROUND: Overexpression of vascular endothelial growth factor (VEGF) correlates with vascularity, metastasis, and proliferation in colorectal cancer but the role of its homologue, placenta growth factor (PlGF), is unknown. The aim of this study was to evaluate expression and clinical implications of PlGF in colorectal cancer. METHODS: We investigated 74 tumour/non-tumour pairs of colorectal cryosections. Clinical staging was based on the UICC-TNM classification. Expression levels of mRNA for PlGF and VEGF were analysed with quantitative real time reverse transcription-polymerase chain reaction. Proteins were analysed by immunohistochemical staining and enzyme linked immunoabsorbant assay. Analysis of the differences in PlGF and VEGF levels between tumour and non-tumour tissues in the same patient were performed by paired t test; differences between localised and advanced disease patients by the Mann-Whitney, chi(2), and Fisher's exact tests and survival curves by the Kaplan-Meier method. RESULTS: Expression levels for both growth factors were significantly higher in tumour than in non-tumour tissues (p</=0.001). The ratio of PlGF expression in tumour to non-tumour in the advanced disease group was significantly higher than for the localised disease group (p = 0.009). Patients with more tumour PlGF mRNA had shorter survival (p = 0.028). The majority of PlGF was expressed in tumour cells. CONCLUSIONS: Our results suggest that PlGF expression correlates with disease progression and patient survival and may be used as a prognostic indicator for colorectal cancer.

Adult↗
PubMed2003

Clinical significance of bone marrow micrometastasis detected by nested rt-PCR for keratin-19 in breast cancer patients.

PURPOSE: Breast cancers in the early phase frequently undergo distant metastasis and survival of patients is greatly dependent on distant metastasis. The occurrence of micrometastasis has been suggested to relate with prognostic features of breast cancer, such as lymph node metastasis and the presence of vascular invasion. The aim of this study was to examine the presence of keratin-19 mRNA of epithelial tumors in bone marrow aspirates obtained from breast cancer patients and its possible correlation with tumor staging and disease-free survival. METHODS: Bone marrow samples were obtained from 59 breast cancer patients at the time of surgery. We separated the mononuclear fraction from the samples and carried out nested reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of keratin-19 mRNA with two different pairs of primers. After operation, the patients were followed up at 3-month intervals. We studied the possible correlation of the detection of keratin-19 mRNA with tumor size, nodal involvement, stage and recurrence rate. RESULTS: Bone marrow micrometastasis was detected by nested RT-PCR for keratin-19 mRNA in one of four patients with ductal carcinoma in situ (DCIS), 13 of 30 patients with T1, 11 of 20 patients with T2 and all four patients with T3 lesion. Recurrence was observed in seven cases and all of them were positive for micrometastasis in bone marrow. CONCLUSION: The method of nested RT-PCR to detect the presence of keratin-19 mRNA in bone marrow from patients with breast cancer is sensitive and reliable. Moreover, early recurrence was observed in the patients with the tumor mRNA detected in bone marrow. Additional studies with larger numbers of patients and longer follow-up are desirable.

Bone Marrow↗
PubMed1996

Reverse transcriptase-polymerase chain reaction amplification of MDR1 gene expression in adult soft tissue sarcomas.

Expression of the multidrug resistance gene MDR1 is reported to be an important determinant of the response to chemotherapy and survival in some cancers. We compared three methods for determining the intrinsic MDR1 expression in soft tissue sarcomas. We studied MDR1 gene expression in 39 samples from 33 cases of soft tissue sarcomas comprising 11 liposarcomas, nine malignant fibrous histiocytomas, six leiomyosarcomas, four malignant schwannomas, three fibrosarcomas, three synovial sarcomas, and three epithelioid sarcomas, and seven cases of benign soft tissue tumors in adult patients. To detect MDR1 mRNA, reverse transcriptase-polymerase chain reaction (RT-PCR) was performed in all samples. Furthermore, RNA dot-blot analysis with digoxigenin-labeled RNA probe and immunohistochemistry with JSB-1 and C-219 antibodies for P-glycoprotein were employed in 34 and 37 samples in soft tissue sarcomas, respectively. We compared these three detection techniques. Of the 39 specimens, 18 (46%) showed MDR1 PCR products. Liposarcomas (six of 11), malignant fibrous histiocytomas (six of nine), leiomyosarcomas (four of six), fibrosarcomas (two of three) revealed high or intermediate MDR1 expression at high frequency. No MDR1 expression was detectable in malignant schwannomas, synovial sarcomas, or epithelioid sarcomas. Of seven benign soft tissue tumors, one ganglioneuroma and one lipomatosis showed low levels of MDR1 expression. By RNA dot-blot analysis, MDR1 transcripts were detectable in 12 of 34 specimens (35%). Four samples were negative by dot blot despite positivity with RT-PCR. Concordance between MDR1 expression by RNA level with RT-PCR and dot blot and at the protein level with immunohistochemistry using C-219 was found in 16 (47%) of the 34 comparable specimens. Eight samples showed positive immunoreactivity for C-219 despite negative results in RT-PCR and dot-blot analysis. The intrinsic MDR1 expression in soft tissue sarcoma seemed to depend on certain tumor types, such as liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and fibrosarcoma. For the evaluation of MDR1 expression, RT-PCR is useful because of its relative simplicity and sensitivity. However, the clinical significance of such low levels of MDR1 expression detected only by RT-PCR must be discussed within systematically treated patient groups.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Prognostic significance of baseline reverse transcriptase-PCR for prostate-specific antigen in men with hormone-refractory prostate cancer treated with chemotherapy.

PURPOSE: Methods accurately categorizing the diverse biology of prostate cancer are needed. A positive baseline reverse transcriptase-PCR for prostate-specific antigen (RT-PCR PSA) in the androgen-independent setting is an independent prognostic marker of survival. The objectives of the current study were to examine the prognostic implication of baseline RT-PCR PSA positivity during treatment with an active chemotherapeutic agent and explore whether an RT-PCR PSA "response" provides prognostic information. MATERIALS AND METHODS: In a combined analysis of a phase I and a randomized phase II trial of BMS-247550 (an epothilone B analogue), 104 patients with hormone-refractory prostate cancer had whole blood samples collected at baseline, then with each cycle of therapy. RT-PCR PSA was assessed and related to time to progression (TTP). RESULTS: From 100 evaluable patients, 368 samples were received, of which 90.8% were evaluable for RT-PCR PSA status. Baseline RT-PCR PSA status was significantly associated with TTP (hazard ratio, 2.22; 95% confidence interval, 1.40-3.52). Twenty-six of 38 patients positive at first assessment had at least one follow-up RT-PCR PSA that was negative ("response"). In univariate analysis, RT-PCR PSA response was not significantly associated with TTP, but in multivariate analysis, RT-PCR PSA response was of borderline statistical significance in predicting TTP (hazard ratio, 0.41; 95% confidence interval, 0.16-1.01). CONCLUSION: These results provide further confirmation that baseline RT-PCR PSA is a statistically significant predictor of TTP in hormone-refractory prostate cancer. Moreover, this is the first report to suggest that RT-PCR PSA response during chemotherapy treatment may predict TTP.

Adult↗
PubMed2006

Reversal of Hartmann's procedure after surgery for complications of diverticular disease of the sigmoid colon is safe and possible in most patients.

BACKGROUND: Although evidence is growing that most patients who need an operation for diverticular disease of the sigmoid colon can be treated by a single-stage procedure, a two-stage procedure will still be necessary in some patients because of significant sepsis or technical difficulties. The outcomes of 65 patients who underwent secondary restoration after a Hartmann procedure for complicated diverticulitis were studied and the factors leading to complications and mortality were identified. PATIENTS AND METHODS: Of 91 patients, in a consecutive 12-year period, whose primary operation was a Hartmann procedure, 72 survived longer than 3 months after discharge. Sixty-five underwent an attempted reversal of the Hartmann procedure. The POSSUM scores were calculated in all patients as well as the morbidity and mortality rates. RESULTS: In 63 (96.9%) patients the bowel continuity could be restored with a morbidity of 38.5% and a mortality of 3.1%. The POSSUM and p-POSSUM scores adequately predicted the mortality in this series. CONCLUSION: This series shows that when surgical treatment for complicated diverticular disease of the sigmoid colon is necessary, the Hartmann procedure is still a valid indication. In a high percentage of patients the Hartmann procedure could be restored with a low mortality.

Adult↗
PubMedDate not supplied

Increased thymidylate synthase gene expression in liver metastases from colorectal carcinoma: implications for chemotherapeutic options and survival.

OBJECTIVES: To determine the association of intratumoral thymidylate synthase (TS) gene expression with resistance to fluoropyrimidines and to study the association of TS gene expression with outcome in patients with liver metastases from colorectal cancer. METHODS: Intratumoral TS gene expression was measured by reverse transcriptase and polymerase chain reaction in 33 patients with liver metastases from colorectal carcinoma. Fifteen patients underwent resection, and 18 were treated with chemotherapy only. Patients with high levels of TS gene expression were compared to those with low levels of TS gene expression. RESULTS: All patients with a high level of TS gene expression were nonresponders to fluoropyrimidine chemotherapy. Median survival in patients with unresectable disease was shorter in those who had high levels of TS gene expression (7 months vs 15 months, P = 0.02). After hepatic resection, median disease-free interval was shorter in patients with high levels of TS gene expression (5 months vs 18 months; P = 0.004). Similarly, survival was shorter after resection in those with high TS gene expression (17 months vs 43 months, P = 0.0002). DISCUSSION: Increased TS gene expression is associated with a poor outcome in patients with liver metastases from colorectal carcinoma, whether resected or treated by chemotherapy only. This is related in part to reduced responsiveness to chemotherapeutic agents, but it also reflects inherently more aggressive behavior of metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy.

BACKGROUND: In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study. METHODS AND RESULTS: Patients (n=141) with advanced heart failure (mean+/-SD age, 64+/-11 years; 73% men) who received CRT were followed up for a mean (+/-SD) of 695+/-491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of > or =9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank chi2=13.26, P=0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank chi2=17.1, P<0.0001), and heart failure events (11.5% versus 33.3%, log-rank chi2=8.71, P=0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause (beta=1.048, 95% confidence interval=1.019 to 1.078, P=0.001) and cardiovascular (beta=1.072, 95% confidence interval=1.033 to 1.112, P<0.001) mortality. Clinical parameters were unable to predict any outcome event. CONCLUSIONS: A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes.

Aged↗
PubMed2006

The reverse dorsal metacarpal flap: experience with 153 cases.

The authors have performed reverse dorsal metacarpal flaps in 153 cases to cover skin defects over fingers or stumps during the past 15 years. Its indications included acute and chronic skin defects over the second to fifth fingers or stumps. The coverage of the flap ranged from the base of the fingers to the distal interphalangeal joint. One hundred forty-three cases survived uneventfully, and 8 cases presented venous congestion postoperatively, which led to epidermal necrosis. The reverse dorsal metacarpal flap is a reliable and excellent method to cover skin defects over the fingers.

Adolescent↗
PubMed1999

[Repairing the defects of volar surface of distal finger with a reverse insular fascial flap of dorsum of juxta positioned digit].

OBJECTIVE: To introduce a method for one-stage repair of skin defects of the volar surface of distal finger or fingers. METHODS: The reverse fascial flap was designed and created on the dorsum of the juxta positioned digit, and it was then rotated 180 degrees to cover the defects of the volar surface of the distal finger. Since May 1992, a total of 20 reverse fascial flaps were used to treat 14 patients. RESULTS: All flaps survived except one with partial necrosis. Follow-up of one half to one year showed satisfactory results functionally and cosmetically. The finger is plump but not swollen. CONCLUSION: The method is easy and effective. The surgical treatment requires short time and causes little pain. The flap has good blood supply, suitable thickness, softness and resistance to wear and tear.

Adolescent↗
PubMed1989

Cytomegalovirus pneumonia: the use of ganciclovir in marrow transplant recipients.

Sixteen bone marrow transplant recipients with cytomegalovirus pneumonia diagnosed by rapid, non-invasive methods were treated with ganciclovir. Seven patients survived the acute infection and there were five long term survivors. Excellent in-vivo suppression of cytomegalovirus was observed. Marrow toxicity was noted in four patients but was rapidly reversible and not life threatening. Clinical features common to surviving patients included good clinical condition, insidious development of infection and evidence of normal alveolar gas exchange. The fulminant onset of symptoms, radiographic abnormalities and hypoxaemia were characteristic of non-survivors. These results offer some encouragement towards further study of ganciclovir for the early treatment of cytomegalovirus pneumonia. To identify such patients, the use of rapid diagnostic methods and aggressive viral surveillance is recommended. Convincing evidence for the efficacy of this drug will only emerge from randomized prospective studies.

Acyclovir↗
PubMed1999

Nonlethal detection of transgene expression in the CNS of founder mice.

Determining whether transgenes targeted to the central nervous system (CNS) are expressed has previously required sacrificing the animal; thus, if a line was to be maintained, it was necessary to generate offspring from the original founder mouse before assay. We describe a method for assaying for the expression of a variety of CNS-targeted transgenes that allows for the survival of the founder mice. Many CNS genes are expressed in the retina, which can be obtained from a mouse by simple survival surgery. We demonstrate that reverse transcription PCR of RNA isolated from a single eye can detect the mRNAs for glial fibrillary acidic protein (GFAP), vimentin, neurofilament light chain (NF-68) and Thy-1, all of whose promoters have been used to direct transgene expression in the CNS. We also show that this method readily detects expression of an astrocyte-specific GFAP-driven lacZ transgene and a neuron-specific L7-driven lacZ transgene.

Animals↗
PubMed1995

Cytokine gene expression and release from epithelial cells. A comparison study between healthy nasal mucosa and nasal polyps.

BACKGROUND: Epithelial cells release cytokines and they probably contribute to chronic inflammation detected in bronchial asthma, rhinitis and nasal polyposis. OBJECTIVES: To investigate the effect of cultures on cytokine gene expression to compare epithelial cell cytokine release by both healthy nasal nucosa (HNM) and nasal polyps (NP), and the modulation by dexamethasone and to investigate which cytokines may promote eosinophil survival. METHODS: Epithelials cells were cultured to confluence, human epithelial cell conditioned media generated with or without dexamethasone, and supernatants measured by ELISA. Cytokine gene expression was investigated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fresh epithelial cells only expressed mRNA for intesleukin-8 (IL-8) and granulocyte macrophage-colony stimulating factor (GM-CSF) while cultured cells expressed mRNA for IL-1 beta, IL-6, IL-8, tumour necrosis factor-alpha (TNF alpha) and GM-CSF. Epithelial cells from NP significantly (P < 0.05) released more IL-8 (25431 +/- 3163 pg/mL), and GM-CSF (1229 +/- 391 pg/mL) than those from HNM (18604 +/- 1723 pg/mL for IL-8; and 611 +/- 98 pg/mL for GM-CSF). Dexamethasone 10 microM inhibited the release of all cytokines, this effect being similar (40-50%) in both HNM and NP, except for IL-6 which was higher in HNM. Eosinophil survival induced by epithelial cell secretions from both HNM and NP was strongly blocked by GM-CSF antibody while it was partially blocked by antibodies to TNF alpha and IL-8. CONCLUSIONS: These findings suggest that although epithelial cell culture procedures may upregulate cytokine gene expression, nasal polyps may represent a more active inflammatory tissue by releasing more cytokines than healthy nasal mucosa this release being inhibited by steroids; and that, in addition to GM-CSF, other cytokines such as TNF alpha and IL-8, may also be involved in the promotion of eosinophil survival.

Base Sequence↗
PubMed2003

Lymph node occult micrometastasis in patients with non-small cell lung carcinoma: genetic diagnosis and its impact on prognosis.

BACKGROUND & OBJECTIVE: Occult micrometastasis to mediastinal lymph node, which could not be detected by routinely histopathologic examination, might be correlated with the prognosis of patients with non-small cell lung carcinoma (NSCLC). The aim of this stud y was to diagnose occult micrometastasis of mediastinal lymph node in NSCLC patients and evaluate its prognostic significance. METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR), 242 stations of mediastinal lymph nodes, which were free of tumor determined by histopathologic examination(pN0), from 58 patients were examined for MUC1 gene mRNA and to diagnose occult micrometastasis. All the patients were followed-up for three years. The survival rate was calculated by Kaplan-Meier method and the survival was compared with log-rank test between the patients with and without occult nodal micrometastasis. RESULTS: The MUC1 gene mRNA was identified in 23 stations of lymph nodes from 16 patients, and nodal occult micrometastasis was diagnosed in the 27.6% of the patients. TNM staging for these patients was up-regulated from stageI(A)-II(B) to stage III(A). The 3-year survival rate in the patients with nodal occult micrometastasis (43.7%) was lower than that in the patients without nodal occult micrometastasis (73.8%) (P< 0.05). CONCLUSION: The expression of MUC1 gene mRNA in mediastinal lymph node is associated with poor prognosis of NSCLC patients with pN0 disease, suggesting that it may be an indicator of poor prognosis.

Adult↗
PubMed1986

Enhanced mutagenesis of UV-irradiated simian virus 40 occurs in mitomycin C-treated host cells only at a low multiplicity of infection.

Treatment of monkey kidney cells with mitomycin C (MMC) 24 h prior to infection with UV-irradiated simian virus 40 (SV40) enhanced both virus survival and virus mutagenesis. The use of SV40 as a biological probe has been taken as an easy method to analyse SOS response of mammalian cells to the stress caused by DNA damage or inhibition of DNA replication. The mutation assay we used was based on the reversion from a temperature-sensitive phenotype (tsA58 mutant) to a wild-type phenotype. The optimal conditions for producing enhanced survival and mutagenesis in the virus progeny were determined with regard to the multiplicity of infection (MOI). Results showed that the level of enhanced mutagenesis observed for UV-irradiated virus grown in MMC-treated cells was an inverse function of the MOI, while enhanced survival was observed at nearly the same level regardless of the MOI. For the unirradiated virus, almost no increase in the mutation of virus progeny issued from MMC-treated cells was observed, while a small amount of enhanced virus survival was obtained. These results show that enhanced virus mutagenesis and enhanced virus survival can be dissociated under some experimental conditions. Enhanced virus mutagenesis, analogous to the error-prone replication of phages in SOS-induced bacteria, was observed, at least for SV40, only when DNA of both virus and host cells was damaged and when infection occurred with a small number of viral particles. We therefore hypothesize that an error-prone replication mode of UV-damaged templates is observed in induced monkey kidney cells.

Animals↗
PubMed1993

Nerve growth factor promotes functional recovery of retinal ganglion cells after ischemia.

PURPOSE: To investigate the effect of a transient complete ischemia on the function of cat retina and to determine whether nerve growth factor (NGF), which was previously shown to enhance retinal ganglion cell (RGC) survival after optic nerve section in the adult rat, can promote recovery of retinal neurons after the ischemic insult. METHODS: Function of distal and proximal retina was assessed by recording the electroretinogram in response to both homogeneous flickering light (FERG) and contrast reversing gratings (PERG), respectively, 30 days after the induction of a 60-minute episode of ischemia. Visual evoked potentials in response to contrast reversing gratings were also recorded to evaluate visual acuity and contrast thresholds. Cell survival after ischemia was assessed in retinal whole-mounts stained with cresyl violet. Cats were intraocularly treated with NGF every other day, 3 times a week, for 30 days. Controls were treated with either phosphate buffered saline or cytochrome c. RESULTS: After ischemia, the FERG was not significantly affected. On the contrary, the PERG, visual acuity, and contrast thresholds were severely impaired. After NGF treatment, PERG response amplitudes were much less reduced compared to controls, and visual acuity and contrast thresholds were virtually normal. In addition, a larger number of presumed RGCs was present in the NGF-treated retinas compared to the cyt c-treated ones. CONCLUSIONS: The more proximally located retinal neurons, in particular RGCs, are highly vulnerable to ischemia. Intraocular NGF treatment was effective in enhancing the survival and functional recovery of these neurons. This suggests that NGF may represent a novel therapeutic agent for the treatment of ischemic ocular pathologies.

Animals↗
PubMed2000

Rapid hypothermic aortic flush can achieve survival without brain damage after 30 minutes cardiac arrest in dogs.

BACKGROUND: Neither exsanguination to pulselessness nor cardiac arrest of 30 min duration can be reversed with complete neurologic recovery using conventional resuscitation methods. Techniques that might buy time for transport, surgical hemostasis, and initiation of cardiopulmonary bypass or other resuscitation methods would be valuable. We hypothesized that an aortic flush with high-volume cold normal saline solution at the start of exsanguination cardiac arrest could rapidly preserve cerebral viability during 30 min of complete global ischemia and achieve good outcome. METHODS: Sixteen dogs weighing 20-25 kg were exsanguinated to pulselessness over 5 min, and circulatory arrest was maintained for another 30 min. They were then resuscitated using closed-chest cardiopulmonary bypass and had assisted circulation for 2 h, mild hypothermia (34 degrees C) for 12 h, controlled ventilation for 20 h, and intensive care to outcome evaluation at 72 h. Two minutes after the onset of circulatory arrest, the dogs received a flush of normal saline solution at 4 degrees C into the aorta (cephalad) via a balloon catheter. Group I (n = 6) received a flush of 25 ml/kg saline with the balloon in the thoracic aorta; group II (n = 7) received a flush of 100 ml/kg saline with the balloon in the abdominal aorta. RESULTS: The aortic flush decreased mean tympanic membrane temperature (Tty) in group I from 37.6 +/- 0.1 to 33.3 +/- 1.6 degrees C and in group II from 37.5 +/- 0.1 to 28.3 +/- 2.4 degrees C (P = 0.001). In group 1, four dogs achieved overall performance category (OPC) 4 (coma), and 2 dogs achieved OPC 5 (brain death). In group II, 4 dogs achieved OPC 1 (normal), and 3 dogs achieved OPC 2 (moderate disability). Median (interquartile range [IQR]) neurologic deficit scores (NDS 0-10% = normal; NDS 100% = brain death) were 69% (56-99%) in group I versus 4% (0-15%) in group II (P = 0.003). Median total brain histologic damage scores (HDS 0 = no damage; > 100 = extensive damage; 1,064 = maximal damage) were 144 (74-168) in group I versus 18 (3-36) in group II (P = 0.004); in three dogs from group II, the brain was histologically normal (HDS 0-5). CONCLUSIONS: A single high-volume flush of cold saline (4 degrees C) into the abdominal aorta given 2 min after the onset of cardiac arrest rapidly induces moderate-to-deep cerebral hypothermia and can result in survival without functional or histologic brain damage, even after 30 min of no blood flow.

Animals↗