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Biomedical subjects

R Heller

Publications and source records attributed to R Heller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Treatment of hepatocellular carcinoma in a rat model using electrochemotherapy.

The effectiveness of antineoplastic agents has been augmented by applying pulsed electric fields directly to tumours after the administration of the drug. This treatment, known as electrochemotherapy (ECT), has been successful for cutaneous malignancies in animal models and in recent clinical trials. This study was aimed at investigating the applicability of ECT in a surgical setting for hepatocellular carcinomas induced in the livers of rats. Established tumours were injected with bleomycin, and electric pulses were then administered locally. Animals were followed based on tumour volumes and histological samples. Dose response data were obtained for both electric field intensity and bleomycin. Complete response rates for animals treated with electrochemotherapy ranged from 26.67% to 93.33 and were durable. In contrast, tumours that received no treatment, pulses only or drug only responded minimally. This supports the feasibility of using a ECT as a modality for treating hepatocellular carcinoma.

Animals↗
PubMed2001

[Sleep deprivation as a predictor of response to light therapy in major depression].

Light therapy (LT) is regarded as the treatment of choice for seasonal affective disorder (SAD). In nonseasonal depression the results of light therapy are nonconclusive. Sleep deprivation (SD), however, is effective in 50-60% of the patients with major depression. The predictive value of Total Sleep Deprivation (TSD) for the treatment outcome of antidepressiva has been already examined. Purpose of the present study was to test whether light therapy is more beneficial in TSD responders than in TSD nonresponders. 40 inpatients with major depressive disorder completed one night of TSD. Twenty TSD responders and 20 TSD nonresponders were randomly assigned to 14 days of bright light therapy (2500 lux, 7-9 a.m.) or 14 days of dim light therapy (red light 50 lux, 7-9 a.m.). Manova with repeated measurements revealed a significant difference in the course of depression over the time between TSD responders and nonresponders, but no significant difference between bright and dim light. Questions of placebo effect, of SAD and of personality variables as predictors of response to SD and LT are being discussed.

Adult↗
PubMed2001

In vivo electroporation using an exponentially enhanced pulse: a new waveform.

In vivo electroporation is currently accomplished by one of two types of common waveforms: exponential decay or square-wave pulses. The purpose of this report is to present a new electroporation waveform, the exponentially enhanced pulse (EEP). Pulsing protocols including the EEP resulted in high levels of luciferase expression in muscle and skin, equal to or greater than expression resulting from low-voltage, millisecond square-wave pulses. This high level of expression requires fewer pulses when using an EEP protocol. Therefore, similar or greater plasmid DNA expression levels are obtained using fewer pulses with the EEP protocol than with current protocols. This is the first report of this new waveform and shows the success of using protocols employing the EEP to deliver plasmid DNA to various tissue types.

Animals↗
PubMed2001

Intradermal delivery of interleukin-12 plasmid DNA by in vivo electroporation.

Gene therapy depends on safe and efficient gene delivery. The skin is an attractive target for gene delivery because of its accessibility. Recently, in vivo electroporation has been shown to enhance expression after injection of plasmid DNA. In this study, we examined the use of electroporation to deliver plasmid DNA to cells of the skin in order to demonstrate that localized delivery can result in increased serum concentrations of a specific protein. Intradermal injection of a plasmid encoding luciferase resulted in low levels of expression. However, when injection was combined with electroporation, expression was significantly increased. When performing this procedure with a plasmid encoding interleukin-12, the induced serum concentrations of gamma-interferon were as much as 10 fold higher when electroporation was used. The results presented here demonstrate that electroporation can be used to augment the efficiency of direct injection of plasmid DNA to skin.

Animals↗
PubMed2001

Kinetics of Bartonella birtlesii infection in experimentally infected mice and pathogenic effect on reproductive functions.

The kinetics of infection and the pathogenic effects on the reproductive function of laboratory mice infected with Bartonella birtlesii recovered from an Apodemus species are described. B. birtlesii infection, as determined by bacteremia, occurred in BALB/c mice inoculated intravenously. Inoculation with a low-dose inoculum (1.5 x 10(3) CFU) induced bacteremia in only 75% of the mice compared to all of the mice inoculated with higher doses (> or =1.5 x 10(4)). Mice became bacteremic for at least 5 weeks (range, 5 to 8 weeks) with a peak ranging from 2 x 10(3) to 10(5) CFU/ml of blood. The bacteremia level was significantly higher in virgin females than in males but the duration of bacteremia was similar. In mice infected before pregnancy (n = 20), fetal loss was evaluated by enumerating resorption and fetal death on day 18 of gestation. The fetal death and resorption percentage of infected mice was 36.3% versus 14.5% for controls (P < 0.0001). Fetal suffering was evaluated by weighing viable fetuses. The weight of viable fetuses was significantly lower for infected mice than for uninfected mice (P < 0.0002). Transplacental transmission of Bartonella was demonstrated since 76% of the fetal resorptions tested was culture positive for B. birtlesii. The histopathological analysis of the placentas of infected mice showed vascular lesions in the maternal placenta, which could explain the reproductive disorders observed. BALB/c mice appeared to be a useful model for studying Bartonella infection. This study provides the first evidence of reproductive disorders in mice experimentally infected with a Bartonella strain originating from a wild rodent.

Animals↗
PubMed2001

MR imaging of the breast in patients with invasive lobular carcinoma.

OBJECTIVE: Our objective was to assess the usefulness of MR imaging in patients diagnosed with invasive lobular carcinoma of the breast. MATERIALS AND METHODS: Between July 1993 and September 1999, 32 women (33 cases) diagnosed with pure invasive lobular carcinoma of the breast underwent contrast-enhanced MR imaging examination. One woman was excluded because of lack of follow-up. Correlation was made between the mammographic and sonographic findings, the MR imaging findings, and the final pathology results for the remaining 32 cases. RESULTS: In 18 women who did not undergo excisional biopsy before the MR imaging, MR imaging showed more extensive tumor burden or the detection of the primary lesion that was occult on conventional imaging in seven (38.9%) of 18 women. In nine (50%) of 18 women, MR imaging performed equally as well as mammography and sonography. In one case (5.6%), MR imaging and mammography underestimated disease extent. In another patient (5.6%), MR imaging overestimated tumor burden, although mammography failed to show the cancer. In 14 patients who had excisional biopsy before the MR imaging, residual tumor was shown in eight women (57.1%) with extensive tumor or additional separate foci in five of the eight patients. In two cases (14.3%) that were interpreted as equivocal, residual tumor was shown in both cases on reexcision. In three cases (21.4%), the MR imaging was interpreted as negative, but microscopic tumor was shown around seroma on reexcision. False-positive enhancement was seen in one case (7.1%). CONCLUSION: MR imaging showed more extensive tumor than conventional imaging and affected the clinical management in 16 (50%) of 32 patients with invasive lobular carcinoma.

Adult↗
PubMed2000

Flow cytometric determination of E-selectin, vascular cell adhesion molecule-1, and intercellular cell adhesion molecule-1 in formaldehyde-fixed endothelial cell monolayers.

BACKGROUND: Endothelial cell adhesion molecules are involved in initiation and progression of vascular diseases. The purpose of this study was to determine conditions of fixation and dissociation of human umbilical vein endothelial cell (HUVEC) monolayers that permit a reliable flow cytometric determination of intracellular and surface content of E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). METHODS: TNFalpha-treated HUVEC monolayers were fixed with 0.5% formaldehyde at the end of the experimental incubation. Subsequently, either the monolayer was trypsinized and thereafter the cells were subjected to indirect fluorescence labeling or the monolayer was first labeled and then dissociated by trypsinization. Cell integrity was assessed by vimentin staining. Total adhesion molecule content was detected in saponin-permeabilized cells. RESULTS: HUVEC integrity was maintained when the fixation time of the monolayer did not exceed 5 min and trypsin/EDTA was used for dissociation. Surface adhesion molecules were partially hydrolyzed by trypsin when trypsinization preceded labeling but antibody binding protected adhesion molecules from degradation. VCAM-1 and E-selectin exhibited substantial trypsin-sensitive surface fractions but surface ICAM-1 was mainly trypsin resistant. Permeabilization with 0.06% saponin allowed the detection of considerable intracellular pools of the investigated adhesion molecules. CONCLUSIONS: The described method permits the reliable determination of surface and intracellular fractions of adhesion molecules in formaldehyde-fixed HUVEC monolayers and may be used for studies on the regulation of adhesion molecule expression.

Cell Membrane Permeability↗
PubMed2000

Accuracy of sentinel lymph node biopsy in patients with large primary breast tumors.

BACKGROUND: Patients with large breast tumors are increasingly undergoing neoadjuvant treatment to downstage local disease; however, accurate staging of the axilla before the initiation of chemotherapy remains problematic. In the current study, the authors report on the accuracy of sentinel lymph node (SLN) biopsy in such patients to determine the feasibility of applying this technique before induction chemotherapy. METHODS: One hundred three patients with 104 tumors classified as American Joint Committee on Cancer (AJCC) T2 (tumor >/= 2 cm but </= 5 cm) or larger were recruited at the University of Pennsylvania and the Mayo Clinic. In the majority of cases, combined blue dye and radiotracer was used for SLN identification. After SLN identification, a completion axillary lymph node dissection was performed in 87 cases. The SLN was evaluated with hematoxylin and eosin and immunohistochemistry. RESULTS: The SLN was identified in 99% of cases. The overall rate of lymph node metastasis was 59% (95% exact confidence interval [95% CI], 49-68%) (61 of 104 cases). The SLN false-negative rate was 2% (95% exact CI, < 1-11.5%) (2 patients). In 56 tumors >/= 3 cm, 1 false-negative result (2% [95% exact CI, < 1-15%]) was identified, and the rate of lymph node metastasis was 62.5% (95% exact CI, 48. 5-75%) (35 of 56 tumors). Within 30 SLN positive patients with tumors >/= 3 cm and complete axillary lymph node dissection, 3 of 8 patients (37.5% [95% exact CI, 8.5-75.5%]) with micrometastasis (</= 2 mm) to the SLN had positive non-SLN compared with 21 of 22 patients (95.5% [95% exact CI, 77-100%]) with macrometastasis (> 2 mm) to the SLN (P = 0.002). CONCLUSIONS: SLN biopsy for patients with large breast tumors is technically feasible and highly accurate. SLN biopsy should be considered for the staging of clinically negative axilla in patients scheduled to receive neoadjuvant chemotherapy.

Adult↗
PubMed2000

Theory and in vivo application of electroporative gene delivery.

Efficient and safe methods for delivering exogenous genetic material into tissues must be developed before the clinical potential of gene therapy will be realized. Recently, in vivo electroporation has emerged as a leading technology for developing nonviral gene therapies and nucleic acid vaccines (NAV). Electroporation (EP) involves the application of pulsed electric fields to cells to enhance cell permeability, resulting in exogenous polynucleotide transit across the cytoplasmic membrane. Similar pulsed electrical field treatments are employed in a wide range of biotechnological processes including in vitro EP, hybridoma production, development of transgenic animals, and clinical electrochemotherapy. Electroporative gene delivery studies benefit from well-developed literature that may be used to guide experimental design and interpretation. Both theory and experimental analysis predict that the critical parameters governing EP efficacy include cell size and field strength, duration, frequency, and total number of applied pulses. These parameters must be optimized for each tissue in order to maximize gene delivery while minimizing irreversible cell damage. By providing an overview of the theory and practice of electroporative gene transfer, this review intends to aid researchers that wish to employ the method for preclinical and translational gene therapy, NAV, and functional genomic research.

Electroporation↗
PubMed2000

Designing a research study.

There are 10 steps to consider in any research study. These steps can be used to perform a critical appraisal of a published paper, or to design your study in the first place. The use of a simple system such as this can ensure that biases in study design are avoided and that an appropriate study is developed. (1) What is the study hypothesis? (2) What is the study type? (3) What are the outcome measures? Is their measurement biased in any way? (4). What is the study factor (the intervention being offered to the children)? Is there bias in this? (5) Is there a possibility of confounding? (6) What are the reference population, source population and study sample? How have the sampling and selection into the study been performed? (7) Study methods that might threaten the internal validity of the study. (8) Statistical considerations. (9) Are the results clinically and socially significant? (10) Will the conclusions of the study be relevant to the kind of patients you see, or communities you work with?

Bias↗
PubMed2000

[Hyperbaric oxygen therapy in retinal artery occlusion].

UNLABELLED: Retinal artery occlusion (RAO) is an ophthalmological emergency that causes a major decrease of visual parameters in most of the cases. Purpose of this pilot study was to evaluate the effect of adjunctive hyperbaric oxygen therapy (HBO) on visual acuity (VA). PATIENTS AND METHODS: Patients with acute central or branch artery occlusion (CRAO/BRAO) consecutively admitted to our hospital were offered adjunctive HBO. Standard therapy consisted of ocular massage for 3 minutes, paracentesis and intravenous acetazolamide. HBO (3 x 30 minutes at 240 kPa) was applied t.i.d. on the first day, b.i.d. on day 2 and 3 and o.d. for at least another 4 days. Patients who refused HBO or had contraindications served as controls. VA was measured according to the guidelines of ETDRS. The follow up was 3 months. RESULTS: HBO: 8 patients with CRAO showed a mean increase in VA of 1 line, 4 of 8 patients had an increase of 2 lines and more, in 3 of 8 patients VA was unchanged and one patient suffered a decrease of 6 lines. 10 patients with BRAO showed a mean increase in VA of 8 lines, 8 of 10 patients showed an mean increase of 2 and more lines, in 2 of 10 patients VA was unchanged. CONTROLS: 8 Patients with CRAO had a mean increase of 2 lines during follow up, 3 of 8 patients showed an increase of 2 lines and more, in 5 of 8 patients VA was unchanged. 6 patients with BRAO had a mean increase of VA of 4 lines, 3 of 6 patients had an increase of 2 lines and more, one patient lost 3 lines and in 2 patients VA was unchanged. The results are compared to the literature. CONCLUSIONS: HBO seems to be beneficial for VA in eyes with BRAO. Further investigations are necessary to prove this observation.

Acetazolamide↗
PubMed2000

Quantitation of low level unconjugated polysaccharide in tetanus toxoid-conjugate vaccine by HPAEC/PAD following rapid separation by deoxycholate/HCl.

A simple and rapid acid precipitation method has been applied successfully for separating free capsular polysaccharide of Haemophilus influenzae type b (polyribosyl ribitol phosphate, PRP) from PRP tetanus toxoid conjugate (PRP-T) in a final dosage amount of low-level materials. The unconjugated PRP was found to stay in the supernatant without precipitation, while conjugated PRP-T was fully precipitated. High performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) has been applied for analysis of the PRP content in the supernatant after the separation. This method requires minimum sample handling and is specific, sensitive and reproducible making it suitable for release and stability testing of PRP-T in final containers.

Anion Exchange Resins↗
PubMed2000

Electrically mediated plasmid DNA delivery to hepatocellular carcinomas in vivo.

Gene therapy by direct delivery of plasmid DNA has several advantages over viral gene transfer, but plasmid delivery is less efficient. In vivo electroporation has been used to enhance delivery of chemotherapeutic agents to tumors in both animal and human studies. Recently, this delivery technique has been extended to large molecules such as plasmid DNA. Here, the successful delivery of plasmids encoding reporter genes to rat hepatocellular carcinomas by in vivo electroporation is demonstrated.

Animals↗
PubMed2000

Tea tree oil as an alternative topical decolonization agent for methicillin-resistant Staphylococcus aureus.

The combination of a 4% tea tree oil nasal ointment and 5% tea tree oil body wash was compared with a standard 2% mupirocin nasal ointment and triclosan body wash for the eradication of methicillin-resistant Staphylococcus aureus carriage. The tea tree oil combination appeared to perform better than the standard combination, although the difference was not statistically significant due to the small number of patients.

Administration, Cutaneous↗
PubMed2000

Toxicity of anticancer agents mediated by electroporation in vitro.

Electroporation is a physical event that temporarily reduces cell membrane barrier properties. Diminished membrane barrier properties are achieved by exposing cells to pulsed electric fields. When a cell has been treated with electric fields it is possible for extracellular agents to gain access to the cell interior. This process has been used in vivo to increase the uptake of chemotherapeutic agents by tumor cells which results in dramatically higher response rates than when drug is used alone. This type of treatment is called electrochemotherapy (ECT); bleomycin is most often used as the drug for this type of treatment. It was hypothesized that electroporation could be used to augment the cytotoxicity of other anticancer agents. Therefore, this study was performed in order to screen 44 different combinations of drug and cell type in vitro to identify drugs that may have higher cytotoxicity when combined with electroporation. Results from seven cell types indicate that the IC50 of bleomycin can be reduced by a factor of 100-5000 when electroporation is used to facilitate internalization. The IC50 values of cisplatin and carboplatin could be reduced by factors ranging from 3 to 13 in six different cell lines as a result of electroporation. These IC50 reductions in multiple cell lines suggest that cisplatin and carboplatin may be effective in vivo as part of ECT treatment.

Antineoplastic Agents↗
PubMed2000

In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunity.

When cancer cells, including melanoma cells, are genetically altered to secrete cytokines, irradiated and injected into subjects, long-term antitumour immunity is induced. Optimally, existing melanomas induced to produce cytokines in vivo could stimulate this same immune response. Although in vivo electroporation enhances plasmid expression, electroporation of plasmids encoding granulocyte-monocyte colony stimulating factor (GM-CSF) and interleukin-2 (IL2) into B16 mouse melanomas did not significantly alter tumour growth at the concentration tested. Electrochemotherapy, which causes short-term, complete regressions of treated tumour but no resistance to challenge, was combined with plasmid delivery. The combination treatment resulted in the induction of long-term immunity to recurrence and resistance to challenge in up to 25% of mice.

Animals↗