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Biomedical subjects

R Heller

Publications and source records attributed to R Heller.

At least 55 records · Page 3Linked to original sources
PubMed2000

Bartonella birtlesii sp. nov., isolated from small mammals (Apodemus spp.).

Three strains isolated from Apodemus spp. were similar to Bartonella species on the basis of phenotypic characteristics. Futhermore, genotypic analysis based on sequence analysis of the 16S rRNA and gltA genes and on DNA-DNA hybridization showed that the three isolates represented a distinct and new species of Bartonella. The name Bartonella birtlesii is proposed for the new species. The type strain of B. birtlesii sp. nov. is IBS 325T (= CIP 106294T = CCUG 44360T).

Animals↗
PubMed2000

Coyotes (Canis latrans) as the reservoir for a human pathogenic Bartonella sp.: molecular epidemiology of Bartonella vinsonii subsp. berkhoffii infection in coyotes from central coastal California.

Bartonella vinsonii subsp. berkhoffii was originally isolated from a dog suffering infectious endocarditis and was recently identified as a zoonotic agent causing human endocarditis. Following the coyote bite of a child who developed clinical signs compatible with Bartonella infection in Santa Clara County, Calif., this epidemiological study was conducted. Among 109 coyotes (Canis latrans) from central coastal California, 31 animals (28%) were found to be bacteremic with B. vinsonii subsp. berkhoffii and 83 animals (76%) had B. vinsonii subsp. berkhoffii antibodies. These findings suggest these animals could be the wildlife reservoir of B. vinsonii subsp. berkhoffii. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the gltA and 16S rRNA genes for these 31 isolates yielded similar profiles that were identical to those of B. vinsonii subsp. berkhoffii. Partial sequencing of the gltA and 16S rRNA genes, respectively, indicated 99.5 and 100% homology between the coyote isolate and B. vinsonii subsp. berkhoffii (ATCC 51672). PCR-RFLP analysis of the 16S-23S intergenic spacer region showed the existence of two different strain profiles, as has been reported in dogs. Six (19%) of 31 Bartonella bacteremic coyotes exhibited the strain profile that was identified in the type strain of a canine endocarditis case (B. vinsonii subsp. berkhoffii ATCC 51672). The other 25 bacteremic coyotes were infected with a strain that was similar to the strains isolated from healthy dogs. Based on whole bacterial genome analysis by pulsed-field gel electrophoresis (PFGE) with SmaI restriction endonuclease, there was more diversity in fingerprints for the coyote isolates, which had at least 10 major variants compared to the two variants described for domestic dog isolates from the eastern United States. By PFGE analysis, three Bartonella bacteremic coyotes were infected by a strain identical to the one isolated from three healthy dog carriers. Further studies are necessary to elucidate the mode of transmission of B. vinsonii subsp. berkhoffii, especially to identify potential vectors, and to determine how humans become infected.

Animals↗
PubMed2000

Direct molecular typing of Borrelia burgdorferi sensu lato species in synovial samples from patients with lyme arthritis.

Since Lyme arthritis was first described in the United States, it has now been reported in many countries of Europe. However, very few strains of the causative bacterium, Borrelia burgdorferi, have been isolated from synovial samples. For this reason, different molecular direct typing methods were developed recently to assess which species could be involved in Lyme arthritis in Europe. We developed a simple oligonucleotide typing method with PCR fragments from the flagellin gene of B. burgdorferi sensu lato, which is able to differentiate seven different Borrelia species. Among 10 consecutive PCR-positive patients with Lyme arthritis from the northeastern France, two species were identified in synovial samples: B. burgdorferi sensu stricto in 9 cases and B. garinii in 1 case. Conversely, all B. burgdorferi sensu lato species detected in 10 consecutive PCR-positive biopsies from a second set of patients with erythema migrans from the same geographical area were identified as either B. afzelii or B. garinii (P < 0.001). These results indicate that B. burgdorferi sensu stricto is the principal but not the only Borrelia species involved in Lyme arthritis in northeastern France.

Arthritis, Infectious↗
PubMed2000

A universal precautions education intervention for health workers in Sardjito and PKU Hospital Indonesia.

A non-randomized control trial was conducted to develop and evaluate a culturally appropriate academic detailing intervention on the universal precautions knowledge, attitude and behavior of health care workers in hospitals. Fivety-five health care workers (44 nurses and 11 doctors) participated in the study. They were visited individually to discuss principles of universal precautions as well as the effect of automatic pilot on their work practices. Self-reported measures of knowledge and attitudes were collected from each participant before and after the intervention. A nurse observer collected measures of participants' compliance with the universal precautions guidelines according to a pre-determined protocol before and after the intervention. There was a significantly different level of knowledge, attitudes and compliance on universal precautions between the control and intervention hospital with p=0.0007, p=0.038 and p=0.03 respectively following the intervention. It is concluded that an academic detailing approach of education used in this study has significantly improved knowledge, attitudes and compliance scores.

Health Knowledge, Attitudes, Practice↗
PubMed2000

Adjunctive hyperbaric oxygenation in macular edema of vascular origin.

Macular edema (ME) is a primary reason for permanent decreases of visual acuity (VA) in diabetic retinopathy and retinal vein occlusions. The standard treatment (photocoagulation, rheological treatment) provide only a limited success. We have therefore studied the additional use of hyperbaric oxygenation (HBO2) in patients with persistent ME. Five patients (1 female, 4 male; 7 eyes) were treated by adjunctive HBO2. The average age of the patients was 60.6 (38.9-76.8) yr. The VA was measured with Early Treatment Diabetic Retinopathy Study charts before and after HBO2 with a monthly follow up. Fluorescein angiography was performed before and after HBO2 with a follow up every 3 mo. Each patient received 10-30 HBO2 treatments (median 15). The follow-up period was 15 mo. for every patient. The mean increase in VA was 3.5 (2-4) lines after HBO2. Retinal photocoagulation was performed in six eyes. Diabetic macular edemas showed no morphologic change, while ME originating from retinal vein occlusions (CME) regressed. The VA in our patients with ME of vascular origin seemed to improve with HBO2. Photocoagulation was necessary in most cases. Visual function correlated with the angiographic presentation only for CME.

Acetazolamide↗
PubMed1999

Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo.

Whereas signal transducers and activators of transcription were originally discovered as mediators of normal cytokine signaling, constitutive activation of certain signal transducer and activator of transcription proteins, including Stat3, has been found in increasing numbers of human cancers. Recently, a causal role for Stat3 activation in oncogenesis has been demonstrated, suggesting that Stat3 represents a novel target for cancer therapy. We report here that in vitro expression of a Stat3 variant with dominant-negative properties, Stat3beta, induced cell death in murine B16 melanoma cells that harbored activated Stat3. By contrast, expression of Stat3beta had no effect on normal fibroblasts or the Stat3-negative murine tumor MethA, suggesting that only tumor cells with activated Stat3 have become dependent on this pathway for survival. Significantly, gene therapy by electroinjection of the Stat3beta expression vector into preexisting B16 tumors caused inhibition of tumor growth as well as tumor regression. This Stat3beta-induced antitumor effect is associated with apoptosis of the B16 tumor cells in vivo. These findings demonstrate for the first time that interfering with Stat3 signaling induces potent antitumor activity in vivo and thus identify Stat3 as a potential molecular target for therapy of human cancers harboring activated Stat3.

Animals↗
PubMed1999

Variation in in-patient stroke management in ten centres in different countries: the INCLEN multicentre stroke collaboration.

BACKGROUND AND PURPOSE: Large within-country variations have been described in stroke management and there have been a few studies of between-country variation (in the USA and the UK). We designed a study to examine stroke management across a wide range of countries representing different stages of economic development. Large variations would suggest the need to explore methods of increasing the uptake of evidence-based stroke practice. METHODS: Members of the International Clinical Epidemiology Network (INCLEN) from 14 centres in ten countries agreed to review the records of the last 50 patients admitted to hospital with a clinical diagnosis of stroke. Information on demographic variables, the clinical diagnosis of stroke type, investigations performed and treatments given and the discharge destination of the patient were recorded and sent to the coordinating centre in Australia for analysis. RESULTS: There were statistically significant between-centre differences in the proportions of patients cared for by a neurologist, staying in hospital for at least ten days and having CT or MRI scans. Significant between-centre differences were also seen for treatment, for example, the use of aspirin in non-haemorrhagic stroke varied from 11 to 79%. The variation (for all interventions studied) was no longer statistically significant when examined within strata according to availability of facilities. CONCLUSIONS: The large variation between centres in the management of stroke is largely 'explained' by the availability of resources, even for interventions that do not depend on resource availability. It will be important to develop management guidelines that reflect evidence-based practice of relevance across a range of economic settings.

Age Factors↗
PubMed1999

L-Ascorbic acid potentiates nitric oxide synthesis in endothelial cells.

Ascorbic acid has been shown to enhance impaired endothelium-dependent vasodilation in patients with atherosclerosis by a mechanism that is thought to involve protection of nitric oxide (NO) from inactivation by free oxygen radicals. The present study in human endothelial cells from umbilical veins and coronary arteries investigates whether L-ascorbic acid additionally affects cellular NO synthesis. Endothelial cells were incubated for 24 h with 0.1-100 microM ascorbic acid and were subsequently stimulated for 15 min with ionomycin (2 microM) or thrombin (1 unit/ml) in the absence of extracellular ascorbate. Ascorbate pretreatment led to a 3-fold increase of the cellular production of NO measured as the formation of its co-product citrulline and as the accumulation of its effector molecule cGMP. The effect was saturated at 100 microM and followed a similar kinetics as seen for the uptake of ascorbate into the cells. The investigation of the precursor molecule L-gulonolactone and of different ascorbic acid derivatives suggests that the enediol structure of ascorbate is essential for its effect on NO synthesis. Ascorbic acid did not induce the expression of the NO synthase (NOS) protein nor enhance the uptake of the NOS substrate L-arginine into endothelial cells. The ascorbic acid effect was minimal when the citrulline formation was measured in cell lysates from ascorbate-pretreated cells in the presence of known cofactors for NOS activity. However, when the cofactor tetrahydrobiopterin was omitted from the assay, a similar potentiating effect of ascorbate pretreatment as seen in intact cells was demonstrated, suggesting that ascorbic acid may either enhance the availability of tetrahydrobiopterin or increase its affinity for the endothelial NOS. Our data suggest that intracellular ascorbic acid enhances NO synthesis in endothelial cells and that this may explain, in part, the beneficial vascular effects of ascorbic acid.

Antioxidants↗
PubMed1999

Electrically enhanced drug delivery for the treatment of soft tissue sarcoma.

BACKGROUND: Pulsed electric fields have been shown to increase the effectiveness of antineoplastic agents by temporarily increasing the permeability of cell membranes. This type of drug delivery is called electrochemotherapy, and it has been successful in the treatment of patients with cutaneous malignancies in clinical trials. This study focused on determining the applicability of electrochemotherapy to the treatment of soft tissue sarcoma, using an animal model bearing human sarcomas. The antitumor effects of single and multiple electrochemotherapy treatments were investigated using small (250 mm3) and large (4000 mm3) tumors. METHODS: Established tumors were injected with bleomycin, then electric pulses were administered to the tumor site. Animals were followed based on periodic tumor volume determinations, which were used to categorize treatment of each tumor as a complete response, a partial response, stable disease, or progressive disease. Histologic analysis was used to confirm response data. RESULTS: Animals were randomly assigned to one of four different treatment groups. These groups received no treatment, drug only, electric pulses only, or drug combined with electric pulses. A single electrochemotherapy treatment protocol for small tumors resulted in a 100% complete response rate and a 41.7% cure rate. Multiple treatments of small and large tumors resulted in complete response rates of 83.3% and 100%, respectively. These responses were identical to the cure rates. In contrast, tumors in the groups that received no treatment, electric pulses only, and drug only progressed for both single treatment and multiple treatment scenarios, regardless of tumor size. CONCLUSIONS: In this study, a single electrochemotherapy treatment had a strong cytoreductive effect on small tumors that lasted approximately 35 days, until recurrences began. Multiple treatment of small and large tumors resulted in high complete response rates that lasted at least 100 days after treatment. This indicates the feasibility of electrochemotherapy as a modality of limb-preserving treatment for patients with sarcoma of the extremities.

Animals↗
PubMed1999

Clinical applications of electrochemotherapy.

Electrochemotherapy is a novel treatment which consists of a combination of a chemotherapeutic agent and pulsed electric fields. This relatively new treatment modality relies on the physical effects of locally applied electric fields to temporarily destabilize cell membranes in the presence of a drug to allow increased uptake of the agent into the cytosol. Electrochemotherapy has been used effectively in preclinical and clinical studies. The therapy was shown to be effective regardless of histologic type of tumor including head and neck squamous cell carcinoma, melanoma, basal cell carcinoma, adenocarcinoma and Kaposi's sarcoma. Objective response rates ranging from 72 percent to 100 percent have been reported from these trials. These responses were obtained with minimal adverse side effects. A review of the clinical data for this novel drug delivery method is presented.

Journal Article↗
PubMed1999

In vivo gene delivery by electroporation.

The physical phenomenon of electroporation has been successfully exploited in vitro for the delivery of genes, drugs, and other molecules with increasing frequency over the past two decades. This type of electrically mediated delivery has been translated into an in vivo setting in more recent years with a focus on therapeutic molecules. One promising area is the delivery of genes as a therapy.Advances in molecular medicine have produced a very large amount of information about genes that translate to therapeutic molecules when expressed in living cells. Current standard methods for transferring genes utilize viruses to deliver DNA into cells. These viral methods have not yielded optimal results in most cases. Therefore, there is an increasing interest in nonviral methods for gene delivery. In vivo electrically mediated gene delivery is an attractive alternative because of the site specific nature of delivery as well as the universal applicability of electroporation. A review of the studies performed to investigate and develop this new gene delivery technology is presented.

Journal Article↗
PubMed1999

Nitric oxide inhibits proliferation of human endothelial cells via a mechanism independent of cGMP.

Endothelial cell-derived nitric oxide (NO) has been suggested to inhibit smooth muscle cell proliferation, resulting in the reduction of intimal hyperplasia during atherogenesis. The present study investigates the role of NO from exogenous and endogenous sources on the proliferation of human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (CAEC). Three different NO-generating compounds [sodium nitroprusside (SNP), S-nitroso-glutathione (GSNO) and S-nitroso-acetylpenicillamine (SNAP)] were found to inhibit endothelial cell proliferation measured with three independent methods (cell counting, [3H]thymidine incorporation, DNA histograms) with significant inhibition occurring at concentrations > or = 100 microM. Growth-inhibiting effects were observed after long-term treatment (18-96 h) as well as after short stimulation with NO donors (10 min with a subsequent NO donor-free culture period of 18 h) and were comparable in culture medium (20% serum, growth factor supplementation) and serum-deficient medium (1% serum). The NO donor effects were mediated by the release of NO as they were prevented by NO scavenging. Superoxide dismutase (SOD) was found not to interfere with these effects suggesting that peroxynitrite formation was unlikely to be involved. 1H-[l,2,4]Oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ), a specific inhibitor of the soluble guanylate cyclase, was observed not to alter the antiproliferative effects of NO donors although it completely prevented NO-mediated increase of cyclic guanosine 3',5'-monophosphate (cGMP), suggesting that the NO-induced growth inhibition was not mediated by cGMP. Furthermore, inhibition of endogenous NO production by N-nitro-L-arginine methylester (L-NAME) did not affect endothelial cell growth regardless of using serum plus growth factor supplement, growth factor supplement alone, or thrombin to stimulate proliferation. We suggest that constitutively synthesized NO may not regulate endothelial cell proliferation whereas the growth-inhibiting NO effects may occur when an inducible NO synthase associated with a persistently high NO production is expressed in the atherosclerotic vessel wall.

Analysis of Variance↗
PubMed1999

Reducing coronary heart disease in the Australian Coalfields: evaluation of a 10-year community intervention.

Coronary heart disease is a leading cause of death in Australia with the Coalfields district of New South Wales having one of the country's highest rates. Identification of the Coalfields epidemic in the 1970's led to the formation of a community awareness program in the late 1980's (the healthy heart support group) followed by a more intense community action program in 1990, the Coalfields Healthy Heartbeat (CHHB). CHHB is a coalition of community members, local government officers, health workers and University researchers. We evaluate the CHHB program, examining both the nature and sustainability of heart health activities undertaken, as well as trends in risk factor levels and rates of coronary events in the Coalfields in comparison with nearby local government areas. Process data reveal difficulties mobilising the community as a whole; activities had to be selected for interested subgroups such as families of heart disease patients, school children, retired people and women concerned with family nutrition and body maintenance. Outcome data show a significantly larger reduction in case fatality for Coalfields men (although nonfatal heart attacks did not decline) while changes in risk factors levels were comparable with surrounding areas. We explain positive responses to the CHHB by schools, heart attack survivors and women interested in body maintenance in terms of the meaning these subgroups find in health promotion discourses based on their embodied experiences. When faced with a threat to one's identity, health discourse suddenly becomes meaningful along with the regimens for health improvement. General public disinterest in heart health promotion is examined in the context of historical patterns of outsiders criticising the lifestyle of miners, an orientation toward communal rather than individual responsibility for health (i.e. community 'owned' emergency services and hospitals) and anger about risks from environmental hazards imposed by industrialists.

Adult↗
PubMed1999

Changing patterns of coronary heart disease in the hunter region of New South Wales, Australia.

A population-based observational study of men and women aged 35-69 years in the Hunter Region of New South Wales, Australia, was conducted to assess the impact of risk-factor modification and increased drug therapy on the trends in major coronary events and case fatality. From 1985 to 1993, there were 3006 coronary deaths and 6450 nonfatal major coronary events. Rates of death and nonfatal myocardial infarction declined, but there was an increase in hospital admissions for prolonged chest pain. Reductions in cigarette smoking, diastolic blood pressure, total cholesterol, and increased use of aspirin can fully explain the 3.3% (95% confidence interval [CI] 2.4, 4.2) average annual reduction in rates of major coronary events for men and the 4.1% (95% CI 2.7, 5.5) reduction for women. In contrast, increased use of aspirin, beta-blockers, fibrinolytic therapy, and angiotensin-converting enzyme inhibitors explain less than half of the 8.9% (95% CI 5.9, 11.8) and 6.9% (95% CI 2.7, 10.9) average annual reduction in case fatality in hospital for men and women, respectively. These trends suggest a decline in severity of coronary heart disease consistent with reductions in risk-factor levels and improved acute medical treatment.

Adult↗
PubMed1999

Bartonella alsatica sp. nov., a new Bartonella species isolated from the blood of wild rabbits.

Bartonella species are considered as emerging human pathogens, with at least six different species pathogenic or possibly pathogenic for humans. However, little is known about Bartonella distribution, species polymorphism and pathogenicity in mammalian species. The objective of this work was to determine the presence, the frequency and the distribution of Bartonella species in wild rabbits (Oryctolagus cuniculus) caught in warrens in Alsace, France. Humans may come into contact with wild rabbits when hunting, especially when they are picked up with bare hands and at time of evisceration. Of 30 blood samples collected and cultured from wild rabbits, nine (30%) were positive for organisms morphologically similar to Bartonella spp. The bacteria appeared as small, fastidious, aerobic, oxidase-negative, Gram-negative rods which could be localized within erythrocytes. Their biochemical properties were similar to those of the genus Bartonella. The sequence of the 16S rRNA gene obtained from the rabbit isolates was highly related to the sequences of the different Bartonella species (97.8-99.3% similarity). The high DNA hybridization rate (81-90% similarity) between the three strains isolated from rabbit blood confirmed that they belong to the same bacterial species. Hybridization values, obtained with the nuclease-TCA method, when testing type strains of recognized Bartonella species (9-14% similarity), support the creation of a new species for the rabbit isolates. The name Bartonella alsatica is proposed for these strains isolated from the blood of wild rabbits. The type strain is IBS 382T (= CIP 105477T).

Animals↗
PubMed1998

Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin.

BACKGROUND: Electrochemotherapy (ECT) is performed by locally administering a chemotherapeutic agent in combination with electric pulses. Previous clinical studies have demonstrated the effectiveness of ECT. In these initial trials, the drug was administered intravenously, followed by administration of electric pulses directly to the tumor. This study was initiated to determine whether an intralesional injection of the drug in combination with electric pulses could provide an improved result. A group of 34 patients was studied. METHODS: The dose of intralesional bleomycin was based on tumor volume. This was followed 10 minutes later by 6 or 8 99-microsec pulses of electricity at an amplitude of 1.3 kV/cm. Both the bleomycin and the electric pulses were administered after 1% lidocaine with epinephrine solution was injected around the treatment site. RESULTS: All patients responded to the treatment. Responses were observed in 142 (99%) of 143 metastatic nodules or primary tumors within 12 weeks, with complete responses observed in 130 (91%) of the nodules. No complete responses were observed in nodules treated with bleomycin only or electric pulses only. Random biopsies confirmed the clinical findings. All patients tolerated the procedure well, and no significant side effects were noted. Muscle contraction was evident during administration of each electric pulse but promptly subsided after the pulse. CONCLUSIONS: ECT was shown to be an effective local treatment for cutaneous malignancies. The results suggest that ECT may have a tissue-sparing effect and result in minimal scarring. ECT may be a suitable alternative therapy for the treatment of basal cell carcinoma, local or regional recurrent melanoma, and other skin cancers.

Adult↗
PubMed1998

Overexpression of the p80 TNF receptor leads to TNF-dependent apoptosis, nuclear factor-kappa B activation, and c-Jun kinase activation.

Because they have distinct intracellular domains, it has been proposed that the p60 and p80 forms of the TNF receptor mediate different signals. Several signaling proteins have been isolated that associate with either the p60 or the p80 receptor. By using TNF muteins specific to the p60 and p80 receptors, we have previously shown that cytotoxicity and nuclear factor-kappa B (NF-kappa B) activation are mediated through the p60 form of the endogenous receptor. What signals are mediated through the p80 receptor is less clear. This study was an effort to answer that question. HeLa cells, which express only p60 receptors, were transfected with p80 receptor cDNA and then examined for apoptosis, NF-kappa B activation, and c-Jun kinase activation induced by TNF and by p60 or p80 receptor-specific muteins. The p80 mutein, like TNF and the p60 mutein, induced apoptosis and activation of NF-kappa B and c-Jun kinase in cells overexpressing recombinant p80 receptor but had no effect on cells expressing a high level of endogenous p80 receptor. The apoptosis mediated through the p60 receptor was also potentiated after overexpression of the p80 receptor, suggesting a synergistic relationship between the two receptors. Interestingly, Abs to the p80 receptor blocked apoptosis induced by all ligands but by itself activated NF-kappa B in the p80-transfected cells. Overall, our results show that the p80 receptor, which lacks the death domain, mediated apoptosis, NF-kappa B activation, and c-Jun kinase activation, but only when it was overexpressed, whereas endogenous p60 receptor mediated similar signals without overexpression.

Antigens, CD↗