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Biomedical subjects

C Rosenthal

Publications and source records attributed to C Rosenthal.

At least 19 recordsLinked to original sources
PubMed2004

[Changing attitudes on the surgical treatment of urogenital prolapse: birth of the tension-free vaginal mesh].

OBJECTIVES: To describe, in view of the new standardization, the technique for urogenital prolapse repair using a one-piece synthetic mesh. MATERIALS AND METHODS: The history and development steps through which the Tension free Vaginal Mesh (TVM) technique emerged are described. The use of a mesh was prompted by the 20-30% recurrence rate associated with conventional repair techniques. Selection of the type of mesh is discussed. Non-absorbable synthetic meshes have shown their usefulness in visceral surgery. A list of materials along with their respective advantages and inconveniences is reviewed and particular emphasis is put on both the tolerance and erosion issues, the latter being specific to the vaginal route. The TVM Group selected a one-thread polypropylene mesh, Prolene Soft, which seemed the most appropriate for the transvaginal approach of prolapse surgical repair. The prosthesis and its design rationale are described. Full details are given on the consecutive intervention steps and underlying concepts. RESULTS: The relevant literature is scarce and there is a lack of methodologically sound studies validating the materials and techniques used. After completion of a first step of technique refinement and feasibility assessment involving about 300 surgical interventions, the authors initiated a prospective multicenter study. Clinical outcome assessments using feasibility, complications, and efficacy endpoints will be published after twelve months, three years, and five years of follow-up. CONCLUSION: Fruitful reasoning led to the development of the TVM technique of complete surgical repair of genital prolapse, which uses a synthetic materiel carefully selected after several tests. All surgeons can apply this technique after a short training period.

Female↗
PubMed2004

Disease- or therapy-related bone marrow damage cannot be overcome by changes in stem cell source or dose in allogeneic transplantation.

OBJECTIVE: To test whether the functional impairment of the host bone marrow (BM) microenvironment pre-existing at the time of transplantation could be overcome by the increased content of immature cells in allogeneic peripheral blood stem cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). METHODS: Cobble stone area forming cells (CAFC) were assayed in normal BM and BM after allogeneic BMT and PBSCT after stable engraftment. Groups were compared by two-tailed t-test. RESULTS: While BM from 11 normal controls contained an average of 778.8 CAFC-d35 per 10(6) low density bone marrow cells (LDBMC, range 453-1231 per 10(6) LDBMC), BM from patients after BMT contained an average of 123.7 CAFC-d35 per 10(6) LDBMC (range 38-257) per 10(6) LDBMC. BM from patients transplanted with PBSC after myeloablative conditioning contained 128.3 (range 46-305) CAFC-d35 per 10(6) LDBMC (P = 0.89 compared with BMT). Similar results were obtained when patients after PBSCT with non-myeloablative conditioning were included (P = 0.62 compared with BMT). CAFC numbers in patients transplanted in early stages of myeloid leukaemia (acute myeloid leukaemia first remission, chronic myeloid leukaemia first chronic phase) were significantly higher than CAFC numbers in patients transplanted in more advanced stages (P = 0.008) or myelodysplastic syndrome (P = 0.023). The lowest CAFC numbers were found in two cases of retransplantation. CONCLUSION: Our findings indicate that the functional state of the BM microenvironment rather than stem cell dose or source is limiting for the homing and engraftment of immature haemopoietic cells in clinical transplantation.

Adolescent↗
PubMed2003

Homeopathic treatment in emergency medicine: a case series.

Following a multiple-casualty construction disaster in Israel, members of The Center of Integrated Complementary Medicine joined in the emergency activity of the Shaare Zedek Medical Center. They administered homeopathic treatment to injured patients to supplement conventional orthopaedic treatment. This was to our knowledge the first time that complementary medicine had been used officially in conjunction with conventional medicine in an emergency situation. Our objective is to report and summarize the rationale, procedures and outcome of the complementary medicine intervention. Fifteen orthopaedic patients were included. They were treated by homeopathy in two phases starting 24 h post-trauma. All patients initially received Arnica montana 200CH in a single dose. Anxiety was treated with Aconite 200CH in nine patients, Opium 200CH in three, Ignatia 200CH in two and Arsenicum album 200CH in one according to type of anxiety. One day later, most patients reported a lessening of pain, 58% felt improvement, 89% had reduced anxiety, and overall, 61% felt that homeopathic treatment was helpful. In the second phase, 48 h post-trauma, specific complaints were addressed with classical homeopathy. At discharge patients rated the homeopathic treatment successful in 67% of the specific complaints. Several issues relating to the use of homeopathy in emergency medicine and its relation to conventional treatment are discussed. These include compliance, the conduct of rounds, shortage of time and staff, and the procurement of medicines.

Adult↗
PubMed2001

Restorative plasticity of dopamine neuronal transplants depends on the degree of hemispheric dominance.

The ability of dopaminergic (DA) transplants to restore complex sensorimotor behaviors in experimental Parkinson's disease is dependent on graft survival and reinnervation and is likely to be further modified by complex functional graft-host interactions. Here, we examined the impact of hemispheric dominance and extensive testing regimes on the functional capabilities of DA transplants to restore skilled forelimb movements in rats with unilateral 6-hydroxydopamine lesions. Interestingly, a near complete recovery was observed in DA-grafted animals that did not exhibit a strong hemispheric lateralization for paw use before lesion and implantation surgery, whereas animals with a clear lateralization of paw use and grafted into the contralateral hemisphere exhibited only moderate recovery. Finally, animals grafted ipsilateral to the preferred paw were most resistant to functional improvements in skilled forelimb use. However, the influence of hemispheric dominance on the degree of functional DA graft-induced restoration was specific for skilled forelimb use, whereas no such differences were observed in other tests for motor and sensory functions related to the DA system. Furthermore, functional recovery of DA-grafted animals in skilled forelimb use was significantly promoted by extensive behavioral testing regimes indicative of a "learning how to use" the transplant effect. These findings indicate the importance of the underlying functional architecture of complex sensorimotor behaviors, such as skilled forelimb use, and the DA neurotransmitter system for the plasticity of DA transplants to promoting a more complete behavioral recovery in experimental, and potentially, also in clinical forms of Parkinson's disease.

Amphetamine↗
PubMed2001

Career choices: a comparison of two occupational therapy practice groups.

The increasing number of elderly people in the population and their greater use of the health care system require an increasing number of health care providers to work with older adults. A shortage of health care professionals to provide this care, as well as a reluctance to provide such care have been reported in the literature. The purpose of this qualitative study was to investigate how occupational therapists decide to work with older adults. Using a comparative approach, 40 occupational therapists were interviewed, 20 working in gerontology and 20 working in paediatrics. The findings indicate that social characteristics and experiences of the individual, as well as the context of work are important influences for practice choice decisions. Mapping of career paths led to the development of a typology to further describe the different influences involved in the career choices of these occupational therapists. Recommendations related to education and practice provide practical means by which to implement change.

Adult↗
PubMed2001

[Current approaches in prevention and therapy of chemo- and radiotherapy-induced oral mucositis].

Oral mucositis is a major, often dose-limiting toxicity in modern cancer-therapy, leading to dose reductions or delay in further cancer treatment. It predisposes to life-threatening septic complication during aplasia and substantially reduces quality of life for cancer patients. At present the basic strategies in oral mucositis aim at pain relief and prevention of infectious complications. However, no effective causal prophylaxis or treatment of oral mucositis is widely accepted. The introduction of cytokines, e.g. granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), the use of cytoprotective agents, e.g. amifostine and the stimulation of basal-cell proliferation by soft-laser irradiation or silver nitrate offer new and hopeful approaches in oral mucositis. Large-scale clinical trials to confirm effectiveness and optimize treatment schedules have to be done.

Antineoplastic Agents↗
PubMed2000

Biological effects of stroma-derived factor-1 alpha on normal and CML CD34+ haemopoietic cells.

We compared the biological effects of the CXC chemokine SDF-1alpha on immunomagnetically purified CD34+ cells isolated from human normal bone marrow (NBM), leukapheresis products (LP) and patients with chronic myeloid leukaemia (CML). LP CD34+ cells showed a significantly stronger migration response to SDF-1alpha (100 ng/ml) than CD34+ cells isolated from the peripheral blood (PB) of CML patients (P < 0.05). The chemotactic response to SDF-1alpha was also reduced in CML BM CD34+ cells in comparison to NBM CD34+ cells but the observed differences were not statistically significant. In analogy to normal CD34+ cells circulating CML PB CD34+ cells were less responsive to SDF-1alpha than their BM counterparts (P < 0.05). Furthermore, SDF-1alpha elicited similar concentration-dependent growth suppressive effects on normal and CML CD34+ cells (P > 0.05) in colony-forming cell assays. We then demonstrated that SDF-1alpha triggers intracellular calcium increases in CD34+ cells and there were no differences in the time course and dose response characteristics of normal and CML CD34+ cells. The reduced migration response to SDF-1alpha in CML CD34+ cells was not due to a down-regulation of the SDF-1alpha receptor CXCR-4 as flow cytometric analysis revealed similar CXCR-4 expression levels on NBM, LP, CML PB and CML BM CD34+ cells (P > 0.05). Finally, no differences in the modulation of CXCR-4 levels in response to SDF-1alpha and serum were observed in CML and normal CD34+ cells. Our data suggest that the impaired chemotactic response of CML CD34+ cells to SDF-1alpha is not caused by a lack or complete uncoupling of CXCR-4, but may be due to an intracellular signalling defect downstream of the receptor.

Antigens, CD19↗
PubMed2000

Differential constitutive and activation-dependent expression of prion protein in human peripheral blood leucocytes.

The cellular isoform of the prion protein (PrPC) is a cell surface glycoprotein that has recently been shown to play a role in haemopoietic cell activation and proliferation. We have characterized the constitutive expression of PrPC on human peripheral blood (pB) cell populations, using PrP-specific antibodies in a multiparameter flow cytometry approach. We found that T cells, NK cells and monocytes exhibit similar PrPC levels, whereas PrPC surface staining on B cells was significantly lower and was virtually absent on granulocytes. Within the T-cell compartment, CD8+ cells showed a significantly higher PrPC expression than CD4+ cells. Similarly, CD3+ cells co-expressing the activation marker CD56 (N-CAM) exhibited significantly higher PrPC expression levels than their CD56- counterparts. Culture of CD14+ pB monocytes for 12-48 h in the presence of interferon gamma (IFN-gamma) resulted in a significant increase in PrPC expression in a time- and concentration-dependent manner. This effect was partially abrogated by the addition of the metabolic inhibitor cycloheximide, indicating the role of protein synthesis in this process. Our results show that PrPC expression on human haemopoietic cells correlates with the activation and developmental status of these cells, suggesting an important functional role of PrPC in the haemopoietic system.

B-Lymphocytes↗
PubMed2000

Intercellular communication between bone marrow stromal cells and CD34+ haematopoietic progenitor cells is mediated by connexin 43-type gap junctions.

The existence of functional gap junctions between haematopoietic progenitor cells (HPCs) and stromal cells of the haematopoietic microenvironment in the human system is a controversial issue. Primary CD34+ HPCs isolated from leukapheresis products were co-incubated with the human fibroblastoid bone marrow stromal cell line L87/4 in short-term liquid culture. Using the highly sensitive double whole-cell patch-clamp technique, we found that the majority (91%) of CD34+ HPCs are electrically coupled to L87/4 cells. Importantly, efficient coupling was observed within 1 h of the attachment of CD34+ HPCs to plastic adherent L87/4 cells. By comparison, homologous cell pairs formed by L87/4 cells exhibited a significantly higher electric coupling. Analysis of single-channel conductances revealed an electric profile characteristic of connexin 43 (Cx43)-type gap junctions for both homologous and heterologous cell pairs. The Cx phenotype was confirmed using Cx43-specific monoclonal antibodies in a flow cytometric assay and reverse transcription polymerase chain reaction (RT-PCR) for the detection of Cx43 mRNA. Finally, the electrophysiological studies were complemented by dye-transfer experiments using the recently described 'parachute' technique that allows the monitoring of dye diffusion without disruption of the plasma membrane. Taken together, our data indicate that functional Cx43-type gap junctions exist between stromal cells and immature HPCs and, thus, may provide an important regulatory pathway in haematopoiesis.

Antigens, CD34↗
PubMed1999

Evaluation of IgG, IgM, and IgA antibodies to mycoplasma penetrans detected by ELISA and immunoblot in HIV-1-infected and STD patients, in São Paulo, Prazil.

The aim of the present study was to determine the frequency of IgG, IgA, and IgM antibodies to Mycoplasma penetrans in HIV-1-infected patients and in patients with sexually transmitted diseases. We tested serum samples from 106 HIV-1-positive patients and 110 individuals with clinical symptoms of urethritis. ELISA and the immunoblot test were performed using M. penetrans lipid associated membrane proteins as antigen. By ELISA, we found a higher frequency (P < 0.05) of IgG against M. penetrans in HIV-1-infected and STD patients (25.5 and 17.3%) than in controls (1.2%), as well as a higher frequency of IgA (P < 0.05) (15.1 and 17.3% compared to 1.2%). For IgM, no differences were observed (P >/= 0.05) (3.8, 9.1, and 5. 8%, respectively). When the frequencies of IgG, IgM, and IgA antibodies of the HIV-1-infected patients were compared taking into account the CD4/CD8 cell ratios < 0.3 and >/= 0.3, no significant differences were observed between the two groups (13.3, 10, and 20%, compared to 20, 0, and 5%, respectively) (P > 0.05), possibly due to the low number of samples on which we could perform T-cell counts (53/106). The M. penetrans peptide of 38 kDa, considered immunodominant, was recognized in immunoblot by 51.8% of positive sera by ELISA for IgG, 50.0% for IgM, and 75% for IgA in the AIDS patients group, and by 47.4, 60.0, and 75.0%, respectively, in the sexually transmitted disease group. Cross-reactions in immunoblot for IgG were observed in sera from individuals infected with Mycoplasma pneumoniae and Mycoplasma hominis, and cross-reactions in immunoblot for IgA were observed in sera from individuals infected with M. hominis; all of them were ELISA negative to M. penetrans.

Adolescent↗
PubMed1999

Prophylaxis and treatment of chemo- and radiotherapy-induced oral mucositis - are there new strategies?

Oral mucositis is a major dose-limiting toxic effect of intensive cancer chemotherapy. Oral complications may lead to dose reduction or delay in further cancer treatment. Mucositis can be caused directly by cytotoxic effects and indirectly by sustained neutropenia after cytostatic therapy. An impaired mucosal barrier predisposes to life-threatening septic complications during aplasia. The prevalence of an oral focus in febrile neutropenia has been reported in up to 30% of cases and also reduces quality of life. The basic strategies aim at pain relief and prevention of bacterial and fungal infectious complications. However, no effective causal prophylaxis or treatment of oral mucositis is widely accepted. The introduction of cytokines, eg granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) for oral mucositis may be particularly effective and offer a new and hopeful approach. At present, the optimal growth factor, best schedule, effective dosage and best mode of application is not known.

Antineoplastic Agents↗
PubMed1998

Seizure suppression in kindling epilepsy by grafts of fetal GABAergic neurons in rat substantia nigra.

Compared with studies on models of neurodegenerative diseases, considerably less work has been performed with neural grafts in experimental epilepsy. The potential value of this approach, however, is already shown by evidence that noradrenergic grafts implanted bilaterally into the hippocampus or amygdala-piriform cortex can suppress seizure development in the kindling model of temporal lobe epilepsy. We previously showed that amygdala kindling results in a significant decrease of GABA and its synthesizing enzyme glutamate decarboxylase in substantia nigra (SN), i.e., a region thought to be critically involved in seizure propagation in various models of epilepsy. Thus, transplantation of fetal GABAergic neurons into SN might be an effective means of permanently blocking seizure generalization in kindling epilepsy and probably also other types of epilepsy. To test this hypothesis, three groups of female Wistar rats (n = 10 per group) were kindled by electrical stimulation via a bipolar electrode in the basolateral amygdala. After all rats were fully kindled, one group was implanted with GABA-rich cells prepared from the striatal eminence of Wistar rat fetuses at embryonic day 14. The striatal neurons were bilaterally microinjected at various sites over the anterior-posterior axis of the SN, aimed at the pars reticulata. The second group received microinjections of spinal cord cell preparations, whereas the third group received microinjections of cell-free medium only. In all rats, the threshold for focal discharges (afterdischarge threshold [ADT]) as well as afterdischarge duration and severity and duration of seizures occurring at ADT current were determined once weekly before and after transplantation. Eleven to 12 weeks following transplantation, the rats were killed, and location and integration of grafts were examined by immunohistological methods. Rats with GABAergic grafts in SN exhibited a significant increase in ADT and marked reduction in seizure severity compared with pretransplantation values, whereas no such alteration was seen in the other groups. However, the seizure-suppressing effect of GABAergic grafts was not permanent but slowly disappeared over the weeks after transplantation. Although the data indicate that intranigral transplantation of GABA-producing cells is no effective means of inducing long-lasting anticonvulsant effects in experimental epilepsy, this approach may be an initial step to develop more efficient strategies for seizure suppression.

Animals↗
PubMed1998

Differences in acquisition and full performance in skilled forelimb use as measured by the 'staircase test' in five rat strains.

Skilled forelimb use was examined in five different rat strains (DA/Ztm, LEW/Ztm-ci, LEW.1W/Ztm, SD/Ztm, SPRD/Ztm-Cu3) by means of the 'staircase test', as originally described by Montoya et al. [20] (C.P. Montoya, H.L. Campbell, K.D. Pemberton, S.B. Dunnett, The 'staircase test': A measure of independent forelimb reaching and grasping abilities in rats, J. Neurosci. Methods 36 (1991) 219-228). Strain-dependent differences were observed most prominently during the acquisition phase, and less pronounced, at the full performance level. SD/Ztm and DA/Ztm rat strains seemed to be particularly skilled in their forelimb use, although with varying levels of activity. Interestingly, significant differences in skilled forelimb movements were found between the related Sprague-Dawley derived and Lewis congenic rat strains. No clear-cut correlation was found between skilled forelimb use and basic nutrition-dependent measures, such as pretest body weight or weightloss during the test period. Based on previous observations on strain-dependent behavioral variations it seems likely that the differences in skilled forelimb use, as observed in the present study, might be caused by morphological and/or functional strain-dependent alterations in the involved neuronal circuitries, such as motor cortex, caudate-putamen unit and mesotelencephalic dopamine system. However, they should also be considered as potentially influencing parameters in studies related to the behavioral effects of lesions and restorative therapies in the central nervous system.

Animals↗
PubMed1998

Effect of topical oral G-CSF on oral mucositis: a randomised placebo-controlled trial.

Oral mucositis is a dose-limiting toxicity of intensive chemotherapy. It is caused directly by the cytotoxic effect of chemotherapeutic agents and indirectly by sustained neutropenia. Severe oral mucositis is an important predisposing factor for life-threatening septic complications during aplasia. It also reduces quality of life. At present, no effective causal prophylaxis or treatment against oral mucositis is established. We performed a prospective randomised placebo-controlled trial using topical oral r-metHuG-CSF (filgrastim) in high-grade lymphoma patients treated according to the B-NHL protocol, which contains high-dose methotrexate and causes severe oral mucositis (WHO grades I-IV) in >50% of patients. Between August 1996 and July 1997, a total of 32 chemotherapy cycles were documented in eight patients (four male, four female). Mucosal erythema and ulceration were recorded. All patients assessed their oral pain and impact on swallowing daily, using a subjective scale from no to maximal discomfort (1-10). In addition, oral mucositis was assessed according to the WHO score. Filgrastim was administered in 16 cycles as a viscous mouthrinse (carboxymethylcellulose 2%, oleum citrii) 4 x 120 microg/day from days 10 to 16. Sixteen cycles were given to control patients, of these 14 with placebo, and another two cycles with no treatment. Severe mucositis (WHO grade III/IV) was documented in 21 of 32 cycles (65.5%). A difference of borderline significance was observed for the reduction of maximum severity of oral mucositis between G-CSF vs placebo (P = 0.058), with a reduction of WHO grade IV of 50% (four G-CSF vs eight control). The number of days in hospital was reduced significantly in the G-CSF group (P = 0.02). In conclusion, topical oral G-CSF mouthrinses may be beneficial to reduce oral mucositis.

Administration, Topical↗
PubMed1998

A comparison among animal models of acute lung injury.

OBJECTIVES: To compare four widely used animal models of acute lung injury and to determine the changes in physiologic variables associated with each model. DESIGN: A prospective, controlled animal study. SETTING: An animal laboratory of a university-affiliated children's hospital. SUBJECTS: Four groups of anesthetized, paralyzed, and ventilated young Yorkshire pigs, weighing 35 to 45 kg. INTERVENTIONS: Acute lung injury was generated by four different methods: a) intrapulmonary arterial infusion of endotoxin of Escherichia colt; b) bronchoalveolar instillation of 0.05N of hydrochloric acid; c) repeated bronchoalveolar warm saline lavage; and d) intrapulmonary arterial infusion of oleic acid. After each acute lung injury procedure, the temporal changes in various physiologic variables were measured, starting at 60 mins and at 15-min intervals thereafter for a total of 165 mins. Systemic and mixed venous serum immunoreactive tumor necrosis factor (TNF)-alpha concentrations were also measured at the same time points. Analysis of variance for repeated measures was employed to determine the absolute and relative significance of the changes observed. MEASUREMENTS AND MAIN RESULTS: Systemic and mixed venous immunoreactive TNF-alpha did not change following any of the acute lung injury procedures. The animals' heart rates and systemic vascular resistances also did not change. Hydrochloric acid instillation as well as bronchoalveolar lavage resulted in significant hypoxemia with no other hemodynamic effects. Endotoxin infusion did not result in hypoxemia but caused significant increases in mean pulmonary arterial pressure and pulmonary vascular resistance and decreases in mean arterial pressure and cardiac output. Oleic acid infusion resulted in a marked hypoxemia with a pronounced increase in mean pulmonary arterial pressure and pulmonary vascular resistance. It also markedly reduced the mean arterial pressure, cardiac output, and the mixed venous PO2. CONCLUSIONS: The surfactant depletion and hydrochloric acid instillation models produce acute hypoxemia in an otherwise hemodynamically stable animal. A brief endotoxin infusion provides a model for cardiovascular instability and pulmonary hypertension but fails to produce hypoxemia in the pig. The oleic acid infusion creates a model of marked cardiovascular instability, pulmonary hypertension, and profound hypoxemia. However, none of the acute lung injury models described was associated with the production of tumor necrosis factor.

Animals↗
PubMed1998

Dopaminergic graft-induced long-term recovery of complex sensorimotor behaviors in a rat model of Parkinson's disease.

Transplantation of embryonic dopamine neurons has evolved as an alternative neurosurgical treatment strategy for patients with Parkinson's disease and it is therefore of great interest to further optimise this procedure in experimental studies. We have applied a modified microtransplantation approach in unilaterally 6-hydroxydopamine lesioned rats and observed a substantial and long-lasting functional recovery in complex spontaneous behaviors, such as skilled forelimb use and stepping behavior. The results demonstrate that the rat model of Parkinson's disease is a highly useful tool to study mechanisms of neural plasticity and regeneration. The ability of dopaminergic grafts to restore complex sensorimotor behaviors in animals also indicate their great potential for the development of a successful clinical application.

Animals↗