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Biomedical subjects

E Reich

Publications and source records attributed to E Reich.

At least 19 recordsLinked to original sources

Photodynamic efficiency of liposome-administered tetramethyl hematoporphyrin in two human bladder cancer cell lines.

The main problems presented by superficial bladder carcinoma, its high recurrence rate and multifocal appearance, require treatment of the bladder as a whole. Photodynamic therapy (PDT) is one such experimental treatment for superficial bladder carcinoma, involving the administration of a photosensitizer that accumulates in the tumor tissue, and subsequent irradiation of the tumor with light. Since the photosensitizers used in PDT suffer from several drawbacks, new photosensitizers are being sought. Drug delivery systems are also being investigated for the administration of hydrophobic photosensitizers and enhancement of photodynamic efficiency and tumor selectivity. In this study we examined a new photosensitizer, tetramethyl hematoporphyrin (TMHP), in two human bladder cancer cell lines. In the first pair of the experiments, TMHP was bound to unilamellar liposomes. Cellular uptake, dark toxicity and photodynamic efficiency were then studied. Fluorescence microscopy showed TMHP localization in the cytoplasm in a perinuclear region, sparing the nucleus. Dark toxicity occurred after incubation of cells with TMHP above a concentration of 20 micrograms/ml. Irradiation was carried out using an argon-pumped dye laser emitting a wavelength of 630 nm at a fluence of 3.6 and 7.2 J/cm2. Before irradiation, cells were incubated with TMHP at concentrations of 2.5 and 5 micrograms/ml for 1 h. Cell survival rates after incubation with 5 micrograms/ml TMHP and irradiation at 7.2 J/cm2 were 15.7% of control cells for Rec and 4.5% for Waf cells. Uptake studies showed a higher intracellular TMHP concentration in Waf than in Rec cells. This correlates with the higher PDT efficiency seen in Waf cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell

Effect of dimension of luting space and luting composite on marginal adaptation of a class II ceramic inlay.

This study evaluated the in vitro marginal quality at the interproximal cervical margin of class II Cerec restorations. Marginal quality was evaluated separately by (1) SEM analysis before and after simultaneous thermocycling and mechanical loading for the integrity of the restoration surface and (2) dye penetration after thermocycling and mechanical loading to evaluate the strength of the bond within the depth of the cavity. The results reveal that marginal integrity is influenced by the width of the luting space and the luting composite. With a luting space of 100 microns, marginal quality with as little as 3% to 14% loss of adhesion can be obtained. Luting spaces greater than 100 microns can partially be compensated by the luting composite. For Cerec inlays, highly filled luting composites with a high viscosity are recommended.

Adhesiveness

Tongue paralysis following head trauma.

Paralysis of the tongue due to isolated bilateral hypoglossal nerve palsy is a rare occurrence. Due to a trauma the cause in our case may have been a traction injury to both hypoglossal nerves at the base of skull. In some cases a contributing factor may be malformation of the skull base. Most cases have a good prognosis for recovery.

Craniocerebral Trauma

Clinical and radiographical split-mouth-study on resorbable versus non-resorbable GTR-membranes.

The aim of this prospective split-mouth-study was to compare the 5-months-healing results after implantation of resorbable (Polyglactin-910) and non-resorbable (e-PTFE) GTR-membranes. 12 healthy patients with 41 periodontal defects were treated. Radiographical and clinical examinations (papillary bleeding index, gingival recession, probing pocket depth, probing attachment level, and furcation depth) were carried out under standardized conditions immediately before and 5 months after surgery. The vertical relative attachment gain (V-rAG) was calculated as a % of the bony defect depth (intra-operatively measured) at baseline, and the horizontal relative attachment gain (H-rAG) as a % of the furcation depth at baseline. The standardized radiographs were evaluated blind by 4 experienced examiners for changes of the alveolar bone. Furthermore, digital subtraction radiography was carried out using the standard deviation of the grey level histograms in the experimental region and in a control region as a test parameter for bone changes. Both types of membranes achieved an attachment gain. Using the split-mouth-design, no statistically significant (< or = 0.05) difference between the two membranes could be detected (number of defects/median) with regard to V-rAG (Polyglactin: 12/77.5%, e-PTFE: 12/73.2%) or to H-rAG of class-II-furcations (Polyglactin: 5/66.7%, e-PTFE: 5/66.7%), or to bone changes using conventional and subtraction radiographic evaluation. In conclusion based on this 5-months-study, the resorbable membranes provided attachment gain comparable to the e-PTFE-membranes.

Adult

Prognostic factors for prolonged progression-free survival with high-dose chemotherapy with autologous stem-cell support for advanced breast cancer.

PURPOSE: With a median observation time of 50 months from transplant, 13 (22%) of 62 women with metastatic breast cancer treated with high-dose chemotherapy at the Dana-Farber Cancer Institute (DFCI)/Beth Israel Hospital (BIH) remain progression-free. This study determined factors prognostic for prolonged progression-free survival (PFS). METHODS: From June 1988 to January 1992, women who responded to standard chemotherapy received high-dose cyclophosphamide, thiotepa, and carboplatin with autotransplantation. Data encompassing initial breast cancer diagnosis, metastatic presentation, and response to induction treatment were examined for correlations with improved PFS. RESULTS: The 5-year PFS rate for the entire group is estimated to be 21% (95% confidence interval [CI], 10% to 32%). For those patients who attained a complete response (CR) to induction therapy, the 5-year PFS rate is estimated to be 31% (95% CI, 0% to 63%). In univariate analyses, a single metastatic site, CR to induction therapy, prolonged interval from primary diagnosis to first metastases, estrogen receptor (ER)-negative tumors, and older age (> or = 40 years) were associated with prolonged PFS. In multivariate analyses, single metastatic site (P = .002) and attainment of a CR to induction chemotherapy (P = .04) were the most significant predictors for PFS, with a strong trend observed for an interval from primary diagnosis to onset of metastatic disease of 24+ months (P = .066). CONCLUSION: We and others have shown that 10% to 25% of women with metastatic breast cancer are progression-free after high-dose chemotherapy with autotransplantation. Those with chemosensitive disease, minimal tumor bulk, and a prolonged disease-free interval appear to benefit most. Emphasis should continue to focus on the development of more effective cytotoxic regimens and biologic approaches to increase the percentage of patients who may benefit from this approach.

Adolescent

Uptake and phototoxic effects of aluminum-chlorophthalocyanine (AlSPc) in human bladder carcinoma cells.

In vitro experiments were performed on human bladder carcinoma cells to evaluate the uptake of aluminum-chlorophthalocyanine (AISPc) and the subcellular target of phototoxicity. In order to quantify the correlation of intracellular uptake and incubation time and to identify the primary subcellular target of phototoxicity, fluorescence and absorption measurements have been carried out as well as electron microscopic studies. Absorption and fluorescence measurements showed the largest value after 24 h of incubation time. Fluorescence microscopic studies suggested the sensitizer to be located in a brighter patch within cytoplasm. Electron microscopic studies using DAB (3,3' diaminobenzidine) staining showed that the mitochondria are the primary target of phototoxic activity of AlSPc and that the majority of vacuoles of treated cells were originally mitochondria.

Carcinoma, Transitional Cell

Photodynamic therapy of human bladder carcinoma cells in vitro with pH-sensitive liposomes as carriers for 9-acetoxy-tetra-n-propylporphycene.

In vitro experiments were performed on human bladder carcinoma cells to evaluate the efficiency of the recently synthesized photosensitizer 9-acetoxy-tetra-n-propylporphycene (ATPPn) for photodynamic therapy. To improve cytoplasmic delivery of this hydrophobic compound, we prepared pH-sensitive liposomes composed of phosphatidylethanolamine (PE) and cholesteryl hemisuccinate (CHEMS) in comparison with pH-insensitive liposomes consisting of phosphatidylcholine (PC) and CHEMS. Dynamic light scattering measurements were used to monitor the acid-induced liposome destabilization. After incubation with liposome-bound ATPPn, bladder carcinoma cells were irradiated by a dye laser with increasing light fluence rates from 1 to 48 J/cm2. The photodynamic effects were then assessed from cell survival curves. No dark or phospholipid toxicity was measured for 2 micrograms ATPPn/1.5 ml medium. Qualitative cellular uptake of ATPPn was determined by fluorescence microscopy, while photodamage was elucidated by transmission and scanning electron microscopy. Absorption spectra performed up to 42 days revealed changes in shape for the pH-sensitive liposomes after storage at room temperature. ATPPn was proved to be an encouraging photosensitizer, capable of reducing cell survival to 0.1% after short-term incubation of 60 min with a drug dose of 2 micrograms ATPPn/1.5 ml medium. Although pH-sensitive PE/CHEMS liposomes showed significantly (P < 0.05) more photokilling effects at 24 J/cm2 and 48 J/cm2, no further advantages over non-pH-sensitive PC/CHEMS liposomes were found.

Carcinoma

Recombinant human erythropoietin for the treatment of the anaemia associated with autologous bone marrow transplantation.

Patients with solid tumours undergoing high-dose chemotherapy with autologous bone marrow transplantation use an average of 10 units of packed red blood cells (PRBC) while awaiting haemopoietic reconstitution. They are also known to have inappropriately low endogenous erythropoietin levels for their degree of anaemia. This pilot study was designed to determine the effects of recombinant human erythropoietin (rHuEPO) on erythroid recovery and PRBC transfusion requirements. Ten patients received high-dose chemotherapy (days -7 to -3), bone marrow reinfusion (day 0), and then rHuEPO (day 1 onward). RHuEPO (200 units/kg intravenous bolus daily), along with iron supplementation, was administered for 28 d or until a haematocrit (Hct) of 35% (independent of transfusions) was reached, whichever occurred first. PRBCs were routinely given for Hct < or = 25% and platelets for counts < 20,000/microliters. Eight (80%) patients developed a brisk reticulocytosis (median peak reticulocyte count 0.32 x 10(9)/l) and a haematocrit > or = 30% independent of red blood cell transfusions within 32 d of receiving marrow, as compared to 20/37 (54%) similarly treated controls. An unexpected finding was the more rapid engraftment in myeloid and platelet lineages in a subset of rHuEPO-treated patients. Quick return of red blood cells (17 v 33 d) (P = 0.0001), platelets (14 v 19 d) (P = 0.04), and neutrophils (13 v 25 d) (P = 0.01) (with circulating myeloblasts and early myeloid forms) characterized recovery from an ifosfamide-based intensification with rHuEPO support. Similar trilineage enhancement of haemopoiesis did not occur with the possibly more myeloablative cyclophosphamide-based regimens. Despite the enhancement by rHuEPO on reticulocytosis, there was no significant decrease in PRBC transfusion requirements. RHuEPO proved to be a well-tolerated agent in enhancing reticulocytosis following high-dose chemotherapy. Further study to elucidate the activity of erythropoietin on both erythroid and non-erythroid growth and maturation appears warranted.

Adult

Double dose-intensive chemotherapy with autologous marrow and peripheral-blood progenitor-cell support for metastatic breast cancer: a feasibility study.

PURPOSE: Twenty-seven percent of responding metastatic breast cancer patients remain progression-free a median 29 months following one intensification course of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). European investigators report high complete response (CR) rates with melphalan for breast cancer. This trial studied the feasibility of two tandem high-dose intensification therapies in an attempt to optimize disease response and duration. PATIENTS AND METHODS: Women with at least partial responses (PRs) to induction therapy received melphalan (140 to 180 mg/m2), followed 24 hours later by chemotherapy and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral-blood progenitor cells (PBPCs) and subsequent G-CSF until WBC recovery. The women were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Twenty women were assessable. Fourteen (70%) required admission for fever (10% infection) or mucositis (35%) after melphalan (median stay, 5 days). Median days of absolute neutrophil count (ANC) less than 500/microL and platelet count less than 20,000/microL were 6 and 5.5, respectively. Patients received CTCb 25 days after starting melphalan and had a hospital stay of 25 days. After CTCb, median days of ANC less than 500/microL and platelet count less than 20,000/microL were 11.5 and 24, respectively. Grade 3 toxicities included venoocclusive disease (VOD) (10%), mucositis (45%), and infection (20%). Toxicities were reversible without mortality. CONCLUSION: With mobilized PBPCs and growth factors, double dose-intensive chemotherapy is feasible with acceptable toxicity. When compared with trials using marrow alone, these supportive adjuncts decrease sepsis and organ toxicity. The concepts of dose and dose-intensity may now be more effectively and safely studied in chemosensitive tumors, including breast cancer.

Adult

Photodynamic therapy of bladder cancer--uptake and phototoxicity of photosan in vitro.

The uptake of photosan and the intracellular sites of photoradiation-induced damage were investigated in vitro in bladder carcinoma cells and in normal bladder cells. Cells were examined by phase contrast, fluorescence and electron microscopy. The concentration of photosan, measured in microgram/10(6) cells, showed a good correlation to the incubation time. At all incubation times, control cells showed a lower uptake when compared with tumor cells. Following photodynamic therapy (PDT), phase-contrast microscopy revealed marked changes in tumor cells, whereas only minor effects could be detected at the cell membrane of the control cells. Following PDT, most of the investigated cells showed changes of the mitochondria and cytoplasma. These changes consisted of dissolution of the cristae, predominantly in the central part of the mitochondria. Twenty-four hours after PDT the shape of the mitochondria had changed markedly and the cristae were found to be completely destroyed. Moreover, the cystoplasma showed numerous vacuoles, and the number of mitochondria was decreased compared to non-treated cells.

Antineoplastic Agents

Prospective study of manikin-only versus manikin and human subject endotracheal intubation training of paramedics.

STUDY OBJECTIVES: To determine the effect of manikin-only training on field success of endotracheal intubation by paramedics. DESIGN: Prospective evaluation of individual field endotracheal intubation success rates for paramedics after they participated in a manikin-only or a manikin-plus-cadaver training program. TYPES OF PARTICIPANTS: Paramedics responding to emergency calls involving adult medical or trauma victims. INTERVENTIONS: All participants were trained using a controlled manikin training program; then, half were randomly selected for additional instruction using fresh human cadavers. MEASUREMENTS AND MAIN RESULTS: Individuals trained using only the manikin program had mean +/- SD individual success rates of 82 +/- 32%, and individuals who received additional cadaver training had mean individual success rates of 83 +/- 31%. Overall success rates for the two groups were 86% for the manikin-only group and 85% for the manikin-plus-cadaver-trained group. The sample size was not adequate to allow rejection of the null hypothesis. CONCLUSION: Paramedics trained in endotracheal intubation using a systematic manikin-only teaching program can attain acceptable individual success rates in the actual field setting.

Cadaver

[Glass ionomer cement and "sandwich" restorations after two years of clinical service].

Esthetic restorations for class V lesions extending into root dentin often show marginal discoloration after some time. In this clinical study the long term quality of glass ionomer cement and "sandwich" restorations was compared with each other. In 19 patients 83 class V lesions with the apical margin in dentin were restored with glassionomer cement (I: Fuji II/G-C Dental; II: Ketac Fil/ESPE) or with a glass ionomer liner (III: Lining Cement/G-C Dental; IV: Ketac Bond/ESPE) and laminated with a composite. Where necessary the margins were prepared apically with a butt joint. The observation period between placement and last follow-up check varied between 18 and 44 months. Modified Ryge criteria were used for the clinical assessment of 77 restorations. Marginal quality was assessed in the SEM using replicas. 15.8% of the "sandwich" type and 5% of the glass ionomer cement restorations were lost. All restored teeth remained vital. Clinically the best marginal quality was found with a glass ionomer cement (II) whereas only two thirds of the sandwich restorations and the other glassionomer cement (I) had perfect margins. In the SEM the glassionomer cements had significantly less marginal openings than one of the sandwich restorations (III).

Composite Resins

[Marginal fit of ceramic and composite inlays in vitro].

Direct and indirect composite and ceramic inlays exhibit a space between inlay and tooth, which is filled with a luting composite resin. The aim of the present study was to evaluate the influence of the width of this space upon the quality of the marginal seal of the inlay system. The marginal quality of class II-inlays with small (0.2 mm) and large (0.4 mm) spaces was examined using quantitative SEM analysis and dye penetration. Regular class-II composite fillings served as controls. After thermal and mechanical loading the composite inlays with the wider composite layer showed more marginal gaps than both groups of ceramic inlays. The ceramic inlays did not show a significant deterioration of the margins. The least amount of dye penetration was observed in ceramic inlays with a wider composite layer at the interproximal cavity wall. Composite fillings showed more dye penetration than inlays.

Ceramics

Direct measurement of the bactericidal effect of chlorhexidine on human dental plaque.

The purpose of the present study was to determine by means of a fluorescence test the ratio between vital and dead bacteria in dental plaque before and after 0.1% chlorhexidine rinses. Plaque was stained by fluoresceindiacetate (FDA), which gave a green color to the living micro-organisms, and by ethidiumbromide (EB), which introduced a red color into the nucleic acids of the dead bacteria. 1-, 2- and 3-day-old undisturbed plaque harbored 80 to 85% living micro-organisms. 1 h after chlorhexidine use, this % was reduced to a plateau of 19 to 34% of vital bacteria present in the sampled plaque. Between 6 and 8 h later, this % rose towards its original value. This study has shown that FDA/EB staining provides a method for direct measurement of bacteria vitality in dental plaque and, as such, can be of great value for testing the efficacy of various antiplaque agents.

Adult

[Marginal gaps of combined composite and glass ionomer cement fillings in different preparations in vitro].

In 34 extracted molars with class V cavities (coronal margin in the enamel, apical margin in the dentin) a shoulder or a shoulder with bevel were prepared on the apical aspect. The dentin was covered with glass ionomer cement (GIC) and after beveling the neighboring enamel composite material was applied on top with enamel etching. 24 other cavities filled with either composite or glass ionomer cement served as controls. The specimen were exposed to 2000 alternating thermal tests (1 min. at 8 degrees C, 1 min at 60 degrees C) and alternations of the filling margins were recorded quantitatively using replicas in the SEM. After the alternating thermal tests GIC controls showed statistically significant better margin in enamel and dentin with shoulder preparations alone than the combined or pure composite fillings. Combined fillings with beveled apical cavity margins were superior to shoulder preparations alone. Glass ionomer cement seems to be better for the treatment of class V cavities in terms of margin tightness than composite alone or in combination.

Composite Resins

[In vivo contact angle measurements on filling materials before and after surface polishing].

The adhesion of oral bacteria on teeth and filling materials is a function of the surface energy and consequently the contact angle of a drop of fluid on the respective material. This study determines the contact angle on various filling materials (composites, glass ionomere cement) before and after surface polishing. Thirty and sixty minutes after application of the filling materials composites demonstrated contact angles which partly were significantly smaller than on natural enamel. Glass ionomere cements did not show any significant differences from enamel. After surface polishing, one composite material and one glass ionomere cement showed significantly larger contact angles than before. Further studies are required to elucidate the clinical relevance of different contact angles.

Chemical Phenomena