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Biomedical subjects

R Braun

Publications and source records attributed to R Braun.

At least 73 records · Page 4Linked to original sources

Adenovirus-mediated TNF-alpha gene transfer induces significant tumor regression in mice.

Recombinant adenovirus vectors are highly efficient at in vitro and in vivo gene delivery. The in vitro infection of a mouse colon adenocarcinoma cell line MCA-26 with the adenovirus AdV-LacZ can reach a maximal 75% of infectivity at an MOI of 1000. Intratumoral injection of AdV-LacZ (2X10(9) pfu) resulted in substantial gene transfer in nearly 70% of MCA-26 tumors. After the in vitro infection of AdV-TNF-alpha, infected MCA-26 cells showed significant secretion of TNF-alpha (45 ng/ml/10(6) cells) in tissue culture. The secretion peaks at day 2 and is diminished at day 4 following the viral infection. Infected MCA-26 tumor cells secreting TNF-alpha significantly reduced their tumorigenicity in syngeneic BALB/c mice. In mice bearing small tumors, intratumoral injection of 2X10(9) pfu of AdV-TNF-alpha virus with a repeated booster treatment resulted in complete regression of three tumors and significant diminution of the other two with a mean tumor-weight of 0.16 g; this is in contrast to 0.85 and 1.62 g for tumors injected with the control AdV-pLpA and PBS respectively (p < 0.01). Mice with complete tumor regression further developed protective immunity against the second challenge of MCA-26 inoculation. In mice bearing large tumors, this treatment also caused significant inhibition of tumor growth with a mean tumor weight of 0.65 g vis-a-vis 3.05 g for tumors injected with the control AdV-pLpA. On the contrary, in mice bearing large tumors, the treatment of tumors with pCI-TNF-alpha delivered by the gene gun did not induce significant tumor inhibition. These results indicate that the adenoviral delivery of TNF-alpha gene is more efficient than the particle-mediated gene gun device, and that adenovirus-mediated cytokine gene therapy may be a useful approach in the clinical management of human solid tumors.

Adenocarcinoma↗

Health status disparities among public and private emergency department patients.

OBJECTIVE: To explore whether patients in a public ED had poorer health than patients in a private ED, the authors compared the physical and mental health statuses of patients seeking emergency care. METHODS: A cross-sectional observational study of all adult patients, regardless of acuity, seen during two 24-hour periods in spring 1997 in an urban county trauma center (68,000 annual visits) and a private community ED (35,000 annual visits). Scores on the Physical Component Summary (PCS) and the Mental Component Summary (MCS) scales of the Medical Outcomes Study 12-Item Short-Form Health Survey (SF-12) were compared between sites, with published national norms, and with hospital admission. RESULTS: Of 571 eligible patients, 392 (69%) completed the SF-12. Patients in the public ED had a mean PCS score of 40.1, compared with 43.7 for patients in the private ED, for a difference of 3.6 points (p < 0.01; 95% CI = 0.9 to 6.1). After controlling for age, sex, ethnicity, triage acuity, ambulance arrival, and insurance status, this difference increased to 3.9 points (p = 0.02; 95% CI = 0.7 to 7.0). The mean MCS score among public ED patients was 44.1, compared with 46.5 in the private ED population, for a difference of 2.4 (p = 0.08; 95% CI = -0.3 to 5.0); after adjustment this difference increased to 2.5 (p = 0.15; 95% CI = -0.9 to 5.8), but remained statistically not significant. While all scores were significantly lower than national norms (mean PCS 50.1, mean MCS 50.0), patients in the public ED scored consistently lowest. PCS score was significantly inversely correlated with admission, with each point decrease in PCS score increasing the odds of admission by 0.05 (95% CI = 0.01 to 0.08), and conferring an odds ratio of 5.1 (95% CI = 1.2 to 21.1) for admission among the 25th percentile for PCS scores. CONCLUSIONS: Patients seeking care in the public ED had lower adjusted physical health status scores than comparable patients obtaining care in a private ED. The SF-12 is sufficiently responsive to detect hypothesized differences between ED populations, and correlates well with admission decisions.

Adult↗

Compatibility of plasmids expressing different antigens in a single DNA vaccine formulation.

One anticipated advantage of DNA immunization is the potential to create multivalent vaccines. We have examined the effects of mixing plasmids into single formulations using plasmids expressing four different membrane bound glycoproteins from bovine herpesvirus-1 (BHV-1), bovine parainfluenzavirus-3 (bPI3) and human influenza virus (HINF). Plasmids were delivered by intradermal injection into the tails of mice and the types of responses generated were clearly affected by the expressed antigen. Plasmids expressing glycoproteins B and D of BHV-1, and the haemagglutinin/ neuraminidase of bPI3, generated responses with a predominance of IgG1, suggestive of a Th2 type of response. In contrast, the plasmid expressing HINF haemagglutinin induced an antibody response biased towards IgG2a, indicating a Th1 type of response. In most instances the mixing of plasmids had only slight effects on the magnitude or bias of the responses to the individual components. However, under certain conditions we found that addition of a second plasmid converted an IgG2a biased response to a response with primarily IgG1 antibody. The reverse situation (i.e. an IgG1 conversion to IgG2a), however, was not found. These findings have important implications for the development of multivalent vaccines.

Animals↗

Evidence for eosinophil activation in bronchiectasis unrelated to cystic fibrosis and bronchopulmonary aspergillosis: discrepancy between blood eosinophil counts and serum eosinophil cationic protein levels.

BACKGROUND: Increased serum levels of eosinophil cationic protein (ECP) have been detected in adolescent patients with cystic fibrosis. However, ECP concentrations in adult patients with bronchiectasis unrelated to cystic fibrosis have not been studied. METHODS: Eosinophil numbers and serum concentrations of ECP were determined in 14 patients with known or newly diagnosed bronchiectasis and compared with age and sex matched patients with allergic bronchial asthma, chronic obstructive pulmonary disease (COPD), and controls in whom bronchiectasis or obstructive pulmonary disease could be excluded. RESULTS: Serum ECP levels were significantly raised both in patients with bronchiectasis (median (range) 22.5 micrograms/l (7-85)) and allergic asthma (35.0 micrograms/l (7-128)) compared with the sex and age matched subjects suffering from COPD (6.7 micrograms/l (1.5-28); p < 0.006) and non-obstructive normal controls (7.5 micrograms/l (3.5-19); p < 0.003). In contrast, significantly increased peripheral eosinophil numbers were observed in patients with bronchial asthma (305 x 10(6)/l; p < 0.01) but not in those with bronchiectasis (10(2) x 10(6)/l), COPD (117 x 10(6)/l), and healthy controls (101 x 10(6)/l). CONCLUSIONS: The discrepancy between eosinophil counts and eosinophil numbers in patients with bronchiectasis suggests that serum ECP levels may be more relevant in assessing local eosinophil involvement than blood eosinophil numbers.

Adult↗

Admission interviews: questions of utility and cost in masters of physical therapy programs in the United States.

PURPOSE: The purpose of this research was twofold. The first purpose was to assess the predictive validity of the interview process in student completion of entry level Masters of Physical Therapy programs on the conventional schedule for the university. The second was to provide a descriptive study of interview formats currently used by these institutions and the cost to the institution, estimated by hours of labor used exclusively for the interview process. METHOD: A questionnaire was mailed to the Director of Admissions of 63 accredited Masters of Physical Therapy programs in the United States. Forty-three responded to the questionnaire for a response rate of 68.3%. Twenty-eight programs (65.1%) performed interviews and fifteen (34.9%) programs did not. RESULTS: A two-tailed t-test revealed that no significant difference existed between programs that interview and those that did not with regards to the attrition rate of students. There was great diversity between the programs in interview content and structure. The cost to the institutions in terms of hours averaged 261 hours per school for faculty and support staff combined. CONCLUSION: The schools of physical therapy that award the Masters of Physical Therapy degree vary markedly in the interview content and format both between schools and with recommendations known to enhance validity and reliability. Since, no difference exists in attrition of students between schools that interview and those that do not, the expense and time invested by both the institution and the students are important considerations. The findings of this study indicate the need for continued investigation of the effectiveness of the interview process and alternative methods of valid and reliable student selection.

Costs and Cost Analysis↗

Nitrate removal from drinking water using a membrane-fixed biofilm reactor.

Biological treatment of drinking water is a cost-effective alternative to conventional physico/chemical processes. A new concept was tested to overcome the main disadvantage of biological denitrification, the intensive post-treatment process to remove microorganisms and remnant carbon source. The biological reaction zone and carbon supply were separated from the raw water stream by a nitrate-permeable membrane. Denitrification takes place in a biofilm, which is immobilized at the membrane. In a series of bench-scale runs, different types of membranes and reactor configurations were investigated. The best denitrification rates achieved were 1230 mg NO3(-)-N m-2 day-1. In one run, raw water containing 100 mg NO3- 1-1 was completely freed from nitrate. The membrane and the attached biofilm also represent a barrier against the passage of the C source and nutrients into the raw water. At concentrations of 20 mg 1-1 ethanol and 15 mg 1-1 phosphate in the bioreactor no diffusion through the membrane into the treated water was observed. Without any post-treatment, the effluent met nearly all the relevant criteria for drinking water; only the colony count was slightly increased.

Biofilms↗

Environmental emergencies.

This article reviews the pearls and pitfalls of high-altitude sickness, decompression sickness, and barotrauma; new findings relevant to the near-drowning patient; continued controversies on hyperbaric oxygen for carbon monoxide poisoning; pitfalls in hypothermia management; and updates on the management of venomous snakebites.

Altitude Sickness↗

Epiluminescent light microscopy of melanocytic lesions after dermoepidermal split.

BACKGROUND: In vivo epiluminescent light microscopy (ELM) of pigmented skin lesions reveals numerous elementary structures. Among them, the pigment network (PN), black dots (BD) and brown globules (BG) constitute important semiologic features. Based on histological extrapolations, it has been postulated that PN should reflect the presence of melanin in the epidermis and its honeycomb aspect should result from the dermoepidermal architecture. OBJECTIVE: To demonstrate this directly by analyzing separately by ELM the epidermal and dermal sides of melanocytic lesions. METHODS: We split the epidermis from the dermis of 10 pigmented lesions (6 lentigos, 4 nevocytic nevi) by incubation with dispase. ELM images were done in vivo before excision, then ex vivo on the whole specimen and separately on the split epidermis and dermis. Epidermal and dermal specimens were finally controlled by histology. RESULTS: PN was observed only on the epidermal side of the split. Its organization was remarkably conserved after the procedure as compared with prior in vivo images. In contrast, pigmentation observed on dermal sides of the splits showed no organized pattern and corresponded to melanophages. BG were found on the dermal side and BD on the epidermal side of the split lesions, which confirms previous hypotheses. CONCLUSION: By subtracting the dermal pigmentation and vessels from the image, the split technique has thus established the epidermal origin of the PN and given a more detailed ELM analysis of network components.

Culture Techniques↗

Expression of NM23 protein in acquired melanocytic nevi, malignant melanoma and metastases of malignant melanoma: an immunohistological assessment in human skin.

BACKGROUND: It has been suggested that nm23 may exert metastasis suppressor function in human tumors. OBJECTIVE: We have analyzed expression of nm23 polypeptide in acquired melanocytic nevi (n = 19), dysplastic nevi (n = 19), malignant melanomas (n = 22) and metastases of malignant melanomas (n = 47) in situ. METHODS: Nm23 protein was detected immunohistochemically on paraffin sections using the highly sensitive labeled avidin-biotin technique. RESULTS: We found that (1) nm23 polypeptide is predominantly expressed in the cytoplasmic but also in nuclear and membrane compartments of melanocytic human cells, (2) expression of nm23 protein does not correlate with benign or malignant phenotype in melanocytic tumors of human skin. CONCLUSION: Our study challenges the hypothesis that nm23 may function in malignant melanomas as a tumor suppressor gene.

Antigens, Neoplasm↗

Characterization of a 14 kDa oocyst wall protein of Eimeria tenella and E. acervulina.

We have extracted a protein of 14 kDa from purified oocyst walls of several Eimeria species. Polyclonal antibodies were raised in rats against the 14 kDa proteins of E. acervulina and E. tenella. On immunoblots these antisera reacted in a highly specific manner with the homologous 14 kDa antigens, but not with heterologous antigens. In addition, specific binding of the two antisera to oocyst wall fragments of E. acervulina and E. tenella was demonstrated by immunofluorescence. Partial amino-terminal sequences comprising 20 amino acid residues were obtained from the 14 kDa oocyst wall proteins of E. acervulina and E. tenella. They are characterized by an abundance of amino acids containing hydroxyl groups in their side chains (serine, tyrosine, threonine). Binding of the oocyst wall protein of E. tenella by peanut agglutinin indicates the presence of O-linked carbohydrates.

Amino Acid Sequence↗

[Postoperative pulmonary function after lung surgery. Total intravenous anesthesia with propofol in comparison to balanced anesthesia with isoflurane].

After lung resection, early extubation and the rapid return of the patients ability to cooperate is the predominant goal. Propofol anaesthesia is characterised by rapid awakening and recovery of cognitive and psychomotor functions and is consequently desirable for such operations. Experience so far in lung surgery, however, is limited. Besides the level of consciousness we investigated various spirometric parameters after lung resection. Total intravenous anaesthesia was performed with propofol, while balanced anaesthesia was performed with isoflurane. METHODS. A total of 93 patients evaluated electively for wedge excision or lobectomy were enrolled in an open, prospective, randomised, interindividual comparative study. Sixty-three patients could be evaluated with complete data sets. In the evening and the morning before the operation the patients were premedicated orally with clorazepate 0.5-0.7 mg/kg. Anaesthesia was induced in group 1 with propofol (1.0-2.5 mg/kg) and maintained with propofol (4-12 mg/kg) in 50% O2/air. The patients in group 2 received methohexital (1-2 mg/kg) for induction and isoflurane (0.4-2.0 vol%) in 50% O2/air for the maintenance of general anaesthesia. In both groups analgesia was achieved by using fentanyl (up to 10 micrograms/kg) and muscle relaxation by using atracurium. Psychomotor tests (minimal mental state, reaction time) were performed the day before the operation (t1), immediately prior to induction of anaesthesia (t2) and 5 min, 30 min, 60 min, 90 min, 24 h, and 7 days after extubation (t3-t8). Spirometry (forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC; peak expiratory flow, PEF) was carried out at times t1, t2 and t5-t8. RESULTS. The two groups were comparable regarding preoperative status (age, sex, preoperative risk score, psychomotor tests, and spirometric values) and the operation performed (wedge excision/lobectomy, duration of anaesthesia). The extubation time was slightly shorter in the propofol group (18 +/- 8 min) than in the isoflurane group (20 +/- 6 min). Also, the results of the psychomotor tests were somewhat better in the propofol group than those in the isoflurane group. The clearest differences were found in the early postoperative period, but not all differences were significant. Statistically highly significant differences between the two groups were found for the three spirometric parameters. Based on the FEV1 value of the 7th postoperative day, FEV1 taken 60 min after extubation declined by 27.9% in the propofol group vs. 51.7% in the isoflurane group (P = 0.01). At 90 min after extubation the corresponding decline in the propofol group was 26.6%, in the isoflurane group 51.1% (P = 0.003). In addition, the decline of FVC and PEF measured 60 min and 90 min after extubation was significantly smaller in the propofol group than in the isoflurane group. CONCLUSION. The postoperative impairment of lung function after lung resection under propofol anaesthesia is statistically significantly smaller than under isoflurane anaesthesia. Total intravenous anaesthesia with propofol is particularly suitable for this kind of operation.

Adult↗