Biomedical subjects

K Orr

Publications and source records attributed to K Orr.

30 records · Page 2Linked to original sources

PubMed1992

The cerebral radioprotective effect of alternative barbiturates to pentobarbital.

The potential for normal brain tissue injury is one of the limiting factors in the use of radiotherapy for brain tumors. As attempts to enhance brain tumor radiation sensitivity have been unsuccessful, the use of cerebral radioprotectants provides an attractive alternative. Pentobarbital has recently been shown to be a cerebral radioprotectant in the rodent and primate models of single fraction radiation injury. Because daily high doses of pentobarbital bring certain significant risks, the potential usefulness of alternative barbiturates was explored. Seven groups of rats received 70 Gy of whole-brain-only irradiation in the single fraction. Group 1 was treated while awake. Groups 2, 3, and 4 received pentobarbital, thiopental, and methohexital, respectively. Groups 5, 6, and 7 received increasing doses of phenobarbital. Mean group survival at 30 days after treatment was determined and compared with the survival of animals treated while awake. Thiopental enhanced survival, similar to pentobarbital. Methohexital and phenobarbital were of no radioprotective value. The differences in the hypnotic effects of these barbiturates is based on dissimilar effects on the kinetics of chloride ion channel patency. We propose that these differences also influence their radioprotective properties. Thiopental is a shorter acting alternative to pentobarbital for cerebral radioprotection. Use of it should permit safer and easier investigation of this radioprotective effect in human trials.

Animals↗

PubMed1991

Rapid inter-strain comparison by pyrolysis mass spectrometry in nosocomial infection with Xanthomonas maltophilia.

Seventeen strains of Xanthomonas maltophilia and one strain of Pseudomonas cepacia were examined by pyrolysis mass spectrometry (PYMS). The Xanthomonas strains comprised 11 clinical and environmental isolates from a suspected outbreak of colonization and infection on a heart-lung transplant intensive care unit, two strains from patients elsewhere in the same hospital and four strains from a national reference collection. The single isolate of Pseudomonas cepacia was from a sink in the same affected intensive care unit. A series of discriminant analyses performed on the PYMS-derived data showed that, whereas six strains of Xanthomonas from the respiratory tract, blood and ventilatory equipment of one of the affected patients were indistinguishable, all the other isolates were distinct. The results of PYMS rapid inter-strain comparison were in accord with those of an epidemiological investigation which suggested that the episode was due to unauthorized reuse of disposable nebulizers and not to cross-infection between patients. Pyrolysis mass spectrometry with rapid data analysis is a potentially useful technique for the investigation of nosocomial infections due to organisms such as X. maltophilia.

Bacteriological Techniques↗

PubMed1990

Protection by indomethacin against acute radiation esophagitis.

The mechanism of radiation induced damage to the mucosal lining of the gastrointestinal tract, as well as mucositis, is not fully characterized. Prostaglandins may partially mediate the inflammatory response to radiation damage. The effect of the prostaglandin synthetase inhibitor indomethacin on radiation induced esophagitis, pneumonitis, and tumor response was evaluated in the C3H mouse. The effects of indomethacin on radiation induced damage to the esophagus was determined by evaluation of weigh lost, survival, and histologic findings at doses of 28-34 Gy. Although there is a clear difference that supports the use of indomethacin for the prevention of esophagitis, the radiation dose response for esophagitis is steep and likewise, the therapeutic index for the indomethacin amelioration of radiation esophagitis is narrow. Since the tumor response to radiation is unchanged and since indomethacin clearly lessens radiation induced esophagitis in the mouse, this study suggests that indomethacin should be studied in humans for lessening radiation mucositis without jeopardizing the therapy of tumors.

Acute Disease↗

PubMed1990

Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection.

To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise "unsafe" doses of radiation in patients with CNS neoplasms.

Animals↗

PubMed1990

Enhancement of the efficacy of x-irradiation by pentobarbital in a rodent brain-tumor model.

Radiation therapy is an important component of brain tumor treatment, but its efficacy is limited by its toxicity to the surrounding normal tissue. Pentobarbital acts as a cerebral radioprotectant, but the selectivity of its protection for the central nervous system has not been demonstrated. To determine if pentobarbital also protects tumor against ionizing radiation, five groups of Fischer 344 rats were observed after exposure to varying combinations of the presence or absence of implanted tumor, pentobarbital, and radiation treatment. The first three groups underwent cerebral implantations of a suspension of 9L gliosarcoma cells. Group 1 was left untreated and served as tumor-bearing controls. Group 2 received 30 Gy of whole-brain x-irradiation without anesthesia 8 days after tumor implantation. Group 3 received the same radiation treatment 15 minutes after pretreatment with 60 mg/kg of pentobarbital intraperitoneally. Groups 4 and 5 served as radiation controls, receiving 30 Gy of x-irradiation while awake and 30 Gy of x-irradiation after pentobarbital administration, respectively. Survival was calculated from the death of the last tumor-bearing rat. The mean survival time in tumor-bearing control rats was 20.8 +/- 2.6 days (+/- standard deviation). X-irradiation alone significantly enhanced the period of survival in rats implanted with the 9L tumor (29.7 +/- 5.6 days, p less than 0.03). Further significant prolongation of survival was seen with the addition of pentobarbital to the treatment regimen (39.9 +/- 13.5 days, p less than 0.01). Nontumor-bearing rats irradiated while awake (Group 4) survived 30.9 +/- 2.3 days. All of their pentobarbital-anesthetized counterparts in Group 5 survived. If pentobarbital had offered radioprotection to the tumor, then Group 3 would have had a shorter survival period than Group 2. This implies that the enhancement of survival time after irradiation results from selective protection of normal brain in this model.

Animals↗

PubMed1990

Cerebral radioprotection by pentobarbital: dose-response characteristics and association with GABA agonist activity.

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose (60 mg/kg intraperitoneally). Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time. Ketamine and hypothermia were without protective effect. Protection from acute radiation-induced mortality by pentobarbital in the rat model is a reproducible phenomenon and is associated with the GABA agonistic activity of the compound. This property of GABA agonists offers the potential for a novel approach to enhancement of the efficacy of radiation therapy in the treatment of brain tumors.

Anesthesia, General↗

PubMed1989

Evolution of acute chest syndrome in sickle cell trait: an ultrastructural and light microscopic study.

Light and electron microscopic studies of a patient with sickle cell trait who had an episode of sickling during coronary artery surgery, from which he died, showed fibrin thrombi, focal alveolar wall necrosis, and epithelial cell damage. It is suggested that in cases of sickle trait full precautionary measures should be taken to prevent sickling in these circumstances.

Acute Disease↗

PubMed1987

The effect of toluidine blue and methylene blue in immunochemical reactions in vitro.

Our observation that the effect of a patient's autoantibody with a potent antithrombin activity could be inhibited by toluidine blue and methylene blue led us to investigate the effect of these dyes in several immunochemical reactions in vitro. Both dyes reduced the titer or prevented the detection of IgG-specific single- and double-stranded DNA-binding antibodies and rheumatoid factors but did not reduce the titer of antinuclear factor and had no effect on detection of microsomal and thyroglobulin antibodies. These dyes did not aggregate or precipitate the immunoglobulins and their inhibitory effect in serum could be removed by dialysis of serum. The possible mechanism of action of these dyes in immunochemical reactions is discussed.

Antibodies, Antinuclear↗

PubMed1982

IgD kappa plasma cell dyscrasias: extraosseous manifestations including isolated leptomeningitis.

IgD kappa plasma cell Dyscrasias are rare. Two cases with unusual presentations and courses area described. One of these patients had myelomatous pleural effusions, and subsequently experienced myelomatous leptomeningitis. The significance of this combination is discussed and the literature reviewed. The value of immunofluorescent techniques in identifying plasma cells in the cerebrospinal fluid and pleural fluid is emphasized.

Humans↗

PubMedDate not supplied

Lymph node metastasis and cell movement: ultrastructural studies on the rat 13762 mammary carcinoma and Walker carcinoma.

The aim of this study was to determine whether tumor cells move actively through the linings of lymph node sinuses. Using 13762 carcinoma in F344 rats, and Walker carcinoma in Wistar rats, 20 X 10(6) tumor cells were injected into the footpad, and the ipsilateral popliteal lymph node examined by transmission electron microscopy. The same tumors were examined by making standard cell spots on plastic or glass surfaces, and examining these by phase and reflection contrast microscopy, fluorescent microscopy after anti-actin and phallacidin staining and transmission electron microscopy. The 13762 cells do not migrate through the lining of the lymph node sinusoid, nor move actively in vitro. Ultrastructural appearances of the Walker rat carcinoma cells suggest that they move actively through the sinus lining. After 24 h in vitro the Walker rat carcinoma cells in the centre of the spot are adherent to the surface. There is some movement of the edge of the sheet, and individual tumor cells at the edge of the sheet move actively and independently. We conclude that the Walker rat carcinoma invades the lining of the lymph node sinusoid by active cell movement, and the 13762 carcinoma does not.

Adenocarcinoma↗

PubMedDate not supplied

Neoplastic invasion in experimental carcinoma of the colon: abnormal differentiation and release of mucus.

Carcinomas of the colon were induced in F344 rats with dimethylhydrazine (20 mg/kg for 12 weeks). The invasive edges of the lesions were examined with the electron microscope. As in human colorectal cancer, the invasive edges show neoplastic cells with abnormal differentiation of apical cytoplasmic rootlets and processes at the basal or invasive edge of the cell, 'apical reversal'. Mucous carcinoma cells release material into the interstitial connective tissue matrix. The features may contribute to the complex phenomenon of neoplastic invasion.

Adenoma↗

PubMedDate not supplied

Variation in sexual orientations among men who have sex with men, and their current sexual practices.

PURPOSE: To explore group variations in sexual risk-taking among different sexual orientations of men who have sex with men (MSM). METHOD: A convenience sample of men was recruited in gay-identified venues. An analysis was conducted to determine the independence of sexual orientation (gay, gay-previously heterosexual, currently bisexual), age and risk-taking. RESULTS: Bisexual men were younger, lived outside metropolitan areas and socialized more in bathhouses. In general, bisexuals reported the safest sexual practices and previously heterosexual men the most unprotected. CONCLUSIONS: Among MSM, variation in sexual orientations was associated with differences in unprotected sex for older age groups. For the youngest age group, a similar level of risk-taking of the different orientation groups suggests uniform sociocultural influences.

Adult↗