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Biomedical subjects

W L Russell

Publications and source records attributed to W L Russell.

At least 19 recordsLinked to original sources
PubMed1992

Frequency and nature of specific-locus mutations induced in female mice by radiations and chemicals: a review.

The inducibility of heritable mutations in female mammals has been measured in the mouse specific-locus test (SLT). For radiation-induced mutations, a large body of data has been accumulated that includes information about biological and physical factors that influence mutation yields. However, relatively few SLT studies in females have been conducted with chemicals to date. A single estimate of the spontaneous mutation rate in oocytes, 6/536,207, has been derived as the most appropriate one to subtract from experimental rates. This rate is highly significantly below the spontaneous mutation rate in males. Mutations recovered from females mutagenized at any time after about the 12th day post-conception are induced in non-dividing cells. In adult females, most oocytes are arrested in small follicles; maturation from this stage to ovulation takes several weeks. High-dose-rate radiations are more mutagenic in mature and maturing oocytes than in spermatogonia of the male; on the other hand, no clearly induced mutations have been recovered from irradiated arrested oocytes. Efficient repair processes have been invoked to explain the latter finding as well as the upward-curving dose-effect relation for acute irradiation, and the fact that dose protraction drastically reduces mutation yield from mature and maturing oocytes. The dose-protraction effect is much greater than that found in spermatogonia. Radiation-induced mutation rates in embryonic, fetal, and newborn females are overall lower than those in the mature and maturing oocytes of adults. A dose-protraction effect has also been demonstrated at an early developmental stage when the nuclear morphology of mouse oocytes most resembles that of the human. Of only 5 chemicals so far explored for their effect in oocytes, 2 (ethylnitrosourea, ENU, and triethylenemelamine, TEM), and possibly a third (procarbazine hydrochloride, PRC), are mutagenic--with at least one of these (ENU) mutagenic in arrested as well as maturing oocytes. However, the mutation rate is, in each case, lower than for treated male germ cells. By contrast, ENU-induced mutation yield for the maternal genome of the zygote is an order of magnitude higher than that for the zygote's paternal genome or for spermatogonia. A high proportion of mutants derived from chemical treatment of oocytes (including the oocyte genome in zygotes) are mosaics, probably owing to lesions affecting only 1 strand of the DNA. A characteristic of specific-locus mutations induced in oocytes is that they include a considerably higher percentage of large (multi-locus) lesions (LLs) than do mutations induced in spermatogonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Limb salvage versus traumatic amputation. A decision based on a seven-part predictive index.

In severe traumatic injuries to the lower extremity, it is often a difficult decision to attempt heroic efforts aimed at limb salvage or to amputate primarily. To answer this question, the authors performed a 5-year review of 70 limbs in 67 patients. Patients were identified as presenting with major lower extremity trauma and an associated arterial injury. Nineteen (27%) of the 70 limbs were amputated. Limb salvage was not related to the presence or absence of shock and order of repair (orthopedic or vascular). No statistical difference was noted between the time of injury to operative repair in either the amputated or limb salvage group. Limb salvage was related to warm ischemia time and the quantitative degree of arterial, nerve, bone, muscle, skin, and venous injury. A limb salvage index (LSI) was formulated based on the degree of injury to these systems. All 51 patients with an LSI score of less than 6 had successful limb salvage (p less than 0.001). All 19 patients with an LSI score of 6 or greater had amputations (p less than 0.001). Although statistics cannot replace clinical judgment, this index can be a valuable objective tool in the evaluation of the patient with a severely traumatized extremity.

Adolescent↗
PubMed1990

Release of histamine in rat hypothalamus and corpus striatum in vivo.

Histamine has remained a putative neurotransmitter for many years, partially because some of the criteria necessary to define it as a central nervous system neurotransmitter have not been established. The demonstration of in vitro release and the quantification of turnover as an indirect measure of release have been complicated by the histological evidence for multiple histamine pools in the central nervous system. In brain, there are multiple cell types which probably contain histamine. These cells include mast cells, neurolipomastocytoid cells, microvascular endothelial cells, and a histaminergic neuronal system which has been visualized using immunocytochemical methods. Using in situ brain microdialysis and a sensitive and specific radioenzymatic assay for histamine, we have identified histamine in the extracellular space of the rat hypothalamus and corpus striatum in vivo. Following neuronal selective stimuli, significant increases in extracellular histamine levels only were observed in the posterior hypothalamus, where dense histaminergic neuronal terminals have been described. However, after manipulations targeted towards histamine-containing mast cells, such increases were seen in both the posterior hypothalamus and corpus striatum. In summary, this study demonstrates that endogenous histamine can be released from the posterior hypothalamus by stimuli targeted towards histamine neurons and that histamine may also be released by non-neuronal mast cell elements.

Animals↗
PubMed1990

Oxysterols and alcoholic liver disease.

A new theory is presented implicating oxidative cholesterol metabolism and oxysterols as possible factors in the development of alcoholic liver disease. Our present studies have revealed the accumulation of cholesta-3,5-dien-7-one, 13.05 +/- 2.75 micrograms/g (n = 8), and cholesta-4,6-dien-3-one, 2.26 +/- 0.88 micrograms/g (n = 8) in fatty alcoholic liver, as compared with controls, 0.21 +/- 0.12 microgram/g (n = 7) and 0.3 +/- 0.33 microgram/g (n = 7), respectively. Acetaldehyde at 1 to 6 micromolar concentration in the blood and tissues of alcoholics cannot account for the extent of tissue damage, nor can it adequately explain liver steatosis characterized by accumulation of cholesterol and fatty acids and their esters in the liver of alcoholics known for their poor dietary habits. Oxysterols may be the primary cause for the development of alcoholic liver diseases and damage to accessory tissues. Significantly lower levels of 7-ketocholesterol in fatty liver, 6.8 +/- 3.5 micrograms/g (n = 8), as compared with control, 36.85 +/- 22.25 micrograms/g (n = 7), may be responsible for the increased cholesterol content of the alcoholic liver due to the inhibitory properties of this sterol on HMG-CoA reductase in cholesterol biosynthesis.

Cholesterol↗
PubMed1990

Leukotriene receptor antagonism and augmentation of beta-receptor-mediated events by LY171883.

LY171883, (1-[2-hydroxy-3-propyl-4-[4(1H-tetrazol-5-yl)butoxy)phenyl]etha none), a leukotriene (LT) D4/E4 receptor antagonist, was assessed in comparison with two well known phosphodiesterase inhibitors, isobutylmethyl-xanthine (IBMX) and theophylline, for its ability to augment beta-receptor-mediated responses. Relaxation of carbachol-contracted guinea-pig trachea by isoprenaline was enhanced by the three agents in a dose-dependent manner. A two-fold enhancement of isoprenaline-induced smooth muscle relaxation was produced by 2.5 microM IBMX, 28 microM LY171883, or 140 microM theophylline. Similar concentrations of IBMX or theophylline did not antagonize LTE4-induced tracheal contractions; LY171883 totally inhibited the response and had significant LTE4 receptor antagonist activity even at 10-fold lower concentrations. Antigen-induced release of histamine and LTC4 from guinea-pig lung was reduced by isoprenaline. Prior treatment with LY171883, IBMX, or theophylline did not enhance this action. Isoprenaline reduced histamine-induced bronchospasm in anaesthetized guinea-pigs. LY171883, 30 mg kg-1, or IBMX, 1 mg kg-1, did not affect the isoprenaline-induced decrease in the histamine response. IBMX, 3 mg kg-1, and theophylline, 30 mg kg-1, augmented the isoprenaline-induced bronchodilation. LTE4-induced bronchoconstriction was not affected by IBMX or theophylline whereas LY171883 antagonized this response at doses as low as 3 mg kg-1. Therefore, in both in-vitro and in-vivo test systems, LY171883 functioned primarily as a leukotriene receptor antagonist with minimal pharmacological activity attributable to its ability to potentiate isoprenaline.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Management of Lyme disease.

The microbiology, transmission, epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Lyme disease are reviewed. Lyme disease, a tick-borne syndrome, was first described in 1975. The etiologic agent of Lyme disease is Borrelia burgdorferi, a slow-growing spirochete. Lyme disease is the most prevalent tick-borne disease in this country; endemic areas in the United States include the northeastern, north central, and western regions. Both infectious and immunologic mechanisms are important factors in the pathogenesis of Lyme disease. The primary mechanism, however, is thought to be infectious. Three stages of Lyme disease have been described; stage I, characterized by erythema chronicum migrans and flu-like symptoms; stage II, characterized by dermatologic, ophthalmologic, neurologic, and cardiac disorders; and stage III, characterized by arthritis, a multiple sclerosis-like syndrome, psychiatric disorders, and a chronic fatigue syndrome. Therapy with penicillin or tetracycline hastens the resolution of stage I symptoms. Treatment duration normally ranges between 10 days and three weeks. Tetracycline or doxycycline appears to be more effective than penicillin in preventing the development of late Lyme disease. Although intravenous penicillin G and ceftriaxone are both effective for the treatment of late Lyme disease, many clinicians consider ceftriaxone to be the agent of choice. Whether exposed patients from endemic areas should receive antimicrobial prophylaxis is controversial. Further clinical studies are needed to determine optimal therapy for the various stages of Lyme disease, particularly Lyme arthritis.

Borrelia burgdorferi Group↗
PubMed1989

Reminiscences of a mouse specific-locus test addict.

This paper describes some of the historical events surrounding the development of and achievements with the mouse specific-locus test in radiation and chemical mutagenesis. Some ongoing and future contributions of the test to research in molecular genetics are also mentioned.

Animals↗
PubMed1989

Chlorambucil effectively induces deletion mutations in mouse germ cells.

The chemotherapeutic agent chlorambucil was found to be more effective than x-rays or any chemical investigated to date in inducing high yields of mouse germ-line mutations that appear to be deletions or other structural changes. Induction of mutations involving seven specific loci was studied after exposures of various male germ-cell stages to chlorambucil at 10-25 mg/kg. A total of 60,750 offspring was scored. Mutation rates in spermatogonial stem cells were not significantly increased over control values; this negative result is not attributable to selective elimination of mutant cells. Mutations were, however, clearly induced in treated post-stem-cell stages, among which marked variations in mutational response were found. Maximum yield occurred after exposure of early spermatids, with approximately 1% of all offspring carrying a specific-locus mutation in the 10 mg/kg group. The stage-response pattern for chlorambucil differs from that of all other chemicals investigated to date in the specific-locus test. Thus far, all but one of the tested mutations induced by chlorambucil in post-stem-cell stages have been proved deletions or other structural changes by genetic, cytogenetic, and/or molecular criteria. Deletion mutations have recently been useful for molecular mapping and for structure-function correlations of genomic regions. For generating presumed large-lesion germ-line mutations at highest frequencies, chlorambucil may be the mutagen of choice.

Animals↗
PubMed1988

Effect of X-ray and ethylnitrosourea exposures separated by 24 h on specific-locus mutation frequency in mouse stem-cell spermatogonia.

Specific-locus mutation frequencies in mouse stem-cell spermatogonia were determined in 3 experiments in which mature male mice were exposed to 100,m 300, or 500 R of X-rays followed, 24 h later, by intraperitoneal injection of 100 mg/kg of ethylnitrosourea (ENU). The purpose was to find out if the mutation frequencies would be augmented over those expected on the basis of additivity of the effects of the separate treatments. Such augmentation had been observed in earlier work in which exposure to 100 or 500 R of X-rays was followed 24 h later by a second exposure of 500 R. No augmentation was observed for X-rays followed by ENU. The mutation frequencies in all 3 experiments actually fell below those expected on the basis of additivity, although the reductions were not statistically significant.

Animals↗
PubMed1988

Therapeutic substitution in the health maintenance organization outpatient environment.

Health maintenance organizations (HMO) are growing in number as a cost-effective way of providing health care. In some, stringent formulary management policies including programs authorizing therapeutic substitution are practiced. Under this concept a drug that has been previously determined to be therapeutically equivalent to a second drug, even though it is not chemically equivalent to the prescribed drug, is automatically dispensed without contacting the prescriber. This study was undertaken to learn the extent and conditions under which therapeutic substitution is being practiced in the HMO setting. A survey was sent to all HMO in the U.S. inquiring into the operation of the pharmacy services. Specific focus was on the operation of the formulary and the policies and procedures being followed. The main goal was to learn how many programs authorize therapeutic substitution, what drugs are allowed, and what procedures are followed once the substitution is made. Of the 481 surveys sent out, 192 (40 percent) usable responses were received. Results indicate that 30.5 percent of HMO pharmacy plans allow therapeutic substitution. These programs were most likely to be of the staff-model or the group-model and least likely to be of the independent practice association type. HMO with an inhouse pharmacy more frequently had policies allowing therapeutic substitution than those using outside pharmacy services.

Data Collection↗
PubMed1988

Crisamicin C, a new isochromanequinone antibiotic. Isolation, structure determination, and biosynthesis.

Micromonospora purpureochromogenes subsp. halotolerans was found to produce crisamicin C, a novel antibiotic, together with crisamicin A. Crisamicin C was purified by silica gel column chromatography and its physico-chemical properties, structure and biosynthesis were studied. Crisamicin C, mp 260 degrees C (dec), showed UV maxima at 392 (epsilon 9,497), 261 (epsilon 32,959) and 232 nm (epsilon 24,623) in CH3CN, and gave an IR spectrum with absorbances at 1782 (lactone), 1705 and 1655 (quinone) cm-1. Crisamicin C plasma desorption mass spectrometry (PD-MS) m/z 615.9 [M + H)+, hydroquinone) was 16 amu higher than crisamicin A PD-MS m/z 600 [M + H)+, hydroquinone) suggesting that the two antibiotics differ by one additional oxygen in crisamicin C. Analysis of 1H and 13C NMR spectra, in comparison with those of crisamicin A, indicated that crisamicin C was the 4'a, 10'a epoxide derivative of crisamicin A. Carbon-thirteen labeled acetate feeding experiments were used to confirm the positions of the epoxide and other structural features. Crisamicin C was a more potent antibiotic than crisamicin A, but shared the same spectrum of antimicrobial activity (Gram-positive only).

Anti-Bacterial Agents↗
PubMed1988

Comparison of histamine release induced by morphine and oxymorphone administration in dogs.

Cardiovascular effects (vasodilatation, hypotension) of morphine administration have been attributed to central actions and peripheral histamine release. In the study reported here, we compared plasma histamine (Hm) concentrations after morphine sulfate and oxymorphone HCl administration in conscious dogs. Five healthy adult dogs (mean body weight, 10.1 kg) were randomly administered morphine (2 mg/kg of body weight, IV) or oxymorphone (0.2 mg/kg, IV) by a 5-second bolus injection at weekly intervals. Venous blood samples (5 ml) were collected from jugular veins before and at 1, 2, 5, 15, 30, and 60 minutes after drug administration. Behavioral changes were recorded. Plasma was analyzed by a radioenzymatic technique, using purified histamine N-methyltransferase as an enzyme catalyst (sensitivity of assay, 40 pg Hm/ml). Mean base-line Hm value for all dogs was 0.55 ng/ml. The mean Hm value was significantly higher (P less than 0.05) than the base-line value at 1, 2, 5, 15, and 60 minutes after morphine administration (531.4, 251.0, 113.0, 31.5, and 1.0 ng of Hm/ml, respectively), but there were no significant increases in histamine values from base-line values at any time after oxymorphone administration. All dogs given morphine and 1 dog given oxymorphone showed excitatory behavior; 2 dogs given morphine and 3 dogs given oxymorphone salivated profusely.

Animals↗
PubMed1986

Lack of clinically significant in vitro and in vivo interactions between ranitidine and sucralfate.

The hypothesis that the cytoprotective agent sucralfate (sucrose octakis(hydrogen sulfate)-aluminum complex) interacts with the H2-antagonist ranitidine (N-[2-[[dimethylamino)methyl]furfuryl]- thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine) by decreasing ranitidine absorption was tested in vitro and in vivo. The in vitro results show that ranitidine may bind to a small extent (approximately 10%) to sucralfate paste in the gastrointestinal fluids. The in vivo ineraction of 150 mg of ranitidine and 1 g of sucralfate was evaluated in a crossover study in six healthy volunteers. The results indicate no significant difference in pharmacokinetic parameters when ranitidine was given alone and in combination with sucralfate. Thus, ranitidine bioavailability is not diminished by sucralfate and the two drugs can be given concomitantly. For the determination of bioavailability, it has to be taken into account that renal clearance of ranitidine is lower after oral than after intravenous administration, and that enterohepatic recirculation of the drug is likely.

Adult↗
PubMed1986

Combined cold- and heat-induced cholinergic urticaria.

A 36-year-old white woman with a 20-year history of cutaneous, respiratory, and cardiovascular symptoms triggered by physical activity and by exposure to either heat or cold was evaluated. A routine evaluation for the cause of her condition was positive only for certain physical factors. Cutaneous testing for dermatographism, ice-cube challenge, and exposure to ultraviolet A and ultraviolet B light were negative. A methacholine skin test was positive. Sitting in a cold room (4 degrees C) induced micropapular wheals on exposed areas similar to those classically associated with cholinergic urticaria. Placing both feet in warm water (44 degrees C) induced similar but more intense cutaneous lesions at sites not exposed to heat, light headedness, and severe asthma. Exercise for 10 minutes caused confluent and punctate urticarial lesions. Simultaneous measurement of plasma histamine during cold and heat challenges revealed increases paralleling the course of symptoms. Repeat challenge with cold, heat, and exercise after beginning treatment with both H1 and H2 histamine antagonists resulted in marked reduction in symptoms; however, significant rises in plasma histamines were still noted.

Adult↗
PubMed1986

Effect of concomitant antacid administration on plasma cimetidine concentrations during repetitive dosing.

Previous research has suggested that concurrent administration of antacid and cimetidine results in lower than expected plasma levels of cimetidine. Because these studies were all of single-dose design, this study was undertaken to determine the nature of the interaction after repeated administration of both drugs. There was no statistically significant difference demonstrated for any of the pharmacokinetic parameters evaluated in the study. Based on these findings, the previous recommendation that administration of antacid and cimetidine be separated in time may not be necessary.

Adult↗