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Biomedical subjects

L L Smith

Publications and source records attributed to L L Smith.

At least 109 records · Page 6Linked to original sources

Intralesional vinblastine for cutaneous Kaposi's sarcoma associated with acquired immunodeficiency syndrome. A clinical trial to evaluate efficacy and discomfort associated with infection.

BACKGROUND: Intralesional vinblastine has been used to treat Kaposi's sarcoma associated with acquired immunodeficiency syndrome (AIDS-KS). Injections are painful and anticipated response rates are not well documented. OBJECTIVE: Eleven homosexual men were studied to evaluate the efficacy and pain associated with intralesional vinblastine with or without 1% bicarbonate buffered lidocaine (BBL). METHODS: Six lesions on each patient were selected and treated with either vinblastine, vinblastine mixed with BBL, or vinblastine 5 minutes after BBL injection. Control lesions received BBL, saline, or no treatment. Patients recorded injection pain on a visual analog scale. RESULTS: There was a complete or partial clinical response in 88% of vinblastine-treated lesions. Pain scores for BBL, vinblastine, and the mixture of BBL and vinblastine were not statistically different. CONCLUSION: Intralesional vinblastine is effective therapy for AIDS-KS. Local anesthesia does not reduce efficacy of treatment, or reduce the pain experienced by the patient.

Acquired Immunodeficiency Syndrome↗

The effects of static and ballistic stretching on delayed onset muscle soreness and creatine kinase.

The purpose of this study was to determine if static and ballistic stretching would induce significant amounts of delayed onset muscle soreness (DOMS) and increases in creatine kinase (CK). Twenty males were randomly assigned to a static (STATIC) or ballistic stretching (BALLISTIC) group. All performed three sets of 17 stretches during a 90-min period, the only group difference being that STATIC remained stationary during each 60-s stretch while BALLISTIC performed bouncing movements. Subjective ratings of DOMS (scale: 1-10) and serum CK levels were assessed before and every 24 hours post stretching, for 5 days. A repeated measures ANOVA revealed a significant main effect due to time (p < 0.05), with peak soreness occurring at 24 hours after (M = 2.8 +/- 1.6). Surprisingly, a group effect (p < .05) demonstrated that DOMS was significantly greater for STATIC than for BALLISTIC. At 24 hours there was a 62% (p < .05) increase in CK for combined groups. These findings indicate that similar bouts of static and ballistic stretching induce significant increases in DOMS and CK in subjects unaccustomed to such exercise. Furthermore, static stretching induced significantly more DOMS than did ballistic.

Adult↗

Allergic bronchopulmonary aspergillosis in patients with and without evidence of bronchiectasis.

Allergic bronchopulmonary aspergillosis (ABPA) may complicate 1% to 2% of all cases of chronic asthma. Twenty-eight patients fulfilling the diagnostic criteria for ABPA but without evidence of proximal bronchiectasis [ABPA-S (seropositive)] were identified over a 12-year period and classified by stage. The majority of patients were in remission but all had chronic asthma. Serum anti-Aspergillus fumigatus (Af) IgG was lower in ABPA-S (n = 28) versus ABPA-CB (central bronchiectasis) (n = 58) at the time of initial presentation (IgG-Af index 3.62 versus 7.80, t = 3.46, P < or = .001). Serum IgG1-Af was significantly lower in ABPA-S as compared with ABPA-CB (t = 2.37, P = .011), as was serum IgG2-Af (t = 1.91, P = .031) and serum IgG4-Af (t = 1.78, P = .041). There were trends toward lower concentrations of total serum IgE, serum anti-Af-IgE, and anti-Af-IgA in ABPA-S. Eleven patients with ABPA-S were evaluated closely for a total of 63 patient-years and only four exacerbations with pulmonary infiltrates were identified. No patient in either group was observed to progress to end-stage or irreversible lung disease when early recognition and treatment were instituted. We conclude that ABPA-S represents the earliest stage or apparently a less aggressive form of ABPA.

Adolescent↗

Meningitis in neonatal calves: 32 cases (1983-1990).

Case records of 32 neonatal calves with the antemortem diagnosis of meningitis were reviewed. Mean age at admission was 6 days (range, 11 hours to 30 days), and the most common concurrent clinical problem was diarrhea (16/32). Twenty-seven of the calves were available for necropsy. At postmortem, there was evidence of septicemia in 22 (81%) of these calves. Escherichia coli was the organism most frequently isolated (11/16; 69%) from the CNS. The major clinical signs of CNS disturbance observed over the course of hospitalization were lethargy, recumbency, anorexia, loss of suckle reflex, and coma. Leukocytosis and a left shift was evident in 11 of 15 (73%) calves. Concurrent metabolic problems that could have aggravated the CNS disturbance included hyperkalemia and respiratory acidosis. Analysis cerebrospinal of fluid from 22 of the calves, revealed pleocytosis, xanthochromia, turbidity, and high total protein concentration. Cytologically, neutrophils predominated in the CSF in calves with acute disease. Mononuclear cells dominated in calves with chronic disease. Microscopically, bacteria were evident in 10 of 22 (45%) of the antemortem CSF samples and bacteria were isolated from slightly more than half (11/19) of the specimens subjected to microbial culturing. Escherichia coli was the agent most frequently isolated from the CSF. Two of the 9 E coli isolates were resistant to trimethoprim potentiated sulfonamide drugs and all (4/4) of the CSF E coli isolates tested for susceptibility to triple-sulfonamide drugs were resistant. Twenty-seven of the 32 calves died or were euthanatized within 2.43 days after hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rabies in horses: 21 cases (1970-1990).

The records of 21 horses with rabies were reviewed. Results of fluorescent antibody testing for rabies antigen in brain tissue were positive in each case. According to the histories, 5 of the horses had been vaccinated for rabies between 4 to 24 months prior to the onset of the clinical signs. Bite wounds were not observed on any of the horses, and exposure to a suspected rabid animal was witnessed in only 5 cases. Clinical signs of disease at the time of initial examination included ataxia and paresis of the hindquarters (9/21, 43%), lameness (5/21, 24%), recumbency (3/21, 14%), pharyngeal paralysis (2/21, 10%), and colic (2/21, 10%). The major clinical signs observed over the course of hospitalization included recumbency (21/21; 100%), hyperesthesia (17/21; 81%), loss of tail and anal sphincter tone (12/21; 57%), fever (11/21; 52%), and ataxia and paresis of the hindquarters (11/21; 52%). Mean survival time after the onset of clinical signs was 4.47 days (range, 1 to 7 days). Supportive treatment, given to 9 horses, had no effect on survival time and did not correlate with the detection of negri bodies at necropsy. Cerebrospinal fluid (CSF) was obtained from 6 horses and was determined to be abnormal in 5. The most common abnormality was a slightly high total cell count (5/6), with a predominance of lymphocytes (4/6). The CSF total protein concentration was high in only 2 horses. At necropsy, there was gross evidence of diffuse brain edema, meningeal congestion, and focal areas of hemorrhage in 5 horses (24%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cysteine isopropylester protects against paracetamol-induced toxicity.

Cysteine isopropylester (CIPE), a novel ester of cysteine, has been synthesized in order to evaluate its potential as a chemoprotectant. The increased lipophilicity of the ester relative to cysteine should facilitate its entry into cells where, following hydrolysis, it should act as an intracellular source of cysteine or be utilized for the synthesis of glutathione so protecting the cell against various types of chemical insult. In this study, we evaluate the ability of CIPE to protect against paracetamol-induced hepatotoxicity in mice. When administered to mice, CIPE produced a rapid but transient elevation of levels of non-protein sulphydryls (NPSH) in liver, lung, kidney and spleen. The greatest increase in NPSH was seen in the lung, but after 60 min all NPSH values had returned to control levels, demonstrating the capacity of the mouse to rapidly metabolize both CIPE and cysteine. In mice pretreated with benzo(a)pyrene, CIPE protected against paracetamol-induced toxicity as measured by the prevention of mortality, the fall in hepatic NPSH and the decreased elevation of serum transaminases. CIPE (1.5 mmol/kg) appeared as effective as N-acetylcysteine (1.5 mmol/kg). Higher doses of CIPE (3.0 mmol/kg) alone were toxic to mice induced with benzo(a)pyrene but not to control or phenobarbitone-induced mice. The mechanism of this increased toxicity is unclear. CIPE has a short in vivo half life but was capable of protecting against paracetamol-induced toxicity. The potential of CIPE and other related cysteine esters to act as chemoprotectants merits further investigation.

Acetaminophen↗

Chronic intestinal pseudoobstruction in a patient with heart-lung transplant. Therapeutic effect of leuprolide acetate.

After orthotopic heart-lung transplantation and immunosuppression, a patient developed intractable nausea and vomiting in association with chronic cytomegalovirus infection. Chronic intestinal pseudoobstruction was documented by antroduodenal manometric study. The patient was treated with leuprolide acetate with resolution of symptoms and improvement of intestinal motility abnormality. This case demonstrates an association of chronic viral infection with acquired intestinal motor disorders. Gastrointestinal complications that are common after organ transplantation might be due to acquired neuromuscular disease. The potential efficacy of leuprolide in such neuromuscular disorders provides a rationale for diagnostic motility studies in patients with "functional" gastrointestinal disorders.

Adolescent↗

Methylene chloride--an inhalation study to investigate pathological and biochemical events occurring in the lungs of mice over an exposure period of 90 days.

Male B6C3F1 mice were exposed to 4000 ppm methylene chloride (MC) for 6 hr/day, 5 days/week for up to 13 weeks. Groups of mice were killed at intervals from Day 2 to Week 13. Whole lungs were examined morphologically, immunocytochemically, and biochemically. Biochemical and morphological examination was also performed on isolated Clara cells. The major initial morphological effect seen in lungs was acute Clara cell damage after one exposure to MC. However, this damage appeared to resolve after five consecutive daily exposures to MC. After a 2-day interval the Clara cell lesion reappeared on subsequent reexposure to MC. However, the severity of the lesion decreased over the duration of the study. The appearance and disappearance of the lesion in the Clara cell correlated well with the activity of cytochrome P450 monooxygenase in the Clara cell as assessed immunocytochemically (cytochromes P450IIB 1 and 2) in the whole lung and biochemically in the freshly isolated Clara cell (determined by ethoxycoumarin O-dealkylation and aldrin epoxidation). When there was a marked decrease in cytochrome P450 monooxygenase activity the lesion was not present. This suggested that with time the lung (Clara cell) has developed tolerance to MC possibly due to the inactivation of a cytochrome P450 isozyme. The glutathione S-transferase metabolism of MC by the lung cytosol remained virtually unaltered throughout the study. Events accompanying the discussed changes include (1) a significant increase in nonprotein sulfhydryl in the lungs of all exposed animals, (2) altered plating characteristics of the isolated Clara cells from exposed lungs after 24 hr in culture, and (3) an increase in the number of bronchiolar cells in the S-phase after the first exposure to MC. The study also demonstrates the advantages of target cell isolation and study over whole lung biochemical investigation alone.

Administration, Inhalation↗

Genotoxic potential of tamoxifen and analogues in female Fischer F344/n rats, DBA/2 and C57BL/6 mice and in human MCL-5 cells.

Chronic administration of tamoxifen to female rats causes hepatocellular carcinomas. We have investigated damage to liver DNA caused by the administration of tamoxifen to female Fischer F344/N rats or C57B1/6 or DBA/2 mice using 32P-postlabelling. Following the administration of tamoxifen for 7 days (45 mg/kg/day) and extraction of hepatic DNA, up to 7 radiolabelled adduct spots could be detected after PEI-cellulose chromatography of the 32P-labelled DNA digests. Tamoxifen caused a time-dependent increase in the level of adduct detected up to a value of at least 1 adduct/10(6) nucleotides after 7 days dosing. A dose response relationship was demonstrated over the range of 5-45 mg/kg/day (0.013-0.12 mmol/kg/day). On cessation of dosing there was a loss of adducts from the liver DNA. These adducts were not detected in DNA from vehicle-dosed controls or in DNA from kidney, lung, spleen, uterus or peripheral lymphocytes. Pyrrolidinotamoxifen caused a similar level of adduct formation as tamoxifen. In contrast, no significant adduct formation could be detected in liver DNA from rats given droloxifene or toremifene. Mice given tamoxifen (45 mg/kg/day for 4 days) showed levels of adducts in the liver which were 30-40% of those present in rats. Exposure of rat hepatocytes to tamoxifen in vitro, resulted in induction of unscheduled DNA synthesis, when preparations from rats which had been pretreated with tamoxifen in vivo were used. No such increase could be detected in hepatocytes from control rats, suggesting tamoxifen may induce enzymes responsible for its own activation. Tamoxifen induced a significant increase in micronucleus formation in a dose dependent manner in cultures of MCL-5 cells, a human cell line that expresses 5 different human cytochrome P450 isoenzymes, as well as epoxide hydrolase.

Animals↗

Role of the frozen tissue bank in molecular pathology.

The new discipline of molecular pathology requires that high-quality, intact genomic DNA, mRNA, and proteins be available from frozen tissue samples. It is now necessary for pathology laboratories to establish consistent guidelines for the preparation and storage of frozen tissue samples in order to have properly preserved tissues available for diagnostic molecular techniques. Maintaining a frozen tissue bank requires a pathologist to oversee this program and to integrate it into the routine surgical pathology activities. A member of the laboratory technical staff can serve as a tissue bank coordinator and have responsibility for preparation of tissue samples, their systematic storage and retrieval, and routine maintenance of equipment and supplies. Tissue sampling must be done as soon as possible after excision of the specimen and is the responsibility of a qualified pathologist. The samples may be snap frozen without cryoprotection at -78 degrees C or colder for subsequent use in procedures requiring the extraction of genomic DNA, mRNA, or protein. To preserve tissue architecture and cytologic features for immunohistochemistry and in situ hybridization, the tissue should be frozen at -78 degrees C or colder with a cryoprotectant such as OCT. Long-term storage of the frozen tissue is recommended at -140 degrees C or colder in a locked liquid nitrogen freezer, and the record of sample inventory can easily be kept in a computerized database. Tissues sampled and stored under these conditions have been used successfully in a wide variety of molecular techniques. In addition to malignant tumor tissue, samples from benign lesions and normal tissues should be frozen.(ABSTRACT TRUNCATED AT 250 WORDS)

Cryopreservation↗

Effect of iron chelators on paraquat toxicity in rats and alveolar type II cells.

There is general agreement that the lung damage seen in paraquat poisoning is due to the generation of free radicals in alveolar epithelial cells. We have recently shown that the iron chelator and antioxidant deferoxamine (DF) reduces the mortality caused by paraquat in vitamin-E-deficient rats. In the present study we investigated the effect of DF and the lipid soluble iron chelator compound 51 (CP51) of the hydroxypyridin-4-one family on paraquat poisoning in rats with a normal vitamin E status and on isolated alveolar type II cells (ATTC). Adult rats were intravenously injected with a lethal dose of paraquat (40 mg/kg) while concurrent treatment with a continuous intravenous infusion of DF or CP51 was started. Survival of rats receiving DF at 25 and 50 mg/kg/24 h was not significantly increased compared with PBS-treated control animals. CP51, however, significantly (p less than 0.01) reduced the mortality caused by paraquat. When rats were treated with 25 mg/kg/24 h, eight of 15 rats survived the study period of 35 days compared with three in the PBS-treated control group (n = 27). In ancillary in vitro studies radiolabeled [51Cr]ATTC were incubated in a medium containing 100 microM paraquat in the absence or presence of DF and CP51. Paraquat-induced ATTC lysis increased to approximately 25% after 7 h of incubation. At the highest tested concentration (500 microM) of chelator, injury decreased markedly (80%), whereas at the lowest tested concentration (50 microM) cytotoxicity was not prevented.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coping with disability. Nurse administrators' obligations under the Americans with Disabilities Act.

Many nurses who have disabilities view the Americans with Disabilities Act of 1990 as a piece of legislation that will have significant implications for nurse administrators and managers at all levels. This legislation becomes fully operational in July 1992, and little has been written in nursing literature about its implications. As a nurse administrator, are you ready to "cope with disability?"

Adaptation, Psychological↗

Protection of rats against the effects of alpha-naphthylthiourea (ANTU) by elevation of non-protein sulphydryl levels.

We have investigated the influence of the elevation of pulmonary glutathione (GSH) levels on the toxicity of the rodenticide alpha-naphthylthiourea (ANTU) to rat lung. Administration of phorone (diisopropylidene acetone; 200 mg/kg i.p.) caused an initial depletion of both pulmonary and hepatic GSH followed after 48 hr by a marked elevation in both tissues, due most probably to a compensatory rebound synthesis. In control rats, ANTU produced a dose-dependent lethality, hydrothorax and loss of ability of lung tissue to accumulate adenosine and spermidine (markers of endothelial and epithelial cell function, respectively). These effects were prevented or markedly ameliorated when ANTU was given 48 hr after pretreatment with phorone. The mechanism of the protection by phorone pretreatment against ANTU-induced pulmonary toxicity is unclear. It may be due, in part, to elevated GSH levels in pulmonary endothelial cells and, in addition, to increased detoxification of ANTU in the liver, resulting in a decreased availability to the lung.

Adenosine↗

Molecular features necessary for the uptake of diamines and related compounds by the polyamine receptor of rat lung slices.

The influence of 17 putrescine analogues on the uptake of putrescine and/or paraquat by rat lung slices has been determined. Most of these compounds are competitive inhibitors of putrescine and/or paraquat uptake, but three show no inhibiting activity. Apparent Ki values of the putrescine derivatives increase, and thus the inhibitory effects decrease, with increasing N-methylation. Comparison of N-methyl-1,4-diaminobutane (Ki = 8 microM) with N,N'-bis-methyl-1,4-diaminobutane (Ki = 25.5 microM) shows that a single primary amino group is desirable for high inhibiting activity. Dimethylation at one amino function does not greatly decrease inhibitory potential (thus N,N-dimethyl-1,4-diaminobutane has Ki = 11.5 microM). Increasing the size of N-alkyl substituents in putrescine derivatives, decreased their inhibitory action on the uptake of putrescine. Investigation of the effect of conformationally-restricted analogues of putrescine shows that both (E) and (Z) isomers of 1,4-diaminobut-2-ene are poor inhibitors of putrescine uptake. Analogues of putrescine with bulky substituents on the butyl chain, i.e. the meso- and rac-isomers of 1,1-dichloro-2,3-diaminomethylcyclopropane, do not inhibit putrescine uptake. Inhibiting putrescine derivatives which contain aziridine groups are competitive inhibitors of putrescine and paraquat uptake. Surprisingly, N-(4-aminobutyl)aziridine is the most effective inhibitor of putrescine uptake studied, and is a better inhibitor of paraquat uptake than the endogenous polyamine, putrescine. N-(4-Aminobutyl)aziridine binds reversibly to the polyamine transporter and its inhibitory effects do not appear to be due to any cytotoxic activity of the aziridine. The parameter A (mM)-1 defined as 1000/Ki (where Ki units are microM) was taken as a measure of the affinity of a compound for the polyamine receptor in this paper.

Affinity Labels↗

Valve disruption for in situ vein bypass: use of a new technique.

Following its introduction in 1960, the in situ bypass technique has gradually gained acceptance among vascular surgeons. This can be explained, in part, by the lack of a reliable method for rendering vein valves incompetent. Several instruments developed by Skagseth and Hall, Leather and Karmody, and others have been used. Although most are relatively easy to use, one common drawback is the difficulty in controlling rotation of the cutting blade. This is due to insufficient torsional rigidity of the shaft and the lack of a blade plane indicator. Edwards, in 1936, described the consistent orientation of vein valves, whose margins are always parallel to the overlying skin surface. This knowledge facilitates complete midline incision of the valve cusps, provided that the surgeon is able to control the cutting blade. With this fact in mind, we have developed a new set of instruments. They feature satisfactory torsional rigidity, as well as blade plane indicators at the handle. For the endoscopist, the blade plane is made visible by a mark at the tip of each instrument. Precision-manufactured of stainless steel and welded with laser technology, the instruments are suitable for multiple use, which we consider an advantage from an economic, as well as an ecological viewpoint.

Equipment Design↗

Another cholesterol hypothesis: cholesterol as antioxidant.

Current emphasis on cholesterol as agency if not cause of human atherosclerosis and subsequent cardiovascular disease ignores the essentiality of cholesterol in life processes. Additionally ignored is the ubiquitous presence of low levels of oxidized cholesterol derivatives (oxysterols) in human blood and select tissues, oxysterols also implicated in atherosclerosis. Whereas such oxysterols may be regarded putatively as agents injurious to the aorta, an alternative view of some of them is here proposed: that B-ring oxidized oxysterols of human blood represent past interception of blood and tissue oxidants in vivo by cholesterol as an ordinary aspect of oxygen metabolism. Such interception and subsequent efficient hepatic metabolism of oxysterols so formed, with biliary secretion and fecal excretion, constitute as in vivo antioxidant system. Whether cholesterol, oxysterols, oxidized lipoproteins, or oxidants in blood, singly or in concert, cause or exacerbate human atherosclerosis remains to be understood.

Antioxidants↗