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Biomedical subjects

W Anderson

Publications and source records attributed to W Anderson.

At least 19 recordsLinked to original sources

Improved detection of antibodies to hepatitis C virus in dialysis patients using a second-generation enzyme immunoassay.

We tested serum samples from 99 patients undergoing maintenance hemodialysis for hepatitis C virus (HCV) antibodies using a first-generation, licensed anti-HCV enzyme immunoassay (EIA) and a second-generation anti-HCV EIA that detect three gene products c100-3, NS3, and core. Specimens that were repeatedly reactive by either or both screening assays were further evaluated by testing with supplemental EIAs and a dot blot immunoassay. There was 87.9% agreement between the licensed HCV EIA and the HCV EIA second generation. HCV EIA Second Generation detected 10 more positive specimens than HCV EIA, for an increase in detection from 33.3% (33/99) to 43.4% (43/99). We conclude that HCV EIA Second Generation improves detection of HCV infection in hemodialysis patients.

Adult

Diagnostic value of pleural fluid cytology in occult Boerhaave's syndrome.

When Boerhaave's syndrome presents with atypical clinical features and eludes prompt diagnosis, delays in surgical therapy increase complications and mortality. We present a patient with occult Boerhaave's syndrome who had nondiagnostic esophageal contrast studies and thoracic computed tomography. Pleural fluid cytologic analysis established the presence of esophageal rupture by detecting undigested food particles.

Esophageal Diseases

Redox derivatives of tranylcypromine: syntheses, properties, and monoamine oxidase inhibitor activity of some chemical delivery systems.

Several brain-targeting chemical delivery systems (CDS) based on a dihydropyridine----pyridinium salt type redox system were synthesized for the monoamine oxidase (MAO) inhibitor tranylcypromine (TCP). The dihydronicotinate moiety was chemically attached to the amino group of TCP by either an amide or substituted carbamate linkages. Physicochemical studies of the new derivatives, including chromatographic Rm determinations, were performed. Only the substituted carbamate-type derivatives manifested an increased lipophilicity relative to the parent compound. In vitro oxidation stability studies were also performed on selected derivatives using a ferricyanide-mediated method. Results of this assay showed that the dihydropyridine-type derivatives oxidized to the respective quaternary salt forms with stabilities which empirically correlated with other effective CDSs. Preliminary in vivo studies performed in rats indicated that some of the new derivatives exerted significant biological activity.

Animals

Brain, blood, and cerebrospinal fluid distribution of a zidovudine chemical delivery system in rabbits.

Improved brain delivery of zidovudine (AZT) was shown to occur after iv dosing of a chemical delivery system (CDS) for the modified deoxynucleoside. Specifically, administration of a 25-mg/kg dose of 5'-[(1-methyl-1,4-dihydropyridin-3-yl)carbonyl]-3'-azido-3'-deoxyt hymidine (AZT-CDS) generated higher and more sustained levels of AZT in brain tissue of rabbits than did dosing with AZT itself. The significant increase in the area under the AZT brain concentration-time curve occurred with lower AZT present in the systemic circulation and with similar AZT levels in cerebrospinal fluid. These results, as well as previously published reports examining AZT-CDS in mice, rats, and dogs, indicate that this delivery system may be beneficial in the treatment of AIDS-related encephalopathy.

Animals

Length of stay in a general hospital psychiatric unit.

Fifty psychiatric inpatients with a prolonged length of stay were compared to 50 control admissions for factors associated with prolonged hospitalizations in a general hospital. Seven variables were found to be significantly overrepresented among the long stayers, including treatment with electroconvulsive therapy, medical consultations, underemployment, dementia, disposition to a place other than home, absence of alcohol or drug abuse, and presence of psychosis without affective symptoms. The clinical and policy implications of these finding are discussed.

Cost Control

Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model.

Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers and perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds (wt 20-25 kg) received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy. These experimental data suggest that intraoperative doses of less than 20 Gy may not result in clinically significant peripheral nerve injury with follow-up of 3.5 years. Longer (5 yrs) follow-up with planned sacrifice of the remaining dogs is scheduled to assess any late peripheral nerve damage.

Animals

Acute theophylline intoxication.

We describe a case of intentional acute theophylline intoxication with cardiac, cerebral, and gastrointestinal features of moderate-to-severe toxicity. The unusual metabolic and hematologic sequelae included hypokalemia, hyperglycemia, metabolic acidosis, extreme neutrophilia, increased creatinine levels attributed to muscle damage, and hematuria. The implications of these unusual findings for the management of acute theophylline intoxication include the recognition that these effects can be due to intoxication per se and do not necessarily indicate a primary endocrine disorder or infection.

Acidosis

Pulmonary nodule: evaluation with spiral volumetric CT.

Spiral volumetric computed tomography (CT) was used prospectively in 20 patients with a suspected solitary pulmonary nodule less than 1 cm in diameter on plain chest radiographs. Four additional nodules were detected with spiral CT than were detected with conventional CT. This technique required a 12-second breath hold; patient cooperation was excellent.

Humans

The New York Needle Trial: the politics of public health in the age of AIDS.

During the past 5 years, the exchange of sterile needles and syringes for dirty injecting equipment has gained increasing acceptance outside the United States as a potential means of reducing the transmission of the human immunodeficiency virus (HIV) among intravenous drug users. This article describes the controversy over attempts to establish a needle and syringe exchange scheme in New York City between 1985 and 1991. The response to a health crisis is used as an indicator of patterns of social and institutional practice. Advocates of needle exchanges had reached a stalemate with the promoters of law enforcement, and the strategic reformulation of the policy problem in terms of the research process seemed to offer a solution. The article discusses the practical limitations on designing and carrying out a controversial health promotion policy; the use (under constraint) of a restrictive research process to constitute--rather than simply to guide or monitor--public policy; and the potential ethical hazards of health professionals' seeking a polemical recourse to the clinical trial. The efforts to establish a needle exchange in New York thus illustrate more general problems for AIDS prevention.

Acquired Immunodeficiency Syndrome

Cochlear implantation of totally deaf ears. Histologic evaluation of candidacy.

Successful cochlear implantation depends on the presence of stimulatable neural elements, which are believed to be the spiral ganglion, neurons, or their axons. We examined the 1,152 temporal bones in our laboratory to determine how many with a total sensorineural hearing loss would be implantable. We defined implantable as having 3,500 neurons or more, as determined by successful implant stimulation in two ears from our collection with less than 3,500 neurons. Of 46 bones with deafness, 37 had 3,500 neurons or more and would be considered implant candidates. The types of deafness in the potentially implantable ears and in ears with sufficient neural elements will be discussed.

Cochlear Implants

Tumor induction following intraoperative radiotherapy: late results of the National Cancer Institute canine trials.

Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a "collision" tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months (median 40 months). The IORT dose range associated with tumor development was 20-35 Gy (median 30 Gy). The carcinogenesis capability of single fraction, high dose radiation in animals is discussed, as are the implications of these data for continued research and clinical usage of IORT in the treatment of humans.

Animals

[3H]prostaglandin uptake in vivo by rabbit uterine tissues and blastocysts.

Day-6 pregnant rabbits were anesthetized and subjected to a mid-ventral laparotomy. [3H] Prostaglandin F2alpha) (PGF2alpha) [3H]PGE2, [14C]Urea or [14C]Sucrose were instilled into the uterine lumen via the uterotubal junction. The amounts instilled/uterine horn were respectively 3.7 +/- 0.3, 3.5 +/- 0.3, 5.7 +/- 1.3 and 2.7 +/- 1.6 muCi in 20mul of buffer. Animals were killed at 1, 2, 9, 19 or 21 h after radioactive instillation, and the amounts of radioactivity in blastocysts, uterine tissue, peritoneal cavity washings and urine evaluated by liquid scintillation spectrometry. A gradient of radioactivity was observed from the uterotubal junction to the cervical end of the uterus. Large amounts of [3H]PG were found in the injected horn and associated blastocysts with a considerable crossover to the non-injected horn, but little in the associated blastocysts. Much of the blastocysts associated- [3H]PG remained unmetabolized. Large amounts of metabolized [3 H] were found in urine. [14C]Urea was taken up by uterine tissue in the injected horn, but there was little cross over to the non-injected horn. Urea was also found in urine. Much of the [14C]Sucrose remained in the injected horn, and little was recovered from the urine. It was found that at 9 h, but not at 19 h, after [3 H]PG instillation, the PG was localized at the site of the blastocysts in the injected but not in the contralateral horn. Significantly more [3H]PGF2alpha than [3H]PGE2 was localized in this situation. [14C]Urea was not localized at the site of the blastocysts in urea injected horns. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Antihypertensive activity of redox derivatives of tryptophan.

The essential amino acid, tryptophan, has been shown to lower blood pressure in rats when administered orally or intravenously. In order to potentially enhance this action, a brain-targeting chemical delivery system (CDS) approach was applied to this compound. The CDS is based on a dihydropyridine----pyridinium ion redox system, chemically analogous to the naturally occurring NADH----NAD+ system. The dihydropyridine moiety containing carrier is chemically attached to the amino group by an amide-type bonding while the carboxylic acid functionality is esterified to various alcohols. Physicochemical studies of the new derivatives were performed. The determined chromatographic Rm values indicate an increased lipophilicity for the CDSs compared to the parent compound. Oxidation stability studies performed on selected compounds using a ferricyanide-mediated method showed that the CDSs are oxidized to the respective quaternary salt forms. Activity studies performed in deoxycorticosterone acetate induced hypertensive rats, demonstrated that the delivery system for tryptophan reduced blood pressure more efficiently for a longer time than did the parent compound.

Animals

Hypothermia increases calcium content of hypoxic myocytes.

To test the hypothesis that hypothermia prevents myocardial Ca2+ loading during reoxygenation, we examined the effects of 2 h of hypoxia with and without hypothermia on the Ca2+ content of cultured chick embryo ventricular cells. When compared with hypoxic cells at 37 degrees C, hypoxia at 11 degrees C (hypothermia) augmented the 45Ca content of cardiocytes after 30 min of normothermic reoxygenation from 3.85 +/- 0.2 to 4.7 +/- 0.1 nmol/mg protein (P less than 0.001). The Na+ content of hypoxic myocytes was also increased at the end of 2 h of hypoxia from 648 +/- 59 to 1,026 +/- 68 nmol/mg protein in cells exposed to hypoxia at 11 degrees C (P less than 0.001). Hypothermia ameliorated hypoxia-induced depression of cellular ATP content and did not result in significant membrane injury as determined by lactate dehydrogenase release. These data indicate that hypothermia augments rather than decreases the Ca2+ content of hypoxic myocytes during reoxygenation after hypoxia. Ca2+ loading appears to be secondary to an increase in Na+ content, creating a favorable gradient for Ca2+ influx through Na(+)-Ca2+ exchange or an unfavorable gradient for Ca2+ extrusion.

Adenosine Triphosphate

Pharmacokinetics and distribution of recombinant secretory leukocyte proteinase inhibitor in rats.

Secretory leukocyte proteinase inhibitor (SLPI) is a potent elastase, trypsin, and chymotrypsin inhibitor occurring in all mucous secretions. Its inhibitory potency and profile suggested that it may become a therapeutic adjuvant in diseases where proteinases play a pathogenetic role. In the course of developing recombinant SLPI for therapeutic purposes, we studied its pharmacokinetics after intravenous, intraperitoneal, and intratracheal application to rats. In plasma, SLPI was determined with an ELISA or by following a radiotracer [( 35S]SLPI). In bronchoalveolar lavage fluid (BALF), SLPI was determined additionally by a functional assay (elastase inhibitory capacity). Intravenously applied SLPI (2 mg/kg) was rapidly cleared, with half-times of distribution of 6 min and half-times of elimination of 50 min. Very little (less than 5%) appeared in the urine even after 24 h. Approximately 80% of intraperitoneally injected SLPI (12 mg/kg) was absorbed and generated maximal plasma concentration of 6 to 10 micrograms/ml 30 to 120 min after administration. When given intratracheally (8.6 mg/kg), SLPI disappeared from the lungs, with a half-time of 4 to 5 h. This value was the same whether the remaining SLPI in BALF was determined radiometrically, by ELISA or by the functional assay, indicating minimal metabolism in the lung. As in the case of intraperitoneal application, SLPI was absorbed systemically, resulting in a maximal plasma level of about 2 micrograms/ml 1 to 2 h after application. In contrast to the measurements in BALF, the ELISA and radiotracer measurements in plasma correlated only for the first 2 h after application and diverged progressively after that, suggesting breakdown of the molecule once it reaches the plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals