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Biomedical subjects

R W Hudgens

Publications and source records attributed to R W Hudgens.

At least 19 recordsLinked to original sources
PubMed1993

The turning of American psychiatry.

Philosophic changes and the "re-medicalization" of psychiatry in the past half century are associated with: evolution of the biopsychosocial model; new techniques for biologic studies; drug treatment for mental disorders; funding for research and training; and development of a criteria-based nosology for psychiatric disorders. The last development owes much to the work of four Washington University faculty members, beginning in the 1950's. The second part of this paper will examine their early careers and the institutional policies that fostered their work.

History, 20th Century↗
PubMed1989

Isoproterenol inhibits the increase in microvascular membrane permeability produced by bradykinin.

Bradykinin (BRADY) is hypothesized to cause the "capillary leak" syndrome in patients with sepsis, trauma, and burns. Our purpose was to determine if isoproterenol (ISO) reversed a BRADY-produced accelerated loss of intravascular fluid and protein into the interstitium of skin. An increase in microvascular permeability in canine hind paw skin was sustained by a continuous femoral artery infusion of BRADY (0.2 micrograms/kg/min). After 2 hours of BRADY, skin lymph flow (LYM FLOW microliters/min) increased nine-fold and skin lymph-to-plasma total protein concentration ratio (RTP) was substantially increased. Mean blood flow in the femoral arteries was increased four-fold by the BRADY infusion. After 2 hours of BRADY-induced increased permeability, five of the ten dogs were started on intravenous ISO (2 micrograms/min continuously) which increased heart rate from 182 +/- 15 to 222 +/- 11 beats/min. ISO reversed the increase in RTP produced by the BRADY. After 8 hours of BRADY, there was less tissue albumin in the dogs given ISO (14.5 +/- 2.0 vs. 29.5 +/- 6.6 mg/gram dry wgt, p less than 0.05 unpaired t-test). ISO can reverse the sustained increase in skin microvascular permeability produced by BRADY.

Animals↗
PubMed1987

Hypertonic saline resuscitates dogs in endotoxin shock.

In this experiment we determined if infusions of hypertonic saline (HS, 1080 Na meq/liter) could resuscitate dogs in endotoxin shock as effectively as Ringer's lactate (RL, 130 Na meq/liter). Anesthetized dogs received iv 0.5 mg/kg of Escherichia coli endotoxin, and mean arterial pressure (MAP, mm Hg) decreased from 148 +/- 5 to 58 +/- 14 within 30 min. To resuscitate the dogs 13 meq/kg of sodium was intravenously infused over 90 min as either a 10% body weight load of RL (n = 5) or a 1.2% body weight load of HS (n = 5). Both solutions produced an equivalent hemodynamic resuscitation 3 to 4 hr postinfusion with an increase in MAP (RL, 119 +/- 4; HS, 108 +/- 7), the restoration of cardiac outputs to baseline (RL, 2.0 +/- 0.2; HS, 1.9 +/- 0.3 liter/min), and similar renal inulin clearances (RL, 48 +/- 16; HS, 44 +/- 7 ml/min). The net fluid gain (resuscitation fluid volume infused minus urine output as percentage of body weight) was much greater in the RL group (7.2 +/- 1.0%) than in the HS group (0.48 +/- 0.2%). Plasma volume (PV, percentage of body weight) was measured with Evans blue dye in these splenectomized dogs. The increase in PV in the RL dogs (1.25 +/- 0.04%) was slightly greater than the increase in the HS group (0.94 +/- 0.13). Prenodal skin lymph was collected from both hindpaws, and the fractional increase in skin lymph flow after RL (4.5 +/- 2.9) was greater than the increase in the HS group (1.7 +/- 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Increased skin lymph protein clearance after a 6-h arterial bradykinin infusion.

When bradykinin (0.15-0.28 micrograms.kg-1.min-1) was infused into both femoral arteries of 11 anesthetized dogs, skin lymph flows increased by 25-371% within 2 h, and mean lymph protein concentrations increased by one-third. To determine whether, in addition to the initial increase in permeability, a 6.5- to 10-h bradykinin infusion caused a sustained effect, the bradykinin infusion into one hindpaw was stopped after 2 h (2HR), whereas the contralateral hindpaw was infused continuously (CONT). Two hours after the bradykinin infusion was stopped, Ringer lactate equal to 10% of the dog's body weight was given intravenously to further increase lymph flow. After Ringer lactate infusion, increase in lymph protein clearance from the CONT hindpaws was greater than that from the 2HR hindpaws (change in clearance from before Ringer lactate infusion to final: 2HR, 6.9 +/- 1.4 to 8.8 +/- 1.1; CONT, 23.4 +/- 2.5 to 40.2 +/- 4.8 microliters/min). In the final lymph samples of the CONT, but not 2HR, hindpaws, the lymph-to-plasma ratio for immunoglobulin G and immunoglobulin M divided by the albumin lymph-to-plasma ratio exceeded the value of these ratios in the base-line samples. An intravenous bolus of Evans blue dye was given less than 2 h before the end of the experiment. The concentrations of dye in the final lymph samples were greater in CONT hindpaws (12.6 +/- 3.7% plasma equivalents) than in the 2HR hindpaws (1.1 +/- 0.5%). A continuous 6.5- to 10-h intra-arterial bradykinin infusion produced a sustained increase of transvascular protein clearance in skin that is consistent with a sustained increase in microvascular membrane permeability.

Animals↗
PubMed1986

Effect of sidestream and mainstream smoke exposure on in vitro interferon-alpha/beta production by L-929 cells.

A peristaltic pump smoking machine that allows simultaneous generation of mainstream (active) and sidestream (passive) smoke from a cigarette was used to expose cultures of murine L-929 cells, a potent producer of interferon, to smoke. The cigarette used was the University of Kentucky 2R1 reference cigarette. The dosages of smoke used for exposure were the highest doses possible that generated a minimum toxic effect, and they were serially diluted to lower doses. Dosages were determined by the number of smoke puffs generated, the volume of smoke puffs generated, and the total particulate matter deposited on Cambridge filters in the smoke machine. Viability of exposed cells was equivalent to control cell cultures. Interferon-alpha/beta was induced by addition of polyriboinosinic-polyribocytidylic acid to the cells. Interferon production was substantially reduced in viable cells exposed to mainstream or sidestream smoke. Aging of smoke by delaying time of exposure of the cells to the smoke, or filtration of smoke through activated charcoal substantially decreased the alteration of interferon production by smoke exposure. These results suggest that actual exposure of cells to mainstream or sidestream smoke can inhibit in vitro interferon-alpha/beta induction, but the cells can be protected from these effects by smoke manipulation.

Animals↗
PubMed1985

The effect of smoke generation and manipulation variables on the cytotoxicity of mainstream and sidestream cigarette smoke to monolayer cultures of L-929 cells.

A system for the simultaneous exposure of monolayer cell cultures to mainstream (MS) and sidestream (SS) smoke from the same cigarette was utilized to study the effects of smoke generation and manipulation variables on the cytotoxicity of smoke to monolayer cultures of mouse fibroblast-like L-929 cells. The cytotoxicity of MS smoke was decreased with increasing smoke age (up to 8.7 s), smoke dilution, and the quantity of activated charcoal in filters. Acetate filters had little effect on cell mortality, and the age-of-smoke effect was not evident for MS smoke generated with a low puff volume and rapid dilution. The cytotoxicity of SS smoke also decreased rapidly with increasing smoke age and dilution. The results indicate that the gas phase of smoke may be of major importance in generating the observed toxic effects. These results may be of potential future significance in defining the requirements for a less toxic cigarette, in considering the hazards of SS smoke, and in evaluating in vivo inhalation studies.

Animals↗
PubMed1984

Effect of aromatic carcinogens and noncarcinogenic analogs on the induction of murine alpha/beta interferon.

The effects of several aromatic carcinogens and their noncarcinogenic analogs on the production of alpha/beta interferon by mouse embryo fibroblasts were determined. The carcinogens 2-naphthylamine and 9,10-dimethylanthracene significantly depressed alpha/beta interferon production, while their poorly or noncarcinogenic analogs, 1-naphthylamine and anthracene, respectively, had no significant effect. Neither the carcinogen benzidine nor its poorly carcinogenic analog 3,3',5,5'-tetramethylbenzidine had any effect on alpha/beta interferon production. These data, taken together with previous findings, suggest the possibility of drawing a high correlation between the carcinogenic potential of a chemical and its effect on interferon production.

Animals↗
PubMed1984

Dosage limitations of the effects of difficult-to-detect carcinogens on in vitro interferon induction.

Several carcinogens have been shown to depress in vitro interferon (IFN) induction, while closely matched weakly or noncarcinogenic analogues had no effect on IFN induction. In this study, specific carcinogens that were difficult to detect by the Ames Salmonella assay were tested for their effects of IFN-alpha/beta induction. The carcinogens were applied to mouse embryo fibroblast cultures, and were then removed. IFN-alpha/beta induction was then carried out using polyriboinosinic-polyribocytidylic acid. Application of urethane, which was undetectable by the Salmonella assay except under special conditions, significantly depressed IFN-alpha/beta induction. Treatment with cyclophosphamide or dimethylcarbomyl chloride, both of which required extremely large dosages to be detected by the Salmonella assay, had no effect on IFN-alpha/beta induction at the dosages used. Higher dosages of these carcinogens were toxic to the cells used in this system.

Animals↗
PubMed1983

Effect of environmental carcinogens and other chemicals on murine alpha/beta interferon production.

Mouse embryo fibroblast cultures were pretreated with a variety of chemicals found in the environment. After chemical treatment, polyriboinosinic-polyribocytidylic acid was added to the cultures to induce alpha/beta interferon. Pretreatment of the cell cultures with the chemical carcinogens chloroform and beta-propiolactone severely inhibited the production of alpha/beta interferon, while pretreatment of the cell cultures with their poorly or noncarcinogenic analogs 1,1,1-trichloroethane and gamma-butyrolactone had no effect on interferon induction. Pretreatment of the cell cultures with the possible carcinogen diethylstilbestrol had no effect on alpha/beta interferon induction. Pretreatment of the cells with the poor or noncarcinogens pyrene and ascorbic acid did not effect interferon induction; in fact, treatment with ascorbic acid may have enhanced interferon production. These results augment previous findings that most potent carcinogens can inhibit the induction of alpha/beta interferon.

Animals↗
PubMed1983

Effect of carcinogenic components of cigarette smoke on in vivo production of murine interferon.

Mice were treated with several different potentially carcinogenic components of tobacco smoke. The chemicals used were: 4-aminobiphenyl and aniline-HCl, which are found in high concentrations in sidestream tobacco smoke; hydrazine sulfate, which is found in high concentrations in mainstream tobacco smoke; and 2-methylquinoline, which is found in intermediate concentrations in both sidestream and mainstream smoke. The chemicals were injected i.p. into mice, and then alpha/beta interferon was induced in the mice by i.v. injection of polyriboinosinic-polyribocytidylic acid. The interferon was induced either 2, 24, or 48 hr after treatment with the tobacco smoke components. Mice treated with 4-aminobiphenyl showed some depression of interferon production 2 hr after treatment, maximum inhibition of interferon induction 24 hr after treatment, and a return to control levels of interferon 48 hr after treatment. Mice treated with hydrazine sulfate showed maximum inhibition of interferon induction 24 hr after treatment but no effects at any other treatment time. These components were the most carcinogenic chemicals of those utilized in this study. Treatment of mice with aniline-HCl, a chemical whose carcinogenic potential is still debated, resulted in marginal depression of interferon induction 24 hr after treatment. 2-Methylquinoline, the chemical with the lowest carcinogenic potential in this study, had no effect on interferon induction after administration to mice. In vivo interferon induction was, therefore, inhibited by treatment of mice with chemical carcinogens found in tobacco smoke. The efficacy of the chemical in inhibiting interferon induction was not influenced by the mainstream or sidestream smoke predominance of the chemical.

Aminobiphenyl Compounds↗
PubMed1978

Undiagnosed psychiatric illness in adolescents. A prospective study and seven-year follow-up.

Twenty-four psychiatrically ill adolescents, unclassifiable by diagnostic criteria, were followed up after seven years. Fifteen had been ill in the interval, and the conditions of 12 of these could, as adults, be diagnosed according to established syndromes because atypical adolescent psychiatric disorder became more typical in adulthood. Nine subjects remained well. Their original disorders had been characterized by depressed mood, reactivity, and conflicts with parents. Such a clinical picture in the absence of drug or alcohol abuse had good prognosis. Among many clinical and sociological features present at the time of the original study, only the presence of a "psychotic" symptom (hallucinations, delusions, formal thought disorder, or bizarre behavior) differentiated those who would be sick at follow-up from those who would be well. Poor outcome was predicted by such a symptom regardless of what the diagnosis later turned out to be.

Adolescent↗