Long-term maintenance of psoriatic human skin on congenitally athymic (nude) mice.

Transplantation of involved psoriatic and nonpsoriatic human skin onto congenitally athymic (nude) mice has been performed successfully. Although biopsies at selected intervals demonstrate that the excess glycogen deposition normally seen in psoriasis is no longer consistently present, the psoriatic grafts did retain the usual characteristic histologic differences throughout the life of the animal, up to 11 weeks. This grafting procedure potentially represents a useful method whereby the study of psoriasis can be made in a nonhuman, living system.

Inflammatory and immune cell function in psoriasis: II. Monocyte function, lymphokine production.

We have previously confirmed that subjects with psoriasis have an alteration of cell-mediated immune responses. We now report a possible in vitro corollary; the amount of lymphokine (lymphocyte-derived chemotactic factor) released by both antigen-stimulated and control lymphocytes is decreased in psoriatic subjects; 61% of similar values for normal subjects. Monocyte migration to complement-derived chemotactic factors is reported to directly correlate to skin tests; however, in psoriasis the relation is inverse, i.e., a 200% increase in complement factors and 136% increase to lymphocyte-derived chemotactic factor in monocyte migration is noted in psoriatic subjects when compared with normal subjects. This increased migration does not correlate with amount of disease and is still present in "disease-free" subjects. Culturing monocytes from psoriatic subjects in media alone demonstrates they reduce more (205%) nitroblue tetrazolium than do monocytes of normal subjects. These data demonstrate that monocytes from subjects with psoriasis are altered and suggest an apparent inherent metabolic disorder.

Chloroephedrine: contaminant of methamphetamine synthesis with cardiovascular activity.

Chloroephedrine is an intermediate and possible contaminant formed when methamphetamine is manufactured using ephedrine or pseudoephedrine as precursors. The purpose of this study was to determine whether this contaminant has biological activity and might contribute to methamphetamine-induced cardiovascular toxicity. In conscious rats, the (-) and (+) isomers of chloroephedrine (0.1 and 1.0 mg/kg, i.v.) dose-dependently increased mean arterial pressure (MAP) and heart rate (HR). The potency of the pressor effects of (-) and (+)-chloroephedrine was between that of ephedrine and pseudoephedrine. The increases in HR elicited by the four stimulants were similar except that the tachycardia elicited by all doses of ephedrine and pseudoephedrine were preceded by a brief decrease in HR. The i.v. administration of 10 mg/kg of (+) or (-)-chloroephedrine produced biphasic (decrease followed by increase) the MAP and HR responses. Ephedrine and pseudoephedrine did not decrease MAP at any dose tested. The initial decrease in HR elicited by (-)-chloroephedrine was significantly reduced and the hypotensive response abolished by atropine, indicating that these components of the MAP and HR responses resulted from vagal activation. The secondary pressor response elicited by (-)-chloroephedrine was significantly reduced and the tachycardia significantly increased by pretreatment with phentolamine (3 mg/kg, i.v.). The increase in HR was reversed by propranolol. These results indicate that (-) and (+)-chloroephedrine have sympathomimetic properties similar to other known sympathomimetic stimulants. In addition, larger doses of chloroephedrine can activate the vagus nerve. The combination of (+)-methamphetamine and (-)-chloroephedrine did not markedly alter the magnitude of the MAP and HR responses of (+)-methamphetamine alone except at high doses of (-)-chloroephedrine (10 mg/kg). Contamination of illicit methamphetamine with chloroephedrine may have toxic consequences.

Willingness of health-professions students to treat patients with AIDS.

This 1988-89 survey of 319 students in the medical, dental, nursing, and allied health-care professions revealed that over one-third had some reservations about treating acquired immunodeficiency syndrome (AIDS) patients. Most were unwilling to perform mouth-to-mouth resuscitation on patients with AIDS, and most also believed that health-care workers had the right to refuse care to AIDS patients. Unwillingness to treat AIDS patients was strongly associated with homophobic attitudes and concerns that patients with AIDS posed a risk to health professionals. AIDS education for health professionals should emphasize methods for the prevention of HIV infection among health workers, and include teaching strategies designed to deal with the irrational feelings that AIDS often engenders.

Octreotide does not alter endotoxin lethality in mice or endotoxin-induced suppression of human leukocyte migration.

Octreotide, a somatostatin analog, was evaluated for its effects on long-term survival in a mouse model of endotoxemia and for its effects on endotoxin-induced suppression of human leukocyte migration. Swiss Webster mice were simultaneously rendered endotoxemic with a single intraperitoneal injection of 800 micrograms E. coli Lipopolysaccharide (LPS) and treated with one of four doses of subcutaneous (s.c.) octreotide (1.0 mg/kg in 0.4 ml saline, 0.1 mg/kg in 0.4 ml saline, 0.1 mg/kg in 0.04 ml saline, or 0.001 mg/kg in 0.04 ml saline) or saline alone (fluid-resuscitated control group: 0.4 ml saline s.c.; or non-fluid-resuscitated control group: 0.04 ml saline s.c.). Octreotide was continued with or without supplemental s.c. fluid resuscitation (0.4 ml saline) at eight hour intervals for either twenty-four or forty hours. There was no statistical significance to differences in long-term survival between comparable groups of octreotide treated vs saline treated animals during the entire fourteen day period of observation. Fluid resuscitation during the first forty hours following endotoxemia induction delayed death, but did not significantly improve long-term survival. In vitro work was conducted to determine the effect of octreotide on endotoxin-induced suppression of human leukocyte migration. Octreotide at concentrations ranging from 3.05 x 10(-5) Molar to 3.05 x 10(-11) Molar had no significant effect on leukocyte migration. In this study octreotide treatment failed to improve long-term survival in mice with endotoxemia and did not alter endotoxin-induced suppression of leukocyte migration.

Cardiovascular and sympathetic responses and reflex changes elicited by MDMA.

The recreational use of 3,4-methylenedioxymethamphetamine (MDMA) has increased as have the number of clinical reports linking MDMA use with cardiovascular toxicity. Nonetheless, the cardiovascular and sympathetic nerve responses elicited by MDMA have not been well characterized. The purpose of this study was to characterize the mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve responses elicited by the acute administration of MDMA and to determine whether neurotoxic doses of MDMA change cardiovascular and/or cardiovascular reflex function. In conscious rats, MDMA or d-amphetamine elicited similar dose-dependent increases in MAP. MDMA elicited significant bradycardia at doses above 1.0 mg/kg. Pretreatment with phentolamine significantly reduced the duration but not the magnitude of the pressor response elicited by MDMA. In pentobarbital-anesthetized rats, MDMA (0.1 mg/kg) increased renal sympathetic nerve activity (RSNA; 33 +/- 10%), while larger doses significantly decreased RSNA (-91 +/- 3%, max). Neurotoxic doses of MDMA (20 mg/kg, s.c., b.i.d. for 4 days) significantly enhanced the bradycardic component of the Bezold-Jarisch reflex elicited by i.v. serotonin when tested either 2 days or 2 weeks after the last neurotoxic treatment. However, neurotoxic treatment did not significantly affect baroreceptor reflex function. These results indicate that the acute administration of MDMA and d-amphetamine produce similar cardiovascular and sympathetic responses. Neurotoxic doses of MDMA can also significantly alter cardiovascular reflex function. These findings raise the possibility that MDMA may have the potential to produce cardiovascular and/or cardiac toxicity similar to that elicited by other amphetamine analogs.

Multicystic renal oncocytoma.

The usual gross appearance of a renal oncocytoma is that of a well-circumscribed homogeneous tan-brown tumor with no evidence of necrosis or hemorrhage, but with a central fibrous scar. We describe a case of renal oncocytoma with the unusual gross appearance of a cystic tumor. While cystic change has occasionally been mentioned in an oncocytoma to our knowledge, this degree of cyst formation has not previously been described.

The effect of body position on the respiratory rate of infants with tachypnea.

In neonatal disease states where lung compliance is reduced (e.g., inadequate resorption of fetal lung fluid or, surfactant deficiency) an infant's normally low functional residual capacity (FRC) decreases even further. Tachypnea is an efficient compensatory maneuver for the newborn. We evaluated the effect of different bed and body positions on the increased respiratory rate observed in infants with transient tachypnea of the newborn (TTN), infant respiratory distress syndrome (RDS), and bronchopulmonary dysplasia (BPD). Seventeen infants were studied (TTN, n = 6; RDS, n = 6; BPD, n = 5) in four different positions: supine flat, supine elevated, prone flat, and prone elevated. Respiratory rate and heart rate were evaluated in each position. Analysis of variance for the three patient groups showed a lower respiratory rate when the bed was elevated 20-30 degrees compared to flat (P = 0.0001), in the prone posture compared to supine (P = 0.031), and no significant difference in heart rate. The lowest mean respiratory rate occurred when patients were in the prone elevated position. The significant improvement in tachypnea seen in the prone and elevated positions was likely related to improved FRC resulting from reduced cephalad stress on the diaphragm from the abdomen. Positioning neonatal patients with respiratory insufficiency was a simple and safe therapeutic maneuver with prompt and demonstrable benefit.

Assessing substance abuse among health care students and the efficacy of educational interventions.

Approximately 10 per cent of nurses are chemically dependent, and, for many, substance abuse begins while attending nursing school. Faculty must be able to assess the extent of the problem, understand the contributing factors, recognize signs and symptoms, and use educational interventions in identifying and preventing chemical dependency in nurses. Beginning in 1989, the authors sampled all entering students in four colleges on a health science campus using the Standardized Substance Abuse Attitude Survey and obtained resurvey data from two of the colleges' 1989 entering classes in fall 1991. Each college developed educational interventions. Some clear differences between nursing and pharmacy students emerged and indicated that a greater emphasis on drug and alcohol education can pay dividends. Establishing a data base over a period of more than 2 years provides a foundation to evaluate further interventions.

Evaluation of the use of coconut to treat chronic diarrhea in rhesus macaques (Macaca mulatta).

BACKGROUND: Chronic diarrhea can be challenging to manage in captive rhesus macaques (Macaca mulatta) leading to ongoing diagnostics, medications, monitoring, and potential euthanasia. Coconut has been used as a dietary supplement for people with inflammatory bowel disease, with anecdotal reports of decreased diarrhea following the dietary addition. A dietary trial in rhesus macaques was initiated to evaluate the hypothesis that dietary coconut decreases symptoms of chronic diarrhea in rhesus macaques. METHODS: Ten rhesus macaques with chronic diarrhea were selected for the trial. Five of the subjects were fed coconut macaroons and five of the subjects were fed a sham cookie. Stool consistency was monitored daily for both groups. RESULTS AND CONCLUSIONS: Data of chi-squared analysis obtained from eight rhesus macaques with chronic diarrhea showed that the use of coconut macaroons as a dietary supplement did not have a statistically significant effect on their diarrhea.

Histamine regulates lymphocyte mitogenic responses through activation of specific H1 and H2 histamine receptors.

In previous studies we have reported that patients with mild atopic eczema have enhanced lymphocyte mitogenesis while those with severe disease have markedly suppressed responses. Similarly, histamine in low concentrations enhanced mitogenesis while higher levels inhibit mitogen stimulated thymidine uptake. In the present study, we investigated the kinetics of this response and the interaction of histamine with its cell-surface receptors on lymphocytes. Histamine (10(-3) M) markedly inhibited [3H]-thymidine incorporation to 27% of control levels when added at the beginning of a 72 h culture period. When added after 24 and 48 h of culture, however, the suppression was much less (62 and 88% of control). Lymphocyte cultures pulsed for 1 h with histamine, washed free of the agent and then cultured with mitogen also showed marked suppression of [3H]-thymidine uptake. The kinetics of the response suggest that histamine acts to inhibit initial processing or recruitment steps in the mitogenic assay. Cimetidine, an H2-receptor blocking agent, prevented the suppressive effect of high levels of histamine while diphenhydramine, an H1 blocker, abolished the enhancement observed with low levels. Pre-incubation of mononuclear cell suspensions, which has been shown to decrease suppressor activity, resulted in a decreased response to added histamine. This change in histamine responsiveness was associated with an alteration in H1:H2 histamine binding as determined with a radiolabelled ligand-binding assay. Histamine suppression of mitogenesis was associated with an increase in cellular cAMP levels while enhancement was accompanied by a small increase in cGMP. These data suggest that lymphocyte function may be regulated, in part, by histamine receptor bearing cells with H1 stimulation having a role in enhancement of mitogenesis and H2 stimulation resulting in normal suppressor activity.

In vitro quantitation of cell-mediated immunity in guinea-pigs by macrophage reduction of nitro-blue tetrazolium.

In the cell-mediated immune (CMI) system lymphocytes from sensitized animals incubated with antigen manufacture and release lymphokines which activate the hexose-monophosphate shunt in macrophages. The rate-limiting enzyme of this activation is NADPH oxidase, the activity of which can be quantitated by the amount of nitro-blue tetrazolium reduced to formazan, a blue precipitate. Data is presented which demonstrates that lymphokine-activated macrophages can be microscopically quantitated, both in the direct and indirect assays, by counting the number of macrophages containing formazan precipitate. The indirect component of this assay correlates directly to the skin test diameter. Further, it correlates better to the skin test than another assay for CMI, the macrophages aggregation factor assay. The simplicity and reproducibility of this assay provides another method whereby lymphokine activation of physiological events in macrophages can be determined.

Compromised bone density 11.4 years after diagnosis of anorexia nervosa.

This investigation evaluated bone density in 36 premenopausal women (mean +/- SD age = 29.5 +/- 8.4 years) an average of 11.4 years after diagnosis for anorexia nervosa. Twenty-nine women were aged 20-45 years, and seven were aged 16-19 years. Body composition, age of menarche, length of amenorrhea, estrogen exposure, and lumbar spine and proximal femur bone density were determined. Average appendicular bone density for those > or = 20 years was found to meet World Health Organization T score criteria for osteopenia: total femur T = -1.22 and femoral neck T = -1.33. The average total lumbar Z score for all 36 participants was -0.95, which was 90% of the mean for their age, and the mean Z scores for adolescent subjects were within 91% of the mean for their age (Z = -0.84). Years of estrogen exposure were correlated with lumbar mineral content (r = 0.50, p = 0.002). A modest but significant inverse relationship was observed between length of amenorrhea and femoral and lumbar bone density. The total proximal femur and trochanteric bone densities were best predicted, using stepwise regression, by the number of years after diagnosis and years of amenorrhea, respectively (R2 = 0.23, p = 0.02 and R2 = 0.21, p = 0.04). Lumbar density was best predicted by years of amenorrhea and current percent of ideal body weight (%IBW)(R2 = 0.25, p = 0.02). Length of amenorrhea, estrogen exposure, and %IBW independently contribute to axial and appendicular bone density. Because of risk for compromised bone density, women with a history of anorexia nervosa should be followed longitudinally to maximize premenopausal bone replacement.

Fetal hydantoin syndrome, neuroblastoma, and hemorrhagic disease in a neonate.

This is the first patient report of maternal ingestion of anticonvulsants associated with the triad of fetal hydantoin syndrome, neuroblastoma, and hemorrhagic disease. The neuroblastoma, a neural crest tumor, is the fourth of such origin reported after in utero exposure to phenytoin, suggesting that phenytoin is a transplacental carcinogen. Infants of epileptic mothers receiving anticonvulsants should be closely examined at birth for the fetal hydantoin syndrome and monitored for hemorrhagic problems. The neural crest tumor may be found at birth or later in childhood.

Clinical and urodynamic effects of ephedrine in elderly incontinent patients.

The effect of ephedrine, an adrenergic receptor agonist, was investigated in 24 elderly patients with urinary incontinence associated with unstable detrusor contractions. After 3 weeks of oral ephedrine repeat cystometry showed mean increases of 21 per cent in bladder capacity and of 23 per cent in urethral pressure. Of 21 patients studied 7 became continent and 12 were improved. However, the urodynamic improvement did not reach statistical significance even in the continent group and, thus, the clinical improvement was unlikely to be owing to ephedrine. Therefore, open studies of drug treatment for detrusor instability may be misleading unless clinical and cystometric data are obtained.