Contextual control of long-term habituation in rats.

This study examined contextual control of long-term habituation and whether such effects are dependent on the habituating response system. Habituation of the acoustic startle response transferred from the home cage to the testing context, whereas habituation of lick suppression was context specific (Experiments 1 and 2). Contextual control of habituation was demonstrated between 2 experimental contexts for lick suppression to a tone (Experiment 3) and bar-press suppression to a light (Experiment 4). Experiment 5 extinguished habituation of lick suppression and the orienting response to a tone with 27 exposures to the habituation context. Context specificity of both responses also was found. Previous failures to demonstrate contextual control of habituation may be due to the choice of response system and to less sensitive procedures to detect response recovery. The habituation mechanism for startle is independent from the process or processes that underlie habituation in other response systems, but the nature of these mechanisms is not yet known.

Comparison of the skin irritation potential of two testosterone transdermal systems: an investigational system and a marketed product.

Effective transdermal therapy provides controlled release of the appropriate amount of a therapeutic agent while minimizing local irritation. Transdermal administration of testosterone has the potential to produce skin irritation. This open-label, randomized, 14-day, outpatient study compared the skin irritation of an investigational testosterone transdermal system (System I) with that of a marketed testosterone transdermal system (System II) in healthy men. In Part 1 of the study. System I was applied 10 times over 14 days to the same skin site on the backs of 26 healthy men. In Part 2, the skin irritation resulting from daily application of Systems I and II was assessed over 14 days in 17 men less than 65 years of age and 16 men 65 years of age or older. At the end of Part I of the study, 65.4% of the subjects experienced no erythema, 15.4% of subjects had faint erythema, and 19.2% had moderately intense erythema immediately after System I removal. At the completion of Part 2, none of the System I application sites were assessed as having moderately intense erythema, whereas one third (33.3%) of System II application sites demonstrated moderately intense erythema. There were no differences in erythema rates between younger and older subjects with either transdermal system. During this study, repeated application of System I to the same skin site resulted in acceptable noncumulative irritation, suggesting that application-site rotation may not be necessary. A comparison of the two systems demonstrates that System I results in significantly less application-site irritation than does System II and that older men do not have a higher rate of skin reactions.

Long- and short-term habituation of acoustic startle is not frequency specific in the rat.

Two experiments examined the frequency specificity of habituation of the acoustic startle response in the rat. Following the long-term habituation of startle to one of two pure tone stimuli in Experiment 1, animals were presented with the other stimulus. Startle response asymptotes were unaffected by this change in stimulus frequency. Short-term habituation of startle also was insensitive to stimulus frequency. In Experiment 2, pure tone stimuli were used to provoke both a startle response and the interruption of drinking. Long-term habituation of startle to either stimulus was unaffected by a change in frequency. Animals that received the two stimuli on alternating days showed as rapid a habituation as did the groups receiving only one stimulus frequency during acquisition. Conversely, the lick suppression measure was found to be frequency specific. Lick suppression durations rose to pre-habituation levels when the frequency of the stimulus was changed. Animals that received the two stimuli on alternating days showed retarded habituation compared to those groups presented with only one stimulus frequency during acquisition. Although long-term habituation of startle is not stimulus specific, it is mediated by central processes and thus remains a valuable model in the study of neurophysiological mechanisms of behavioral change.

Daily fluoxetine administration impairs avoidance learning in the rat without altering sensory thresholds.

1. Male rats given daily intraperitoneal injections of fluoxetine (10 mg/kg) were slower to escape foot shock by jumping a low barrier. 2. When switched to a shuttle task requiring two crosses to terminate shock, the FLU-treated animals failed to learn in 55 trials. 3. A second experiment found FLU-treated animals could learn a one-way avoidance response, but were significantly slower to learn than control animals. 4. FLU-treated animals were no different than controls on tests of sensory thresholds for foot shock or heat. 5. Tests of motor behaviors revealed no differences in latency to traverse a narrow beam to reach a goal box, however FLU-treated animals were less active in an open field. 6. Several hypotheses can account for these data, the most promising being that a central motivational system (fear) is less active in FLU-treated animals.

Allergy and topical irritation associated with transdermal testosterone administration: a comparison of scrotal and nonscrotal transdermal systems.

BACKGROUND: Topical effects are the most common adverse event for the scrotal and nonscrotal transdermal testosterone systems. OBJECTIVE: The study compared topical irritation rates for scrotal (Testoderm Testosterone Transdermal System; ALZA Corporation, Palo Alto, CA) and nonscrotal (Androderm Testosterone Transdermal System; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) products. METHODS: This open-label, crossover study randomized 60 healthy, adult males to 14 days each of two treatments: one 40-cm2 scrotal system delivering approximately 4 mg testosterone over 24 hours, or two 37-cm2 nonscrotal systems worn on the back or upper outer arm, providing approximately 5 mg testosterone over 24 hours. Severity of topical effects was scored at system removal. RESULTS: Allergic contact dermatitis and spontaneous flaring of prior application sites occurred in 7 (12%) subjects using nonscrotal systems on Day 12; no confirmed cases of allergy to the scrotal system were observed (p < 0.001). For scrotal and nonscrotal systems respectively, moderately intense irritation was noted immediately after system removal in 5% and 32% of subjects (p < 0.001), and in 1% and 7% of systems applied (p < 0.001). CONCLUSION: Scrotal systems produced no confirmed contact allergy and less topical irritation than nonscrotal systems. The four subjects with contact allergy to nonscrotal systems used the scrotal system without a reaction, suggesting testosterone was not the allergen.

Effect of coadministration of corticosteroids on the development of contact sensitization.

BACKGROUND: Transdermal administration of drugs can increase patient compliance and reduce side effects, but it can also cause contact sensitization. Corticosteroids frequently are used to suppress the local immune response; however, their use as a pretreatment for transdermal system application sites is not practical. OBJECTIVE: Our purpose was to determine the feasibility of suppressing contact sensitization by delivering a corticosteroid with the transdermal delivery systems. METHODS: Materials were applied continuously for 3 weeks to the same (protocol SS) or different (protocol AS) skin sites. Skin flux and appearance of sensitization were determined. RESULTS: Coadministration of hydrocortisone reduced the incidence of sensitization by d-chlorpheniramine and benzoyl peroxide from 45% to 7.5% and from 20% to 2.3%, respectively, under protocol SS. Under protocol AS, sensitization by d-chlorpheniramine was reduced from 15% to 1%. Frequent exposure to the sensitizer plus corticosteroid induced tolerance to the sensitizer. CONCLUSION: Sensitization by moderately immunogenic drugs after any length of exposure may be reduced to acceptable levels by the coadministration of hydrocortisone.

Clinical evaluation of the contact sensitization potential of a transdermal nicotine system (Nicoderm)

BACKGROUND: Transdermal nicotine therapy has shown promise as a smoking cessation aid, but questions about its contact sensitization potential and long-term topical safety have been raised. The purpose of this study was to determine the contact sensitization potential of one nicotine transdermal system (Nicoderm, Marion Merrell Dow Inc, Kansas City, Mo, and ALZA Corporation, Palo Alto, Calif) in a population who were allowed to continue smoking. METHODS: This study comprised two phases separated by a 2-week rest interval. During phase 1, a 42-day open-label induction period, subjects wore only active transdermal nicotine systems. During phase 2, a 4-day double-blind challenge period, subjects wore active and placebo systems concurrently. Upon removal of each patch, skin sites were evaluated for signs of irritation, and subjective complaints such as itching or burning were recorded. RESULTS: Of the 186 subjects completing the study, 3 (1.6%) exhibited evidence of delayed contact sensitization manifested as erythema with or without infiltration and confined solely to sites of active transdermal nicotine system application. Nonallergic skin irritation was observed in less than 3% of all applications. All reactions resolved without incident. No subjects developed systemic reactions. CONCLUSIONS: The transdermal nicotine system used in this trial had a low contact sensitization incidence and was well tolerated topically with minimal irritation.

Pressure dermatitis from an implanted pacemaker.

In this eleventh report of dermatitis conforming to the outline of an underlying pacemaker, the authors suggest that most of these reactions are isomorphic responses to expansion of the subcutaneous tissues by the hard device. Allergic contact dermatitis has been documented in a few cases.

Mesencephalic reticular formation lesions made after habituation training abolish long-term habituation of the acoustic startle response in rats.

Lesions to the mesencephalic reticular formation (MRF) in rats severely attenuate the acquisition of long-term habituation of the startle response when the lesions are made prior to habituation training. The present experiments extend the finding of habituation deficits to animals with MRF damage made after the animals have habituated to an auditory stimulus. Following habituation training, some animals received lesions to the MRF. The startle amplitudes of these animals immediately changed from control levels to levels indistinguishable from those of animals that never habituated across days--animals with MRF lesions made prior to habituation training. The mechanism responsible for long-term habituation appears to be a progressive increase in activity within a long-term habituation pathway extrinsic to the reflex circuit for the startle response, but the synaptic mechanisms responsible for this change are unknown.

Element content in tissues of four rodent species sampled in the Geysers geothermal steamfield.

Liver and kidney tissue samples from four rodent species collected in the Geysers geothermal steamfield of northern California were analyzed for content of 28 elements. Element concentrations in samples from the developed region of the Geysers were compared with samples from undeveloped reference regions to determine the influence of geothermal power development on element content in small mammal tissues. Eight elements (B, Ca, Cu, Mg, Mn, P, Sr, Ti) were enriched in samples from the Geysers, 12 (Ag, Al, Co, Cr, Fe, K, Mo, Na, Ni, Pb, Si, Zn) were decreased within the Geysers, Ba and Li were inconclusive, and six (As, Be, Cd, Hg, Sn, V) were below the minimum analytical limits. The longest-lived species (Neotoma fuscipes) had the greatest occurrence of statistically significant differences in element content. Sites in grassland habitat produced more significant differences in element content than either chaparral or streamside habitats for samples from Peromyscus maniculatus. Peromyscus boylii and P. truei provided additional data, but no distinct advantages for element monitoring. The data indicate regional influences from geothermal power development on element levels in rodent tissues.

DERM/INFONET: a concept becomes a reality.

The DERMatology INFOrmation NETwork (DERM/INFONET) of the American Academy of Dermatology has become a reality. DERM/INFONET consists of a number of data bases providing information and educational programs for the dermatologist. Currently the components are: DERM/MLS (Medical Literature Search), DERM/RX (dermatologic therapy), DERM/USP (United States Pharmacopeia data base), DERM/ALLERGENS (Food and Drug Administration and Environmental Protection Agency Listings of allergens); Melanoma Prognosis Model; Electronic Mail; Bulletin Board; Meetings Calendar; ICD/CPT (International Classification of Diseases/Current Procedural Terminology) codes; AAD Membership/Committee Directories; and Dermatology Quiz. Additional data bases are planned. As audiovisual and alphanumeric communication systems evolve, newer opportunities for enhancing the DERM/INFONET Biomedical Communication Network will undoubtedly provide even greater opportunities for aiding the dermatologist in delivering state-of-the art management for their patients.

Clinical effects of diaper types on the skin of normal infants and infants with atopic dermatitis.

Cloth diapers, cellulose core diapers (conventional disposable diapers), and cellulose core diapers containing absorbent gelling material were examined for their effects on diaper rash and skin microbiology of normal infants and infants with atopic dermatitis in a 26-week double-blind clinical trial. Infants with atopic dermatitis wearing the diapers containing absorbent gelling material had significantly lower diaper rash grades than infants with atopic dermatitis wearing cloth diapers at five of eight grading visits. Infants with atopic dermatitis wearing conventional cellulose core diapers had statistically less rash at one of eight visits. There was no statistically significant difference between diaper types at three of the eight visits. At no time did the cloth group have less diaper rash than the conventional cellulose or absorbent gelling material disposable diaper group. A statistical correlation between the severity of general atopic dermatitis outside the diaper area and the diaper rash condition under the diaper occurred only in the atopic dermatitis group wearing cloth diapers. Isolation of microorganisms from the intact, uninvolved skin surface both inside and outside the diaper showed no biologically significant changes in the presence or numbers of selected skin organisms. Repeated isolation, at multiple grading visits of Staphylococcus aureus from uncompromised skin inside the diaper area was infrequent but correlated with the diagnosis of atopic dermatitis when observed.

Herpes zoster as a sign of AIDS-related complex.

Herpes zoster has recently been reported in young patients with risk factors for AIDS. In high-risk patients under age 55, herpes may be the first manifestation of AIDS or AIDS-related complex. Dissemination of zoster does not appear to be greatly increased in this group, but corticosteroid therapy should be withheld.

Atypical fibroxanthoma in a patient with xeroderma pigmentosum.

A 3-year-old boy with xeroderma pigmentosum developed a papule on the right ala nasi that had the light-microscopic, immunohistochemical, and ultrastructural features of atypical fibroxanthoma. This lesion most commonly arises on the sun-exposed skin of older adults. The occurrence of an atypical fibroxanthoma in such a patient adds weight to the concept that this tumor of "fibrohistiocytic" origin is induced by ultraviolet exposure. Mechanisms of tumor formation in a patient with xeroderma pigmentosum may be similar to those occurring in the more typical situation in adults.

Clinical and microbial effects of cloth, cellulose core, and cellulose core/absorbent gel diapers in atopic dermatitis.

Atopic dermatitis (AD) is an inherited cutaneous inflammatory condition which may affect 10% of infants. Persons with this diathesis are more susceptible to irritants and to superficial infections. Little is known about diaper rash and diapering materials in AD. In this study we set firm criteria to identify a large group of infants with AD for comparison with a nonatopic, normal control group in terms of severity of diaper dermatitis; relationship of diaper dermatitis to diaper materials; and influence of modifying factors (bacterial and candidal colonization/infection, diarrhea, antibiotics, other illnesses, food allergy or intolerance). Babies with eczema were recruited and, from a group of 2,443 respondents, 87 satisfied carefully defined criteria for atopic dermatitis. A similarly sized (90) control group matched for age, sex, and weight was selected for absence of features of atopy or familial atopic history. Infants were assigned into balanced subgroups wearing cloth diapers, conventional cellulose diapers, or diapers containing cellulose and absorbent gelling material (AGM). Assessment of grading for atopic parameters showed statistically significant differences between the AD and normal groups at every visit. Mean diaper rash grades, as assessed by the same physicians at each visit, were significantly higher in the AD group wearing cloth diapers compared with those in AGM subgroups at five of eight visits. There was significant correlation between AD severity and diaper rash scores overall and in the AD cloth group, but not in other subgroups. Quantitative total bacterial plate counts were significantly lower in AGM than cloth diaper areas on three of eight sampling periods in the AD group.(ABSTRACT TRUNCATED AT 250 WORDS)

DERM/INFONET achieves "very friendly" status.

DERM/INFONET, a group of dermatologic data bases, has been reorganized for easy log-ons and log-offs, plus fast, unambiguous selections from simplified menus. DERM/RX and DERM/PHARM data bases are dermatologic exclusives. The medical literature search will retrieve the most unencumbered dermatologic information for both the academician and clinician for getting the day's work done.

Regulation of the circadian clock in the Aplysia eye: mimicry of neural action by serotonin.

In Aplysia, activity of efferent fibers in the optic nerve can influence the circadian clock in the eye. In addition, serotonin (5-HT) is present in the eye and influences the function of the clock. Accordingly, we hypothesized that 5-HT is the transmitter of the optic efferents, and tested the prediction that exogenous 5-HT would mimic the action of the optic efferents on the clock. We also tested the prediction that the action of the efferents would be prevented by blocking synaptic secretions with high Mg2+, low Ca2+ (HMLC). Activity of the optic efferents enhances clock resetting in response to the onset of darkness. We used this neural enhancement as a measure of neural action on the eye clock. We found that HMLC blocked neural enhancement. Serotonin enhanced resetting to the same extent as efferent activity. Enhancement by 5-HT did not summate with neural enhancement. High concentrations of 5-HT ([5-HT] greater than or equal to 6 X 10(-4) did not cause enhancement. High concentrations of 5-HT also blocked neural enhancement. Enhancement by 5-HT depended on the phase of drug application, much as neural enhancement depends on the phase of neural activity. Enhancement by 5-HT depended on day length in a manner similar to the enhancement by neural activity. HMLC did not block the facilitatory action of 5-HT. Several other transmitters that may be active in the eye did not enhance resetting.(ABSTRACT TRUNCATED AT 250 WORDS)