Local injection of MK801 modifies oscillatory activity in the nucleus accumbens in awake rats.

Pharmacological blockade of NMDA receptors is used to model certain aspects of schizophrenia. It had been shown previously that ketamine dose dependently enhances high-frequency oscillations in the rodent nucleus accumbens, a structure implicated in schizophrenia. Here, the authors examined the effect of intra-accumbal and systemic administration of MK801 on delta, gamma and high-frequency oscillatory activity recorded in the nucleus accumbens of freely moving rats. In this study, rats were implanted with electrodes in the nucleus accumbens for chronic local field potential recording. Rats received either bilateral injections of MK801 (1 and 4 microg) or intraperitoneal injections of the drug (0.1 and 0.5 mg/kg). Saline was used as control in each instance. Both local and systemic injections significantly enhanced the power and frequency of high-frequency oscillations and caused an increase in the occurrence, duration and amplitude of high-frequency oscillatory bursts. In contrast, no effect or a decrease in the power of delta and gamma bands was observed following local or systemic administration of MK801, respectively. These findings suggest that the dominant change in oscillatory activity after administration of NMDA receptor antagonists affect high frequencies. Moreover, direct NMDA blockade in the accumbal circuitry is sufficient to generate increases in high-frequency oscillations. The presence of abnormal oscillatory activity in the accumbens may be associated with the psychomimetic effects of NMDA receptor antagonists.

State-dependent changes in high-frequency oscillations recorded in the rat nucleus accumbens.

Among the local field potentials recorded in the rat nucleus accumbens (NAc) spontaneous high frequency oscillations (HFO) are typically represented by a small peak in the power spectra in the range of 140-180 Hz. These HFO are known to occur in the awake state, but their distribution over the sleep-wake cycle has not been investigated. To address this issue we firstly examined the power of HFO during periods of quiet waking, slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Since general anesthesia resembles certain features of naturally occurring SWS we went on to examine the effect of pentobarbital, isoflurane or urethane anesthesia on spontaneous and ketamine-induced increases in HFO. With respect to waking, the power of spontaneous HFO decreased significantly during periods of SWS but did not differ during bouts of REM sleep. General anesthetics also reduced the power of spontaneous HFO recorded in the NAc and prevented the ketamine-induced increase. These findings suggest that behavioural states where the generation of mental activity is most intense are associated with the presence of HFO in the NAc. In line with this, states which lead to decreased mentation, such as naturally occurring SWS and general anesthesia are associated with reductions in the power of HFO. Our results also suggest that the awake state is necessary for NMDA antagonists to produce enhancement of HFO.

Environmental stimulation increases survival in mice transgenic for exon 1 of the Huntington's disease gene.

Mice transgenic for the first exon of the human Huntington's disease (HD) gene carrying an expanded CAG repeat expansion (R6/2 line) develop a progressive neurologic phenotype with symptoms resembling those seen in HD. The overt symptoms of R6/2 mice worsen with age, resulting in a rapid decline in health and premature death between 13 and 18 weeks of age. In this study, we characterized the onset and progression of the overt phenotype in R6/2 mice and examined factors that affect the phenotype and life expectancy of these mice. In particular, the effects of altering home cage environment, through changing feeding regimes and providing environmental stimulation, were investigated. We show that changes in feeding regimes significantly improved the general well-being and life expectancy of R6/2 mice. Furthermore, we find that various forms of environmental stimulation, including regular behavioral testing, significantly improved the survival of R6/2 mice over and above that resulting from the enhanced feeding regime. The fact that environmental stimulation improves the health and life expectancy in R6/2 mice not only enables the mice to serve as more useful research tools, but also suggests that environmental stimulation may have a beneficial impact on the progression of HD in patients.

Reconstruction of the nasal tip using a nasalis myocutaneous flap.

Reconstruction of nasal tip defects is a technical and aesthetic challenge for dermatological surgeons, due to the limited reservoir of available skin and its thick, inflexible nature. The myocutaneous flap described in this paper, using the vascular pedicle of the transverse nasalis muscle, is an excellent option for repair of defects of the nasal tip. It provides a cosmetically superior result to skin grafting, particularly in noses of 'sebaceous' quality, by providing similar local skin. The flap maintains normal nasal tip contour and, being an axial pattern flap, its blood supply is reliable.

Selective discrimination learning impairments in mice expressing the human Huntington's disease mutation.

Cognitive decline is apparent in the early stages of Huntington's disease and progressively worsens throughout the course of the disease. Expression of the human Huntington's disease mutation in mice (R6/2 line) causes a progressive neurological phenotype with motor symptoms resembling those seen in Huntington's disease. Here we describe the cognitive performance of R6/2 mice using four different tests (Morris water maze, visual cliff avoidance, two-choice swim tank, and T-maze). Behavioral testing was performed on R6/2 transgenic mice and their wild-type littermates between 3 and 14.5 weeks of age, using separate groups of mice for each test. R6/2 mice did not show an overt motor phenotype until approximately 8 weeks of age. However, between 3.5 and 8 weeks of age, R6/2 mice displayed progressive deterioration in specific aspects of learning in the Morris water maze, visual cliff, two-choice swim tank, and T-maze tasks. The age of onset and progression of the deficits in the individual tasks differed depending on the particular task demands. Thus, as seen in humans with Huntington's disease, R6/2 mice develop progressive learning impairments on cognitive tasks sensitive to frontostriatal and hippocampal function. We suggest that R6/2 mice provide not only a model for studying cognitive and motor changes in trinucleotide repeat disorders, but also a framework within which the functional efficacy of therapeutic strategies aimed at treating such diseases can be tested.

IgA multiple myeloma presenting as an acquired bullous disorder.

A 63-year-old man presented with an intensely pruritic vesiculo-bullous eruption on the limbs and was subsequently found to have an IgA kappa multiple myeloma. The eruption clinically and histologically was suggestive of linear IgA disease (LAD), dermatitis herpetiformis (DH), epidermolysis bullosa acquisita (EBA), or bullous lupus erythematosus (LE), with the skin biopsy revealing subepidermal bullae and dermal papillary micro-abscesses. However, direct immunofluorescence showed a unique pattern of diffuse dermal IgA staining. Although chemotherapy produced a dramatic resolution of the lesions, which paralleled the fall in serum IgA paraprotein level, the myeloma later became progressive and the resulting paraprotein increase was accompanied by recurrence of the eruption. We propose that this patient's rash was the presenting manifestation of his multiple myeloma, and was a consequence of transudation of IgA paraprotein into the dermis.

Generalized pustular psoriasis responsive to PUVA and oral cyclosporin therapy.

A patient with acute generalized pustular psoriasis was successfully treated with a combination of oral cyclosporin (6 mg/kg per day) and photochemotherapy (PUVA). Although early inpatient treatment with weak topical steroids and PUVA produced initial improvement, the patient's clinical condition fluctuated, with the subsequent development of erythroderma. The addition of oral cyclosporin produced dramatic improvement within 1 week of its commencement. The patient remained in remission 12 months following cessation of therapy.

Hidradenitis suppurativa, Dowling Degos disease and perianal squamous cell carcinoma.

A patient with hidradenitis suppurativa (HS) is described in association with Dowling Degos disease and perianal squamous cell carcinomas. As the initial treatment for HS failed to give any satisfactory relief he sought no further medical help for the subsequent 40 years. This patient illustrates the management difficulties in HS and the need for regular surveillance to exclude the development of anogenital squamous cell carcinoma. Previous reports of hidradenitis suppurativa in association with Dowling Degos disease are reviewed and the aetiology is discussed.

Vesiculobullous Hailey-Hailey disease: successful treatment with oral retinoids.

A 56-year-old male presented with a pruritic, generalized vesiculobullous eruption. His past history revealed classical symptoms of limited Hailey-Hailey disease for 34 years. Clinically, vesicles, bullae and occasional pustules were present and multiple biopsies confirmed this to be an unusual presentation of Hailey-Hailey disease. Various therapeutic modalities including topical and oral antibiotics, oral prednisone and dapsone failed to achieve sustained remission. Treatment with low-dose oral etretinate (25 mg daily) produced marked clinical improvement with complete suppression of new vesicle formation after 6 weeks.

Black breast milk due to minocycline therapy.

We report the unusual case of a 29-year-old female who developed black discoloration of breast milk 3 weeks after commencing oral minocycline therapy for acne vulgaris. Histochemical analysis of the breast milk revealed the presence of pigment particles within macrophages with iron staining characteristics. We propose that the pigment may represent an iron chelate of minocycline or one of its derivatives.

Minocycline-induced hyperpigmentation in leprosy.

A 36-year-old man was treated with dapsone, rifampicin and clofazimine for borderline lepromatous leprosy. After 9 months, his leprosy plaques became progressively more red and after 23 months, the clofazimine was stopped and he was given minocycline instead. Six weeks later, he developed blue-black pigmentation in his leprosy lesions. The histology was consistent with minocycline-induced hyperpigmentation. This is the first report of minocycline-induced pigmentation in leprosy. We suggest it is important to consider this side-effect before the administration of minocycline in leprosy, particularly if it is prescribed in place of clofazimine.

Pustular psoriasis of pregnancy.

The case of an 18 year old woman who developed generalized pustular psoriasis of pregnancy in the 23rd week of her first pregnancy is reported. Treatment with topical therapies was unsuccessful and oral steroids were introduced with rapid response.

Spontaneous regression of human melanoma/nonmelanoma skin cancer: association with infiltrating CD4+ T cells.

Spontaneous regression occurs in some human malignant melanomas and basal cell carcinomas (BCCs). We have compared the cellular infiltrate in regressing and nonregressing tumors in order to analyze the mechanism by which regression occurs. Regressing primary melanomas and BCCs were infiltrated with a larger number of CD4+, but not CD8+, T lymphocytes than were seen in nonregressing tumors. The number of interleukin 2 receptor-positive (early activation marker) but not transferrin receptor-positive (intermediate activation marker) T cells was increased, indicating that the infiltrating T cells were activated. Large numbers of Langerhans cells, macrophages, and other class II major histocompatibility complex (MHC)-expressing cells were present but were not increased in the regressing tumors. There were no detectable B lymphocytes, and the regressing tumor cells displayed levels of HLA-DR expression similar to those of the nonregressing tumors. Comparison of squamous cell carcinoma (SCCs) with keratoacanthomas (KAs), which are likely to be a spontaneously regressing form of SCC, also showed increased infiltration of activated CD4+, but not CD8+, T cells within the KA. A murine ultraviolet (UV)-induced squamous tumor that spontaneously regresses when transplanted into immunocompetent syngeneic mice was also infiltrated with increased numbers of activated CD4+, but not CD8+, T cells prior to and during rejection. These results indicate that spontaneous regression of human skin tumors is likely to be immunologically mediated, and that CD4+ T lymphocytes seem to mediate this regression.

Event-related potentials and the categorical perception of speech sounds.

OBJECTIVE: To determine whether there are physiological correlates of categorical perception. DESIGN: Human evoked potentials were recorded in response to computer-modified speech sounds from a nine-stimulus continuum between /ba/ and /da/. In the first experiment, subjects listened to trains composed of 52% /ba/ or /da/ and 6% of each of the other eight stimuli and classified the stimuli as "ba" or "da." In the second experiment, subjects read a book and ignored trains containing a standard stimulus (p = 80%) and two deviant speech sounds (p = 10% each), one within the same category as the standard and the other across the category-boundary. The third experiment was similar to the first except that the subject was reading. The fourth experiment compared the responses to stimuli that deviated from standards in terms of their phonemic category or intensity. RESULTS: An N2-P3 complex was evoked by those stimuli in the more improbable category when the stimuli were attended to in the first experiment. In the second and third experiments, there was a clear mismatch negativity (MMN) for the across-category deviant stimuli when the standard stimulus came from the /ba/ end of the continuum. However, when the standard stimulus came from the /da/ end of the continuum, there was no definite MMN. The overall frequency-content of our /da/ stimulus was broader than that of the /ba/ stimulus. A deviant stimulus from the /da/ end of the continuum thus contained frequencies which were not present in the /ba/-standard stimuli and these frequencies could elicit a MMN. In the fourth experiment the MMN evoked by a small change in intensity was much larger than that evoked by a change in phonemic category. CONCLUSIONS: The N2-P3 complex accurately reflects the phonemic categorization of speech stimuli. The MMN evoked by changes in speech sounds may indicate the detection of acoustic rather than phonetic changes.

Routine inquiry of organ and tissue donation: the Oregon experience.

This article introduces the critical care nurse to a successful statewide effort to promote organ and tissue donation. Because it was one of the first to implement routine inquiry, the state of Oregon's experience was watched closely by the nation. The need for, implementation, and effects of the first routine inquiry legislation in the United States are recounted and analyzed in this article.

Regression in basal cell carcinoma: an immunohistochemical analysis.

Spontaneous regression of some cutaneous tumours is well recognized, and is thought to result from an immunological response to the tumour. Regression has previously been noted in basal cell carcinomas, but no studies defining the role of the immune response in the regression of this malignancy have been performed. We have examined 45 primary basal cell carcinomas (BCCs) (20 nodular, 25 superficial) and identified the cellular phenotypes and activation states of the cells infiltrating primary regressing and non-regressing BCCs, by immunocytochemistry. We have found a significantly increased number of CD3+ and CD4+ T cells infiltrating regressing compared with non-regressing tumours, and the expression of interleukin-2 receptor (an early activation marker for T cells) was also increased. There were no significant differences in class II major histocompatibility complex (MHC), CD1, or macrophage antigen expression in these groups. These findings suggest that activated CD4+ cytokine-secreting cells are important in the regression of BCCs.

A comparative study of gluconolactone versus benzoyl peroxide in the treatment of acne.

Alpha hydroxy acids (AHA's) or "fruit acids" are a special group of organic acids found in many natural foods. They have been described in the literature for the treatment of a number of conditions in which abnormal keratinization consistently contributes to pathogenesis. These include the icthyoses, warts, psoriasis, eczema and acne. We have performed a double-blind clinical trial on 150 patients to evaluate the efficacy and skin tolerance of the alpha hydroxy acid gluconolactone 14% in solution (Nuvoderm lotion) in the treatment of mild to moderate acne when compared with its vehicle (placebo) and 5% benzoyl peroxide lotion. The results of this study showed that both gluconolactone and benzoyl peroxide had a significant effect in improving patients' acne by reducing the number of lesions (inflamed and non-inflamed). Furthermore, fewer side-effects were experienced by patients treated with gluconolactone when compared with benzoyl peroxide.

Aberrant immunoglobulin and c-myc gene rearrangements in patients with nonmalignant monoclonal cryoglobulinemia.

The status of the immunoglobulin (Ig) genes was investigated in patients with idiopathic nonmalignant monoclonal IgG cryoglobulinemia (NCG). In NCG, monoclonal antibodies are synthesized at an accelerated rate by nonmalignant B lymphocytes. In order to determine whether this high production rate is related to a clonal B cell expansion, the rearrangement of the Ig genes was investigated by Southern blot analysis of genomic DNA extracted from the peripheral blood lymphocytes of four NCG patients. In three of four (VI, BR, and CH) clonal expansion of B cells was detected using probes specific for the c kappa, JH, c gamma 4 genes (in accordance with detecting IgG kappa cryoproteins in these patients). BamHI digestion of DNA from VI and BR produced three rearranged fragments which cohybridized with JH and c mu probes. This finding suggested the presence of additional nonsecretory B cell clones and/or disruption of the gene segments spanned by and detected with the probes. In VI the idiotype of the IgG cryoglobulin was also detected in association with IgM in the supernatant of Epstein-Barr virus-stimulated B lymphocytes using a murine monoclonal anti-idiotypic antibody. In addition, the possibility of aberrant gene rearrangements was supported by noting the alteration of the c-myc gene locus in genomic DNA from peripheral blood leukocytes of VI and CH. Northern blot analysis of RNA isolated from peripheral blood B cells of VI and CH demonstrated aberrant transcripts of the c-myc gene, showing an active role of the altered c-myc locus. Detection of c-myc rearrangement in NCG patients clearly shows that this event may not be a final step in malignant B cell transformation; however, it may be related to the clonal expansion and high rate of cryoglobulin synthesis of nonmalignant B lymphocytes.

Waist-hip circumference ratio and its relation to age and overweight in British men.

Waist-hip circumference ratio (WHC ratio) and body mass index (BMI) were calculated from measurements of a semi-random, age-stratified sample of 4349 British men, aged 20-64 years, body weight 75.6 +/- 11.6 kg (mean +/- s.d.) and BMI 24.7 +/- 3.4 kg/m2. The mean WHC ratio was 0.89 +/- 0.06; it increased with age and overweight separately and in combination, R2 = 47 per cent. BMIs greater than or equal to 30 were found in 7 per cent of the sample and WHC ratios greater than or equal to 1 in 4 per cent of the sample. Forty-seven per cent of these latter individuals also had BMI greater than or equal to 30, but only 28 per cent of individuals with BMI greater than or equal to 30 had WHC ratios greater than or equal to 1. These indices suggest that in men abdominal obesity and whole-body obesity are usually separate conditions and that abdominal obesity is less common than obesity.