Treatment of psoriasis with calcipotriol and other vitamin D analogues.

The discovery of a high-affinity receptor for the bioactive form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25[OH]D3), in most skin cells has led to the finding of previously unknown effects of vitamin D on epidermal growth and on the skin immune system. 1,25(OH)2D3 inhibits epidermal proliferation and promotes epidermal differentiation. These properties provided the rationale for introducing 1,25(OH)2D3 in the treatment of psoriasis vulgaris. In addition to 1,25(OH)2D3, the synthetic vitamin D3 analogues 1 alpha(OH)D3, 1,24(OH)2D3, and calcipotriol have undergone clinical evaluation. Calcipotriol has been studied most extensively. Compared with 1,25(OH)2D3, calcipotriol is about 200 times less potent in its effects on calcium metabolism, although similar in receptor affinity. In double-blind, placebo-controlled, randomized studies, topical calcipotriol (50 micrograms/gm, up to 100 gm weekly) has been shown to be efficacious and safe for the treatment of psoriasis. A similar therapeutic profile has been seen in long-term studies. In comparative studies topical calcipotriol is slightly more efficacious than betamethasone 17-valerate and dithranol. The mode of action of calcipotriol and other vitamin D3 analogues in psoriasis is not known. Although vitamin D3 analogues affect epidermal growth, their immunosuppressive properties may be equally important for their antipsoriatic effect.


Spitz nevi.

The Spitz nevus has long been defined as a benign melanocytic lesion that shares many histologic features with malignant melanoma. Despite the diagnostic criteria established for these two entities, their histologic similarities continue to make their distinction somewhat difficult. Uncertainties also exist with regard to the natural history of the Spitz nevus; the true pattern of this lesion's biologic behavior remains elusive. As a result, controversies exist with respect to appropriate therapy. To examine these controversies, the epidemiology, clinical features, and histopathology of Spitz nevi, as well as the role of recent molecular and immunohistochemical diagnostic studies, are discussed. However, the primary focus of this article is the natural course, prognosis, and treatment of the Spitz nevus. A review of 716 cases of Spitz nevi, compiled from 13 papers published from 1948 to 1990, is presented. After analyzing this and other available data, we propose that at this time Spitz nevi and malignant melanoma cannot easily be categorized as distinct entities and that perhaps they actually exist along one continuum of disease. Because of this uncertainty and the difficulties in differentiating these two lesions, we recommend that treatment include complete excision of all Spitz nevi followed by reexcision of positive margins if present.


Cutaneous findings in a new syndrome of autosomal recessive ectodermal dysplasia with corkscrew hairs.

The association of hair shaft abnormalities with the phenotypic findings of a new, distinct form of an autosomal recessive syndrome of ectodermal dysplasia was present in 27 patients from seven families. Our purpose was to present the cutaneous findings that characterize this syndrome with particular attention given to the hair shaft abnormalities. Multiple field visits were used to gather data on phenotypic findings and prospectively evaluate their prevalence. Corkscrew hair, an exaggeration of pili torti, represents the most striking feature of this syndrome. Prominent cutaneous findings include scalp keloids, follicular plugging, keratosis pilaris, xerosis, eczema, palmoplantar keratodermia, cutaneous syndactyly, onychodysplasia, and conjunctival neovascularization. Other features include typical facies, anteverted pinnae, malar hypoplasia, cleft lip and palate, and dental abnormalities. A syndrome characterized by pili torti and corkscrew hairs, previously reported in only one patient, can be recognized.


Cyclosporine in atopic dermatitis. Modulation in the expression of immunologic markers in lesional skin.

In previous studies, oral cyclosporine was highly effective in the treatment of patients with severe atopic dermatitis. In this study seven patients with severe and therapy-resistant atopic dermatitis underwent therapy with cyclosporine, 5 mg/kg/day, for 6 weeks. The effect of cyclosporine on the expression of cytokines, which probably play a role in this disease, was examined. The study was performed with a panel of antibodies as markers of inflammatory cells, adhesion molecules, and cytokines (interferon-gamma [IFN-gamma], tumor necrosis factor-alpha [TNF-alpha] and interleukins 1 alpha, 1 beta, and 8 [IL-1 alpha, IL-1 beta, and IL-8, respectively]). They were visualized by indirect immunoperoxidase techniques. After 2 weeks of cyclosporine therapy, a reduction of 60% in the disease (severity and extent) was observed. This reduction was 89% after 4 weeks and 90% after 6 weeks of therapy. Results of indirect immunoperoxidase stains performed on lesional skin sections after 2 weeks of treatment showed statistically significant reduced numbers of CD14+, CD25 (IL-2R+) and IL-8+ inflammatory cells in the dermis and CD36(OKM5)+ cells in both the epidermis and dermis. The number of cells expressing IFN-gamma and TNF-alpha, assumed to be the products of the helper T-cell (TH)1 subset, was unaltered despite the impressive clinical benefit observed. Keratinocytes in lesional atopic skin did not express intercellular adhesion molecule type 1 (ICAM-1). The expression of the adhesion molecules ICAM-1, lymphocyte function-associated (LFA) type 1, and LFA-3 on inflammatory cells also remained unaffected by cyclosporine treatment. A statistically significant reduction in the number of activated T cells and in the number of cells expressing the IL-2 receptor (CD25) paralleled a marked improvement in the disease and supports the view that atopic dermatitis is based on a T-cell-mediated immune inflammation.


Lichen planopilaris: clinical and pathologic study of forty-five patients.

We review the findings in a large series of patients with lichen planopilaris. Clinical, histologic, and direct immunofluorescence findings were reviewed in 45 patients. Scalp biopsy specimens for routine histologic examination and direct immunofluorescence were reviewed. Clinical data and follow-up were obtained. Women were affected more commonly and had patchy hair loss, with perifollicular erythema, perifollicular spines, and scarring. Half had or developed glabrous skin, mucous membrane, or nail changes typical of lichen planus. Follicular involvement was limited to the infundibulum and isthmus and included lichenoid inflammation and cytoid formation, with few or no changes in interfollicular epidermis. Direct immunofluorescence showed cytoid body staining with anti-IgM and anti-IgA and patchy or linear fibrinogen deposition along the basement membrane zone. The various therapeutic options used were usually unsuccessful. To make the correct diagnosis, patients with scarring alopecia should be evaluated histologically and with direct immunofluorescence. They should also be followed up to assess whether lichen planus develops elsewhere.


Quantification of skin color in patients undergoing maintenance hemodialysis.

In patients undergoing long-term hemodialysis, a peculiar hyperpigmentation develops, the intensity of which may or may not be related to the duration of treatment and use of erythropoietin. Our purpose was to conduct a comparative cross-sectional study of white patients with distinct diseases that modify their skin color. A reflected-light colorimeter was used to compare the color of the forehead and forearms of 61 white patients receiving hemodialysis with that of matched controls and of patients with anemia or icterus. Significant differences were found in both reflectance and chromaticity between these groups of patients. Duration of hemodialysis and use of erythropoietin did not significantly influence the colorimetric measurements. The use of a color-reflectance meter allows precise evaluation of subtle changes in skin color and may be used to monitor several diseases.


Kimura's disease and angiolymphoid hyperplasia with eosinophilia: clinical and histopathologic differences.

There has been considerable controversy about the relation between Kimura's disease and angiolymphoid hyperplasia with eosinophilia (ALHE). We describe the clinical and histopathologic differences between the two diseases. We reviewed clinical findings and histopathologic changes in two cases of Kimura's disease and three cases of ALHE. Kimura's disease shows typical lymphoid follicles. It is associated with lymphadenopathy and is always accompanied by peripheral eosinophilia. ALHE shows typical changes in endothelial cells. It is characterized by superficial papules or nodules with no lymphadenopathy and is less frequently accompanied by peripheral eosinophilia. Kimura's disease and ALHE are separate entities.


Sterility of refrigerated injectable collagen syringes after injection of patient.

Injectable collagen has been used for more than 15 years to correct soft tissue cosmetic defects. After injection, the collagen remaining in the syringe is often refrigerated for later use in the same patient, despite manufacturer and Food and Drug Administration recommendations to discard the unused collagen. This study examined the incidence of bacterial contamination of stored collagen. Syringe needle tips and collagen from 50 previously used syringes containing either Zyderm I, Zyderm II, or Zyplast were cultured separately under aerobic and anaerobic conditions. Bacterial isolates were identified. Propionibacterium acnes was cultured from 7 of 50 needle tips. One positive needle tip culture grew both P. acnes and Staphylococcus aureus. Bacteria were isolated from only one collagen sample that grew a nonhemolytic streptococcus that may have represented a laboratory contaminant. Syringes of collagen stored for repeated use rarely become contaminated with bacteria despite frequent contamination of their needle tips. Skin abscesses after collagen injection should be cultured under anaerobic, as well as aerobic, conditions so that infections caused by P. acnes will not be missed.


Allergic contact dermatitis from formaldehyde resins in permanent press clothing: an underdiagnosed cause of generalized dermatitis.

Formaldehyde resins have been used to impart wrinkle resistance to clothing fabrics since 1926. After several patients with positive patch tests to formaldehyde resins had been examined, a study was undertaken of the records of all patch tests performed at the University of Louisville Patch Test Clinic and the Allergy Section of the Skin and Cancer Clinic of New York University Medical Center from January 1988 through April 1990 to determine the prevalence of positive patch-test reactions to formaldehyde-based textile resins and the clinical and demographic patterns associated with textile resin allergy. Seventeen patients were identified at the two centers. Twelve were allergic to formaldehyde as well as to formaldehyde textile resins. Several clinical patterns were found, including accentuation of dermatitis in areas of tight clothing, primary occurrence in clothing-covered areas, and a chronic recalcitrant course. Ethylene urea melamine formaldehyde resin was the best screening agent with 14 definite positive reactions and one equivocal reaction. Formaldehyde textile resin allergy is more common than has been previously recognized. Patch testing with one or more formaldehyde textile resins is indicated in patients with a particular pattern of dermatitis.


Angiomatosis with luminal cryoprotein deposition.

Angioendotheliomatosis has recently been separated into two types. Malignant angioendotheliomatosis is a lymphoma in which the neoplastic cells accumulate in vascular lumens. Reactive angioendotheliomatosis is a proliferation of capillaries that is less well characterized. Our purpose was to describe the clinical and histopathologic features of three cases of reactive angiomatosis in patients with cryoproteinemia. Clinical and histologic data were correlated. Immunoperoxidase staining and electron microscopy were used in the histologic evaluation. All three cases showed tufts of capillaries with luminal deposits of cryoproteins. Immunohistochemical studies showed that the cellularity of the tufts was primarily caused by a proliferation of pericytes. Cryoproteinemia can cause angiomatosis that simulates a vascular neoplasm.


Mycosis fungoides--type cutaneous T-cell lymphoma arising before 30 years of age. Immunophenotypic, immunogenotypic and clinicopathologic analysis of nine cases.

Cutaneous T-cell lymphomas (CTCLs) rarely arise before 30 years of age; therefore the characteristics of these lymphomas are largely unknown. Our purpose was to assess the clinical and pathologic aspects of CTCL in young persons. We identified nine patients who had epidermotropic CTCL by 30 years of age and analyzed their lymphoma phenotypes and genotypes. The diagnosis of CTCL was made an average of 6 years after the reported onset of the lesion. Histologic examination revealed the mycosis fungoides (MF) form of CTCL, and none of the patients underwent conversion to nonepidermotropic or large-cell variants of CTCL. The immunophenotypes were typical of MF-type CTCL; seven of eight lymphomas tested were predominantly CD4+ although in only three were abnormal CD4/CD8 ratios present. All four cases tested were CD7- (Leu-9-), and seven of eight specimens tested exhibited deficient Leu-8 expression. The loss of one or more pan-T-cell markers was found in four of eight patients tested. Clonal beta-chain T-cell receptor gene rearrangements occurred in skin samples from four of eight tested cases. A persistent eruption, even in youths and young adults, should be thoroughly evaluated for possible CTCL.


Photodynamic therapy in the treatment of Bowen's disease.

The treatment of Bowen's disease in anatomically difficult areas or especially large lesions can challenge accepted modalities of treatment. The purpose of this study was to illustrate the effectiveness of photodynamic therapy in the treatment of Bowen's disease. In addition, photodynamic therapy may be used as adjuvant therapy for difficult lesions. Six patients with Bowen's disease in various anatomic sites were treated with photodynamic therapy. Four were in a difficult anatomic site, or were especially large, or both. Photofrin, 1.0 mg/kg, was administered intravenously and laser treatment was given approximately 48 hours later with the argon dye laser. Light was administered at a wavelength of 630 nm and the light dose ranged from 185 to 250 joules/cm2. Treatment was given by surface radiation only. Eight lesions were treated. All showed a complete response at 3 months (100%) and continue to show a complete response at 6 and 12 months. Morbidity was low; the most significant side effects were moderate pain and edema. Healing time varied depending on the size of the lesion. Photodynamic therapy is an effective and useful alternative for Bowen's disease, especially those lesions in anatomically difficult areas or those that are especially large.


Efficacy and safety of calcipotriol (MC 903) ointment in psoriasis vulgaris. A randomized, double-blind, right/left comparative, vehicle-controlled study.

The biologically active form of vitamin D3, calcitriol, may offer a new therapeutic approach to psoriasis. Calcipotriol, a new vitamin D3 analogue, is at least 100 times less calcemic than calcitriol. Our purpose was to study the efficacy and safety of calcipotriol in the treatment of psoriasis vulgaris. In a right/left comparative, double-blind study, treatment with calcipotriol ointment (50 micrograms/gm) twice daily and placebo was given for 4 weeks. The preferred treatment was continued, without opening the code, for another 4 weeks. Efficacy, as measured by the Psoriasis Area and Severity Index and by the investigator's and patient's global assessment, and safety were assessed every 2 weeks. The mean Psoriasis Area and Severity Index fell in 4 weeks from 14.2 to 6.3 with calcipotriol and from 14.1 to 9.2 with placebo (p < 0.001; 95% confidence interval for difference: 1.78-->3.94). Local side effects were equally common with calcipotriol and placebo. The mean serum calcium remained unchanged. Topical application of up to 50 gm of calcipotriol ointment per week was found to be an effective and safe treatment of psoriasis vulgaris.


Dihydroxyacetone-containing sunless or self-tanning lotions.

Dihydroxyacetone-containing sunless or self-tanning topical preparations are enjoying a resurgence of use in recent years. The chemistry of dihydroxyacetone, mechanism of action, application, safety, indications, and available products are reviewed.


Intraepidermal IgA pustulosis.

Since 1979, 29 patients with intraepidermal IgA detected by direct immunofluorescence have been reported. A review shows that they have a cutaneous disease clinically similar to subcorneal pustular dermatosis, or Sneddon-Wilkinson disease. The pustules may be subcorneal or intraepidermal. IgA deposits are usually found on the intercellular substance of the epidermis, although a subcorneal linear pattern has also been described. Circulating IgA class antiepidermal autoantibodies may be present. The disease usually responds to dapsone. In six cases, a monoclonal IgA gammopathy was present. Although little is known about the pathogenesis of this condition, we believe that it represents a distinct entity among the group of the neutrophilic dermatoses. Various diagnostic terms have been used; we propose intraepidermal IgA pustulosis.


Enhancing effects of fluorescein on beta-lactam rash. I: High incidence of cefclidin rashes in an ophthalmological volunteer trial.

Disseminated maculopapular eruptions were frequently observed in a volunteer trial of cefclidin's use in ophthalmological and neurological examinations (8/12; 67%) It appeared at 8-12 days (mean +/- SD, 9.6 +/- 1.1 days) from the initiation of the trial and subsided within 1-2 days (mean +/- SD, 1.8 +/- 0.4 days). Patch testing with cefclidin produced a +/- reaction in 1 of 8 cases, and the drug-induced lymphocyte stimulation test (DLST) elicited a positive response (SI: 2.8) in 1 of 8 and a weakly positive response (1.8 < or = SI < 2) in 2 of 8. From these findings, it seems likely that the eruptions may be partially mediated by delayed type hypersensitivity (DTH) reactions to cefclidin. No such eruption was observed in the phase II trial of cefclidin where only 2.8% of 1.122 volunteers developed the eruption. The volunteers were given both fluorescein and oxybuprocain in their eyes to measure ocular tension on days -1, 0, 1, 3, 5, 7, 9, 11, 13 and weeks 3, 5, 7 after the initiation of cefclidin. Fluorescein and/or oxybuprocain may affect cefclidin to induce these abnormal reactions in the volunteers.


Enhancing effects of fluorescein on beta-lactam rash. II: Enhancing effects of fluorescein on generalized rash induced by beta-lactam antibiotics in guinea pigs.

Healthy volunteers, who were receiving intravenous injections of cefclidin (CFCL) with frequent concomitant use of fluorescein (F) and oxybuprocain (O) in the eyes for measurement of ocular tension, developed drug eruptions at the high frequency of 66.7%. The injection of CFCL alone induced the eruptions at an incidence of 2.8%. The cause of this high eruption rate was thought to be the simultaneous treatment with F and/or O. Therefore, we conducted experiments with CFCL-induced generalized rash (GR) in guinea pigs. Guinea pigs treated with F and O during both the phases of immunization and intraperitoneal elicitation developed CFCL rashes at a high frequency. This CFCL-rash was augmented by the treatment with F during either phase, but not by the treatment with O. Skin testing induced delayed type hypersensitivity (DTH) reaction to O in some animals, but the DTH to F was not induced in animals immunized with F in complete Freund's adjuvant. Furthermore, F augmented rashes induced not only by CFCL but also by other beta-lactam antibiotics such as cefsulodin and sulbenicillin. Accordingly, it is likely that F played a dominant role in the high incidence of drug eruptions during the volunteer trials with measurement of ocular tension.


Aneuploidy in chronic actinic dermatitis.

DNA content and cell cycle distributions in paraffin-embedded blocks of 19 skin biopsy specimens from 17 patients with chronic actinic dermatitis (CAD) [8 patients showed typical actinic reticuloid (AR)] were estimated by DNA cytometry. Sixty-three percent (12/19) of the skin specimens showed aneuploidy. In the 4 cases with the highest DNA indices (DI), ranging from 1.65 to 1.88 (mean: 1.84), the proportions of cells in S and G2/M phases were increased, ranging from 15-48% (mean: 20%) and from 64-76% (mean: 70.5%), respectively. In 8 cases with DI ranging from 1.15-1.75 (mean: 1.5), the proportion of cells in S-phase was also increased, ranging from 30-90% (mean: 81.1%). Histologically, it seems likely that the relatively high frequency of aneuploidy, DI, and proportions of cells in the S and/or G2/M phases were not proportional to epidermal or vascular endothelial hyperplasia, but they might be related to dermal lymphoid infiltration.


Classic Kaposi's sarcoma: a review of 90 cases.

A series of 90 cases of classic Kaposi's sarcoma observed and treated over the last 25 years was examined retrospectively. Fifty-one were the localized and 39 the disseminated form. Outpatient surgery for the localized and vinblastine chemotherapy for the disseminated form are probably the best treatments. Radiotherapy may be a valid alternative.


Angiokeratoma of the clitoris: a subtype of angiokeratoma vulvae.

A 24-year-old married woman had an angiokeratoma of the vulva measuring 3 x 3 x 4 mm localized at the clitoris. The nodule was noticed when she was pregnant with her first child. This tumor grew with occasional tenderness and bleeding during pregnancy, but its size did not change after delivery. The growth of this tumor might be attributable to an increase in venous pressure or serum progesterone levels; therefore this disorder might be classified as a subtype of angiokeratoma of the vulva. This is the first case of angiokeratoma localized at the clitoris.


Actinic cheilitis granulomatosa.

A granulomatous lesion of the lips caused by UVB-photosensitivity is described. A 31-year-old Japanese man developed depigmented, swollen, erythematous lips with some erosions and bloody crusts which were present for 11 months. Histologic examination revealed a dense dermal infiltration composed mainly of lymphoid-histiocytic cells. Suprabasal clefts were associated with the invasion of lymphoid cells around them. Results of patch and photopatch testing were negative. The minimal erythema dose 24 h after irradiation was lower than normal, ranging from 295 to 330 nm. The lesion was reproduced by repeated irradiation with monochromatic light of 310 and 320 nm, but not by exposure to 250, 260, 270, 280, 290, 300, or 330 nm. Topical injection of glucocorticoids and application of sunscreen led to improvement. We propose the name "actinic cheilitis granulomatosa" for this case.


A case of cytophagic histiocytic panniculitis with sicca symptoms and lupus nephritis.

A 48-year-old Japanese woman presented with many subcutaneous nodules. The skin was purplish in color and tender; the nodules were scattered over the entire surface. Histological findings of biopsy specimens from the nodules indicated septal panniculitis comprised of histiocyte and/or macrophage infiltrates, often with erythro- and/or leukophagocytosis. Phagocytic cells were OKM1 (CD11b), MT1 (CD43), LeuM3 (CD14), and histiocyte antigen positive, indicating the presence of histiocytes and/or macrophages. The patient had sicca symptoms, positive homogenous, speckled pattern ANA (x320), and diffuse proliferative lupus nephritis.


Ultrasonic attenuation estimation in-vivo using the difference ratio correction method.

In recent years, B scanners have been widely used clinically. Obviously, it is of particular importance to use the commercial B scanners to characterize tissue by estimating its ultrasonic attenuation in vivo. However, there are a lot of difficulties in doing so because the output of a B scanner is affected by many unknown factors. In this paper, a time domain method named the difference ratio correction (DRC) method is proposed to estimate the ultrasonic attenuation of tissue in vivo. In this method, three tissue-mimicking phantoms with known acoustical properties were employed to eliminate the instrumentation errors of the B scanner and the measuring system and to correct beam diffraction for correct attenuation estimation. Other advantages of this method are that it is very convenient to apply this method clinically and there is no need to change the inner construction of the B scanner because this method only utilizes the video output. Experimental and clinical results have proved the validity of this method.


Diversity and commonality in music performance: an analysis of timing microstructure in Schumann's "Träumerei".

This study attempts to characterize the temporal commonalities and differences among distinguished pianists' interpretations of a well-known piece, Robert Schumann's "Träumerei." Intertone onset intervals (IOIs) were measured in 28 recorded performances. These data were subjected to a variety of statistical analyses, including principal components analysis of longer stretches of music and curve fitting to series of IOIs within brief melodic gestures. Global timing patterns reflected the hierarchical grouping structure of the composition, with pronounced ritardandi at the ends of major sections and frequent expressive lengthening of accented tones within melodic gestures. Analysis of local timing patterns, particularly of within-gesture ritardandi, revealed that they often followed a parabolic timing function. The major variation in these patterns can be modeled by families of parabolas with a single degree of freedom. The grouping structure, which prescribes the location of major tempo changes, and the parabolic timing function, which represents a natural manner of executing such changes, seem to be the two major constraints under which pianists are operating. Within these constraints, there is room for much individual variation, and there are always exceptions to the rules. The striking individuality of two legendary pianists, Alfred Cortot and Vladimir Horowitz, is objectively demonstrated here, as is the relative eccentricity of several other artists.


Time normalization in voice analysis.

The harmonics-to-noise ratio (HNR) has been widely accepted for quantifying the irregular or noise component of voice. HNR, however, is usually inflated by cycle-to-cycle variations of fundamental frequency period because zero padding is used for time normalization of the wavelet. In this study, a new method was developed for analyzing waveform perturbations of voice. In this method, noise components of voice were calculated from the discrepancies between wavelets after they had been optimally aligned in time. The optimal time normalization of wavelets was accomplished using procedures of dynamic time warping (DTW). This method was evaluated using both synthetic and natural voices, and significant reductions in noise were obtained. The harmonics-to-noise ratio obtained using DTW for time normalization was also shown to be independent of fundamental frequency perturbations.


Measurement of sound-pressure distribution in replicas of the oral cavity.

The spatial distributions of sound pressure in artificial oral cavities were measured to examine the characteristics of wave propagation in the vocal tract. The measurement was performed with plaster replicas of the oral cavity, and pure tones were used as the driving signals to obtain both amplitude and phase distributions at varied frequencies. Plane-wave propagation, which has been widely assumed for speech production models, was examined from the measured spatial distributions of sound pressure. Trajectories of media particles and vectorial maps of acoustic intensity, which can be computed from the measured pressure distributions, were also presented to visualize the acoustic field in the oral cavity. The results showed that at certain frequencies there existed points where sound pressure was absolutely zero, with the phase spatially circulating around them. Up to about 4 kHz, except at these certain frequencies, the wave front was almost one-dimensional, though an amplitude gradient was seen in the vertical direction.


Spectral shape discrimination of narrow-band sounds.

Measurements are reported on the detectability of signals added to narrow-band sounds. The narrow-band sounds had a bandwidth of 20 Hz and were either Gaussian noise with flat amplitude spectra or sets of equal-amplitude sinusoidal components whose phases were chosen at random. Four different kinds of sinusoidal signals were used. Two signals produced symmetric changes in the audio spectrum adding a component either at the center of the spectrum or at both ends. The other two signals produced asymmetric changes adding a component at either end of the spectrum. The overall level of the sound was randomly varied on each presentation, so that the presence of a signal was largely unrelated to the absolute level of the signal component(s). A model is proposed that assumes the detection of the symmetric signals is based on changes in the shape of the power spectrum of the envelope. Such changes in the envelope power spectrum are probably heard as changes in the "roughness" or "smoothness" of the narrow-band sound. The predictions of this model were obtained from computer simulations. For the asymmetric signals, the most probable detection cues were changes in the pitch of the narrow-band sound. Results from a variety of different experiments using three listeners support these conjectures.


Two experiments on the spectral boundary conditions for nonlinear additivity of simultaneous masking.

The present paper describes the results from two experiments which explored the spectral boundaries for the nonlinear additivity of simultaneous masking. The first experiment measured the threshold for detection of a 2-kHz tone in the presence of two 800-Hz-wide bands of noise that had varying degrees of spectral overlap with each other and the 2-kHz signal. Results revealed an abrupt transition from linear to nonlinear additivity of masking as the spectral separation between the two maskers varied from some overlap to none. The second experiment examined alternative explanations for the data. Explanations based on restricted-listening or distortion-product-detection hypotheses were not supported by the results of this experiment. These data indicate that nonlinear additivity of simultaneous masking holds for maskers that do not overlap within the critical band centered on the signal frequency. This interpretation is also consistent with a large body of data on the monaural and binaural summation (additivity) of loudness.


Narrow-band sound localization related to external ear acoustics.

Human subjects localized brief 1/6-oct bandpassed noise bursts that were centered at 6, 8, 10, and 12 kHz. All testing was done under binaural conditions. The horizontal component of subjects' responses was accurate, comparable to that for broadband localization, but the vertical and front/back components exhibited systematic errors. Specifically, responses tended to cluster within restricted ranges that were specific for each center frequency. The directional transfer functions of the subjects' external ears were measured for 360 horizontal and vertical locations. The spectra of the sounds that were present in the subjects' ear canals, the "proximal stimulus" spectra, were computed by combining the spectra of the narrow-band sound sources with the directional transfer functions for particular stimulus locations. Subjects consistently localized sounds to regions within which the associated directional transfer function correlated most closely with the proximal stimulus spectrum. A quantitative model was constructed that successfully predicted subjects' responses based on interaural level difference and spectral cues. A test of the model, using techniques adapted from signal detection theory, indicated that subjects tend to use interaural level difference and spectral shape cues independently, limited only by a slight spatial correlation of the two cues. A testing procedure is described that provides a quantitative comparison of various predictive models of sound localization.


Effects of roving level variation on monaural detection with a contralateral cue.

Monaural detection with a contralateral cue (MDCC) was measured with and without a 20-dB overall roving level to determine the contribution of loudness to performance on this task. Psychometric functions were obtained for three normal-hearing subjects as a function of the signal-to-noise ratio for pure-tone and 1/3-oct noiseband signals at 500 and 4000 Hz with a wideband noise masker. At 4000 Hz, the roving level degrades performance for the narrow-band noise signal by about 5.3 dB. In addition, the presence of the contralateral cue degrades performance for both the pure-tone and narrow-band noise signals at 4000 Hz by 3 to 6 dB. At 500 Hz, however, performance is not affected by the roving level, and is improved by 3 to 6 dB by the contralateral cue. These results indicate that loudness is being used as a cue only for detection of the 4000-Hz narrow-band noise.


Discriminability of bursts of reproducible noise.

The ability of human listeners to discriminate pairs of bursts of reproducible noise was examined. A same-different psychophysical method was used. Bursts in a pair were identical on same trials. On different trials, bursts were identical except for tau ms of independent noise located at either the beginning, middle, or end of the pairs of bursts. As the temporal position of the tau ms of independent noise was moved from the beginning to the end of the bursts of noise, discriminability increased. For each temporal position of the independent noise, discriminability was a function of the ratio of the duration of the independent noise (tau) to the total burst duration.


Behavioral measures of frequency selectivity in the chinchilla.

A simultaneous masking procedure was used to derive four measures of frequency selectivity in the chinchilla. The first experiment measured critical masking ratios (CRs) at various signal frequencies. Estimates of the chinchillas' critical bandwidths derived from the CRs were much broader than comparable human estimates, indicating that the chinchilla may have inferior frequency selectivity. The second experiment measured critical bandwidths at 1, 2, and 4 kHz in a band-narrowing experiment. This technique yielded narrower estimates of critical bandwidth; however, chinchillas continued to exhibit poor frequency selectivity compared to man. The third experiment measured auditory-filter shape at 0.5, 1, and 2 kHz via rippled noise masking. Results of the rippled noise masking experiment indicate that auditory filters of humans and chinchillas are similar in terms of shape and bandwidth with chinchillas showing only slightly poorer frequency selectivity. The final experiment measured auditory filter shape at 0.5, 1, 2, and 4 kHz using notched noise masking. This experiment yielded auditory filter shapes and bandwidths similar to those derived from man. The discrepancy between the indirect estimates of frequency selectivity derived from CR and band-narrowing techniques and the direct estimates derived from rippled noise and notched noise masking are explained by taking into account the processing efficiency of the subjects.


Influence of spectral locus and F0 changes on the pitch and timbre of complex tones.

Harmonic complex tones comprising components in different spectral regions may differ considerably in timbre. While the pitch of "residue" tones of this type has been studied extensively, their timbral properties have received little attention. Discrimination of F0 for such tones is typically poorer than for complex tones with "corresponding" harmonics [A. Faulkner, J. Acoust. Soc. Am. 78, 1993-2004 (1985)]. The F0 DLs may be higher because timbre differences impair pitch discrimination. The present experiment explores effects of changes in spectral locus and F0 of harmonic complex tones on both pitch and timbre. Six normally hearing listeners indicated if the second tone of a two-tone sequence was: (1) same, (2) higher in pitch, (3) lower in pitch, (4) same in pitch but different in "something else," (5) higher in pitch and different in "something else," or (6) lower in pitch and different in "something else" than the first. ("Something else" is assumed to represent timbre.) The tones varied in spectral loci of four equal-amplitude harmonics m, m + 1, m + 2, and m + 3 (m = 1,2,3,4,5,6) and ranged in F0 from 200 to 200 +/- 2n Hz (n = 0,1,2,4,8,16,32). Results show that changes in F0 primarily affect pitch, and changes in spectral locus primarily affect timbre. However, a change in spectral locus can also influence pitch. The direction of locus change was reported as the direction of pitch change, despite no change in F0 or changes in F0 in the opposite direction for delta F0 < or = 0-2%. This implies that listeners may be attending to the "spectral pitch" of components, or to changes in a timbral attribute like "sharpness," which are construed as changes in overall pitch in the absence of strong F0 cues. For delta F0 > or = 2%, the direction of reported pitch change accord with the direction of F0 change, but the locus change continued to be reported as a timbre change. Rather than spectral-pitch matching of corresponding components, a context-dependent spectral evaluation process is thus implied in discernment of changes in pitch and timbre. Relative magnitudes of change in derived features of the spectrum such as harmonic number and F0, and absolute features such as spectral frequencies are compared. What is called "spectral pitch," contributes to the overall pitch, but also appears to be an important dimension of the multidimensional percept, timbre.


Evidence for two discrete sources of 2f1-f2 distortion-product otoacoustic emission in rabbit. II: Differential physiological vulnerability.

In a previous report, it was shown that, in normal rabbit ears, the amplitude and phase of 2f1-f2 distortion-product otoacoustic emissions (DPOAEs) elicited by low-level (< 60-70 dB SPL) stimuli display a differential dependence on stimulus parameters to those evoked by high-level (> 60-70 dB SPL) stimuli, indicating differences in the underlying generation mechanisms. In the present study, the physiological vulnerability of DPOAEs in each of the two 2f1-f2 DPOAE-response regions identified on the basis of differential parametric properties, was characterized. Thus emissions evoked using stimulus levels from 45-75 dB SPL were measured over time upon: (1) induction of lethal anoxia, (2) acute injection of ethacrynic acid, and (3) acute injection of ethacrynic acid 2 h after a single administration of gentamicin. The DPOAEs evoked by low-level stimuli (45 dB SPL) were abolished within 3-4 min of induction of anoxia, whereas DPOAEs evoked by high-level stimuli (75 dB SPL) were unchanged in this period. The high-level emissions decreased with a complex time course postmortem, and demonstrated behaviors, including evidence of susceptibility to fatigue, suggesting a dependence upon a cochlear energy supply. Low-level DPOAEs could be temporarily abolished, with complete recovery, by an acute administration of ethacrynic acid that had little effect on high-level DPOAEs. Treatment with the gentamicin and ethacrynic-acid combination, which would be expected to produce widespread hair-cell damage, eliminated low-level DPOAEs, and greatly reduced high-level emissions. In combination with previously published data, these findings strongly suggest that low- and high-level 2f1-f2 DPOAEs arise from discrete sources. The data are consistent with the proposal that the low-level DPOAE source is an active, micromechanical process, but suggest that the proposed origin of high-level DPOAEs exclusively in the passive macromechanics of the cochlear partition may be incorrect. The elimination of both low- and high-level DPOAEs revealed the presence of a third, residual 2f1-f2 DPOAE component, approximately 75-80 dB below the stimulus-tone levels, that may reflect the true passive-distortion response of the cochlea.


Physiological studies of central masking in man. I: The effects of noise on the 40-Hz steady-state response.

In a typical masking situation, two Békésy waves overlap on the basilar membrane, and each of them initiates a stream of nerve impulses that enters the brain via the auditory nerve. Much is known about the overlapping of the cochlear waves, but much less about where, how, and even if at all, the impulse streams interact once they get inside the brain. In these experiments the incoming impulses are measured electrophysiologically using the auditory brainstem response (ABR), and, simultaneously, using the 40-Hz auditory steady-state response (SSR) to monitor events at a probable site of their interaction, the auditory cortex. The principal finding is that, when progressively increasing levels of continuous noise are presented to the contralateral ear, the SSR to the signal drops to about half its control amplitude. Second, low levels of ipsilateral noise reliably enhance SSR amplitude. Third, moderate levels of ipsilateral noise reduce SSR latency. In none of these cases does the ABR show similar effects. These findings are interpreted to mean that, in each case, impulses excited by the signal interact with impulses excited by the noise, and regardless of ear of origin the interactions take place beyond the brainstem level where ABR wave V is generated, either before the impulses reach the cortex, or in the cortex itself.


Physiological studies of central masking in man. II: Tonepip SSRs and the masking level difference.

The auditory steady-state response (SSR), an evoked response generated in the auditory cortex, was initiated by monaural trains of 500-Hz tonepips repeated at rates near 40 Hz while wideband noise was being delivered to the same or opposite ear. Contralateral noise reduced SSR amplitudes in an intensity-dependent manner, whereas ipsilateral noise enhanced the SSR amplitudes at low levels and depressed them at high levels. Systematic phase changes accompanied the amplitude changes. These results, obtained with tonepips, closely resemble those previously reported for clicks. A third experiment, a masking level difference (MLD) experiment, examined changes in the SSR measures during four successive tonepip-plus-noise conditions: (1) monaural tonepips alone; (2) adding ipsilateral noise; (3) then adding contralateral noise; (4) finally, adding contralateral tonepips. The SSR amplitude changes measured in the experiment did not always correspond with the changes in perception reported by the subject.


Qualitative acoustic analysis in the study of motor speech disorders.

Traditional measurements performed on the acoustic signals of normal speech are frequently used to quantify the acoustic characteristics of disordered speech as well. This letter demonstrates how important aspects of speech production deficits in motor speech disorders may be overlooked if stringent quantification procedures are employed, especially in the stage of exploratory data analysis. It is suggested that qualitative procedures, wherein phenomena are inferred from visual examination of certain acoustic displays, are useful to supplement traditional measurements, and moreover, that they be used to point to the types of measurements that should be made in the finer-grained stages of quantitative analysis.


A placebo-controlled trial of light treatment for winter depression.

We studied 32 patients with winter seasonal affective disorder (SAD) in a counterbalanced crossover design comparing 1 h of morning light treatment (about 7000 lux) to 1 h of morning placebo treatment (deactivated negative ion generator). Both treatments significantly reduced depression ratings, but there was no difference between the antidepressant response to light and to placebo. Several possible explanations for this result were discussed including an inadequate 'dose' of light (e.g., ineffective duration or intensity), an unusual sample of patients, and a placebo mechanism.


Brain phosphorous metabolism in depressive disorders detected by phosphorus-31 magnetic resonance spectroscopy.

Brain phosphorus metabolism was measured in 22 patients with depressive disorders. Ten of them had DSM-III-R bipolar disorder, and 12 had major depression. In bipolar patients, phosphomonoester (PME) and intracellular pH were significantly increased in the depressive state than in the euthymic state, while those values in the euthymic state were significantly low as compared to age-matched normal controls. Phosphocreatine (PCr) was significantly decreased in severely depressed patients compared to mild depressives. These findings suggest that high energy phosphate metabolism, intracellular pH and membrane phospholipid metabolism are altered in depressive disorders.


Cortisol levels in saliva and mood changes in early puerperium.

Cortisol levels in saliva were measured in 22 women, daily from the 2nd to 7th day after they had given birth and in 7 control women for 6 consecutive days. During the same period the mothers filled out a mood self-rating scale. The cortisol levels of the mothers were higher than those of the controls and progressively decreased after birth except for the 4th day post-partum when there was an increase. Five mothers had post-partum blues, but their cortisol levels were not different from those of other mothers. However, there was a significant correlation between cortisol level and the mood of mothers who bottle fed their babies.


Biological and clinical features of recurrent brief depression: a comparison with major depressed and healthy subjects.

Recurrent brief depression (RBD) has recently been proposed as a new subtype of affective disorder characterized by episodes of major depression which last less than two weeks. The aim of this study was to further evaluate the validity of this putative subtype by means of clinical and biological data. DST, TSH response to TRH and sleep EEG variables were compared in 25 RBD patients sex- and age-matched to 25 major depressed (MD) and 25 healthy subjects. Family history, age at onset, and psychiatric comorbidity did not discriminate RBD from MD. Recurrent unipolar depression was found to be more prevalent in MD. Although less severely depressed during the biological tests, patients with RBD did not significantly differ from those with MDD on basis of DST non-suppression, blunted TSH response and shortening of REM latency. Compared to controls, a greater sleep onset latency was observed both in RBD and MD and a lower total sleep time in MD patients only. These results suggest that RBD could be viewed as a subtype of affective disorder sharing many characteristics with MDD.


Climate and admissions for mania in the tropics.

Seasonality of admissions for mania has been commonly reported. Most reports are from temperature zones. We analyzed admissions for mania covering a 9 year period and looked for any seasonal trends using existing methods. No seasonal variation was found. The hospital lies in the tropical zone with a relatively constant climate. This may influence the seasonal pattern of relapses in affective disorder.


Components of major depression examined via the Beck Depression Inventory.

Although more than 20 factor analytic studies have been published on the Beck Depression Inventory (BDI), only Steer and co-workers (1987) have used a sample composed exclusively of patients diagnosed with depression. The component structure found in their study of depressed patients differs in important respects from the structure summarised in several reviews. The main aim of the present study was to investigate whether this structure could be confirmed with the BDI responses of an independent sample of 139 patients diagnosed with DSM-III Major Depressive Episode. Three principal components were extracted and rotated to maximum congruence with a target based on the results of Steer et al. (1987). The significance of the fit to this target was then evaluated by rotating the same matrix of loadings to 5000 random permutations of the target. The fit was found to be highly significant, though some possible improvements could be identified ad hoc. An alternative factor structure for the BDI, derived from covariance structure analysis by Tanaka and Huba (1984), was also tested but could not be confirmed.


Malignant pheochromocytoma: clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases.

Twenty patients, 16 males and 4 females, aged 11-76 yr, were treated for a metastatic pheochromocytoma at our institution between 1985 and 1990. A neurofibromatosis was associated in 4. Thirteen patients had a unilateral adrenal tumor, 3 had an extraadrenal retroperitoneal tumor, 2 had a bilateral adrenal pheochromocytoma, one had a unilateral tumor with a contralateral medullary hyperplasia and one an adrenal and an extraadrenal pheochromocytoma. Metastases occurred in all patients, at presentation in 11, 10 to 30 months later in 7, and 9 and 28 yr later, respectively in two. Histology did not afford conclusive evidence for malignancy. Catecholamine hyperproduction was present in all, predominantly affecting norepinephrine. Neuron Specific Enolase level was elevated in 11, Neuro-Peptide Y level in 9 and procalcitonin level in 11/18. High dopamine, methoxytyramine and homovanillic acid excretion levels seemed to correlate with large tumors or terminal stage. MIBG uptake was found in 16 after a diagnostic dose and in 1 only after a therapeutic dose. Surgery was performed on primary tumor in 18 and on distant metastase in 10. Iodine-131 MIBG therapy was performed in 11, among whom 9 were evaluable. Cumulative activity ranged from 100 to 711 mCi, in 1 to 6 courses. Symptomatic improvement occurred in 5 patients, stabilization was observed in 3 and tumor partial response in two, which lasted for 28 and 9 months, respectively terminating in a rapidly progressing disease with bone marrow involvement. Moderate myelosuppression occurred in 4 patients. Chemotherapy gave no response in 7 evaluable patients. Fourteen patients died with a median survival of 16 months from diagnosis of metastases (range 3-60). Response to therapy was poor and warrants further cooperative trials.


Malignant pheochromocytoma: a series of 14 cases observed between 1966 and 1990.

We report 14 patients (9 males, 5 females) aged 15-59 years, treated for malignant pheochromocytoma. These patients were observed during the 1966-1990 period along with 68 other patients presenting benign pheochromocytomas. From the initial general presentation of the 14 patients, two groups could be individualized. In seven patients, the initial presentation seemed benign. After the excision, the recovery was complete, but patients recurred on average 7.8 yr later (range 1-22 yr). Tumors were intraadrenal in six cases (5 single, 1 bilateral) and extraadrenal in one case. In the seven remaining patients, malignancy was evident from the first examination. The tumors were intraadrenal in 2 cases, extraadrenal in 5 cases. Frequency of extraadrenal locations (6/14) was in this series significantly higher than in benign forms (9/68). Diagnosis of malignancy was based on metastases in 12 cases (lymph nodes in 5, bones in 5, liver in 4, lung in 2, brain in 1) and on peritumoral extension in 2 cases. No biological specificity was detected in urinary excretion of catecholamines or its metabolites. In 6 patients so far studied, an uptake of 131I MIBG was found in the tumor and/or metastases. Four patients received therapeutic doses of 131I MIBG and in three of them, this treatment led to a good result within a follow-up range of 12 to 66 months.(ABSTRACT TRUNCATED AT 250 WORDS)


High incidence of malignant pheochromocytoma in a surgical unit. 26 cases out of 100 patients operated from 1971 to 1991.

In this surgical series of 100 pheochromocytomas (PH), where 91 cases were studied and followed up, the frequency of malignancy appears high (29%) on macroscopic criteria observed at the first operation (25 out 26 cases of malignant PH) or thanks to the occurrence of metastases (1 case out of 26 malignant PH). While some clinical signs are suggestive, there is no excretory profile predictive of malignancy. Isolated or predominant secretion of dopamine is not specific of malignancy event if it occurs more frequently and severely in malignant PH. Bilateral involvement, occurring in the setting of phacomatosis or of multiple endocrine neoplasia (MEN II), or in a sporadic case, is not a predictor for malignancy. Contrarily, extraadrenal involvement is a major feature indicative of malignancy. A CT scan which demonstrates possible locoregional invasion, and a MIGB scan revealing distant localizations raise the suspicion of malignancy. The preferred surgical approach is via a laparotomy, thus allowing the exploration of all possible abdominal chromaffin site and the search for intraabdominal metastases. Intraoperative MIBG scanning checks the completeness of the excision. Flow cytometric DNA ploidy studies have been performed in 25 of our patients. The follow up of benign or malignant PH, after excision "for cure" must be life-long: clinically, biologically and by MIGB scan. Persistence of the disease after surgery or recurrence with unresectable metastases can benefit from MIGB and chemotherapy.


A neuroendocrinological approach to evidence an impairment of central cholinergic function in aging.

A hypothalamic pathogenesis for the reduced GH secretion in aging has been reported for both animal and man. To further address this issue we studied in 31 elderly normal subjects (6 males and 25 females, aged 66-90 yr) and in 22 young healthy controls (13 males and 9 females, aged 20-35 yr) the GH responses to GHRH test (GHRH29, 1 microgram/kg i.v. as a bolus at 0 min) alone and combined with pyridostigmine, a cholinesterase inhibitor (PD, 120 mg po 60 min before GHRH), or with arginine (ARG, 30 g in 100 ml infused from 0 to 30 min). Serum IGF-I levels were lower in elderly than in young subjects (mean +/- SE: 86.9 +/- 7.2 vs 288.7 +/- 22.1 micrograms/L, p < 0.01). The GHRH-induced GH increase was lower in elderly than in young subjects (p < 0.01). PD increased the GH response to GHRH in both groups (p < 0.001), but in elderly subjects this response persisted lower (p < 0.0001) than that observed in young adults. Also ARG coadministration potentiated the GHRH-induced GH release in both groups (p < 0.0001) but in this case the elderly's responses overlapped with the young's. The GH increase observed after combined administration of ARG and GHRH was higher (p < 0.0001) than that elicited by PD plus GHRH in elderly but not in young subjects. Analyzing individual GH responses, a GH peak below the limit of normality for young adults was observed in 19 (61.3%) elderly subjects after PD plus GHRH administration while ARG plus GHRH test elicited a normal GH peak in all but one.(ABSTRACT TRUNCATED AT 250 WORDS)


Metastatic renal cell carcinoma to the pituitary gland presenting with hypopituitarism.

A 57-year-old man with pituitary metastasis from renal cell carcinoma is reported. He underwent right nephrectomy and total pancreatectomy for renal cell carcinoma and its pancreatic metastasis, respectively. Imaging studies showed an intrasellar mass lesion. The examination revealed panhypopituitarism, diabetes insipidus and bitemporal hemianospia. Metastatic renal cell carcinoma was diagnosed by the biopsy of the pituitary tumor. Metastatic renal cell carcinoma to the pituitary gland, which is extremely rare, appears to have unique features of presenting with hypopituitarism and visual disturbance more frequently than other metastatic pituitary tumors.


In vitro effect of hCG on steroidogenesis in the testicular tissue from a patient with complete androgen resistance.

The present study was performed to determine the in vitro steroidogenic capacity of a gonadal sample from a patient suffering from a complete androgen resistance syndrome. Testosterone and estradiol production by the testicular tissue from this patient as well as gonadotropin binding to a membrane fraction prepared from this tissue were measured. hCG bound with high affinity but with a very low capacity and the gonadotropin induced a clear dose response for both testosterone and estradiol production. The ED50 of hCG on testosterone and estradiol production were 2.5 and 5.0 nM, respectively. We conclude that estradiol originates from Leydig cell activity, since estradiol synthesis does not depend on testosterone availability and it shows a clear hCG dose response.


Disruptive behavior in elderly nursing home residents: a survey of nursing staff.

A significant number of nursing home residents exhibit behavior disturbances that are disruptive to the living and working environment in the nursing home. The most common disruptive behaviors cited by licensed nursing personnel included hitting/slapping, verbally aggressive remarks, screaming, pacing, wandering, and repetitive verbal requests. Self-injurious behavior, property destruction, and hiding things were not mentioned. Many of the nursing strategies listed by nursing staff as being used to alleviate disruptive behaviors are traditional care activities, eg, talking to and counseling patients, touching, or altering care. However, chemical and physical restraints were also frequently listed.


Osteoporosis: identifying high-risk persons.

Osteoporosis is the most common systemic bone disorder causing thousands of injuries and deaths each year. The pathogenesis of osteoporosis is a complex puzzle that contains many interlocking pieces involving both genetic and environmental factors. The prevention of age-related bone loss, which could be gained through health teaching by the nurse, should be optimized. Nurses and other caregivers can make significant contributions toward the initial identification of those persons at risk or who may already have the debilitating disease by using the Osteoporosis Risk Questionnaire.


Self-care teaching for congestive heart failure patients.

1. Elderly patients with congestive heart failure (CHF) have a high incidence of mortality, morbidity, and hospital readmission. 2. Descriptive research of 41 patients with chronic CHF found that almost all patients could not correctly define CHF, less than half could correctly identify their medications, and almost three fourths of patients did not weight themselves daily. 3. The self-perceived reasons for hospitalizations included shortness of breath, swelling of limbs, exercise intolerance, and eight other symptoms. 4. Some of these patients were able to follow self-care intervention during their hospital stay, which included daily weigh-ins, taking medications at the bedside, ordering a low-salt diet, and identifying symptoms of CHF.


Urinary incontinence: correlates among cognitively impaired elderly veterans.

1. Although a range of factors can contribute to urinary incontinence in long-term care residents, it is more closely associated with a decline in both cognitive and functional status. 2. Although all subjects had to be cognitively impaired to participate in the study, the incontinent group had a significantly lower mean score on the mental status examination than did the continent group. 3. Incontinent subjects were more dependent in activities of daily living and took significantly longer to carry out functional tasks specifically related to toileting. 4. Urinary incontinence was strongly associated with a history of urinary tract infections, positive urine cultures, epididymitis, hematuria, and fecal incontinence. Medical diagnosis, medications, and affective status were not associated with the problem.


Constipation: proposed natural laxative mixtures.

The treatment of constipation in the elderly is one of the most common problems encountered by the geriatric nurse practitioner (Aman, 1990; Brocklehurst, 1983; Shefts, 1984). Management of bowel habits with this age group is difficult, often resulting in mismanagement and the need for invasive measures, such as suppositories and enemas. Yet, it is possible bowel habits for these patients might be regulated by maintaining their dietary, dentition, and mobility requirements so that the use of invasive measures as well as associated product costs are minimized. A review of the literature revealed normal defecation ranges in frequency from three times a day to three times a week (Connel, 1965). As reported by Wright and Staats (1986), however, the "interval between bowel movements generally lengthens in debilitated older people."


Constipation--a sign of a disease to be treated surgically, or a symptom to be deciphered as nonverbal communication?

Constipation is not a sign but a symptom, which is not measurable scientifically. It has emotional components and must be dealt with in a holistic manner. The scientific approach aims only at the physiological derangement and serves to place the complaint in a more objective perspective. An algorithm can be constructed to select treatment including surgery, but there is no gold standard at present because the natural history of the symptoms is unknown. Most physicians confuse normality with epidemiology, neglecting in the process the evolution of mankind in terms of behavior. Constipation now means less than five stools per week, while it used to mean three. Thus, all complaints should be addressed. As for surgery, it should be performed in few, high select patients with no dysfunction other than that in the colon and in conjunction with a fully normal thorough psychological evaluation.


Short-term treatment of refractory reflux esophagitis with different doses of omeprazole or ranitidine.

Sixty patients who presented with erosive/ulcerative refractory reflux esophagitis were randomized to receive a 4- to 8-week treatment with omeprazole 20 mg daily, or ranitidine 150 mg twice daily. Patients not healed after treatment were given the same drugs at doubled doses for a second period of equal duration. Patients still unhealed after this received open treatment with omeprazole 20 mg twice daily for a third period of 4 to 8 weeks. Endoscopic assessment and clinical and laboratory evaluation were performed every 4 weeks until there was complete esophageal mucosal repair. After 4 weeks, complete healing was observed in 50% of patients on omeprazole 20 mg daily, compared with 20.7% on ranitidine 150 mg twice per day (p < 0.01). After 8 weeks, the figures were 79.3% versus 34.5% (p < 0.5). With doubled doses after 4 weeks, complete healing was achieved in 96.6% of patients on omeprazole 40 mg daily, compared with 64.2% on ranitidine 300 mg twice per day (p < 0.05). The eight still "refractory" patients (one omeprazole, seven ranitidine) healed completely with 8 more weeks of omeprazole 20 mg twice daily. Patients treated with omeprazole experienced faster relief of heartburn, which disappeared in 60% of patients after 4 weeks, as compared to 21% of patients treated with ranitidine (p < 0.006). Apart from the mode of treatment, the only factor that proved to be related to healing at multivariate analysis was the pretreatment severity of gastroesophageal reflux, as measured by esophageal pH monitoring. Our study confirms that omeprazole, even at a low dosage, is the choice for refractory reflux esophagitis.


Idiopathic ulcerative proctitis may be the initial manifestation of Crohn's disease.

Of 213 patients with proctitis of all etiologies seen between 1977 and 1987, we studied an original cohort of 96 patients with idiopathic ulcerative proctitis (mean follow-up of 62 months). The diagnosis was made according to strict inclusion criteria, and all cases with any initial feature suggestive of Crohn's disease were excluded. Follow-up showed that 13 patients (13.6%) eventually progressed to Crohn's disease, usually within the first 3 years of the initial diagnosis of idiopathic ulcerative proctitis. Their clinical, endoscopic and histological features at initial presentation were indistinguishable from those in whom the diagnosis remained that of idiopathic ulcerative proctitis. In nine of 13 of these patients (70.0%), the clinical course was characterized by a more protracted course and a poorer response to standard treatment. Such features were not found in those in whom the diagnosis of idiopathic ulcerative proctitis was maintained. Clinicians should be aware that Crohn's disease may present initially as apparent idiopathic ulcerative proctitis.


Gastrocolic and duodenocolic fistulas in Crohn's disease.

Crohn's disease is a rare cause of gastrocolic and duodenocolic fistulas. Only 83 examples (27 gastric, 52 duodenal, four both) have been described. Weight loss, abdominal pain, and diarrhea are common features but fail to distinguish a fistula from active inflammatory bowel disease. Fecal vomiting is pathognomic but is present in one third of gastrocolic and only 2% of duodenocolic fistulas. Diagnosis is most readily made by contrast radiography, with barium enema being more sensitive than barium meal. Although several gastrocolic fistulas have been successfully treated with long-term 6-mercaptopurine, surgery is the mainstay of therapy. An isolated duodenocolic fistula should not be regarded as the primary indication for operation because most are asymptomatic. Ileocolonic resection with simple gastric or duodenal repair is safe and effective in most cases. An ileocolonic anastomosis should be positioned away from the stomach or duodenum or protected with omentum to prevent recurrent fistulization. A number of fistulas appear to have arisen from gastric or duodenal Crohn's, but the vast majority originate from diseased colon.


Selection of constipated patients as subtotal colectomy candidates.

We evaluated 224 consecutive patients referred for severe constipation prospectively by strict criteria to determine their candidacy for subtotal colectomy. Eighteen patients had insufficient symptoms to warrant evaluation. Two hundred six patients had anorectal manometry and defecography, and 182 had colonic transit measurement. Forty-nine patients had normal or minimally abnormal studies. One-hundred twenty-nine patients had abnormalities such as outlet obstruction, mild colonic inertia, diffuse gut dysfunction, or combinations of factors not favoring subtotal colectomy. Twenty-eight patients had colonic inertia without outlet obstruction and with disabling symptoms; 19 of these patients underwent subtotal colectomy. Follow-up > or = 12 months was available in 14 patients from this group. Of these patients, 12 (86%) were clinically improved. Preoperative evaluation accurately predicted postoperative fecal incontinence and likely reduced postoperative constipation. Small-bowel obstruction occurred postoperatively in 4 patients (29%), and remains a major risk of subtotal colectomy even in carefully selected candidates.


Open-access, flexible, fiberoptic sigmoidoscopy in a regional primary-care clinic.

We established an open-access, flexible, fiberoptic sigmoidoscopy service in an outpatient clinic in Kiriat-Shmona, Northern Israel. Twenty-eight general physicians in the city and in 41 surrounding rural residences (population 40,000) were encouraged to refer patients for sigmoidoscopy. In the first operative year, flexible sigmoidoscopy was performed on 255 patients (age range 10-90 years, mean 54). The male to female ratio was 123:132; women were slightly older than men (mean age 55.9 years vs. 51.1). Rectal bleeding and change in bowel habits were the most common indications. The sidmoidoscope was passed to the splenic flexure in 156 patients (61%). In five patients (2%) the instrument could not be inserted beyond the rectosigmoid junction. Excluding hemorrhoids and anal lesions, abnormalities were detected in 69 patients (27%). In 29 patients (11.4%) a cancer or polyp was found. Analysis of referral indications showed an increased positive predictive value for neoplastic lesions in patients referred for anemia (22.2%), weight loss (20.0%), abdominal pain (17.8%), and positive fecal occult blood test (15.4%). There were only two patients with polyp or cancer of 55 (3.6%) < 40 years of age, in contrast to 27 of 200 (13.5%) > 40 (p < 0.05). Sixty-six patients underwent further investigation, and 26 had positive results: colonic lesions were confirmed in 20 patients, sigmoid colon cancer was found on barium enema in one, and lesions outside the colon were detected in seven. Such open-access, flexible sigmoidoscopy gave higher yield for colorectal polyps or cancers than open-access or hospital-initiation barium enema.(ABSTRACT TRUNCATED AT 250 WORDS)


Cholangiographic appearances of ductular rejection of ABO-incompatible liver transplants.

Two patients, after ABO-incompatible liver transplant, developed a picture of chronic cholestasis that was associated with unique ductular appearances within the donor graft on retrograde cholangiography. We believe that the appearance of progressive ductular ectasia within liver grafts indicates a specific immunologically mediated injury to ductular epithelium, probably because of ductular epithelial expression of ABH antigens.


Gastrointestinal and hepatic effects of Amanita phalloides ingestion.

Three residents of New Jersey suddenly developed vomiting, abdominal pain, and watery diarrhea 12 h after ingesting five to 13 hand-picked Amanita phalloides-type mushrooms. The group was led by an amateur mycologist who had been eating hand-picked mushrooms without complications for 20 years. The patients developed mild to severe acute hepatic injury, with a peak serum aspartate aminotransferase level ranging from 133 to 826 Karmen U/L, and a peak serum alanine amino-transferase level ranging from 163 to 1176 Karmen U/L. One of the patients developed a transient severe coagulopathy, but no one developed renal failure or hepatic coma, and all rapidly improved. These three cases demonstrate that mycetismus can occur in the heavily urbanized northeastern United States, that consuming hand-picked mushrooms even under the guidance of an experienced amateur may be dangerous, and that Amanita phalloides ingestion produces a biphasic illness with early gastrointestinal symptoms and subsequent hepatic injury.


Mushroom poisoning: the role of orthotopic liver transplantation.

Mushroom poisoning, mycetismus, is a well-recognized cause of fulminant hepatic failure in Western Europe and is increasingly seen in the United States. We present a case of fulminant hepatic failure secondary to mushroom poisoning treated successfully with an orthotopic liver transplant.


Halitosis and Helicobacter pylori. A possible link?

The exact pathophysiological mechanism of halitosis is not clear, and in many patients the etiology is an enigma. We followed three couples in which one member or both had halitosis. All the subjects had evidence of Helicobacter pylori infection. All received a treatment course of colloidal bismuth subcitrate four times a day and 250 mg metronidazole three times a day. There was impressive improvement in their symptoms, the halitosis disappearing along with eradication of the organism. We call the attention of physicians to the possible connection between halitosis, H. pylori infection, and familial occurrence. Further studies to confirm this surprising association are in order.


Acute acalculous cholecystitis. A review.

Acute acalculous cholecystitis is an uncommon but very serious illness, that, if undiagnosed, may lead to gallbladder perforation and death. The condition has numerous causes that result in bile stasis and ischemia leading to inflammation and infection in the gallbladder wall. The bedside diagnosis may be difficult, especially in critically ill patients. Current imaging techniques including ultrasonography, computer tomography, and radionuclide cholescintigraphy are very helpful. Depending on the clinical situation, the gallbladder should either be drained by a surgical or percutaneous cholecystostomy under local anesthesia or removed.


Foley feeding catheter migration into the small bowel.

Percutaneous endoscopic gastrostomy provides a non-surgical alternative to enteral feeding. The tube may deteriorate or be expelled accidentally from the stomach and require replacement. We report a patient in whom the replacement Foley catheter migrated into the jejunum, resulting in impaction of the hub into the abdominal wall with resultant localized infection and impaction at the stoma site. We review this problem and suggest a simple technique to prevent the complication.


Unusual splenic complication of acute pancreatitis.

Splenic complications of acute pancreatitis are rare. We describe a spontaneous subcapsular splenic laceration during an episode of acute pancreatitis, without any evidence of one of the currently reported predisposing factors. Its spontaneous resolution suggests that conservative therapy can be proposed in such complications.


Ancient remedies revisited: does Allium sativum (garlic) palliate the hepatopulmonary syndrome?

Hypoxia in the setting of liver disease is often multifactorial. Obstructive or restrictive lung disease, pleural effusions, and tense ascites are common underlying disorders. Less often observed and frequently unrecognized is hypoxia related to diffuse intrapulmonary shunting--the hepatopulmonary syndrome. Its etiology is unknown but may result from disordered gut peptide metabolism. Symptoms may be ameliorated by somatostatin and reversed by successful liver transplantation. Here we report a patient with severe hepatopulmonary syndrome who failed somatostatin therapy and declined liver transplantation. On her own the patient took large daily doses of powdered garlic (Allium sativum). She has experienced partial palliation of her symptoms and some objective signs of improvement over 18 months of continuous self-medication. The possible effects of garlic's main physiologically active compound, allicin, on gut peptide metabolism and pulmonary vasculature are unknown. This innocuous compound may deserve further investigation given the limited therapeutic options for this disorder.


Acute hepatitis by Listeria monocytogenes in an HIV patient with chronic HBV hepatitis.

We report a young male IVDA with CAH caused by HBV who was infected with HIV and who contracted listeriosis in the form of acute hepatitis and bacteremia, with epithelioid granulomas in the liver. Treatment with ampicillin and a aminoglycoside for 3 weeks was followed by rapid and maintained improvement. Involvement of the liver is unusual in listeriosis and, as far as we are aware, it has not been described previously in patients with HIV infection.


The clinical and endoscopic spectrum of the watermelon stomach.

The watermelon stomach is an uncommon but treatable cause of chronic gastrointestinal bleeding. We report our experience with the clinical and endoscopic features of 45 consecutive patients treated by endoscopic Nd:YAG laser coagulation. The prototypic patient was a woman (71%) with an average age of 73 years (range of 53-89 years) who presented with occult (89%) transfusion-dependent (62%) gastrointestinal bleeding over a median period of 2 years (range of 1 month to > 20 years). Autoimmune connective tissue disorders were present in 28 patients (62%), especially Raynaud's phenomena (31%) and sclerodactyly (20%). Atrophic gastritis occurred in 19 of 19 (100%) patients, with hypergastrinemia in 25 (76%) of 33 patients tested. Antral endoscopic appearances included raised or flat stripes of ectatic vascular tissue (89%) or diffusely scattered lesions (11%). Proximal gastric involvement was present in 12 patients (27%), typically in the presence of a diaphragmatic hernia. Endoscopic laser therapy after a median of one treatment (range of 1-4) resulted in complete resolution of visible disease in four patients (13%) and resolution of > 90% in 24 patients (80%). Hemoglobin levels normalized in 87% of patients over a median follow-up period of 2 years (range of 1 month to 6 years) with no major complications. Blood transfusions were not necessary after laser therapy in 86% of 28 initially transfusion-dependent patients. The characteristic clinical, laboratory, and endoscopic features allow for a confident diagnosis that can lead to successful endoscopic treatment.


Some data on GABA-ergic innervation of nucleus rotundus in chicks.

The EM preparates displayed in the nucleus rotundus also symmetrical type of synapses with flattened vesicles, known this type as inhibitory synapsis. To prove this supposition and to find the sources of inhibitory terminals GABA-immunostaining was applied in the diencephalon of chicks. The preparates were examined by light- and electronmicroscope. In nucl. rotundus the large terminal profiles on the cell membrane of principal neurons, on the dendrites and branching areas of terminal branchings of dendrites proved to be GABA positive. The sources of GABA-ergic fibers seemed to be the subpretectal and ventral posterior thalamic nuclei.


Regressional changes of human cerebellar cortex and hypoglossal nucleus during development.

In the development of nervous system, two processes are of a particular interest. It is well known that after a primary migration of cells, there appears a consecutive regression in cellular number, closely connected with the maturation of the nervous system. The dynamics of this reduction was investigated following the changes in number of cells in nucleus hypoglossus as well as that of Purkinje cells in two structures of cerebellar cortex--in vermis and in hemispheres. Cell nuclei were counted using the stereological technique, after a usual preparation. Data were collected from 20 human brains of different gestation age, i.e. at 12.5, 14, 17.5, 19.5, 24, 31, weeks of gestation and 6 day old newborn. After the graphical and numerical analysis of the data obtained, an adequate mathematical model was proposed. It is confirmed that a close agreement between biological data and decreasing two-exponential equation can be demonstrated, pointing out that the cellular reduction shows a proportional relation. The possible explanation could be that only the cells forming proper and useful connections and entering the informational system have a privilege to survive, and that all improper contacts lead to the rejection of cells or even of groups of cells.


The perivascular fibrotic reaction in rat brain in the late period after experimental clinical death. I. Capillary vessels.

In this paper we studied the pericapillary zone of the hypothalamic neurosecretory nuclei and temporal cerebral cortex of rats 6-12 months after experimentally evoked cardiac arrest of 10 minutes duration. The most significant ultrastructural findings were presence of single collagen fibrils and collagen bundles in the compartment between endothelia and pericytes, pericytes and basement membrane and also inside the phagocytic cells. In the animals that survived at least 10 months after resuscitation the capillaries filled with thrombocytes were encountered. Moreover, in the vicinity of these capillaries the dead cells and collagen bundles were observed. We interpret these findings as the evidence of the reparatory process in the border between capillaries and the surrounding brain cells. We discuss the hypothesis that the non-fibroblastic cells present in rat brain are able to synthesize collagen that leads to a process comparable with the fibrosis of parenchymal organs.


Ultrastructural alterations of brain cortex in rat following intraperitoneal administration of mercuric chloride.

Intraperitoneal administration of a single dose (6 mg/kg body weight) of mercuric chloride (HgCl2) results in ultrastructural changes in brain cortex of the rats. 18 hours after administration of HgCl2 the accumulation of dense deposits of mercury in nerve and glial cell cytoplasm was observed. The quantity of microglia in neuropil was also increased in this experimental group. We postulate that these cerebral macrophages can play an important role in the process of intoxication, too. 5 days after administration of mercuric chloride many of these changes reversed.


Light- and electron microscopic study of oligodendrocytes in the lateral line area of the medulla in Chelon labrosus (Teleostei).

The oligodendrocytes of the medullary lateral line area of the teleost Chelon labrosus were studied with light and electron microscopy. Oligodendrocytes are sharply differentiated from neurons or other class of glia cells from their ultrastructural characteristics. The three subtypes of oligodendrocytes (light, medium and dark) that have been recognized are not homogeneously distributed but have preferential locations related to the size of nearby myelinated fibres. No perineuronal oligodendrocytes are present in this medullary center. Oligodendrocytes show a variety of dense bodies, sometimes of bizarre shapes, in addition to characteristic mitochondria and endoplasmic reticulum. Three types of intercellular junctions were observed in these cells: gap junctions, tight junctions and puncta adhaerentia. Gap junctions and puncta adhaerentia link oligodendrocyte somata and astrocytic processes. Tight junctions were observed both between oligodendrocytes and between oligodendrocytes and astrocytic processes. The significance of these results is discussed in relation to the maturation and function of oligodendrocytes and the characteristics of fish brains.


An atlas of the brain of the tench (Tinca tinca L., 1758; Cyprinidae, Teleostei).

This report provides an atlas of the tench brain in the transverse plane. The brain atlas is based on paraffin-embedded brains which are serially sectioned and stained with cresyl violet. It consists of drawings and photographs at several levels throughout the main divisions of the tench brain. The brain of the tench shows important variations in the shape, extension and boundaries of different brain areas and nuclei in comparison with those previously described in the brain of other teleosts.


Cytoarchitecture and ultrastructural characteristics of the area octavolateralis of the urodele amphibian Pleurodeles waltlii.

The cytoarchitecture of the area octavolateralis (AOL) in Pleurodeles waltlii is studied by means of normal stained material. In addition, the main ultrastructural features of the cells in the AOL are described. In the AOL, three columns, one upon the other (dorsal, intermediate and ventral), are present. Each one includes a medially located cell group and lateral neuropil. While rostrally the three are well represented, the dorsal subdivision do not reach the same caudal extent where the intermediate column forms a small lobe. The ultrastructure of the neurons in the AOL reveals similarities with other cell types in the amphibian brain. A comparative analysis of the ultrastructure of vestibular cells with other vertebrates is also discussed.


Experimental approaches to the study of degenerative and regenerative processes in the nervous tissue. I). Morphological changes in the frog cerebellum after unilateral transection of the VIII statoacustic nerve.

The cell density was evaluated in Purkinje neuron and internal granule cell layers of the frog (Rana esculenta L.) cerebellum at 3, 8, 14, or 30 days after unilateral transection of the VIII statoacustic nerve. After 3 days, the cell density of the Purkinje cell layer was markedly reduced, the cellular loss amounting to 30% at 30 days. In the internal granule cell layer (IGL), after an abrupt decrease in the cell density at 3 and 8 days, the number of cells increased at 14 days and reached the values of control animals at 30 days. In the dorsal part of the ependymal lining of the IV ventricle, there was morphological indication of resumption of the proliferative activity. This can be in relationship with the restored cytoarchitecture of the IGL after the initial cell degeneration. All the above changes were evident in both the ipsi and contralateral parts to the neurotomy though at different extent. This is in agreement with the anatomical data about the nervous circuit connection between the two cerebellar sides and may be also expression of vestibular compensation, induced by unilateral nerve transection in the contralateral side.


A reconsideration of the primary visual system of the turtle Emys orbicularis.

The retinocerebral projections of Emys orbicularis were investigated by means of [3H]-proline or HRP, administered by intraocular injection. Two newly-hatched, two juvenile and seven adult specimens were examined. The results reveal contralateral retinal projections to fifteen sites: two in the hypothalamus (the nuclei suprachiasmaticus and periventricularis), five in the thalamus (the nuclei ovalis, geniculatus lateralis ventralis, geniculatus laleralis dorsalis, dorsolateralis anterior and ventrolateralis), five in the pretectal region (the nuclei geniculatus pretectalis, opticus pretectalis ventrolateralis, lentiformis mesencephali, posterodorsalis and griseus tectalis), two in the optic tectum (the stratum opticum and the stratum fibrosum et griseum superficiale), and one in the tegmentum (the nucleus opticus tegmenti). Ipsilateral projections to nine of these sites at thalamic, pretectal, tectal and tegmental levels, while weak, could be clearly demonstrated. These results differ considerably from those obtained in a previous investigation using a Nauta-paraffin technique; it is suggested that the differences are due to limitations of the latter technique. A review of the existing literature on the Chelonian primary visual system reveals considerable terminological diversity, and a standard nomenclature for the primary visual centres of turtles is proposed.


Volumes of the cytoarchitectonic areas in the rat cerebral cortex.

The volumes of the isocortical, periallocortical and allocortical areas were measured in the brains of nine 6 month old male Wistar rats. After perfusion fixation with Bodian's solution, determination of brain weight, paraffin embedding and serial sectioning, the areal volumes were estimated with the Cavalieri method and corrected for individual brain shrinkage. Thus, fresh volumes were measured. The present report provides comprehensive data on the volumes of the cortical areas of one hemisphere in normal adult rats and can be used as a reference for allometric and experimental studies.


[Morphometric-stereological study of hippocampal long term potentiation with special consideration of the analysis of variance with two-way hierarchical classification].

Regarding the hippocampal formation and especially the external two thirds of it's dentate molecular layer a lot of possible morphological changes after long-term potentiation (LTP) have been described in literature. The present morphometric-stereological study of vesicles in axo-spino-dendritic synapses of the inner third of the molecular layer was done under the aspect of heterosynaptic influences following LTP. Because of the hierarchical link of the three analytic levels (test-group, animal, synapse), for statistical interpretation we used the analysis of variance with two-way hierarchical classification. Between the 3 groups (passive control, active control, LTP-group) we found no significant differences. Because of the great differences between the vesicles even within a single synapse we subsequently investigated the middle third of the molecular layer, i.e. the terminal area of the stimulated perforant path. No differences between the three groups we found here either. There was no confirmation for the expected greater homogenization of the synapses based on the uniform input. As a result of this study pure morphological studies without selective staining of specific population of synapses are considered inadvisable. Only with the help of selective staining in the area of the synapses possible differences between the groups may be found.


Phagocytosis of latex beads by rabbit retinal Müller (glial) cells in vitro.

The ability of rabbit retinal Müller (glial) cells to perform phagocytosis was studied in vitro. Müller cells were feed with various kinds of latex beads either shortly after enzymatical isolation from adult retinae or in monolayer cell cultures derived from neonatal retinae and kept 14 days in vitro. Both types of Müller cell preparations showed intense phagocytosis of latex beads. Moreover, when entire retinae were isolated and exposed (sclerad side up) to latex beads in vitro for 30 min, Müller cells had picked up fluorescent beads and showed, after fixation, intense labeling in radial sections of such retinae. Effective phagocytosis by Müller cells was demonstrated 1.) by transmission electron microscopy, 2.) by bright-field light microscopy of unstained large beads (diameter 660 nm), or 3.) by fluorescence microscopy of small (diameter about 60 nm) and large latex beads labeled with rhodamine. These results suggest that both labeled and unlabeled latex beads are suitable tools to study the phagocytotic activity of retinal glial cells in vitro, thus providing information on important processes occurring in situ during ontogenesis, physiological renewal of retinal receptor cells, and pathological events. We found that movements of cells or cytoplasmic excrescences, and cell-cell interactions, play important roles in removal of foreign particles out of the fluid environment. Engulfed latex beads move through the elongated cells with velocities similar to slow axoplasmic transport.


Neural mechanisms of pupillary abnormality following thalamic lesions: experimental lesion and stimulation studies in cats, and consideration of pupillary findings in thalamic vascular lesions.

Neural mechanisms of the pupillary abnormality in thalamic lesions were experimentally studied in cats. Moderate to considerable anisocoria appeared after kainic acid lesions involving the medial thalamus. The pupil on the side of the lesion was larger than its partner. Only subtle or no pupillary inequality was produced by lateral thalamic lesions. Electrical stimulation of the midline and medial thalamus evoked dilation bilaterally in sympathectomized pupils. Thus, pupillary dilation produced by stimulation of the thalamus was shown to be mediated in part by the oculomotor parasympathetic nerve (OPN). There was no threshold difference between ipsilateral (ipsi) and contralateral (contra) pupils. However, amplitude of dilation was significantly larger in the contra pupil than in the ipsi, when stimulus was given to the pupillo-dilatory medial thalamic nuclei. In these, the mediodorsal, parataenial, central dorsal, paracentral (Pc), and parafascicular nuclei and the medial division of the medial pulvinar nucleus were included. Pupillary dilation mediated by the ocular sympathetic nerve (OSN) was investigated by stimulating Pc and comparing the ipsi-contra difference in the amplitude of dilation between sympathectomized and non-sympathectomized pairs of pupils. In contrast to the results in sympathectomized pairs, there was no ipsi-contra difference in the amplitude of dilation or it was larger in the ipsi pupil in non-sympathectomized pairs. From these, it was inferred that stimulation of Pc activated OSN ipsilaterally or bilaterally with ipsi dominance. It was concluded that the medial and midline thalamus exerts pupillo-dilatory effects through a set of neural mechanisms; 1) ipsi-dominant bilateral OPN inhibition, and 2) ipsi or ipsi-dominant bilateral OSN activation. Neural mechanisms of the pupillary abnormality in thalamic vascular lesions were also considered.


Neuronal ectopia in tiger retina.

Ocular pathology in a ten week-old tiger is described. In the retinae of both glaucomatous eyes, venous congestion and scattered hemorrhages were observed; rare perivascular infiltrates were seen. The basal lamina of the inner limiting membrane was considerably thickened, and serous exudates were widely distributed within the vitreous body. The retina was studied with a series of specific antibodies. Müller (glial) cells were well developed and could be immuno-labelled by antibodies against both vimentin and glial fibrillary protein (GFAP). Neurofilament-specific antibodies revealed the presence of ganglion and horizontal cells, and of a nerve fibre layer which was unusually distant from the inner limiting membrane. Within both plexiform layers, scattered neuronal cells were found. The most important finding was the presence of cells between the nerve fibre layer and the inner limiting membrane, which could be immuno-labelled by neuron-specific antibodies, and which expressed thy typical morphology of migrating neuroblasts. It is suggested that this neuronal ectopia might be due to an inflammatory related reactive change in Müller cells which, in turn, might have lost their orderly guiding function for migrating neuroblasts.


Correlation of thermal parameters with outcome in combined radiation therapy-hyperthermia trials.

Many studies utilizing combined hyperthermia (HT) and radiation therapy (XRT) in the treatment of advanced or recurrent malignancies have reported a correlation between some measure of the minimum temperature achieved and outcome. Previous reported studies at Stanford have demonstrated a statistically significant correlation between the duration of local control and Tmin, the mean over treatments of the minima of (a) measured intratumoral temperatures in fields which contained diffuse or nodular tumours, or (b) measured interstitial temperatures in fields treated for microscopic residual disease. Recently, T90, the mean of the temperatures above which 90% of all measured intratumoral temperatures fall, has been proposed as an alternative characterization of the efficacy of the HT treatment that reportedly has a superior correlation with outcome. To test this hypothesis, T90 was computed by two different methods for three groups of patients treated at Stanford with XRT-HT for superficially located tumor recurrences. Tmin was found to be strongly correlated with T90 calculated by both methods. All three thermal parameters correlated with complete response at 3 weeks and with local control, although Tmin usually demonstrated the strongest correlation.


Dielectric properties of human glioma and surrounding tissue.

Dielectric properties of human glioma and surrounding tissue from five patients were measured. Experiments were performed at frequencies of 5-500 MHz at 24 +/- 0.5 degrees C using a Network Analyser and a coaxial line capacitive sensor. The permittivity and conductivity of tumours were 30% higher than that of the surrounding tissues due to their higher water content. The characteristic of less differentiation in tumours clearly was reflected in the dielectric properties, namely a smaller parameter for the relaxation time distribution of the tumour's dielectric relaxation. With the dielectric data, the power absorption ratios of tumour to surrounding tissue were calculated for four representative electromagnetic (EM) irradiation cases. The calculation shows that power absorption ratios are strongly dependent on the incident direction of the EM wave and optimum frequency. To improve therapeutic efficiency, it is appropriate to have the electric field vector (E) parallel to the interface of tumour/surrounding tissue at optimum frequencies around 100 MHz, and the case of E perpendicular to the interface must be avoided in applications of EM hyperthermia for brain tumours.


Quantitative estimation of the thermal dose-modifying factor for cis-diamminedichloroplatinum (CDDP) in tumour-bearing dogs.

A statistical method for estimating clinical toxicity was used to determine a theoretical isoeffect dose-modifying factor for dogs with disseminated or refractory neoplasia treated with cis-diammine dichloroplatinum (II) plus whole-body hyperthermia or CDDP alone. CDDP was administered every 3 weeks with vigorous saline hydration to 54 dogs (CDDP alone n = 21, CDDP/WBH n = 33) that were eligible for entry into this non-randomized study. CDDP was administered during the plateau phase of WBH in dogs receiving combined therapy. Acute toxicity included myelosuppression (CDDP n = 7; CDDP/WBH n = 5), nephrotoxicity (CDDP n = 1, CDDP/WBH n = 1) and respiratory distress (CDDP/WBH n = 2). Eight dogs experienced chronic renal dysfunction as a result of CDDP (n = 2) or CDDP/WBH (n = 6). A theoretical thermal dose-modifying factor was determined for both acute and cumulative toxicity by comparing the maximum tolerated dose of each treatment group. The maximum tolerated dose (MTD) of CDDP +/- WBH was defined as that dose producing a 50% incidence of moderate acute toxicity or acute plus mild chronic toxicity as estimated from logistic regression analysis of the toxicity data. The MTD (+/- .standard error) of CDDP/WBH for acute toxicity only was 54.6 (4.3) mg/M2 and for CDDP alone the MTD was 73.6 (40) mg/M2. Thus, the isoeffect dose-modifying factor for acute toxicity was 1.35 (0.12). The MTD (SE) of CDDP/WBH for cumulative toxicity (acute plus chronic toxicity) was 46.4 (2.7) mg/M2 and for CDDP alone waas 70.0 (2.9) mg/M2. The isoeffect dose-modifying factor for total cumulative toxicity was 1.5 (0.1).(ABSTRACT TRUNCATED AT 250 WORDS)