bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of All-frans-Retinoic Acid on the Dorsal Skin of: Hairless Dogs
Authors: Klmura Tohru , Doi Kunio
Published: July 2017

Daily topical treatment with all-trans-retinoic acid (t-RA; 0.1% t-RA solution or 0.05% t-RA cream) was compared with its vehicle with regard to improvement of intrinsically aged skin of hairless descendants of Mexican hairless dogs. After 1 mo of treatment with 0.1% t-RA solution, improvements were noted in skin texture, wrinkling, and pigmentation. Treatment with 0.05% t-RA cream caused an intense adverse effect, retinoid dermatitis. Histologically, 0.1% t-RA solution induced restoration of the skin structure of hairless dogs, resulting in an apparent increase in compaction of the stratum comeum and the epidermal thickness. The epidermis became hyperplastic with definite development of the stratum granulosum. The border between the epidermis and dermis became wavy, and dermal papillae were reconstituted. The 0.1% t-RA solution caused a remarkable decrease in melanin granules. In the dermis, the number of small vessels increased and vasodilation was seen. In sites treated with 0.05% t-RA cream, the stratum corneum became involved in dyskeratotic changes. There was a significantly greater increase in epidermal and granular layer thickness. Necrotic and edematous changes were found in the epidermis, and severe inflammatory reactions were also observed in the dermis. In the t-RA– untreated sites, the structure of the aged skin remained histologically unimproved during the study. The results suggest that hairless dogs are useful laboratory animals for evaluating the effectiveness and side effects of t-RA agents.
Nitro-Imidazole Radiosensitizer-Induced Toxicity in Cynomolgus Monkeys
Authors: Breider Mike A. , Ulloa Herm M. , Pegg David G. , Gough Alex W.
Published: July 2017

Intravenously administered nitro-imidazole radiosensitizer and alkylating anticancer compound CI-1010, designated as (R)-a-[[(2-bromoethyl)amino]methyl]-2-nitro-lH-imidazole-l-ethanol monohydrobromide, causes multiorgan toxicity in rodents, including retinal degeneration. This study determined the potential of CI-1010 to induce similar effects in nonhuman primates. One male and 1 female cynomolgus monkey were given single daily doses of CI-1010 intravenously for 5 consecutive days each week for 3 wk. Doses were escalated from 5 mg per kilogram of body weight in week 1 to 40 and 60 mg/kg in week 3. Postdosing emesis occurred in both monkeys at 5 mg/kg, and clinical signs at 40 and 60 mg/kg included more pronounced emesis, reduced food consumption, pallor, weakness, and body weight loss. At study termination, both monkeys had markedly reduced peripheral blood lymphocytes and moderately lowered erythrocyte, hemoglobin, and hematocrit levels, which correlate with a decreased total nucleated bone marrow cell count. At necropsy, the monkeys had pancytic bone marrow hypocellularity, multiorgan lymphoid depletion, pancreatic acinar cell apoptosis, testicular seminiferous tubular degeneration, and bilateral multifocal retinal degeneration involving the photoreceptor and outer nuclear layers. Ultrastructurally, selected inner and outer retinal rod segments were swollen and fragmented, a state associated with cytoplasmic condensation and pyknosis of the outer nuclear cell layer. Thus, CI-1010 induced toxicity of hematopoietic/lymphoid organs, retina, testes, and pancreas in monkeys, findings similar to those of previous studies in rodents.
Mechanisms of Ligand-Induced Aryl Hydrocarbon Receptor-Mediated Biochemical and Toxic Responses
Authors: Wilson Cody L. , Safe Stephen
Published: July 2017

The ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a member of a broad group of halogenated aromatic hydrocarbons (HAHs) that is known to induce a wide range of toxic and biochemical responses in laboratory animals and humans. The effects of HAH exposure are mediated by binding to the cytosolic aryl hydrocarbon receptor (AhR), which is expressed in a tissue- and cell type-specific manner. The AhR is a ligand-activated transcription factor belonging to the basic helix-loop-helix/Per-AhR-Arnt-Sim (bHLH/PAS) superfamily of proteins. The mechanism of induction of gene transcription by TCDD involves Iigand recognition and binding by the AhR, nuclear translocation, and dimerization with the AhR cofactor, AhR nuclear translocator (Arnt). The nuclear heterodimer interacts with cognate xenobiotic responsive elements (XREs) in promoter/enhancer regions of multiple Ah-responsive genes. Subsequent changes in chromatin structure and/or interaction of the AhR complex with the basal transcriptional machinery play a significant role in AhR-mediated gene expression. Although Arnt is a necessary component of a functional nuclear AhR complex, this protein also forms transcriptionally active heterodimers with other bHLH/PAS factors, including those involved in the transcriptional response to hypoxia. Arnt is ubiquitously expressed in mammalian systems, and results from transgenic mouse studies suggest that this protein plays a vital role in early mammalian embryonic development. Similar experiments suggest that the AhR may be involved in development of various organ systems. Thus, molecular mechanistic studies of TCDD action have contributed significantly to an improved understanding of the role of at least 2 bHLH/PAS proteins, as well as organ- and tissue-specific biochemical and toxic responses to this class of environmental toxins.
Erythropoietin mRNA in Hepatocellular Carcinomas and Kidney in Male B6C3F1 Mice with Secondary Polycythemia
Authors: Horinouchi Akira , Miyamoto Saku , Sekiguchi Masahiro , Doi Hisako , Okazaki Shuzo , Ando Takao
Published: July 2017

The purpose of this study was to investigate the cause of polycythemia occurring in hepatocellular carcinoma-bearing control male B6C3F, mice from 2-yr carcinogenicity studies. Erythrocyte counts and plasma levels of erythropoietin in mice with hepatocellular carcinomas were significantly increased compared with the values in non-tumor-bearing mice. Erythropoietin mRNA in 4 of 5 non-tumor-bearing mice was detected in the kidney, but no visible signals for hepatic erythropoietin mRNA in 5 of 5 non-tumor-bearing mice were detected by the reverse transcriptase competitive polymerase chain reaction method. Erythropoietin mRNA was expressed in neoplastic hepatocytes from 8 of 9 hepatocellular carcinoma-bearing mice, and this expression was accompanied by decreased expression of erythropoietin mRNA in the kidneys from these mice. The present findings show that polycythemia in hepatocellular carcinoma-bearing mice occurs secondary to excess synthesis of erythropoietin mRNA by neoplastic hepatocytes.
Vestibulo‐oculomotor disturbances caused by industrial solvents
Authors: ÖDkvist Lars , Larsby Birgitta , Tham Richard , Hyden Dag
Published: July 2017

Animal experiments show that intoxication with hydrocarbon solvents influences the vestibulo‐oculomotor reflex arc and indicate that the solvents block the inhibition of the vestibulo‐oculomotor reflex presumably exerted by the cerebellum. The blood concentrations necessary to elicit oculomotor disturbances in animals were smaller than those that disturbed the vestibular function. Accordingly, in human experiments styrene and toluene exposure did not elicit any positional nystagmus but caused an increased saccade speed and a diminished visual suppression of vestibular nystagmus. Some cerebellar clinical pathologic process in patients who suffer from a psycho‐organic syndrome caused by solvents leads us to believe that the cerebellum might be the most vulnerable part of the brain. Some patients had a positional nystagmus, but the most prominent pathologic signs were elicited by the visual suppression test. Our findings compare well with the increased saccade speed and diminished visual suppression in patients with cerebellar tumors and infarctions.
Comparative study of the sensitivity of head and neck cell lines to methotrexate (MTX) and the analog 10‐ethyl, 10‐deazaaminopterin (10‐EdAM)
Authors: Brown D. H. , Braakhuis B. J. M. , Van Dongen G. A. M. S. , Snow G. B.
Published: July 2017

Squamous cell lines cultured in vitro provide a potential test system for the selection of analogs that have an improved therapeutic index. The growth inhibitory effects of methotrexate and the new folate analog 10‐ethyl, 10‐deazaaminopterin were compared in three in vitro‐cultured human head and neck squamous cell carcinoma cell lines. The inhibitory concentrations of the new analog were 10‐ to 100‐fold lower than the inhibitory concentrations of methotrexate. The sensitivity of these three head and neck squamous cell carcinoma cell lines to both drugs was essentially the same as the sensitivity of a rhabdomyosarcoma cell line known to be very sensitive to methotrexate when the cell line is grown as a xenograft in athymic nude mice. These data indicate that 10‐ethyl, 10‐deazaaminopterin may be a new and effective agent against head and neck squamous cell carcinoma.
Abductor vocal cord spasm
Authors: Aviv Jonathan E. , Sanders Ira , Biller Hugh F.
Published: July 2017

The purpose of this study is twofold. First, to introduce a new phenomenon—abductor vocal cord spasm, or abductor laryngospasm. Second, to reconcile a longstanding discrepancy involving the effect of lung inflation on vocal cord position. Abductor laryngospasm was induced in six anesthetized, tracheotomized dogs by the administration of continuous positive airway pressure (CPAP) after occlusion of the trachea for 60 seconds. Abductor laryngospasm was characterized by sustained vocal cord abduction with concomitant massive, continuous posterior cricoarytenoid muscle (PCA) electromyography (EMG) activity and little or no laryngeal adductor muscle EMG activity. Vocal cord opening was sustained for up to 90 seconds. In the same dogs, administration of CPAP, after hyperventilation of the animal, resulted in adductor laryngospasm. Adductor laryngospasm was characterized by steady apposition of the vocal cords, massive laryngeal adductor muscle EMG activity, and silent PCA EMG activity. Abductor laryngospasm appears to be the physiologic converse of adductor laryngospasm. The results of this study show that lung inflation can produce either vocal cord abduction or adduction, depending on whether the dog is hypoventilated or hyperventilated before administration of CPAP.
Soft tissue effects of the holmium‐YSGG laser in the canine trachea
Authors: Shapshay Stanley M. , Aretz H. Thomas , Setzer Suzanne E.
Published: July 2017

A holmium‐yttrium scandium gallium garnet laser is a pulsed midinfrared crystalline laser (wavelength 2.1 μm). which is easily transmissable through flexible quartz fibers. With use of a 300‐μm fiber delivery system, this laser was applied in the canine trachea to create a standard 5‐mm diameter lesion through mucosa and submucosa. Power settings of 400 mJ and 600 mJ per pulse at 2 pulses per second were used, and wound healing was studied over a 2‐week period. Excellent control of depth of tissue ablation was noted, with uncomplicated wound repair. Although healing was somewhat slower compared with healing when the CO2 laser was used, less granulation and fewer inflammatory changes were noted. Further studies need to be performed to determine ideal laser dosimetry before this laser is applied clinically.
Intraoperative facial nerve monitoring Technical aspects
Authors: Beck Douglas L. , Benecke James E.
Published: July 2017

Intraoperative facial nerve monitoring (FNM) is widely used as a method of assessing the anatomic and physiologic integrity of the facial nerve during procedures in which the nerve may be in jeopardy. The doctors of the Otologic Medical Group use intraoperative FNM during all neurotologic procedures. This technique can also be used for congenital ear surgery and complicated revision chronic ear surgery. On the basis of experience gained from more than 200 cases in which FNM has been used, definitive conclusions can be made in regard to technical aspects. This article will discuss indications for intraoperative FNM, electrode design, visual and auditory feedback, and the particulars about stimulators.
Metastasierendes Lymphosarkom bei einer Riesenschlange, Eunectes murinus (Linnaeus, 1758)
Authors: Frank Werner , Schepky Arwid
Published: July 2017

This report of a tumor of the hematopoietic system in an anaconda snake, Eunectes murinus, is the first of such a growth in a reptile. The primary site was apparently in undifferentiated mesenchymal cells in the liver and secondarily deposits occurred in the thyroid, spleen, pancreas, and kidneys. The lymphoblast was the predominant cell type in all of these organs; hence the tumor is designated as a lymphosarcoma.
Polioencephalomalacia in a White-tailed Deer (Odocoileus virginianus borealis)
Authors: Kurtz Harold J. , Karns Patrick D.
Published: July 2017

In an adult white-tailed deer affected by polioencephalomalacia the lesions were acute ischemic-type necrosis, malacia, and hemorrhage in the cerebral cortex, vestibular nuclei, caudal colliculi, oculomotor nuclei, geniculate nuclei, thalamus, and ventral portion of the cerebellar vermis. The deer also had granulomas associated with Pneumostrongylus tenuis in the spinal leptomeninges.
Role of prolactin-opiate interactions in the central regulation of pain threshold
Authors: Nicoletti Ferdinando , Drago Filippo , Speciale Carmela , Kovacs L. Gabor , Scapagnini Umberto
Published: July 2017

Endogenous hyperprolactinaemia induced by anterior pituitary transplantation under the kidney capsule has been found to reduce the behavioural responsiveness to electrical footshock and to increase morphine-induced analgesia. The apparent analgesic effect of prolactin has been related to the stimulation of nigro-striatal dopaminergic transmission, as suggested by the increase in striatal dopamine turnover observed in hyperprolactinaemic rats. It seems likely that central opiate system is involved in the behavioural effects of prolactin. Thus, naloxone prevents the effects of hyperprolactinaemia on footshock responsiveness and heroin self-administration is decreased in hyperprolactinaemic rats.

Il a été remarqué que l'hyperprolactinémie causée per la greffe de l'hypophyse antérieure sous la capsule rénale réduit la réponse comportamentale au footshock électrique et augmente l'analgésie produite par la morphine. L'effet analgésique apparent de la prolactine a été mis en relation avec le stimulus de la transmission dopaminergique nigro-striée, comme il est suggéré par l'augmentation du turnover de la dopamine striée chez les rats hyperprolac-tinémiques. Il est probable que le système central opioide joue un rôle dans les effets comportamentaux de la prolactine. Le naloxone est donc à même de prévenir les effets de l'hyperprolactinémie sur la réponse au footshock et de réduire l'autoadministration de l'héroine chez les rats hyperprolactinémiques.

L'iperprolattinemia indotta da trapianto di ipofisi anteriore sotto la capsula renale è nota ridurre la risposta comportamentale al footshock elettrico e l'analgesia indotta da morfina. Questo apparente effetto analgesico della prolattina è stato messo in rapporto con la stimolazione della trasmissione dopaminergica nigro-striatale, come suggerito dall'incremento del turnover di dopamina striatale osservato in ratti iperprolattinemici. Sembra quindi verosimile che il sistema oppioide centrale sia coinvolto negli effetti comportamentali della prolattina. Il naloxone peraltro è in grado di prevenire gli effetti della iperprolattinemia sulla risposta al footshock come di ridurre l'autosomministrazione di eroina nei ratti iperprolattinemici.
Pituitary secretions and wake–sleep cycle
Authors: Passouant P.
Published: July 2017

Neurohumoral correlations of sleep are considered from three aspects: 1. Metabolism and cerebral blood circulation (CBF, EEG, endocranial pressure, cerebral temperature); 2. Neuromediators and neuropeptides (5-HT, hypnogen neuropeptides); 3. The influence of the sleeping–waking cycle on adeno-hypophyseal secretion rhythms (GH, PRL, LH, TSH). Variations of these parameters can play an important role in the onset of night crises of migraine and cluster headache.

Les liens neuro-humoraux du sommeil sont considérés selon trois points de vue: 1. Circulation cérébrale et métabolisme (CBF, EEG, pression endocrânienne, température cérébrale); 2. Neuromédiateurs et neuropeptides (5-HT, neuropeptides hypnogènes); 3. Influence du cycle sommeil-veille sur les rythmes de sécrétion adénohypophysaire (GH, PRL, LH, TSH). Des variations de ces paramètres peuvent jouer un rôle important dans le déclenchement des crises nocturnes de migraine et de céphalée à grappe.

Le correlazioni neuroumorali del sonno vengono considerate da 3 punti di vista: 1. Circolazione cerebrale e metabolismo (CBF, EEG, pressione endocranica, temperatura cerebrale); 2. Neuromediatori e neuropeptidi (5-HT, neuropeptidi ipnogeni); 3. Influenza del ciclo sonno-veglia sui ritmi di secrezione adenoipofisaria (GH, PRL, LH, TSH). Variazioni di questi parametri possono svolgere un ruolo importante nello scatenamento delle crisi notturne di emicrania e di cefalea a grappolo.
Lithium salts in cluster headache treatment
Authors: Savoldi Faustino , Bono Giorgio , Manzoni Gian Camillo , Micieli Giuseppi , Lanfranchi Marina , Nappi Giuseppe
Published: July 2017

The short and long-term effects of Lithium carbonate in 90 patients with episodic (68 cases) and chronic (22 cases) cluster headache are reported. The results are discussed in particular in relation to the response of the episodic forms, the development of tolerance, the ability of the substance to modify the natural history of the disease, and the side-effects from long-term treatment.

On a évalué l'efficacité thérapeutique de l'administration, à court et à long terme, de lithium carbonate dans 90 patients atteints de formes épisodiques (68 cas) ou chroniques (22 cas) de céphalée en grappe. On discute les résultats en considérant en particulier la réponse des formes épisodiques, le développement des phénomènes de tolérance, la capacité du traitement d'interférer avec l'histoire naturelle de la maladie, l'apparition d'effects collatéraux dans les traitements prolongés.

E’ stata valutata l'efficacia terapeutica della somministrazione, a breve e lungo termine, di litio carbonato in 90 pazienti affetti da forme episodiche (68 casi) o croniche (22 casi) di cefalea a grappolo. I risultati sono discussi con particolare riguardo alla risposta delle forme episodiche, allo sviluppo di fenomeni di tolleranza, alla capacità del trattamento di interferire con la storia naturale della malattia, alla comparsa di effetti collaterali in trattamenti prolungati.
Clinical pharmacological aspects of dihydroergotamine timed release: activity on monoamine venospasm
Authors: Franchi Giancarlo , Anselmi Bruno , Bianco Pier Luigi Del , Panconesi Alessandro , Sicuteri Federigo
Published: July 2017

Using the computerized venotest, it is possible to evaluate both the venospastic activity of the vasoactive monoamines (NA,5-HT, DA) and the effects of the relative agonistic and antagonistic drugs. The ergot-derivatives are 5-HT and NA agonists at low doses, and are 5-HT antagonists at high doses. Dihydroergotamine timed release (DHE-TR) administered orally is capable at 12 hours following the last administration of producing a significant increase of 5-HT and NA venospasm. It is hypothesized that 12 hours after the last administration of DHE-TR, hematic concentrations, corresponding to clinical and therapeutic levels, capable of potentiating the monoamine venospasm still exists.

Il est possible évaluer, par le venotest computerisé, soit l'activité venospastique des moamines vasoactives (NA, 5-HT, DA) que l'effect des relatifs médicaments agonistes et antagonistes. Les dérivés de l'ergot en doses moyennes sont agonistes de la 5-HT et de la NA, tandis qu'en doses élevés ils sont antagonistes de la 5-HT. L'administration de la dihydroergotamine à libération programmée (DHE-TR) par os, peut à 12 heures de distance de la dernière administration, prouver une augmentation du venospasme de 5-HT et de NA. On suppose qu'à 12 heures de distance de la dernière administration de DHE-TR, il y a dans le sang une présence de concentrations du médicament relative à celles cliniques-thérapeutiques, qui peut augmenter le venospasme des moamines.

Con il venotest computerizzato è possibile valutare sia l'attivita venospastica delle monoamine vasoattive (NA, 5-HT, DA) sia l'effetto dei relativi farmaci agonisti e antagonisti. Gli ergot-derivati a basse dosi sono agonisti della 5-HT e della NA, a dosi alte sono antagonisti della 5-HT. La dihydroergotamina a liberazione programmata (DHE-TR), somministrata per os, è capace, a 12 ore di distanza dall'ultima somministrazione, di produrre un significativo incremento del venospasmo da 5-HT e da NA. Si ipotizza perciò che a 12 ore di distanza dall'ultima somministrazione di DHE-TR siano ancora presenti nel sangue concentrazioni del farmaco, corrispondenti a quelle clinico-terapeutiche, capaci di potenziare il venospasmo delle monoamine.
Psychological peculiarities in children with recurrent primary headache
Authors: Guidetti Vincenzo , Ottaviano Salvatore , Pagliarini Marina , Paolella Anna , Seri Stefano
Published: July 2017

Thirty-five children with idiopathic headache (average age 10.2 years) were subjected to various examinations and a series of tests (WISC, Bender, Rorschach, Duss, “tree” and “family” tests) on the nature and characteristics of headache with a view to establishing possible psychological peculiarities. The sample was correlated with a random control group of 20 subjects (average age 10.4 years) undergoing all of the above tests except the Rorschach test. This showed a significant decrease in the “digit span” WISC subtest and in the Bender test with respect to normal population, and a drop in “digit span” and in picture completion subtests and in headache length in months. Feelings of being excluded from the family group, insecurity and repressed hostility towards the important figures, were significantly stronger in the headache patients group.

Un groupe expérimental de 35 enfants attient de céphalée idiopathic (a.m. 10.2 ans) a été soumis à des recherches sur la nature et les caractéristiques de la céphalée et à une série de tests (WISC, Bender, Rorschach, Duss, Arbre, Famille) pour mettre en évidence les éventuelles particularitées psychologiques. Le groupe expérimental a été comparé à un groupe de contrôle, casuel, formé de 20 sujets (a.m. 10.4 ans) qui ont été soumis, à la même série de tests excepté le test de Rorschach. Les résultats obtenus révèlent un décalage significatif dans le mémoire de seris de chiffres et dans le test de Bender in par rapport à la population normale et encore plus une relation significative entre le décalage de la mémoire de series de chiffres et le completement d'images et encore la durée (mois) de la céphalée. La sensation d'être exclus du noyau familial, l'insicurité et l'obstilité réprimée enverse les figures significatives, sont résultées plus élevées, de façon significative dans le groupe de sujets atteint de céphalée.

Un campione di 35 bambini con cefalea essenziale (e.m. 10.2) é stato sottoposto a indagini sulla natura e le caratteristiche della cefalea e ad una batteria di test (WISC, Bender, Rorschach, Duss, Albero, Famiglia) onde evidenziare eventuali peculiarità psicologiche. Il campione é stato comparato ad un gruppo di controllo randomizzato composto di 20 soggetti (e.m. 10.4) cui é stata somministrata la stessa batteria di test ad eccezione del Rorschach. I risultati ottenuti evidenziano una caduta significativa nel sub-test di memoria cifre del WISC, e nel test della Bender in rapporto al controllo; nonché una significativa relazione fra caduta nei sub-test di memoria cifre e completamento figure e durata in mesi della cefalea. Sensazioni di essere esclusi dal nucleo familiare, di insicurezza e ostilità repressa verso le figure significative sono risultati significativamente più elevati nel gruppo dei cefalalgici.
Efficacy of β-Blockers in Migraine
Authors: Tfelt-Hansen Peer
Published: July 2017

Five double-blind trials of the prophylactic treatment of migraine with β-blockers were reviewed critically with regard to problem investigated, design, “blindness” of patient, side effects, statistical validity, and conclusions. The initial use of a “responder-finding” period may limit the validity of results from a subsequent double-blind crossover placebo-controlled study because it may impair “blindness”. A d-propranolol versus racemic propranolol versus placebo study was reanalysed with conventional statistical methods, which showed that d-propranolol had no significant effect. In a multicentre study including 96 patients calculation of 95% confidence limits demonstrated that timolol and propranolol are equally effective in common migraine prophylaxis. Metopropolol and propranolol were apparently equally effective in 34 patients, but the calculation of confidence limits showed that a larger study is needed to confirm this conclusion. A group comparison study with three doses of nadolol and placebo lacked statistical evaluation of the results, thereby making it impossible to draw a conclusion about the efficacy of nadolol. It is concluded that there are considerable methodological problems in published papers on β-blocker and migraine.
Beta-Adrenoceptor Blockade, Platelets, and Rheologic Factors
Authors: Winther K , Hedman C
Published: July 2017

Alterations in platelet function and other hemorheologic factors have been reported to occur in patients with migraine. The prophylactic treatment of migraine with beta blockers is at present well established, and non-selective as well as β1-selective beta blockers exert an effect. The aim of this presentation is to summarize how beta blockers, depending on their receptor selectivity, modulate platelet function and hemorheologic factors. We conclude that nonselective beta blockade increases factors, such as platelet aggregability, and decreases fibrinolytic activity compared with β1-selective blockade with metoprolol. These differences do not reflect on their migraine prophylactic effect and indicate that alterations in platelet function are not a primary cause of migraine: rather, they are epiphenomena.
The Classification of Calcium Antagonists by the WHO Expert Committee: Relevance in Neurology
Authors: Agnoli A
Published: July 2017

A new classification of calcium antagonists has been developed by a WHO expert committee. Substances acting primarily via the inhibition of calcium entry into the cell have been divided into four distinct classes. The pharmacological characteristics of these classes that may be relevant for the use in various neurological disorders are highlighted in this paper. Some main differences concern the effects on vascular smooth muscle cells and brain cells. The well-documented clinical applications in neurology are still limited to migraine prophylaxis and vertigo. The evidence concerning the usefulness in cerebral vasospasm secondary to subarachnoid haemorrhage was regarded as reasonable, whereas several neurological indications should still be regarded as being under examination. There is little doubt that calcium antagonists will gain importance in the treatment of several neurological diseases.
Flunarizine (Sibelium) in the Prophylaxis of Migraine. An Open, Long-Term, Multicenter Trial
Authors: Martínez-Lage J Manuel
Published: July 2017

Sixty-four Spanish neurological centers participated in a study designed to evaluate the efficacy and safety of flunarizine in migraine. One thousand four hundred and thirty-five outpatients (367 [25.6%] males and 1,068 [74.4%] females) fulfilling the criteria proposed by the International Headache Society for the diagnosis of migraine entered the study.

Patients were treated with 10 mg of single-dose flunarizine (Sibelium) alone at bedtime in open fashion for 6 months. At the end of this treatment period, flunarizine was withdrawn, but the follow-up of the patients continued for another 6 months. The evaluation criteria used were a rating scale (the GES) based on frequency, duration, intensity, and characteristics of the attacks as well as a checklist of possible side-effects. This clinical assessment was recorded in detail in the patients' rating notebooks at the start and at the end of the third, sixth, ninth, and twelfth month of the study.

A mean decrease of 66.9% in the GES was obtained at the end of the treatment period, which implies a good or excellent result in the prophylaxis of migraine attacks in 69.5% of the patients. This improvement was practically unchanged at the end of the follow-up period. Side-effects were moderate, the most frequent ones being drowsiness and weight gain. Their incidence decreased after the first months of treatment.
Validation of diagnostic criteria for migraine in the Zürich longitudinal cohort study
Authors: Merikangas Kathleen Ries , Whitaker Amy E , Angst Jules
Published: July 2017

This paper reports the results of a systematic assessment of the validity of the specific diagnostic criteria for migraine without aura, as defined by the International Headache Society (IHS), in a longitudinal epidemiologic sample of young adults who were selected from the general population of Zürich, Switzerland. Systematic modification of each of the IHS criteria for migraine without aura yielded one-year weighted prevalence rates ranging from 24% for the unmodified IHS criteria to 9% for the most restrictive definition of migraine. The major implications of the findings for the IHS criteria are: (a) they provide adequate coverage to classify the majority of subjects with headache in the general population; (b) there is little overlap between migraine and tension-type headache, suggesting that the criteria define moderately independent subgroups; (c) the criteria for migraine without aura appear to be too unrestrictive for application in the community, particularly among young adults at the peak period of incidence of migraine; (d) the criteria for “aura” need more precise operationalization; and (e) models of validation of the diagnostic criteria suggest that Criterion D of the IHS criteria for migraine without aura should be modified to require both gastrointestinal symptoms and photophobia and phonophobia.
Atypical facial pain–application of the IHS criteria in a clinical sample
Authors: Pfaffenrath Volker , Rath Michael , Pöllmann Walter , Keeser Wolfgang
Published: July 2017

Atypical facial pain is a residual category for otherwise unclassifiable pain syndromes in the facial region. In 35 patients (31F, 4M) with a mean age of 53.2 ± 14.9 years and a chronic facial pain syndrome we tested the new diagnostic criteria of the International Headache Society (IHS). There was a marked female preponderance, vague description of symptoms and a long history of incorrect diagnoses. A high number of invasive procedures (3.5 ± 3.0 (1–13)) were performed in this group. In agreement with the IHS criteria, an operaiion or injury to the face was a suspected cause in 43%. In contrast to the IHS criteria, our patient sample had dysaesthesiae (63%), bilateral occurrence (37%), remission periods (57%), pain attacks (23%) and superficial as well as deep pain. The IHS classification is insufficient to separate atypical facial pain from other primary headache and facial pain syndromes. We suggest a modified version of the IHS criteria for atypical facial pain.
Pre-clinical pharmacology of zolmitriptan (Zomig™; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine
Authors: Martin Gr
Published: July 2017

Zolmitriptan (Zomig™ formerly 311C90) is a novel 5-hydroxytryptamine (5HT)1B/1D receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura. The drug differs from presently available members of this drug class in that it combines 5HT1B/1D receptor partial agonist activity with robust oral pharmacokinetics and an ability to inhibit trigeminovascular activation centrally as well as peripherally in preclinical studies. Consistent with its selectivity for 5HT1B/1D receptors, zolmitriptan produces constriction of various isolated blood vessels, most notably cranial arteries. In anaesthetized animals, these vascular effects manifest as a selective constriction of cranial arterio-venous anastomoses resulting in a redistribution of carotid arterial blood flow. This effect is produced without significant effects on heart rate, blood pressure or blood flow to the brain, heart or lungs. Zolmitriptan also inhibits trigeminal-evoked increases in cerebral blood flow in anaesthetized cats and blocks trigeminal-evoked plasma protein extravasation in the dura of guinea-pigs. These actions are consistent with a pre-junctional inhibition of neuropeptide release from perivascular afferents of the trigeminal nerve, as confirmed by independent studies showing that zolmitriptan blocks elevations of calcitonin-gene-related peptide in jugular venous blood during electrical stimulation of the trigeminal ganglion. In all of these effects, zolmitriptan is three to four times more potent than sumatriptan, but produces the same maximum response. Zolmitriptan crosses the intact blood-brain barrier to inhibit trigeminovascular activation in the brainstem. This was shown initially by the ability of the drug to block a brainstem reflex provoking vasoactive intestinal peptide release from the VIIth cranial (facial) nerve during trigeminal stimulation. Subsequent ex vivo autoradiography confirmed that intravenously injected [3H]zolmitriptan labels a discrete population of cells in the trigeminal nucleus caudalis (TNC) and nucleus tractus solitarius. Direct evidence for a central neuromodulatory effect of zolmitriptan was provided by electrophysiological experiments which clearly demonstrated that the drug inhibits the excitability of cells in the TNC after systemic administration. This novel preclinical profile not only distinguishes zolmitriptan from sumatriptan, but raises intriguing questions about the clinical relevance of a dual action. Studies to date show that zolmitriptan indeed modulates cranial sensory processing in humans, yet central side-effects are no different from sumatriptan. This property may account for the remarkable consistency in clinical efficacy observed in clinical trials.
Adverse Reactions to St John's Wort
Authors: Parker Vivien , Wong Al bert HC , Boon Heather S , Seeman Mary V
Published: July 2017

Objective:

To re port 2 cases of ad verse re ac tions to St John's wort, a pop u lar herbal treat ment for de pression.

Method:

We pres ent 2 case his to ries and re view the ex ist ing lit er a ture re gard ing St John's wort.

Results:

St John's wort may cause se ro to nin syn drome in sen si tive pa tients. In ad di tion, St John's wort may be as so ci ated with hair loss.

Conclusions:

For clin i cal rea sons, it is im por tant to rec og nize and re port ad verse re ac tions to herbal rem e dies and to doc u ment that these treat ments have side ef fects com men su rate with their po tent ac tion on brain neurochemistry.
Treatment Delays for Involuntary Psychiatric Patients Associated with Reviews of Treatment Capacity
Authors: Kelly Michelle , Dunbar San dra , Gray John E , O'Reilly Rich ard L
Published: July 2017

Objective:

To de ter mine the duration of de lays in treatment initiation when involuntary patients apply for a review of a finding of treatment in capacity and to estimate the cost of keeping patients hospitalized with out treatment in these circumstances.

Method:

Using a computerized da ta base and writ ten records, we identified all patients at 2 psychiatric hospitals in Ontario who applied for a re view of a finding of treatment in capacity during a 10-yearperiod. We recorded clinical and demographic variables, dates of stopping and starting medication, and dates of review board hearings and out comes. We also noted all cases in which a patient appealed a decision from the re view board to the court.

Results:

Two hundred and thirty-seven patients made 334 applications to the re view board. The board over turned the physician's finding of incapacity in only 5 (1.5%) applications; 15 appealed the re view board's finding to the courts. None of these appeals were successful. In the absence of an appeal to the courts, the average delay in initiating treatment was 25 days. For patients appealing to the court, the average de lay was 253 days. The cost of hospitalizing un treated patients while their capacity was under legal review was estimated at $3 867 000, of which $1 333 000 could have been saved if treatment had started immediately after the review board confirmed in capacity.

Conclusion:

We have identified extensive de lays in initiating psychiatric treatment for a number of patients. These de lays are associated with le gal re view of treatment capacity. There are seriousclinical risks and substantial costs as sociated with de lay in treating patients with acute psychiatric illness. Where juris dictions review treatment capacity, we recommend that treatment not be impeded once a re view board has con firmed a clinical finding of in capacity.
Forty Years of Deinstitutionalization of Psychiatric Services in Canada: An Empirical Assessment
Authors: Sealy Patricia , Whitehead Paul C
Published: July 2017

Objective:

To empirically analyze the implementation of the policy of deinstitutionalization of psychiatric services over a 40-year period.

Method:

We assessed the policy of deinstitutionalization in terms of the following components: 1) population-based psychiatric beds, days of care in psychiatric hospitals (PHs); 2) days of care in psychiatric units in general hospitals (GHs); and 3) per capita expenditures on psychiatric services.

Results:

There was a rapid closure of beds in PHs in the 1970s and 1980s, but this was associated with an increasing rate of days of care in psychiatric units in GHs (that is, transinstitutionalization). It was not until the 1990s that the overall days of inpatient care began to decrease. Per capita expenditures on community-based psychiatric services increased throughout this period.

Conclusions:

Standardized rates reveal tremendous variation among the provinces in the timing and intensity of deinstitutionalization.
Acute Day Hospitalization as an Alternative to Inpatient Treatment
Authors: Russell Vincent , Mai François , Busby Keith , Attwood David , Davis Marie , Brown Monica
Published: July 2017

Objective:

This paper describes the administrative process by which the Ottawa General Hospital (OGH) closed 6 beds and used the staff and space resources thus released to set up an acute day hospital (ADH) for the treatment of 8 acutely ill psychiatric patients. Outcome data are presented on the first 160 patients admitted to the ADH.

Methods:

Demographic and clinical information including diagnostic (DSM-III-R; Global Assessment of Functioning [GAF]) and questionnaire data (Symptom Checklist-90 Revised [SCL-90R]; Beck Depression Inventory [BDI]; State-Trait Anxiety Inventory [STAI]; patient satisfaction) were obtained from 160 ADH patients at admission and discharge. Forty-two of these patients provided follow-up data 3 to 6 months postdischarge. The outcome of ADH patients was compared with that of a retrospectively obtained random sample (n = 100) of inpatients on selected diagnostic and demographic variables.

Results:

On clinician-rated and self-report clinical scales, ADH patients showed significant clinical improvement reflected in higher GAF scores and less psychological distress, depression, and anxiety at discharge relative to admission. There were no significant group differences in outcome indices except for shorter length of stay in the ADH group compared with inpatients. The ADH group rated the program highly in help received and quality of service. Short-term follow-up showed that gains made during treatment were maintained 3 to 6 months later.

Conclusions:

These results show that a time-limited day hospital program is clinically effective for acutely ill psychiatric patients and leads to a more efficient use of inpatient resources. We believe that partial hospitalization for the treatment of acute psychiatric disorders may have wide application in psychiatric hospital practice.
Psychogeriatric Consultation Services: Effect and Effectiveness
Authors: Teitelbaum Louise , Cotton Dorothy , Ginsburg M Lynne , Nashed Yousery H
Published: July 2017

Objectives:

To determine the nature of referrals to a psychogeriatric consultation/outreach service, the types of interventions provided, and the effects and effectiveness of the service.

Method:

The study used a prospective approach in which 67 consecutive patients referred for psychogeriatric assessment were followed up 6 to 8 weeks after the initial assessment and then again 6 months after initial contact. Patients were rated at the time of referral and at follow-up on presence of psychiatric diagnosis, need for institutional care, and placement outcome.

Results:

Of the 67 patients initially seen, 51 (76%) experienced memory problems and 46 (69%) had depressed mood. Consistent with this finding, 36 (54%) were diagnosed by consultants as having a dementia, and 15 (22%) received a diagnosis of depression. The most frequent recommendations included medication changes in 34 cases (50%) and further assessments in 37 cases (55%). Although information at 6-week follow-up was available for only 58% (n = 38) of the sample, 18 (46%) patients were generally improved. Interestingly, only 12 (31%) of referring physicians indicated that they had followed the advice of the consultants. Cognitive impairment and depressive symptoms were major concerns among referring physicians. The most common recommendation made involved pharmacotherapy. While compliance of family doctors to recommendations made was poor, patients improved over time. Patients requiring inpatient assessment were very old, living alone, experiencing behavioural problems, and not depressed.

Conclusions:

Psychogeriatric consultations appear most useful in cases where patients are more severely affected and/or are suffering from a greater range of symptoms.
A Young Man with First-Episode Psychosis: Case Presentation and Discussion
Authors: Fallu Angelo , Kopala Lili , Malla Ashok , Thorpe Lilian
Published: July 2017

Objective:

To review and discuss the issues and challenges involved in the treatment of first-episode psychosis in young patients, including choice of appropriate antipsychotic agents and adjunctive medications, dosing regimens, and biopsychosocial interventions.

Methods:

The case of a young man in his late teens with a history of substance abuse who experienced an acute dystonic reaction to treatment for his first psychotic episode is presented and discussed.

Results:

Each contributing author provides an evaluation of the intervention strategies presented in the patient's history and factors that influenced the treatment outcomes.

Conclusions:

The successful management of young patients with psychosis must go beyond the control of positive symptoms. A comprehensive psychosocial and psychoeducational approach combined with a well-tolerated treatment regimen can help the patient achieve positive outcomes.
Correction of Implant Malposition with Capsulorrhaphy: A Retrospective Review and Implementation of Patient Survey
Authors: Haiavy Jacob , Frenzel Clayton A.
Published: July 2017

Introduction:

Aesthetic breast surgery is rapidly evolving and is now the most commonly performed cosmetic surgery; more than 311 000 breast augmentations were performed in 2009. Over the years, the average implant size has increased. It is to be expected that with the increasing number of breast augmentation procedures performed, the rate of implant malposition has increased as well. This problem can be addressed in a systematic way to restore symmetry to the breasts through a surgical procedure consisting of a capsulorrhaphy.

Materials and Methods:

A retrospective chart review was done from August 2004 through May 2009. All patients who had undergone revisional breast surgery involving capsulorrhaphy were included in the study. Patients were asked to complete a 2-page survey. Intraoperatively, correction of implant malposition involved medial, lateral, and/or inferior capsulorrhaphy. The technique of capsule modification will be described in detail.

Results:

During the period from August 2004 through May 2009, 30 patients underwent capsulorrhaphy breast surgery for implant malposition. A 2-page survey was completed by 22 of the 30 patients (73%). Average implant size for patients needing capsulorrhaphy surgery was 502.5 mL and 60% were silicone implants. The time from original breast augmentation to revisional surgery was 53.2 months (36.4 months, excluding 2 patient outliers who were >20 years out from their original breast augmentation). The most common problem was inferior or inferolateral implant malposition, which occurred 79% of the time. Bilateral malposition occurred 21% of the time. In all, 91% of patients needed narcotic pain medicine for less than a week, and 59% discontinued narcotic pain medication within 3 days. Patients were taped on average 3.14 weeks. A total of 82% of patients said they had improvement or marked improvement with their current results, and 36% stated that they currently were very symmetric. Follow-up ranged from 3 months to 62 months; mean time from capsulorrhaphy surgery to completion of the patient survey was 22.2 months. In all, 82% of patients stated that if given a choice, they would undergo revisional surgery again. Finally, when asked about overall satisfaction with their experience and results, 86% of patients stated that they were satisfied, 45% were very satisfied, and 14% of patients were unsatisfied.

Conclusions:

Information collected by the patient survey following our surgical technique shows that the problem of implant malposition following breast augmentation can be addressed and treated by capsulorrhaphy surgery with good aesthetic outcomes and high patient satisfaction. In addition, a recovery with little postoperative discomfort and a decreased need for narcotic pain medicine can be expected. Little information has been published on implant malposition after breast augmentation. More research needs to be dedicated to this common problem.
Immediate Single-Stage Reconstruction of the Breast Utilizing FlexHD and Implant following Skin-Sparing Mastectomy
Authors: Rosenberg Michael , Palaia David , Cahan Anthony , DeChiara Sharon , Arthur Karen , Petro Jane , DeLuca-Pytell Danielle , Spanknebel Kathryn , Magana Rafael , Bonanno Philip
Published: July 2017

Introduction:

Primary reconstruction of the breast is the standard of care for patients undergoing a mastectomy for breast cancer. Surgical techniques involving immediate implant reconstruction following skin-sparing mastectomy can offer improved patient self-image and enhanced aesthetic outcomes compared with other techniques. The use of an acellular dermal matrix (ADM) as a supporting material has been shown to further improve cosmetic results. Here, we describe a technique that allows for primary reconstruction of the breast mound with implant after a skin-sparing mastectomy in a single procedure using a new form of ADM known as FlexHD.

Materials and Methods:

A total of 50 patients (85 breast reconstructions) over a period of 20 months underwent immediate reconstruction with this method using a silicone gel mammary implant. The surgical approach and complications for each patient were documented. In some patients, biopsies were obtained 2 and 6 months after initial placement of FlexHD (at the time of expander replacement) for pathologic and histologic evaluations.

Results:

All reconstructions were completed in a single-stage procedure. The technique resulted in positive aesthetic outcomes and patient satisfaction with few complications and low postoperative pain. Infections were more frequently observed following bilateral mastectomy and in patients who had previous radiation therapy or were smokers. Fibroblast migration and neovascularization of the ADM were observed at 2 months with full incorporation into native tissue at 6 months.

Conclusions:

Our experience suggests that single-stage breast reconstruction with FlexHD is a preferred approach to the primary reconstruction of the breast after mastectomy.