Fingolimod first-dose effects in patients with relapsing multiple sclerosis concomitantly receiving selective serotonin-reuptake inhibitors.

Selective serotonin-reuptake inhibitors (SSRIs), commonly administered for depression and anxiety in patients with multiple sclerosis, are associated with QT interval prolongation. Fingolimod (FTY720; Gilenya(®), Novartis Pharma AG) is a first-in-class sphingosine 1-phosphate receptor modulator approved for relapsing forms of multiple sclerosis. Fingolimod first-dose administration is associated with a transient, generally asymptomatic, slowing of heart rate, which may also prolong QT interval. This posthoc analysis compared cardiac outcomes in over 3300 patients with relapsing multiple sclerosis who were or were not receiving SSRIs during fingolimod treatment initiation, including a subset of patients receiving citalopram or escitalopram. Vital signs were recorded hourly for 6h, and electrocardiograms were obtained pre-dose and 6 h post-dose. Changes in mean hourly heart rate from baseline (pre-dose) to 6 h post-dose were similar among patients not receiving SSRIs (fingolimod 0.5 mg, -7.5 bpm; placebo, 0.0 bpm) and those receiving SSRIs (fingolimod 0.5 mg, -6.6 bpm; placebo, 0.3 bpm). In patients treated with fingolimod 0.5 mg, the mean change in corrected QT interval from baseline to 6 h after treatment initiation was under 10 ms, and few patients had absolute corrected QT intervals of over 450 ms (men) or 470 ms (women), calculated according to Bazett׳s or Fridericia׳s correction methods, irrespective of whether or not they were receiving an SSRI; similar findings were reported in the placebo group. Co-administration of SSRIs and fingolimod was not associated with an increased incidence of any electrocardiogram findings compared with fingolimod therapy alone, and the majority of patients receiving fingolimod (83-86%) were discharged from first-dose monitoring at 6 h irrespective of whether they were also receiving SSRIs. These analyses provide reassurance that concomitant use of SSRIs does not affect cardiac outcomes associated with fingolimod treatment initiation.

Neurofibromatose (Doença de Von Recklinghausen) relato de caso / Neurofibromatosis (Von Recklinghausen Illness) case report

A neurofibromatose I é a forma clássica da doença, descrita em 1882, por von Recklinghausen, transmitida por herança autossômica dominante. Caracteriza-se pela presença de manchas café-com-leite, nódulos fibromatosos (neurofibromas), nódulos de Lisch na íris e efélides axilares. S.T.N.C, 30 anos, feminina, procurou o serviço de Cirurgia Plástica do Hospital de Clinicas com deformidade crânio-facial centrada em órbita direita, que evoluiu com aumento progressivo da área comprometida associada a amaurose. Ao exame, observou-se importante deformidade hemicraniofacial direita, com lesão neurofibromatosa comprometendo as regiões da fossa temporal superficial, frontal, órbito-palpebral, jugal, labial e mandibular com aspecto de gota gigante multilobulada, tracionando e deformando todas as estruturas da face. Apresentava, ainda, macroqueilia, mordida aberta, ausência de ramo ascendente mandibular direito e paralisia facial direita. Diversas lesões nodulares café-com-leite disseminadas pela superfície cutânea foram encontradas. Os exames complementares realizados, radiografia de face e crânio, tomografia computadorizada e ressonância magnética crânio-facial, demonstraram continuidade da lesão com o tecido cerebral e grande número de fístulas artério-venosa volumosas, denotando associação com deformidade vascular grave. De acordo com estes resultados, foi decidido não submeter a paciente a tratamento cirúrgico, devido ao potencial risco de óbito, bem como a pouca melhora estético funcional a se conseguir com a operação.

In 1882, Von Recklinghausen described neurofibromatosis type I, an autossomal dominant inherited disease, with clinical features of “cafe-au-lait” spots neurofibromas, freckling in the axillary or inguinal regions, optic glioma, Lisch nodules in iris and distinctive osseous lesions. STNC, a 30 year old female, was attended by Plastic Surgery staff at the “Hospital de Clínicas da Universidade Federal do Paraná - Brazil with a craniofacial deformity centred at the right orbit, with progressive regional increase in size and with impaired of visual acuity. Physical findings: prominent hemicraniofacial deformity due to a neurofibroma involving superficial temporal fossa, frontal, orbital, la- bial, jugal and mandibular regions with the aspect of multilobuleted giant drop, tractioning and deforming all the structure of her face. Macrocheilia, mandibular teeth didn’t touch maxillary teeth, absence of ascendant mandibular ramus, right facial palsy and “cafe-au-lait” spots were documented. Image Findings: facial and cranial x-rays, CT and MRI showed that the lesion compromised in continuity with cerebral tissue and the presence of huge arteriovenous fistulas. Management: Due to high risk of death during and/or after the surgery, the patient received clinical and psychological treatment and orientation.

Breast cancer in older women: treatment, psychosocial effects, interventions, and outcomes.

It is estimated that 48% of women with breast cancer are age 65 and older; yet, scant research focuses on this cohort. Recent advances in breast cancer management have raised many questions regarding appropriate treatment of older patients with cancer. Despite recent emphasis on medical interventions for older women, there is little focus on the unique clinical presentation and psychological sequelae of breast cancer in this population. While elderly women who survive breast cancer seem to cope better than their younger counterparts, their distress must not be overlooked. Interventions such as use of social support, spirituality, and exercise demonstrate therapeutic benefits for older women with cancer and should be explored. Nurses play a key role in educating and supporting older women with breast cancer and can help dispel many age-related myths and misconceptions.

Visualization of the distribution of autophosphorylated calcium/calmodulin-dependent protein kinase II after tetanic stimulation in the CA1 area of the hippocampus.

Autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) at threonine-286 produces Ca2+-independent kinase activity and has been proposed to be involved in induction of long-term potentiation by tetanic stimulation in the hippocampus. We have used an immunocytochemical method to visualize and quantify the pattern of autophosphorylation of CaMKII in hippocampal slices after tetanization of the Schaffer collateral pathway. Thirty minutes after tetanic stimulation, autophosphorylated CaM kinase II (P-CaMKII) is significantly increased in area CA1 both in apical dendrites and in pyramidal cell somas. In apical dendrites, this increase is accompanied by an equally significant increase in staining for nonphosphorylated CaM kinase II. Thus, the increase in P-CaMKII appears to be secondary to an increase in the total amount of CaMKII. In neuronal somas, however, the increase in P-CaMKII is not accompanied by an increase in the total amount of CaMKII. We suggest that tetanic stimulation of the Schaffer collateral pathway may induce new synthesis of CaMKII molecules in the apical dendrites, which contain mRNA encoding its alpha-subunit. In neuronal somas, however, tetanic stimulation appears to result in long-lasting increases in P-CaMKII independent of an increase in the total amount of CaMKII. Our findings are consistent with a role for autophosphorylation of CaMKII in the induction and/or maintenance of long-term potentiation, but they indicate that the effects of tetanus on the kinase and its activity are not confined to synapses and may involve induction of new synthesis of kinase in dendrites as well as increases in the level of autophosphorylated kinase.

A role for endothelial NO synthase in LTP revealed by adenovirus-mediated inhibition and rescue.

Pharmacological studies support the idea that nitric oxide (NO) serves as a retrograde messenger during long-term potentiation (LTP) in area CA1 of the hippocampus. Mice with a defective form of the gene for neuronal NO synthase (nNOS), however, exhibit normal LTP. The myristoyl protein endothelial NOS (eNOS) is present in the dendrites of CA1 neurons. Recombinant adenovirus vectors containing either a truncated eNOS (a putative dominant negative) or an eNOS fused to a transmembrane protein were used to demonstrate that membrane-targeted eNOS is required for LTP. The membrane localization of eNOS may optimally position the enzyme both to respond to Ca2+ influx and to release NO into the extracellular space during LTP induction.

[Neuroleptic malignant syndrome in elderly hospital patients].

Neuroleptic malignant syndrome (NMS) has gained increasing attention over the past decade. Diagnostic features include exposure to major tranquilizers, acute onset of high fever, extrapyramidal symptoms and markedly elevated CPK. Other common signs include changes in mental status, tachycardia and leukocytosis. It usually runs its course within 10 days. Greater awareness and improved treatment have resulted in markedly decreased mortality. However, failure to diagnose and treat properly results in a significant risk of death. Most cases of NMS reported have been in those with psychiatric illness. Few cases have been reported in elderly patients without a psychiatric history. We describe an 85-year-old man, without previous psychiatric illness, who developed NMS while hospitalized on a general medical ward.

Missile attacks and nursing staff: impact of the Gulf War.

Missile attacks on Israel during the Gulf War created an expected atmosphere of fear and anxiety among hospital nursing staff. There seems to be little doubt that staff group sessions were helpful in alleviating these feelings. The group members openly expressed this sentiment, and it was also the clear impression of the group leaders. The groups were also helpful in dealing with the prevalent theme of conflicting loyalties of the nurses, ie, their profession versus their families. The desire for and benefit from group sessions decreased secondary to a shift in the perceived threat. As the external threat receded, stress became largely due to prolonged hours in close quarters with other staff. It is too early to be aware of any long-term consequences on nursing staff from the recent war situation. Assessments in this regard are intended in the future, most likely in the form of written evaluation and personal interviews.

Staffing and strategy for effective sales.

As the rate of new product development increases, healthcare administrators are looking to their sales departments for an edge against the competition. The author discusses how to attain top-notch performance through effective recruitment, training and evaluation of the sales staff.

The benefit of lithium carbonate adjunct in refractory depression--fact or fiction?

Our group attempted to validate previous claims of rapid success with lithium carbonate adjunct therapy in antidepressant-resistant depression. Seven depressed patients volunteered for a study of placebo controlled, double-blind design. During their treatment on general hospital psychiatric wards, these patients received antidepressant medication for a period of at least 21 days. While continuing to receive antidepressant medication after the 21 day period, four of the patients then received lithium carbonate, and three received placebo. This combination pharmacological therapy continued for a 48 hour period. After this time, six of the seven patients showed no significant improvement. The remaining patient, who had received lithium carbonate, improved markedly over the 48 hour period. However, this patient relapsed within one week. A review of the two most extensive studies claiming significant results with the lithium carbonate adjunct therapy was performed. We feel that they, as presented, leave serious doubt as to the validity of their conclusions. We conclude that on the basis of our work up to this point in time and the analysis of previous reports claiming otherwise, no valid evidence exists for a consistent therapeutic effect of lithium carbonate adjunct in antidepressant-resistant depression. It was also found that methodologic contamination necessitated the exclusion of an additional six patients from the double-blind trial. We conclude that in order to objectively examine the rapidly expanding field of biological psychiatry, teaching of clinical staff in basic research procedure should be stressed as a part of routine ward orientation.

Integrative shifts for the theory and practice of family systems therapy.

This paper describes several disagreements among approaches to family therapy and proposes two conceptual shifts providing a more integrative perspective. The first shift focuses on the implications of different ways therapists orient themselves to the developing structures of the therapy system and to the disabled structures of the client system. The second shift reconsiders theoretical approaches in terms of the types of distance they require of the therapist and the types of information these distances provide and ignore. Finally, the paper also discusses a means for classifying the different types of goals therapists establish for their clients, emphasizing that these goals must be consistent with the clients' views of themselves and the world.

Effects of clinical dosage levels of methylphenidate on two-flash thresholds and perceptual motor performance in hyperactive children.

Three groups (ns = 10) of children (normals, hyperactives, hyperactives on medication) were administered eight perceptual-motor tasks. The normal controls were significantly superior in performance in comparison with the hyperactives taken off methylphenidate on three tasks but only superior on one task (Digit Symbol) when compared to hyperactives on methylphenidate. The hyperactives on medication were also significantly superior to the hyperactives not on medication on the Digit Symbol task.

Atmospheric fungi in the desert town of Arad and in the coastal plain of Israel.

A two years' volumetric survey of the airborne fungi in the arid town of Arad revealed markedly lower spore concentrations than in the coastal region of the country. Low incidence prevailed throughout the year except for high peaks in October-November, closely related to the distribution of Cladosporium spores. Air-spora composition, annual frequency and seasonal variation of fungal genera and species at the two sites were compared.