Prescribing of psychotropics in the elderly: why is it so often inappropriate?

Psychotropic medications are an important treatment approach to mental health disorders; such disorders are common in the elderly population. Elderly patients are more likely to experience adverse effects from these agents than their younger counterparts due to age-related changes in pharmacodynamic and pharmacokinetic parameters. Because of these factors, inappropriate use of psychotropic medications in elderly patients has become a focus of concern. In general an agent is considered inappropriate if the risk associated with its use exceeds its benefit. Implicit and explicit criteria for inappropriate use of medications in the elderly have been created and include psychotropic agents. These criteria vary in their make-up but the explicit criteria tend to agree that amitriptyline, doxepin, and benzodiazepines that have long half-lives are not appropriate. Although explicit inappropriate medication criteria have been in existence since 1991, elderly patients continue to receive inappropriate psychotropic medications. A wide array of factors may be responsible for this practice. Provider-related causes include deficits in knowledge, confusion due to the lack of a consensus on the inappropriate psychotropic criteria, difficulties in addressing an inappropriate medication started by a previous provider, multiple prescribers and pharmacies involved in the care of a patient, negative perceptions regarding aging, and cost issues. Patients may contribute to the problem by demanding an inappropriate medication. Finally, the healthcare setting may inadvertently contribute to inappropriate prescribing by such policies as restrictive formularies or lack of reimbursement for pharmacists' clinical services. Successful approaches to optimising prescribing have been either educational or administrative. Educational approaches (e.g. one-on-one sessions, academic detailing) seek to influence decision making, while administrative approaches attempt to enforce policies to curtail the undesired practice. The US Omnibus Budget Reconciliation Act of 1987, which improved psychotropic medication use in long-term care, is an excellent example of administrative intervention. More research specifically focused on the causes of inappropriate psychotropic medication use and methods to avoid this practice is needed before targeted recommendations can be made.     

Syndrome of cerebrospinal fluid hypovolemia following lumbar puncture cerebrospinal fluid leak in a patient with idiopathic intracranial hypertension

An 11-year-old girl presented with headache of 3 months' duration. There was bilateral disc edema. The cerebrospinal fluid pressure was 50 cm of water with normal cerebrospinal fluid cytology and biochemistry. She developed severe headache (different and disabling), dizziness, vomiting, and backache on sitting up 6 hours after lumbar puncture, and lying supine relieved all of her symptoms. Intravenous fluids, analgesics, and complete bed rest did not relieve her symptoms over the next 72 hours. She was completely relieved of her symptoms on receiving two tablets of Caffergot containing 200 mg of caffeine and 2 mg of ergotamine 72 hours after lumbar puncture. The symptoms recurred 48 hours later, and a repeat dose of Caffergot was required. Magnetic resonance imaging (MRI) done 96 hours after lumbar puncture revealed the entire dura overlying the brain, including the posterior fossa, showing intense enhancement on contrast injection with leak at the lumbar puncture site. Oral caffeine (coffee, three times a day) was advised over 1 week. The patient remained asymptomatic, and a repeat MRI scan after 10 days showed complete clearing of the cerebrospinal fluid leak with no dural enhancement. The syndrome of cerebrospinal fluid hypovolemia following lumbar puncture is reported in a girl with idiopathic intracranial hypertension.     

Pediatric acute blastic natural killer cell leukemia

The goal of this report is to describe a rare case of pediatric blastic natural killer (NK) cell leukemia and to compare pediatric blastic NK cell leukemia/lymphoma to other reported cases of pediatric NK cell leukemia. The patient, a 9-year-old girl, presented with acute leukemia with a phenotype similar to adult blastic NK cell leukemia/lymphoma. The blasts were agranular and expressed CD7, 45, 56, and HLA-DR, but not CD3, 11c, 13, 33, or TdT. She had a complete response to ALL-directed chemotherapy, but had multiple relapses involving the cerebrospinal fluid, nasal sinus, lymph node and skin. In addition to the reported case, a review of the literature identified 9 previously reported cases of NK cell leukemia in patients 18 years of age or less. Cases were subdivided into blastic, acute/aggressive, and myeloid precursor NK cell leukemia based upon CD13/33 expression and morphologic characteristics. Compared to pediatric acute/aggressive NK cell leukemia, children with blastic NK cell leukemia showed greater variation in age and race. Prognosis was poor for all groups. Pediatric blastic NK cell leukemia is a distinct clinicopathologic entity which differs from other types of pediatric NK cell leukemia.     

Lindane stimulates neutrophils by selectively activating phospholipase C and phosphoinositide-kinase activity

The organochlorine insecticide lindane is a known activator of neutrophil responses. In this work we delineated the biochemical pathways by which lindane stimulates neutrophil oxidant production. Plasma membrane GTPase activity was not stimulated by lindane, ruling out a role for lindane-induced activation of G-proteins or G-protein coupled receptors, whereas inhibition of phospholipase C inhibited lindane-induced oxidant production. Together these data pointed to phospholipase C as the direct target of lindane activation. Type I phosphoinositide 3-kinase was not significantly activated by lindane and an inhibitor of phosphoinositide 3-kinases inhibited oxidant production by only 40%. Thus, Type I phosphoinositide 3-kinase played a minor role, if any, in lindane-induced oxidant production. Lindane stimulated an increase in phosphatidylinositol phosphate suggesting a Type II or III phosphotidylinositol 3-kinase or phosphatidylinositol 4-kinase activity was also stimulated.     

Multiple independent functions of arrestins in the regulation of protease-activated receptor-2 signaling and trafficking

The irreversible proteolytic nature of protease-activated receptor-2 (PAR2) activation suggests that mechanism(s) responsible for termination of receptor signaling are critical determinants of the magnitude and duration of PAR2-elicited cellular responses. Rapid desensitization of activated G-protein-coupled receptors (GPCRs) involves both phosphorylation and binding of arrestins. Arrestins also function as scaffolds and transducers of mitogen-activated protein (MAP) kinase signaling cascades. The PAR2 cytoplasmic tail (C-tail) contains multiple sites of phosphorylation and may be an important determinant for arrestin interaction. Desensitization and internalization of activated PAR2 were markedly impaired in arrestin-deficient cells compared with wild-type control cells. PAR2 C-tail truncation mutants displayed normal agonist-induced internalization, caused rapid distribution of betaarr2-GFP to the plasma membrane, and desensitized in an arrestin-dependent manner similar to that of wild-type PAR2. It is interesting that PAR2 C-tail mutants lost the capacity to stably associate with arrestins and consequently, redistributed to endocytic vesicles without betaarr2-GFP, whereas internalized wild-type PAR2 remained stably associated with betaarr2-GFP in endosomes. Moreover, activated PAR2 caused rapid and prolonged activation of endogenous extracellular signal-regulated kinase (ERK1/2). It was striking that in arrestin-deficient cells, activated PAR2 induced an initial peak in ERK1/2 activity that rapidly declined. The inability of internalized PAR2 C-tail mutants to stably associate with arrestins also resulted in loss of prolonged ERK2 activation. Thus, the PAR2 C-tail regulates the stability of arrestin interaction and kinetics of ERK1/2 activation but is not essential for desensitization or internalization. These findings further suggest that the diverse functions of arrestins in regulating PAR2 signaling and trafficking are controlled by multiple independent interactions involving both the intracellular loops and the C-tail.     

Preventive action of food seasoning spices mixture on fructose-induced lipid abnormalities

High fructose feeding in rats induces insulin resistance, hyperinsulinemia, hyperglycemia and dyslipidemia. The present study was undertaken to determine the hypolipidemic effect of food seasoning spices mixture on fructose-fed insulin resistant rats. Male Wistar rats received a daily diet containing either 60% fructose or 60% starch. They were administered with the spices mixture at three different doses (10 mg, 30 mg or 50 mg/day/rat) orally 15 days later. At the end of 45 days of the experimental period fructose-fed rats displayed elevated plasma glucose and insulin levels and dyslipidemia which included elevated levels of cholesterol, triglycerides, free fatty acids, reduced high density lipoprotein cholesterol and increased very low density lipoprotein cholesterol. Alterations in tissue lipid levels were also observed. Simultaneous treatment with spices mixture along with fructose diet resulted in the normalization of plasma glucose and insulin levels and restoration of lipid levels in plasma and tissues. The insulin potentiating action of the active principles in these spices may contribute to the hypolipidemic effect of spices mixture in high fructose-fed rats.     

Mammary presentation of adult-type "juvenile" xanthogranuloma

Juvenile xanthogranuloma (JXG) is a benign histiocytic disorder of infants and childhood. Approximately 15% of cases occur in adults. Adult JXG characteristically affect patients in their 20s and 30s; however, about 5% of patients are older than 60 years. Adult JXGs rarely regress spontaneously, and reports of concomitant extracutaneous lesions are rare. Herein, we report an exceptional case of adult xanthogranuloma in a 74-year-old woman who presented with ipsilateral breast masses and also found to have prior cutaneous lesions. This is the first reported case of cutaneous and extracutaneous adult JXG where the latter manifested in the breast as a spindle cell xanthogranuloma. Histologically, the lesion was composed predominantly of spindle cells with associated multinucleated giant cells and a chronic inflammatory cell infiltrate. Spindle cells were immunoreactive for various histiocytic markers and negative for cytokeratins, S-100, CD34, factor XIIIa, and CD1a. In the breast, the morphologic features of JXG evoked several entities in the differential diagnosis, including spindle cell metaplastic carcinoma, inflammatory pseudotumor, fibromatosis, myofibroblastoma, and phyllodes tumor. With the aid of immunohistochemical stains and appropriate clinical history, the correct diagnosis of extracutaneous adult JXG manifesting as a spindle cell xanthogranuloma can be made.