J Infect 2006 May 19; (Read article online)

Panasiti V, Devirgiliis V, Borroni RG, Spataro A, Melis L, Petrella MC, Pala S

Herpes simplex virus type 2 (HSV-2) infection was one of the first opportunistic infections identified among patients with AIDS. In the literature there are many data suggesting that the natural history of HSV-2 infection is altered in HIV-HSV-2 co-infected patients. Furthermore, a relationship between HIV seropositivity and HBV infection because of their analogous way of transmission is also described. We report the case of a 37-year-old patient who suffered from multiple painful ulcerative lesions of the perianal region. Laboratory examination showed positivity for HIV and HBV infections. In HIV-positive patients perianal HSV-2 can have atypical manifestations, especially if co-infection by Candida albicans occurs.

Bioorg Med Chem 2006 May 17; (Read article online)

Goodell JR, Madhok AA, Hiasa H, Ferguson DM

The discovery of new non-nucleoside antiviral compounds is of significant and growing interest for treating herpes virus infections due to the emergence of nucleoside-resistant strains. Using a whole cell virus-induced cytopathogenic assay, we tested a series of substituted triaryl heterocyclic compounds including acridones, xanthones, and acridines. The compounds which showed activity against Herpes Simplex-1 and/or Herpes Simplex-2 were further assayed for inhibition of topoisomerase activity to gain insight into the mechanism of action. The results indicate that the acridine analogs bearing substituted carboxamides and bulky 9-amino functionalities are able to inhibit herpes infections as well as inhibit topoisomerase II relaxation of supercoiled DNA. Given the mechanism of action of amsacrine (a closely related, well-studied 9-amino substituted acridine), the compounds were further tested in a DNA topoisomerase II cleavage assay to determine if the compounds function as poisons. The results show that the acridines synthesized in this study function through a different mechanism to that of amsacrine, most likely by blocking topoisomerase binding to DNA (akin to that of aclarubicin). This not only suggests a unique mechanism of action in treating herpes virus infections, but also may be of great interest in the development of anticancer agents that target topoisomerase II activity.

Pain Med 2006 May-Jun; 7(3): 243-9 (Read article online)

Weiner DK, Schmader KE

Objective. To describe a series of older adult patients with postherpetic myofascial pain, a heretofore rarely described complication of herpes zoster. Design. Case series. Setting. Outpatient older adult pain clinic. Patients. Five older adults are presented with myofascial pain that developed as a complication of herpes zoster. Results. Pain duration at the time of presentation ranged from 4 months to 7 years. All patients reported functional impairment from pain despite oral analgesics. Myofascial pathology was diagnosed by the presence of taut bands and trigger points in the affected myotome. Upon successful treatment of the myofascial pain with nonpharmacologic modalities (e.g., physical therapy, trigger point injections, dry needling, and/or percutaneous electrical nerve stimulation), all patients reported symptomatic improvement, and four out of five were able to significantly reduce or discontinue their opioids. Conclusion. Postherpetic pain is traditionally conceptualized as a purely sensory phenomenon. Identification of the intrusion of a myofascial component may be worthwhile, both from the standpoint of enhanced pain relief and reduction in the need for oral analgesics. Formal exploration of this phenomenon is needed.

Allerg Immunol (Paris) 2006 Feb; 38(2): 62-4 (Read article online)

Galadari I, Fowzan AW

Fifty patients with oral ulcers were studied clinically and investigated for the detections of Herpes Simplex Virus (HSV) through virus isolation from their lesions (vesicles and ulcers) and detection of the presence of antiviral antibodies (both, IgM and IgG) in their sera using the indirect immunofluorescene (IIF) technique. The results of this study proved that virus isolation is the most reliable method for diagnosis, though the use of antibody serological tests could be a useful adjunct to virus isolation in situations where a rapid laboratory diagnosis is needed. Oral Herpes Simplex virus infection can be viewed, in the main, as a trivial disorder causing patients minor physical discomfort. The prevalence of HSV may be high in innocent infections, as high as 1/3 of the population. However, HSV infection and its complications with troublesome recurrences may make the problem worse. The apparent increase in HSV infection over recent years may be partly due to increased publicity about the disease, the current antiviral treatment, the inclusion of both primary and recurrent cases in clinic follow up and the increased use of viral cultures for diagnosis. The aim of this work is to share in the study of the detection of HSV through virus isolation and detection of antiviral antibodies using IIF technique, as well as the evaluation of the diagnosis by the above mentioned methods.

Scand J Infect Dis 2006; 38(4): 281-9 (Read article online)

Burton CM, Kristensen P, Lützhøft R, Rasmussen M, Milman N, Carlsen J, Christiansen CB, Andersen CB, Iversen M

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality in lung transplant recipients. We investigated the incidence of CMV infection in relation to CMV prophylaxis, and recipient-donor CMV serotype, in a cohort of 250 consecutive lung transplant recipients. All patients received 3 months CMV prophylaxis with acyclovir (n = 67) or gancyclovir (n = 183). Recipient-donor CMV serotype matching was performed in patients receiving acyclovir: R+/D+(n = 38), R+/D-(n = 10), R-/D+(n = 1), R- /D-(n = 16), unknown (n = 2). Recipient-donor CMV serotype matching was not performed in patients receiving gancyclovir: R+/D+(n = 71), R+/D-(n = 42), R-/D+(n = 38), R-/D-(n = 31), unknown (n = 1). The overall incidence of CMV infection was 51% (n = 34) in the acyclovir group, and 42% (n = 77) in the gancyclovir group (p = 0.14). During the first 9 months after transplantation, the rate of CMV infection was higher in the acyclovir group (42%) compared with the gancyclovir group (30%) (p = 0.005). Multivariate analysis demonstrated the incidence of CMV infection during the first 9 months was higher for acyclovir prophylaxis (p<0.001) and R-/D+ serostatus (p<0.001) and lower with R-/D- serostatus (p = 0.02). In conclusion, gancyclovir significantly delays the onset of first CMV infection among lung transplant patients. CMV surveillance and choice of prophylaxis may be modified according to donor-recipient CMV serotype.

Clin Neurol Neurosurg 2006 May 17; (Read article online)

Ginanneschi F, Donati D, Moschettini D, Dominici F, Cermelli C, Rossi A

An active co-infection with CMV and HHV-7 has been never described in immunocompetent patients. The authors describe a case of encephaloradiculomyelitis in an immunocompetent man. Polymerase chain reaction (PCR) performed on cerebrospinal fluid (CSF) showed positivity for DNA of Cytomegalovirus (CMV) and Herpes-virus type 7 (HHV-7), whereas the same test applied on peripheral blood mononuclear cells gave negative result. These results are highly supportive of an infection of the central and peripheral nervous systems, caused by CMV and HHV7. Such viral co-infection has only been described in immune-depressed patients with CMV disease, in which HHV-7 was supposed to act as a cofactor, enhancing clinical manifestations. The same mechanism is presumably responsible for the development of encephaloradiculomyelitis clinical signs in the present case. This is the second case in which DNA of HHV-7 has been found in the CSF of an adult immunocompetent patient. This novel observation suggests that the search for viral DNA in the CSF should be performed also in immunocompetent patients.

Pharm Res 2006 May 25; (Read article online)

Crumb WJ, Ekins S, Sarazan RD, Wikel JH, Wrighton SA, Carlson C, Beasley CM

PURPOSE: To evaluate in vitro and computationally model the effects of selected antipsychotic drugs on several ionic currents that contribute to changes in the action potential in cardiac tissue. METHODS: Fourteen antipsychotic drugs or metabolites were examined to determine whether QT interval prolongation could be accounted for by an effect on one or more myocardial ion channels [I(to), I(Na), I(sus), I(K1), and human ether-a-go-go related gene (hERG)]. Using the patch clamp technique, drug effects on these human cardiac currents were tested. RESULTS: All molecules had little inhibitory effect on ion channels (blocking at concentrations >5 muM) other than hERG. A significant correlation was observed between the estimated hERG blockade and the increase in corrected QT for five of the antipsychotics. Molecular modeling identified hydrophobic features related to the interaction with hERG and correctly rank-ordered the test set molecules olanzapine and its metabolites. A network analysis of ligand and protein interactions around hERG using MetaCoretrade mark (GeneGo Inc., St. Joseph, MI, USA) was used to visualize antipsychotics with affinity for this channel and their interactions with other proteins in this database. CONCLUSION: The antipsychotics do not inhibit the ion channels I(to), I(Na), I(sus), I(K1) to any appreciable extent; however, blockade of hERG is a likely mechanism for the prolongation of the QT interval.

Eur Heart J 2006 May 22; (Read article online)

Levy PY, Fournier PE, Charrel R, Metras D, Habib G, Raoult D

AIMS: Aetiological investigations of pericardial effusion are often negative. We evaluate the interest of systematic analysis of fluid in order to diminish the number of pericarditis classified as idiopathic. METHODS AND RESULTS: We performed a systematic analysis of pericardial fluid and biopsy specimens, using cultures and molecular analyses for the identification of bacteriological, fungal, and viral agents, as well as histopathological examination of 106 pericardial fluid samples. The aetiological diagnosis was determined clinically and by non-invasive procedures in 40 and nine patients, respectively. In the remaining 57 patients, 14 neoplasias and 17 infections were diagnosed. Molecular procedures identified seven viral (Enterovirus, Herpes simplex virus, and Epstein-Barr virus in four, two, and one of the cases, respectively), one fungal (Cryptococcus neoformans), and nine bacterial infections. Four of these bacteria were not diagnosed by culture because of prior antibiotics treatment (Mycobacterium tuberculosis in two cases, Streptococcus pneumoniae in one case, and Actinomyces neuii in one case). The aetiology remained undetermined in 26 patients. CONCLUSION: The systematic use of molecular techniques permitted a significant increase in aetiological diagnoses of punctured pericardial effusions when compared with cultures (39.5 vs. 13.9%, respectively; P<0.01). It is particularly beneficial for patients with a previous antibiotic regimen or suspicion of tuberculosis.

Sleep Med 2006 May 17; (Read article online)

De Silva DA, Ling LL, Yeong NB, Puvanendran K

We present a case of episodic stupor associated with a myriad of neuropyschiatric manifestations that baffled doctors until they were recognized as sleep attacks. Continuous monitoring and recognition of a cyclical pattern of symptoms and signs helped to uncover the underlying cause of a rapidly cycling bipolar disorder. The symptoms abated quickly and persistently when treated by olanzapine and lithium.

Mol Cell Biochem 2006 May 23; (Read article online)

Raeder MB, Fernø J, Vik-Mo AO, Steen VM

Drug-induced weight gain is a major problem in the treatment of psychiatric disorders, especially with some antipsychotic- and antidepressant drugs. We have recently demonstrated that antipsychotic- and antidepressant drugs activate the SREBP (sterol regulatory element-binding proteins) transcription factors in human- and rat glial cells, with subsequent up-regulation of downstream genes involved in cholesterol- and fatty acid biosynthesis. Since stimulation of cellular lipogenesis in the liver could be of relevance for the metabolic side effects of these drugs, we have now investigated the effects of antidepressants, antipsychotic- and mood-stabilizing drugs on cell cultures of human liver cells. For several of the drugs being strongly associated with weight gain (clozapine, imipramine, and amitriptyline), we observed a very pronounced activation of SREBP. Ziprasidone and buproprion, however, which are not associated with weight gain, did hardly stimulate the SREBP system. For haloperidol, olanzapine and mirtazapine, the correspondence between metabolic side effects and SREBP stimulation in liver cells was less obvious. The mood-stabilizers did not increase SREBP activation. The results indicate a relationship between drug-induced activation of SREBP in cultured human liver cells and weight gain side-effects of antidepressant and antipsychotic drugs.

Behav Brain Res 2006 May 19; (Read article online)

Huang XF, Han M, Huang X, Zavitsanou K, Deng C

This study examined regional changes in rat brain mRNA levels encoding 5-HT(2A) and 5-HT(2C) receptors following chronic olanzapine treatment. The immediate effect (2h after the last treatment) was a down-regulation of 5-HT(2A) receptor mRNA expression, predominantly in the hypothalamus, limbic system and striatum, while a rebound effect was observed 48h later. 5-HT(2C) receptor mRNA expressions were decreased in the substantia nigra. Correlations between 5-HT(2A) receptor mRNA expression and total food intake, weight gain and energy efficiency were observed.

Eur J Drug Metab Pharmacokinet 2006 Jan-Mar; 31(1): 17-20 (Read article online)

Yang Q, Hu Q

The pharmacokinetics and bioavailability of acyclovir sustained-release tablets in dogs were investigated. Blood concentrations of acyclovir were determined by RP-HPLC after a single oral dose of two kinds of acyclovir tablets given separately to 6 beagle dogs. The main pharmacokinetics parameters of the acyclovir sustained-release tablet were as follows: T1/2, Tmax and Cmax were 4.10 +/- 0.20 h, 4.05 +/- 0.54 h and 6.90 +/- 0.68 [microg x ml(-1), respectively. MRT was 9.02 +/- 0.44 h. Using acyclovir standard tablet as control, relative bioavailability of the acyclovir sustained-release tablet was 152.2 +/- 49.90%. According to the two-tailed t-test, there was a distinct difference in the data for Tmax, Cmax and AUC between acyclovir sustained-release tablets and acyclovir standard tablets, and the absorbability of acyclovir sustained-release tablets was much better than that of the acyclovir standard tablets.

Atherosclerosis 2006 May 16; (Read article online)

Marchesi S, Lupattelli G, Sensini A, Lombardini R, Brozzetti M, Roscini AR, Siepi D, Mannarino E, Vaudo G

There is much evidence to suggest the existence of racial differences between blacks and whites in the behaviour of endothelial function. Infective state, sustained by viral or bacterial agents, may injure the endothelial surface favouring the onset and progression of atherosclerotic process, mainly by an inflammatory mechanism. The aim of the study was to investigate endothelial function, expressed as brachial flow-mediated vasodilation (FMV), in black and white healthy subjects, along with antibody titer to cytomegalovirus, hepatitis virus (B, C), herpes virus-1 and 2, Epstein-Barr, Chlamydia pneumoniae and the expression of adhesion molecules. We enrolled 22 young (mean age 27+/-8 years) healthy subjects of black race (10 males) and 20 healthy young subjects (10 males, mean age 28+/-9 years) of white race. Total infectious burden (TIB) was defined as the number of serological positive infections. Black subjects have a reduced brachial FMV (6.9+/-3.5% versus 11.6+/-3.0%, p<0.01) and increased values of hsCRP (0.35+/-0.15mg/dL versus 0.07+/-0.08mg/dL, p<0.05), white cells (8578+/-1041/mmc versus 5833+/-998/mmc, p<0.01) and adhesion molecules (respectively: sVCAM-1 945+/-142 versus 779+/-93, sICAM-1 534+/-107ng/mL versus 325+/-80ng/mL; both p<0.01) in comparison to white subjects. The total infectious burden in black race was significantly higher than in white race (5+/-1 versus 2+/-1, p<0.01). At the univariate analysis, brachial FMV was significantly related to the levels of adhesion molecules (respectively: sVCAM-1 r=-0.49; sICAM-1 r=-0.50, both p<0.05), hsCRP (r=-0.47, p<0.05) and white blood cells (r=-0.43, p<0.05). TIB was associated with brachial FMV (r=-0.64, p<0.05), sVCAM-1 (r=0.55, p<0.05) and hsCRP (r=0.47, p<0.05). At the multivariate analysis the only predictive variables for brachial FMV were hsCRP, TIB and brachial diameter (respectively: beta=-0.49, -0.19, -0.54, all p<0.05). This study confirms that endothelial reactivity is impaired in young African black patients; moreover its behavior is strictly related to the inflammatory state and to the total infectious burden.

Pharmacotherapy 2006 Jun; 26(6): 748-58 (Read article online)

Szarfman A, Tonning JM, Levine JG, Doraiswamy PM

Study Objective. To analyze the disproportionality of reporting of hyperprolactinemia, galactorrhea, and pituitary tumors with seven widely used antipsychotic drugs. Design. Retrospective pharmacovigilance study. Data Source. United States Food and Drug Administration's Adverse Event Reporting System (AERS) database. Intervention. We initially identified higher-than-expected postmarketing reports of pituitary tumors associated with risperidone, a potent dopamine D(2)-receptor antagonist antipsychotic, by analyzing reporting patterns of these tumors in the AERS database. To further examine this association, we analyzed disproportionate reporting patterns of pituitary tumor reports for seven antipsychotics with different affinities for blocking D(2) receptors: aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and haloperidol. Measurements and Main Results. To conduct both of these analyses, we used the Multi-item Gamma Poisson Shrinker (MGPS) data mining algorithm applied to the AERS database. The MGPS uses a Bayesian model to calculate adjusted observed:expected ratios of drug-adverse event associations (Empiric Bayes Geometric Mean [EBGM] values) in huge drug safety databases. The higher the adjusted reporting ratio, or EBGM value, the greater the strength of the association between a drug and an adverse event. Risperidone had the highest adjusted reporting ratios for hyperprolactinemia (EBGM 34.9, 90% confidence interval [CI] 32.8-37.1]), galactorrhea (EBGM 19.9, 90% CI 18.6-21.4), and pituitary tumor (EBGM 18.7, 90% CI 14.9-23.3) among the seven antipsychotics, and one of the highest scores for all drugs in the AERS database. Some tumors were associated with visual field defects, hemorrhage, convulsions, surgery, and severe (> 10-fold) prolactin elevations. The EBGM values for risperidone for these adverse events were higher in women, but high EBGM values for these events were also seen in men and children. Moreover, the rank order of the EBGM values for pituitary tumors corresponded to the affinities of these seven drugs for D(2) receptors. Conclusion. Treatment with potent D(2)-receptor antagonists, such as risperidone, may be associated with pituitary tumors. These findings are consistent with animal (mice) studies and raise the need for clinical awareness and longitudinal studies.

J Psychopharmacol 2006 May 19; (Read article online)

Costa AM, de Lima MS, Faria M, Rodrigues Filho S, De Oliveira IR, Mari JD

Second generation antipsychotics have less influence on prolactin levels than conventional antipsychotics (CA), which are commonly associated with sexual dysfunction and hyperprolactinaemia. However, only a few studies have been conducted assessing these newer antipsychotics and sexual function/dysfunction. The aim of this study is to evaluate the sexual function and hormonal profile of male schizophrenic patients taking olanzapine or CA. Sixty-three inpatients with acute episodes of schizophrenia were randomly assigned to take either olanzapine, or go on conventional antipsychotic treatment. The Dickson-Glazer sexual functioning questionnaire was used to assess sexual functioning where serum prolactin, luteinizing hormone, follicle-stimulating hormone, total testosterone, free testosterone, and sex hormone-binding globulin concentrations were measured. All measurements were taken on discharge from the inpatient unit (baseline), and again at 3 and 9 months after discharge. Prolactin levels in the olanzapine group decreased more rapidly and were significantly lower than in the CA group after 3 months (12.1 +/- 6.3 microg/l, p = 0.01; 18.1 +/- 11.2 microg/l, p = 0.564, respectively). After nine months, there was a tendency toward normal levels in both groups, and the frequency of sexual complaints did not differ between the groups. This study showed no difference between olanzapine and conventional antipsychotics regarding sexual complaints in the treatment of schizophrenia, but did show a difference in the hormone level normalization rate.

J Huazhong Univ Sci Technolog Med Sci 2006; 26(1): 145-7 (Read article online)

Deng Y, Yang D, Chen X, Chen Y

In order to investigate the IFN-gamma and IL-4 expression of CD8+ T lymphocytes in the peripheral blood from patients with recurrent genital herpes (RGH) at different clinical periods and their relationship with the pathogenesis of RGH, flow cytometry was used to detect the intracellular cytokines (IFN-gamma and IL-4) of CD8+ T lymphocytes in the peripheral blood of 30 patients with RGH at acute period, 20 patients with RGH at recovery period and 15 healthy volunteers. The results showed that RGH patients at acute period had a lower percentage of Tc1 subsets in peripheral blood than that of healthy controls (P < 0.001), especially a remarkable decreased percentage of Tc1 subsets (P < 0.001) among those RGH patients with recurrent number more than 3 in the recent half a year. Tc1/Tc2 ratio in the RGH patients at acute period was significantly decreased as compared with normal control group (P < 0.05). The recurrent number of acute patients in the recent half a year was significantly correlated with the percentage of Tc1 subsets and the ratio of Tc1/Tc2 (P < 0.05). A decreased percentage of Tc1 subsets was found among the RGH patients with recurrent number more than 3 in the recent half a year at recovery period in comparison with healthy volunteers (P < 0.05), and it was significantly correlated with the recurrent number in the recent half a year (P < 0.05). It is concluded that there are Tc1/Tc2 imbalance and a low level of Tc1 subsets in RGH patients who are relapsing repeatedly in the near period. The low level of Tc1 subsets may be an important factor for the recurrence of RGH and the reactivation of latent herpesvirus infection.

Hum Gene Ther 2006 May; 17(5): 518-530 (Read article online)

O'brien TA, Tuong DT, Basso LM, McIvor RS, Orchard PJ

Donor T lymphocytes genetically engineered to express a "suicide gene" to facilitate negative selection represent a promising strategy for the management of graft-versus-host disease occurring after allogeneic hematopoietic cell transplantation (HCT). For this purpose, the herpes simplex virus thymidine kinase (HSV-tk) gene, although well studied, has limitations. Cytosine deaminase (CD), an alternative gene for negative selection, converts 5-fluorocytosine (5-FC) to the toxic metabolite 5-fluorouracil (5-FU). Sensitivity of cells to 5-FU can be further increased by expression of uracil phosphoribosyltransferase (UPRT), which catalyzes the conversion of 5-FU to 5-fluorouridine monophosphate. By using a chimeric gene (NG/CD) expressing the truncated human nerve growth factor receptor (NGFR) for positive selection fused to the Saccharomyces cerevisiae CD gene, we investigated strategies to achieve optimal T cell eradication by CD and UPRT expression, utilizing a single retroviral vector. Three vector strategies were compared on the basis of NGFR expression by flow cytometry, western analysis, and enzymatic activity. A construct (NG/CDiU) expressing UPRT and NG/CD, using a bicistronic message, provided the greatest UPRT activity and killing, reducing the lethal dose of 5-FC sufficient to eradicate 90% of cells from 38.7 mug/ml (300 muM) (NG/CD expression alone) to 0.13 mug/ml (1 muM). This approach provides an effective alternative to the HSV-tk system for eradication of donor T lymphocytes after allogeneic HCT.

Dig Dis Sci 2006 May 23; (Read article online)

Gupta SK, Hassall E, Chiu YL, Amer F, Heyman MB

Children and adolescents with symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis (EE) of grade >/=2 (n=45) or nonerosive esophagitis (NEE) (n=45) were assessed to determine the relationship between presenting symptoms, esophagitis severity, and patient age. Overall, regurgitation/vomiting, abdominal pain, and cough were the most frequent symptoms. The prevalence and severity of anorexia/feed refusal was significantly greater in EE versus NEE children; this symptom was also significantly more prevalent in younger (1-5 years) children (both NEE and EE groups) compared to older children. Cough was significantly less severe in NEE adolescents than in younger children. Cough, anorexia/feed refusal, and regurgitation/vomiting were more severe and heartburn was less severe in EE children aged 1-5 years compared with older patients. In conclusion, GERD in children manifests differently than that in adults and symptoms vary with patient age. Symptoms were not predictive of presence or lack of mucosal damage.

J Pain Symptom Manage 2006 May; 31(5): 457-464 (Read article online)

Llanes LR, Fassbender K, Baracos VE, Watanabe S

Drugs are indispensable for the management of symptoms in palliative care patients, and account for a significant proportion of expenditures on a Tertiary Palliative Care Unit (TPCU). Drug expenditures for Edmonton's TPCU increased by 40% in 2002 compared to 2001. Fifty-five percent of the increase was attributable to injectable fentanyl, oral and injectable ondansetron, and total parenteral nutrition (TPN). As there was no increase in the unit cost of these drugs between 2001 and 2002, the increased expenditures reflected increased utilization. The hypothesis of this study was that the increased utilization of these drugs reflected appropriate prescribing. The objective was to compare the indications for prescribing these drugs in 2002 against evidence- and consensus-based criteria. Patients who received these drugs while admitted to the TPCU from January 1 to December 31, 2002 were identified through the pharmacy database. Evidence- and consensus-based criteria for drug utilization were developed. Prescribing indications were retrospectively compared against the criteria. Drug prescriptions were categorized as follows: (1) meeting criteria, (2) not meeting criteria, or (3) uncertain. The drugs under study were prescribed during 48 out of 234 admissions to the TPCU in 2002. Prescriptions for fentanyl met criteria in 26 of 29 cases. Indications were unsuccessful therapy with morphine, hydromorphone, and oxycodone (20), requirement for rapid titration from fentanyl patch (5), renal failure (2), and sublingual administration for breakthrough pain (1). Prescriptions for ondansetron met criteria in 19 of 21 cases. Indications were nausea refractory to metoclopramide and dexamethasone (13), and nausea related to radiotherapy or chemotherapy (6). Prescriptions for TPN met criteria for initiation in only one of five cases. However, in all cases, TPN had been started prior to admission. In cases where death was considered imminent, TPN was continued pending consultation with the patient and family regarding discontinuation. These data indicate that the increased prescribing of fentanyl and ondansetron on the TPCU satisfied evidence- and consensus-based criteria in most cases, apparently justifying the associated increase in drug expenditures. This type of analysis may be useful whenever increased drug utilization requires review. A cost effectiveness analysis would be the next step in evaluating the costs vs. the benefits. The issue of discontinuing TPN in palliative care patients requires further investigation.

Dysphagia 2006 May 23; (Read article online)

Ludlow CL, Humbert I, Saxon K, Poletto C, Sonies B, Crujido L

We tested two hypotheses using surface electrical stimulation in chronic pharyngeal dysphagia: that stimulation (1) lowered the hyoid bone and/or larynx when applied at rest, and (2) increased aspiration, penetration, or pharyngeal pooling during swallowing. Bipolar surface electrodes were placed on the skin overlying the submandibular and laryngeal regions. Maximum tolerated levels of stimulation were applied while patients held their mouth closed at rest. Videofluoroscopic recordings were used to measure hyoid movements in the superior-inferior and anterior-posterior dimensions and the subglottic air column position while stimulation was on or off. Patients swallowed 5 ml liquid when stimulation was off, at low sensory stimulation levels, and at maximum tolerated levels (motor). Speech pathologists, blinded to condition, tallied the frequency of aspiration, penetration, pooling, and esophageal entry from videofluorographic recordings of swallows. Only significant (p = 0.0175) hyoid depression occurred during stimulation at rest. Aspiration and pooling were significantly reduced only with low sensory threshold levels of stimulation (p = 0.025) and not during maximum levels of surface electrical stimulation. Those patients who had reduced aspiration and penetration during swallowing with stimulation had greater hyoid depression during stimulation at rest (p = 0.006). Stimulation may have acted to resist patients' hyoid elevation during swallowing.