Polyphenols from Conyza dioscoridis (L.) ameliorate Alzheimer's disease- like alterations through multi-targeting activities in two animal models.

BACKGROUND: Recent investigations suggested that anticancer agents may inhibit the progression of Alzheimer's disease (AD) pathology. Conyza dioscoridis (L.) was demonstrated to have anticancer, antioxidant, anti-inflammatory and antidiabetic effects. This study was carried out to investigate the efficacy of polyphenols from Conyza dioscoridis (L.) extract (PCDE) on AD. METHODS: Impacts of 3 doses of PCDE and donepezil, a reference drug, on the features of Alzheimer's disease in two animal models were investigated. RESULTS: PCDE ameliorated the memory and learning impairment shown in rats following a single dose of scopolamine (scopolamine model) or 17 weeks of high-fat/high-fructose(HF/Hfr) diet coupled with a single dose of streptozotocin, (25 mg/kg) (T2D model). They reduced significantly the high hippocampal cholinesterase activity in the two models of rats. Administration of PCDE for 8 weeks in the T2D model showed a significant reduction in hippocampal GSK-3ß, caspase-3 activity and increase in the inhibited glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). A significant reduction of HOMA-insulin resistance and serum hypercholesterolemia was observed. The Tau hyperphosphorylation and Aß 1-42 generation in the hippocampal of T2D rats were significantly decreased by PCDE. Modulation of the oxidative stress markers, (rise in GH and SOD; decrease in MDA levels) and a significant reduction of TNF-α and IL-1ß in the hippocampus of T2D rats treated by PCDE extract were important findings in this study. The highest dose tested was 4% of the highest safe dose. CONCLUSION: Our study suggests that PCDE is multi-targeting agent with multiple beneficial activities in combating features of AD. This study may provide a novel therapeutic strategy for AD treatment that warrants clinical studies.

Insights of Valacyclovir in Treatment of Alzheimer's Disease: Computational Docking Studies and Scopolamine Rat Model.

BACKGROUND: Alzheimer's Disease (AD) impairs memory and cognitive functions in the geriatric population and is characterized by intracellular deposition of neurofibrillary tangles, extracellular deposition of amyloid plaques, and neuronal degeneration. Literature suggests that latent viral infections in the brain act as prions and promote neurodegeneration. Memantine possesses both anti-viral and N-methyl-D-aspartate (NMDA) receptor antagonistic activity. OBJECTIVES: This research was designed to evaluate the efficacy of antiviral agents, especially valacyclovir, a prodrug of acyclovir in ameliorating the pathology of AD based on the presumption that anti-viral agents targeting the Herpes Simplex Virus (HSV) can have a protective effect on neurodegenerative diseases like Alzheimer's disease. METHODS: Thus, we evaluated acyclovir's potential activity by in-silico computational docking studies against acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase 1 (BACE-1). These findings were further evaluated by in-vivo scopolamine-induced cognitive impairment in rats. Two doses of valacyclovir, a prodrug of acyclovir (100 mg/kg and 150 mg/kg orally) were tested. RESULTS: Genetic Optimisation for Ligand Docking scores and fitness scores of acyclovir were comparable to donepezil. Valacyclovir improved neurobehavioral markers. It inhibited AChE and BuChE (p<0.001) enzymes. It also possessed disease-modifying efficacy as it decreased the levels of BACE-1 (p<0.001), amyloid beta 1-42 (p<0.001), amyloid beta 1-40 (p<0.001), phosphorylatedtau (p<0.001), neprilysin (p<0.01), and insulin-degrading enzyme. It ameliorated neuroinflammation through decreased levels of tumour necrosis factor α (p<0.001), nuclear factor-kappa B (p<0.001), interleukin 6 (p<0.001), interleukin 1 beta (p<0.001), and interferon-gamma (p<0.001). It also maintained synaptic plasticity and consolidated memory. Histopathology showed that valacyclovir could restore cellular density and also preserve the dentate gyrus. CONCLUSION: Valacyclovir showed comparable activity to donepezil and thus can be further researched for the treatment of Alzheimer's disease.

Hyoscine butylbromide in pain reduction associated with ultrasound-guided manual vacuum aspiration: a randomized placebo-controlled trial.

RESEARCH QUESTION: What is the effect of adding an anti-spasmodic drug to an existing ultrasound-guided manual vacuum aspiration (USG-MVA) protocol to alleviate immediate post-procedure abdominal cramping pain in women treated for early pregnancy loss? DESIGN: Double-blind, placebo-controlled, randomized controlled trial conducted between February 2018 and January 2020. Participants were assigned to receive a 1-ml intravenous injection containing 20-mg hyoscine butylbromide (HBB) (n=55) or saline (n =56) as a control immediately before USG-MVA. Primary outcome was reduced abdominal pain after adding a 20-mg dose of HBB to the current pain control regimen. Secondary outcomes were vaginal pain, complications and side-effects, women's pre- and post-procedure psychological state, physiological stress (saliva alpha-amylase) and procedure pain control satisfaction. Two-way mixed ANOVA was used to evaluate the main effects and interactions. RESULTS: VAS abdominal pain scores in the HBB group were 16% lower immediately after and 21% lower 2 h after surgery (not statistically significant). Two-way ANOVA indicated that time (F[1108] = 83.41, P < 0.001) was the only significant main effect for reduced abdominal pain after the procedure and vaginal pain score (F[1108] = 180.1, P < 0.0001) but not drug received. No adverse events were reported. No significant difference was found for psychological state, physiological stress and procedure pain control satisfaction between the two groups. CONCLUSIONS: Anti-spasmodic drugs can help to reduce abdominal cramping pain associated with USG-MVA; HBB produced an insignificant decrease in abdominal pain score. Further studies with longer acting or larger doses of anti-spasmodic drugs are warranted.

The role of perioperative medications in urinary retention following midurethral sling.

AIMS: Postoperative urinary retention (PUR) is a known complication of midurethral sling (MUS) placement. The use of certain perioperative medications may influence the risk of this complication. This study aimed to investigate the association of perioperative medications with urinary retention after MUS. METHODS: This was a retrospective study of women undergoing MUS placement for stress urinary incontinence by a fellowship-trained urologic surgeon between 2015 and 2018, under approval by the Institutional Review Board. Both retropubic and transobturator approaches were included. All patients underwent an active void trial following surgery. Intraoperative medications given by the anesthesia team were retrospectively noted. The Fisher's exact test was used to compare the association of PUR with categorical variables. RESULTS: A total of 82 patients were included, 17 (21%) of whom failed postoperative void trial due to urinary retention. Of 25 patients receiving perioperative scopolamine, 40% failed the postoperative void trial, compared to 12% of patients not receiving scopolamine (p = .048). Groups were then stratified based on scopolamine use due to the observed independent association with PUR. Subgroup analysis revealed a stronger association of postoperative retention with scopolamine in patients undergoing concomitant prolapse surgery. Notably, retention rate and scopolamine use were similar whether patients underwent sling placement alone or in combination with prolapse surgery. Rate of retention was also higher for retropubic versus transobturator slings (36% vs. 9%; p = .005). CONCLUSIONS: Perioperative scopolamine may be associated with an increased risk of postoperative urinary retention following MUS, especially in the setting of a concomitant prolapse surgery.

Clinical Management and Therapeutic Strategies for the Thyroid-Associated Ophthalmopathy: Current and Future Perspectives.

PURPOSE: TAO is an organ specific autoimmune disease associated with thyroid, and inflammation of the orbit and periorbital tissues, which is different from systemic autoimmune diseases such as SLE. However, Grave's disease is a kind of systemic autoimmune syndrome which might involve the thyroid, the eye ball and the anterior tibial tissue. Considering the inexplicable understanding of TAO pathogenesis, the disease worsens for the patients. Therefore, this manuscript provides insights into the recent advancements of clinical features, epidemiology, pathogenesis with gene-interactions, diagnosis, including available and novel treatment options for TAO, based on available data including RCTs, meta-analyses, and systematic reviews. METHODS: Articles with clinical features, epidemiology, pathogenesis, diagnosis, and treatment of the disease were thoroughly studied. To perform the gene expression and pathway analysis, articles were searched on PubMed, MEDLINE Cochrane Library and ClinicalTrial.gov from 1982 to 2020. To predict novel TAO-specific therapeutic molecule, structure-based drug design (SBDD) was performed. RESULTS: We observed gene expression and pathway analysis and SBDD approaches might bring new insights in the field of TAO pathogenesis, diagnosis, and treatment. A genome-wide map of human genetic interactions revealed involvement of crucial cell-signalling pathways, such as TNF-mediated signalling pathway, type-I interferon signalling pathway, toll-like receptor signalling pathway, transforming growth factor-beta receptor signalling pathway etc. Recently, FDA-approved teprotumumab a breakthrough, first drug for the treatment of active thyroid eye disease, which reduces proptosis and the need for orbital decompression surgery. Furthermore, our SBDD results revealed that cost-effective Curcumin, Withaferin A, Resveratrol, Scopolamine, Quercetin, and Berberine may have significant binding affinity for hyaluronan protein and may be exploited for therapeutic purposes in TAO. CONCLUSIONS: Considering the increasing risk and nature of disease, novel drug therapies and markers for prognosis need to be investigated. Moreover, evidence-based non-invasive/minimal surgical therapies should be developed for the better management of the disease. ABBREVIATIONS: ADIPOQ: Adiponectin; CAS: Clinical Activity Score; CCL5: C-C Motif Chemokine Ligand 5; CT: Computed Tomography; DON: Dysthyroid Optic Neuropathy; EUGOGO: European Group of Graves' Orbitopathy; FDA: U.S. Food and Drug Administration; FOS: Fos Proto-Oncogene, AP-1 Transcription Factor Subunit; HLA: Human Leukocyte Antigen; HLA-DRA: Major Histocompatibility Complex, Class II, DR Alpha; ICAM1: Intercellular Adhesion Molecule 1; IFNG: Interferon Gamma; IGF-1: Insulin-like Growth Factor 1; IGF-1R: Insulin-like Growth Factor-1 Receptor; IL12B: Interleukin 12B; IL23R: Interleukin 23 Receptor; IL6: Interleukin 6; IOP: Intraocular Pressure; IRF1: Interferon Regulatory Factor 1; IRF5: Interferon Regulatory Factor 5; IRF7: Interferon Regulatory Factor 7; IRF9: Interferon Regulatory Factor 9; JUN: Jun Proto-Oncogene, AP-1 Transcription Factor Subunit; JUNB: JunB Proto-Oncogene, AP-1 Transcription Factor Subunit; MHC: Major Histocompatibility Complex; MRI: Magnetic Resonance Imaging; NFKB1: Nuclear Factor Kappa B Subunit 1; NFKBIA: Nuclear Factor Kappa B Inhibitor Alpha; OADSCs: Orbital Adipose Derived Stromal Cells; PDGFB: Platelet Derived Growth Factor Subunit B; PPARG: Peroxisome Proliferator Activated Receptor Gamma; RANTES: Regulated on Activation Normal T cell Expressed and Secreted; RARA: Retinoic Acid Receptor Alpha; RCTs (Randomized Controlled Trials; SLE: Systemic lupus erythematosus; SOCS3: Suppressor of Cytokine Signaling 3; STAT1: Signal Transducer and Activator of Transcription 1; TAO: Thyroid-Associated Ophthalmopathy; TED: Thyroid eye disease; TGFB1: Transforming Growth Factor Beta 1; TGFB2: Transforming Growth Factor Beta 2; TGF-ß: Transforming Growth Factor-beta; TLR7: Toll like Receptor 7; TLR9: Toll like Receptor 9; TNFRSF18: Tumor Necrosis Factor Receptor Superfamily Member 18; TNFSF11: Tumor Necrosis Factor Receptor Superfamily Member 11; TNF-α: Tumor Necrosis Factor-alpha; TSHR: Thyroid Stimulating Hormone Receptor; TSIs: Thyroid Stimulating Immunoglobulin; WNT5A: Wingless-Type MMTV Integration Site Family, Member 5A.

Scopolamine Toxicity in an Elderly Patient.

We present a case of a 66-year-old female who was to undergo a scheduled operation and placed on our institution's ERAS (Enhanced Recovery After Surgery) protocol. The intraoperative course was unremarkable. The patient developed delayed emergence in the Post-Anesthesia Care Unit. On physical exam, the patient was noted to have a transdermal scopolamine patch adjacent to an area of skin breakdown. She also displayed signs of central anti-cholinergic toxicity including mydriasis and tachycardia. Following removal of the scopolamine patch and administration of physostigmine, her mental status returned to baseline. This interesting case highlights the importance of considering patient specific factors such as age when implementing ERAS protocols perioperatively. It also demonstrates the risks associated with scopolamine and the importance of risk/benefit analysis prior to administration.

Long-term scopolamine treatment and dental caries.

OBJECTIVES: To investigate whether scopolamine, an anticholinergic agent which induces hyposalivation, represents a risk factor for the occurrence of dental caries. MATERIALS AND METHODS: A retrospective cohort study was carried out among sailors treated with scopolamine for seasickness. The study population included 370 young healthy male adults (18-30 years old) who served in the Israel Navy between 2012 and 2016. Of these, 66 subjects who were chronically treated with intermittent administration of scopolamine, either by the oral or transdermal route, were assigned to the study group. Documented subject characteristics included age, socioeconomic status, level of education, body mass index, smoking history, and dental hygiene. Follow-up lasted 1 to 3.5 years. RESULTS: Two- to 3.5-year follow-up revealed a higher risk of dental caries in 15 of 16 subjects (93.8%) treated with an average of 50.9 mg scopolamine, in contrast to only 71 of 108 control subjects (65.7%) (RR = 1.43, p = 0.02 [95% CI = 1.18-1.72]). Follow-up for 1-1.5 years revealed a lower occurrence of dental caries in both the study group (11/22, 50.0%) and the control group (46/104, 44.2%). Follow-up of 1.5-2 years also revealed less dental caries, in 16/28 subjects (57.1%) in the study group and 51/92 subjects (55.4%) in the control group. The differences were not statistically significant. CONCLUSIONS: In healthy young adults, prolonged intermittent use of scopolamine was found to be a risk factor for the development of dental caries. CLINICAL SIGNIFICANCE: Dental care and hygiene should be intensified when administering hyposalivatory anticholinergic agents.

Improved analgesia and reduced post-operative nausea and vomiting after implementation of an enhanced recovery after surgery (ERAS) pathway for total mastectomy.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) pathways have been shown in multiple surgical disciplines to improve outcomes, including reduced opioid consumption, length of stay, and post-operative nausea and vomiting (PONV). However, very few studies describe the application of ERAS to breast surgery and even fewer describe ERAS for outpatient surgery. We describe the implementation and efficacy of an Enhanced Recovery After Surgery (ERAS) pathway for total skin-sparing mastectomy with immediate reconstruction in an outpatient setting. METHODS: We implemented an evidence-based, multimodal ERAS pathway for all patients undergoing total skin-sparing mastectomy surgery with immediate reconstruction at a single 23-h stay surgery center. Highlights of the ERAS pathway included: preoperative acetaminophen, gabapentin, and scopolamine; regional anesthesia for the breast (Pectoral blocks type 1 and 2 or paravertebral block); and intraoperative dexamethasone and ondansetron. This retrospective study included all American Society of Anesthesiology (ASA) Class 1-3 patients undergoing total skin-sparing mastectomy surgery with immediate reconstruction between July 2013 and April 2016. We compared 96 patients who were in the ERAS pathway (ERAS group) to a retrospective cohort of 276 patients (Pre group). The primary outcome was total perioperative opioid consumption. Secondary outcomes were highest postoperative pain scores, incidence of PONV, and length of stay. RESULTS: Patients in the ERAS group had significantly lower total perioperative opioid consumption compared to the Pre group (mean (SD): 111.4 mg (46.0) vs. 163.8 mg (73.2) oral morphine equivalents, p < 0.001). Patients in the ERAS group also had a lower incidence of PONV (28% vs. 50%, p < 0.001). Patients in the ERAS group reported less pain in the recovery room, with a two-point decrease in highest pain score (median [interquartile range (IQR)]: 4 [2,6] in ERAS group vs. 6 [4,7] in Pre group, p < 0.001). There was no clinically significant difference in length of stay (median [IQR]: 1144 min [992, 1259] in ERAS group vs. 1188 [1058, 1344] in Pre group, p = 0.006). CONCLUSION: Implementation of an ERAS pathway for total skin-sparing mastectomy with reconstruction that incorporates regional anesthesia is feasible in a 23-h-stay hospital. Patients in the ERAS pathway had improved post-operative analgesia and reduced post-operative nausea and vomiting.

Transdermal scopolamine for the prevention of a salivary fistula after parotidectomy.

Our aim was to investigate whether perioperative transdermal application of scopolamine could help to prevent fistulas after parotidectomy, and to this end we retrospectively studied the records of all patients (n=645) who had benign parotid tumours treated by partial parotidectomy between 2011 and 2016. We found that scopolamine led to a significant decrease in the incidence of salivary fistulas from 54/371(15%) in the group not given it to 10/274 (4%) in the group given it (p<0.0001). The "number needed to treat" was 9.17. There was a relatively low incidence of all adverse effects after scopolamine. Our results are encouraging. Thorough consideration of the contraindications and a knowledge of the potential adverse effects are crucial for its successful implementation.

Protein kinase A mediates scopolamine-induced mTOR activation and an antidepressant response.

BACKGROUND: Clinical reports have shown that scopolamine produces a rapid (3-4 d) and potent anti-depressive response without severe adverse effects. Animal experiments have proven that scopolamine induces mTOR pathway activation in an AMPAR dependent manner. The present study aimed to determine the role of PKA in scopolamine-induced potentiation of AMPAR, as well as in mTOR pathway activation and rapid antidepressant effects. METHODS: We utilized electrophysiological recording, Western blotting, and behavior tests to examine the effects of scopolamine, the selective M2 cholinergic receptor antagonist methoctramine, and H89, a PKA specific inhibitor on AMPAR potentiation, mTOR pathway activation, and behavioral responses in a rat depression model of learned helplessness. RESULTS: Scopolamine (1µM) rapidly increased AMPAR-fEPSP amplitudes and membrane GluA1 expression in CA1 region of hippocampal slices, both of which were abolished by H89. Moreover, scopolamine promoted AMPAR phosphorylation on GluA1 ser845, a PKA site involved in GluA1 membrane insertion. H89 disrupted both GluA1 ser845 phosphorylation and mTOR activation, as well as the antidepressant effects of scopolamine as determined via forced swim test. Additionally, methoctramine mimicked the effects of scopolamine on phosphorylation and counter-depressive action in a PKA-dependent manner. LIMITATIONS: Only one test was used to evaluate depressive behavior, and gene knock-out rats were not yet utilized to refine our hypotheses. CONCLUSION: Our findings revealed that PKA pathway is necessary for scopolamine-induced synaptic plasticity and mTOR pathway activation, and indicated that a potential M2-PKA mechanism underlies scopolamine's antidepressant effects. Such findings suggest that GluA1 ser845 phosphorylation may be a trigger event for scopolamine's actions, and that PKA may represent a novel target for the treatment of depressive symptoms.

Postoperative Anticholinergic Poisoning: Concealed Complications of a Commonly Used Medication.

BACKGROUND: Scopolamine is a potent anticholinergic compound used commonly for the prevention of postoperative nausea and vomiting. Scopolamine can cause atypical anticholinergic syndromes due to its prominent central antimuscarinic effects. CASE REPORT: A 47-year-old female presented to the emergency department (ED) 20 h after hospital discharge for a right-knee meniscectomy, with altered mental status (AMS) and dystonic extremity movements that began 12 h after her procedure. Her vital signs were normal and physical examination revealed mydriasis, visual hallucinations, hyperreflexia, and dystonic movements. Laboratory data, lumbar puncture, and computed tomography were unrevealing. The sustained AMS prompted a re-evaluation that revealed urinary overflow with 500 mL of retained urine discovered on ultrasound and a scopolamine patch hidden behind her ear. Her mental status improved shortly after patch removal and physostigmine, with complete resolution after 24 h with discharge diagnosis of scopolamine-induced anticholinergic toxicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although therapeutically dosed scopolamine transdermal patches rarely cause complications, incomplete toxidromes can be insidiously common in polypharmacy settings. Providers should thoroughly evaluate the skin of intoxicated patients for additional adherent medications that may result in a delay in ED diagnosis and curative therapies. Our case, as well as rare case reports of therapeutic scopolamine-induced anticholinergic toxicity, demonstrates that peripheral anticholinergic effects, such as tachycardia, dry mucous membranes, and hyperpyrexia are often not present, and incremental doses of physostigmine may be required to reverse scopolamine's long duration of action. This further complicates identification of the anticholinergic toxidrome and diagnosis.

Oesophageal spasm, vomiting and hyoscine hydrobromide patch.

We report the case of a 60-year-old woman with metastatic breast cancer whose intractable nausea and vomiting were effectively managed with a hyoscine hydrobromide (scopolamine) patch. Contrast swallow revealed oesophageal spasm to be the underlying cause. Symptom relief may be attributed to the antimuscarinic properties of the patch, allowing lower oesophageal sphincter relaxation. Following patch use she was able to enjoy small meals and fluids without symptoms. This is the first time this mechanism of action of scopolamine for alleviating nausea and vomiting has been described in the literature.

Leiomioma cutâneo piloeretor: relato de caso e análise de possibilidades terapêuticas / Cutaneous pilar leiomyoma: case report and analysis of therapeutic possibilities

Introdução: O leiomioma cutâneo piloeretor (LCP) é um tumor benigno de pele, de incidência rara, proveniente do músculo eretor do pelo. Sua apresentação clínica mais frequente é o aparecimento de nódulos isolados ou em grande número. Em geral, são dolorosos, sensíveis ao frio, toque, pressão e à emoção. Vários agentes farmacológicos têm sido utilizados com algum sucesso para redução da dor e do desconforto local. Entretanto, em casos nos quais os sintomas dolorosos são intensos ou causam restrição social, a cirurgia torna-se uma abordagem alternativa a ser considerada. Neste artigo relatamos o caso de um paciente do sexo masculino, portador de múltiplos leiomiomas cutâneos na parede torácica anterior à esquerda e no abdome, bem como a terapêutica utilizada para seu caso. Métodos: O tratamento compreendeu a ressecção cirúrgica total da lesão, com fechamento da ferida com o uso de enxerto de pele parcial, retirado da região anterolateral da coxa direita. Resultados: A reconstrução imediata do defeito resultante, com enxerto de pele parcial, assegurou a cicatrização sem intercorrências. Após o tratamento, houve completa remissão do quadro doloroso, o que permitiu completa reintegração social do paciente, tendo sido alcançado ainda resultado estético aceitável. Conclusão: O LCP constitui patologia de difícil tratamento, embora tenha várias possibilidades terapêuticas. A ressecção cirúrgica completa de múltiplos leiomiomas cutâneos pode impedir a recorrência da doença, embora alguma recidiva local seja relatada na literatura.

Introduction: Cutaneous pilar leiomyoma (CPL) is a rare benign skin tumor arising from arrector pili muscles. Its most common clinical manifestation is the appearance of nodules that may either be isolated or clustered. In general, these tumors are painful and sensitive to cold, touch, pressure, and emotional stimuli. Several pharmacological agents have been used with some success to reduce local pain and discomfort. However, in cases with intensely painful symptoms or that cause social constraints to the patient, surgery becomes an alternative approach. Here, we report the case of a male patient with multiple cutaneous leiomyomas in the left anterior chest wall and abdomen, and the therapeutic approaches used for this case. Methods: The treatment included a complete surgical resection of the tumor and wound closure with partial skin graft taken from the anterolateral region of the right thigh. Results: The immediate reconstruction of the resulting defect with a partial skin graft ensured healing without complications. After the treatment, complete remission of the pain symptoms occurred, in addition to an acceptable aesthetic outcome, which allowed the full social reintegration of the patient. Conclusion: CPL is a disease that is difficult to treat; however, several therapeutic approaches can be used. The complete surgical resection of multiple cutaneous leiomyomas can prevent the recurrence of the disease, although some local recurrences have been reported in the literature.

Nonopioid pharmacological management of malignant bowel obstruction: a New Zealand-wide survey.

BACKGROUND: Malignant bowel obstruction (MBO) is a common condition among palliative patients and has limited management options. There is a paucity of widely accepted national and international evidence-based guidelines to direct the management of MBO in palliative patients. OBJECTIVE: The aim of this study was to survey current practice in New Zealand of nonopioid pharmacological management of MBO and compare it with the available literature. METHODS: The study utilized a survey consisting of three scenarios: probable incomplete malignant bowel obstruction (PIMBO), incomplete malignant bowel obstruction (IMBO), and complete malignant bowel obstruction (CMBO). An online survey was conducted over 2 months targeting palliative medicine practitioners working in a hospital, hospice inpatient unit, or community setting in New Zealand. RESULTS: Forty-eight doctors responded. Of the respondents, 56.3% used guidelines to manage MBO; however, 88.9% of the guidelines used were locally generated at the doctor's institution. Metoclopramide was the drug of choice in treating PIMBO, whereas haloperidol and hyoscine butylbromide (HB) were the preferred drugs as the severity of bowel obstruction increased. Dexamethasone was accepted as standard practice for managing all severities of MBO. A variation in the preferred starting and maximum dose of all the drugs was seen. There was a decrease in the use of laxatives and enemas as the severity of MBO increased. CONCLUSION: Variation in practice for managing MBO was evident among doctors in New Zealand. There is a need for national and international evidence-based guidelines to help define best management for the differing severities of this problematic condition.

Scopolamine detoxification technique for heroin dependence: a randomized trial.

BACKGROUND: Easing psychological symptoms associated with heroin use and heroin relapse are important goals in the treatment of heroin dependence. However, most detoxification methods are designed to decrease withdrawal-related discomfort and complications, but not to reduce the psychological effects of heroin addiction. OBJECTIVE: The objective of this study was to evaluate the efficacy of scopolamine detoxification technique (SDT) relative to standard methadone detoxification (MD) to treat heroin withdrawal and psychological symptoms associated with heroin use and relapse. METHODS: In this 10-week randomized, controlled trial, treatment-seeking heroin-dependent participants were enrolled consecutively from Ningbo Addiction Research and Treatment Center, Ningbo, China. Opioid dependence was confirmed by a naloxone challenge test. Participants were included if they met Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria for opioid dependence, were without major comorbid psychiatric illness, and were not allergic to scopolamine and chlorpromazine. Participants (N = 91; 18-50 years) were admitted to inpatient beds for 15 days and randomly assigned to receive either SDT (N = 46) or MD (N = 45) prior to being discharged and undergoing 8 weeks of outpatient treatment. During the inpatient stay, all participants received methadone during days 1-3. Those in the MD group then underwent a 10-day gradual dose-reduction regimen. Those in the SDT group underwent an SDT, such that subjects were given scopolamine (0.03-0.05 mg/kg, intravenously) and chlorpromazine (0.6-1.0 mg/kg, intravenously) under light anesthesia for 4-6 h once per day on days 4-6 or 4-7, depending on the severity of opioid-withdrawal symptoms. Self-reported withdrawal symptoms were assessed each day during the in-patient treatment phase. Heroin craving (assessed using a visual analog scale), Beck Depression Inventory, Self-Rating Anxiety Scale, and working memory and attention tests (assessed using the Digit-span test and d2 test) were measured before (day 0) and after detoxification (day 15). Retention was assessed during the inpatient phase and the outpatient phase. Urine tests for opioids were assessed twice weekly in the follow-up phase. Reasons for Relapse Questionnaires were completed when each participant's urine sample was positive. RESULTS: The vital signs of participants were stable and no serious adverse anesthetic events were observed during SDT. SDT considerably suppressed heroin withdrawal symptoms, which did not increase during the post-detoxification phase. Although groups did not differ on retention or the percentage of opioid-positive urine samples (SDT 73.2 ± 30.1% and MD 75.1 ± 37.6%), SDT significantly attenuated heroin craving, depression, and anxiety compared with MD (P < 0.001). There was a significant difference in the mean reductions (%) of amount of first heroin use after hospital discharge between the SDT group and the MD group (t 71 = 6.09, P < 0.01). There were no significant differences in the scores of the Digit-span and d2 tests by treatment conditions (P > 0.05). The percentage of participants citing "drug craving" and "anxiety and depression" as the primary reasons for relapse was significantly lower in the SDT group than in the MD group. CONCLUSIONS: SDT may be an alternative to conventional detoxification techniques, especially for patients with psychological symptoms.

Transdermal scopolamine in the management of postparotidectomy salivary fistula.

Parotid fistula represents an uncommon complication in parotid surgery. Its early recognition contributes to successful management. The condition is distressing for both the patient and the surgeon, since conservative and operative treatment frequently fail. There is no consensus on the optimal management of parotid gland fistula. The aim of this study is to describe a new, simple procedure in the treatment of this condition using transdermal scopolamine. We report 3 cases of salivary fistulae occurring after parotidectomy. The patients were admitted to our department with swelling in the parotid region and an output of clear drainage from the drain site during oral intake. The patients were treated with a scopolamine transdermal release system applied to hairless skin overlying the parotid region. A prompt and remarkable decrease in daily salivary output was observed. Fistulae healed completely within 3 days. No collateral effects were observed. Parotid fistulae do not generally occur as a complication of parotidectomies. Their management can be difficult, and several methods of treatment have been attempted. We believe that the use of transdermal scopolamine is a valid option in the treatment of parotid fistulae without causing collateral effects.

[Hypersalivation - inauguration of the S2k Guideline (AWMF) in short form]. / Hypersalivation - Ersterstellung der S2k-Leitlinie (AWMF) in gekürzter Darstellung.

Hypersalivation describes a relatively excessive salivary flow, which wets the patient himself and his surroundings. It may result because of insufficient oro-motor function, dysphagia, decreased central control and coordination. This reduces social interaction chances and burdens daily care. Multidisciplinary diagnostic and treatment evaluation is recommended already at early stage and focus on dysphagia, and saliva aspiration. Therefore, a multidisciplinary S2k guideline was developed. Diagnostic tools such as fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing studies generate important data on therapy selection and control. Especially traumatic and oncologic cases profit from swallowing therapy programmes in order to activate compensation mechanisms. In children with hypotonic oral muscles, oralstimulation plates can induce a relevant symptom release because of the improved lip closure. In acute hypersalivation, the pharmacologic treatment with glycopyrrolate and scopolamine in various applications is useful but its value in long-term usage critical. The injection of botulinum toxin into the salivary glands has shown safe and effective results with long lasting saliva reduction. Surgical treatment should be reserved for isolated cases. External radiation is judged as ultima ratio. Therapy effects and symptom severity has to be followed, especially in neurodegenerative cases. The resulting xerostomia should be critically evaluated by the responsible physician regarding oral and dental hygiene.

Uveitis and desquamating rash of the palms and soles.

Syphilis, a sexually transmitted disease caused by the spirochete Treponema pallidum, can affect nearly every organ system in the body. In particular, skin manifestations of secondary syphilis are common but nonspecific and can be a true masquerader of other skin disorders. Concomitant infection with HIV has been increasing and may cause even more unusual skin presentations. We present a patient with the atypical combination of palmoplantar keratoderma and ocular symptoms that closely resembled reactive arthritis (or Reiter's syndrome). When evaluating patients with HIV infection, clinicians should maintain a high level of suspicion for syphilis to accurately diagnose and treat this curable but potentially fatal disease.

Four essential drugs needed for quality care of the dying: a Delphi-study based international expert consensus opinion.

PURPOSE: The majority of dying patients do not have access to necessary drugs to alleviate their most common symptoms, despite evidence of drug efficacy. Our aim was to explore the degree of consensus about appropriate pharmacological treatment for common symptoms in the last days of life for patients with cancer, among physicians working in specialist palliative care. MATERIAL AND METHODS: Within OPCARE9, a European Union seventh framework project aiming to optimize end-of-life cancer care, we conducted a Delphi survey among 135 palliative care clinicians in nine countries. Physicians were initially asked about first and second choice of drugs to alleviate anxiety, dyspnea, nausea and vomiting, pain, respiratory tract secretions (RTS), as well as terminal restlessness. RESULTS: Based on a list of 35 drugs mentioned at least twice in the first round (n=93), a second Delphi round was performed to determine ≤ 5 essential drugs for symptom alleviation in the last 48 hours of life that should be available even outside specialist palliative care. There was ≥ 80% consensus among the participants (n=90) regarding morphine, midazolam, and haloperidol as essential drugs. For RTS, there was consensus about use of an antimuscarinic drug, with 9%-27% of the physicians each choosing one of four different drugs. CONCLUSION: Based on this consensus opinion and other literature, we suggest four drugs that should be made available in all settings caring for dying patients with cancer, to decrease the gap between knowledge and practice: morphine (i.e., an opioid), midazolam (a benzodiazepine), haloperidol (a neuroleptic), and an antimuscarinic.

Comparison of meperidine versus hyoscine during colonoscopy in the elderly: a prospective randomized study.

BACKGROUND: Colonoscopy is the gold standard in diagnosis of diseases of the colon. Sedation and antispasmodic agents are recommended during colonoscopy. Age is a limiting factor when the surgeon is deciding whether to use these medications or not. SUBJECTS AND METHODS: One hundred twenty patients older than 65 years of age were randomized into two groups. The first group (n=60) received 2 mg of midazolam and 25 mg of meperidine intravenously. The second group (n=60) received 2 mg of midazolam and 20 mg of hyoscine N-butylbromide intravenously. The data collected were colonoscopy procedure time, time to cecum, visual analog pain scale, systolic blood pressure before and after the procedure, pulse, partial oxygen pressure, comfort of the endoscopist, the modified observer's assessment of alertness/sedation scale, and morbidity. RESULTS: Total colonoscopy and cecal reach times were shorter in Group 2 (19.58±4.82 minutes and 10.57±2.54 minutes, respectively) than in Group 1 (25.05±5.93 minutes and 13.78±3.37 minutes, respectively) (P<.001). The sedation score of Group 2 (4.52±0.50) was better than that of Group 1 (3.45±0.75) (P<.001). Nine patients (15%) in Group 1 experienced diaphoresis, temporary memory loss, or lip smacking. Three patients in Group 1 and 1 patient in Group 2 had hypoxia. Three patients in Group 1 had hypotension; this was seen in 1 patient in Group 2. One patient had perforation in Group 1. The visual analog scale score was 4.37±1.38, and the endoscopist satisfaction was 6.72±0.99 in Group 1, while these values were 3.95±0.81 and 7.75±0.89, respectively, in Group 2 (P>.05). CONCLUSIONS: Use of midazolam and hyoscine N-butylbromide during colonoscopy is safe in the elderly and significantly reduces procedure time while increasing comfort for the endoscopist.