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PubMed2003

Use of contemporary biomarkers in the detection of chronic alcohol use.

Alcohol is the most commonly abused substance yet alcoholism is frequently undiagnosed. The misuse of alcohol is common and frequently an occult problem. More than 10% of current drinkers meet diagnostic criteria for alcohol abuse or dependence while the lifetime prevalence for these conditions in outpatient settings ranges from 16 to 36 percent. Long-term, heavy drinking is associated with significant morbidity, mortality, and economic costs. Clues to alcohol use can be discovered from a patient's history and physical stigmata. Validated screening instruments such as the Alcohol Use Disorders Identification Test (AUDIT), CAGE Questionnaire, and Brief Michigan Alcoholism Screening Tests help confirm the clinical suspicion of alcohol dependence. Laboratory abnormalities of mean corpuscular volume, gamma-glutamyl transferase, alkaline phosphatase, or alanine amino transferase levels are non-specific indicators of possible alcohol-induced liver impairment. Newer, less well-known FDA-approved biochemical markers such as the Carbohydrate Deficient Transferrin and the Early Detection of Alcohol Consumption test may also be used to detect heavy alcohol abuse and to monitor relapse episodes. Brief interventions are successful, making identification and diagnosis a vital role for the family physician. Improved awareness of alcohol misuse, increased use of screening tools, and the appropriate use of biochemical markers will facilitate early intervention and successful management of patients with alcohol use disorders.

Alcohol Drinking↗
PubMedDate not supplied

Human endothelial cells grow poorly on vitronectin: role of PAI-1.

The cell adhesive protein vitronectin is a common component of interstitial extracellular matrix and circulates in plasma. It competes effectively with other plasma proteins to adsorb to certain biomaterial surfaces, and is likely to represent an important cell adhesion mediator on the luminal surface of vascular grafts. It is also found associated with certain vascular pathologies. We have shown previously that human endothelial cells grow poorly on a vitronectin surface compared with other extracellular matrix molecules. In this paper we show that endothelial cells seeded on vitronectin and fibronectin produced substantially different profiles of extracellular matrix molecules. The most outstanding difference was in the amount of matrix-localised plasminogen activator-inhibitor-1 which was high on vitronectin and negligible on fibronectin. This was correlated with a small but significant inhibition of cell adhesion to vitronectin compared with fibronectin, and very significant interference with dissociation of cell: extracellular matrix contacts, resulting either from direct inhibition of the proteolytic activity of urokinase, or from interference with urokinase-receptor signaling and consequent focal adhesion turnover. Such interference would inhibit cell proliferation by disabling the cells from loosening their matrix contacts in order to proceed through mitosis. This would seriously compromise endothelial recovery in cases of damage to the vascular wall and placement of stents or grafts, where the presence of surface-adsorbed vitronectin is likely to modulate the tissue response.

Cell Adhesion↗
PubMed1958

Structure and mode of formation of the nucleolus in meristematic cells of Vicia faba and Allium cepa.

Interphase nucleoli from Vicia faba and Allium cepa meristematic cells are roughly classified into two categories: (a) those that commonly show a rather homogeneous texture (except for small light spaces of various sizes) and frequently contain dense particles 140 A in diameter; (b) those found more frequently in Vicia characterized by a very sharp boundary between a dense outer cortex and a much lighter central core. The dense particles are not found in such nucleoli. In Allium the boundary is more irregular and dense particles are sometimes observed in the outer layer. Many nucleoli show a structure intermediate between these two types. They are characterized by a gradient of increasing density from the center to the periphery and occasionally contain dense 140 A granules. During interphase, certain nucleoli are closely associated with segments of chromatin strands which undoubtedly represent nucleolar organizing regions. The dense 140 A granules are followed during the mitotic cycle. In Allium, they are first seen in loose clusters between arms of late anaphase chromosomes where they become more concentrated in early telophase. The substance within which they are scattered slowly increases in density during that time until finally, the particles are limited to small bodies of distinctive character. Evidence is presented suggesting that these small prenucleolar bodies fuse during telophase to give rise to the mature interphase nucleoli. Similar events are described in Vicia material except that a coating of dense substance appears around telophase chromosomes before the formation of prenucleolar bodies.

Anaphase↗
PubMed1991

Losartan, a nonpeptide angiotensin II (Ang II) receptor antagonist, inhibits neointima formation following balloon injury to rat carotid arteries.

Angiotensin-converting enzyme inhibitors have been shown to inhibit intimal thickening following balloon catheterization of rat carotid arteries. To assess the role of the renin-angiotensin pathway and the angiotensin type-I (AT1) receptor in this effect, the nonpeptide Ang II antagonist losartan (DuP 753) or vehicle was infused continuously i.v. in rats from two days before to two weeks after balloon injury to the left common carotid artery; drug effects upon intimal thickening were examined histologically. Losartan produced a dose-dependent reduction in cross-sectional area of intimal lesions determined two weeks post balloon injury. At 5 mg/kg/day a nonsignificant 23% reduction of intimal area was observed. At the higher dose of 15 mg/kg/day, losartan produced a 48% reduction in intimal area (P less than 0.05) compared to the vehicle-infused group. The cellular density of the neointima was not affected by losartan, indicating a probable effect of the drug upon migration and/or proliferation of smooth muscle cells. In separate groups of non-ballooned rats, losartan infusions of 5 and 15 mg/kg/day produced significant rightward shifts (averaging 6.4- and 55-fold, respectively) in curves relating increases in blood pressure to intravenous Ang II in pithed rats determined between 2 and 16 days following initiation of losartan infusion. Mean arterial blood pressure (determined under alpha-chloralose anesthesia) was reduced following continuous losartan infusion for 6 days from 128 +/- 8 mm Hg (vehicle) to 105 +/- 8 mm Hg at 5 mg/kg/day (P less than 0.05), and 106 +/- 4 mm Hg at 15 mg/kg/day (P less than 0.05). Thus, losartan attenuated the vascular response to balloon catheter injury, and this effect was associated with functional block of vascular AT1 receptors. The results support a role for Ang II, acting via AT1 receptors, in myointimal thickening subsequent to balloon injury of rat carotid arteries.

Analysis of Variance↗
PubMed2006

Tissue-engineered calcium alginate patches in the repair of chronic chinchilla tympanic membrane perforations.

OBJECTIVE: Chronic tympanic membrane perforations are a common problem in the United States. A high number of these cases results from placement of pressure equalization tubes. These perforations may initially be treated with paper patch techniques and although safe and well tolerated, the procedure demonstrates poor efficacy. The ideal treatment for small perforations should be rapid, minimally invasive, and efficacious. Calcium alginate-based tissue engineered tympanic membrane patches represent an attractive option, but in vivo data are required. METHODS: A controlled prospective study of tympanic membrane perforation repair using a well-known chinchilla model of chronic tympanic membrane perforation was performed. Calcium alginate-based tympanic membrane patches were created using computer-aided design techniques. A previously described chinchilla model of chronic tympanic membrane perforations was used to create stable perforations ranging from 2 to 5 mm. Ears with chronic perforations were divided into three groups: control (no patch), paper patch, and calcium alginate plugs. At 10 weeks postimplantation, all animals were killed and inspected both grossly and histologically for healing. RESULTS: In the chinchilla model, the alginate grafts demonstrated significantly improved healing rates over both the untreated control group (spontaneous repair) and the paper patch group; nine of 13 healed in the alginate group versus two of nine healed in the paper patch group (P < .05) versus one of 11 healed in the control group (P < .05). CONCLUSION: Calcium alginate tympanic membrane perforation patches offer a significant advantage in the repair of chronic perforations over traditional techniques in the chinchilla perforation model and may offer attractive opportunities in the clinical setting.

Alginates↗
PubMed2007

Development of an anti-porcine CD34 monoclonal antibody that identifies hematopoietic stem cells.

OBJECTIVES: The isolation of porcine hematopoietic stem cells (HSC) would be an important step toward development of porcine-to-human chimerism for induction of tolerance in clinical xenotransplantation. CD34 is a common marker of HSC and has not been developed as a marker in pigs. In this study we have generated and characterized a monoclonal antibody (mAb) that identifies porcine CD34 on a subset of porcine bone marrow (BM) stem/progenitor cells. METHODS: The porcine CD34 gene was cloned and a recombinant protein produced. An anti-porcine CD34 mAb was produced that could detect both the recombinant protein and a subset of porcine BM cells. The CD34(+) cells were phenotyped by lineage and HSC associated markers. Furthermore, the CD34(+) cells were analyzed by colony-forming unit (CFU) assay. RESULTS: Two splice variants of the porcine CD34 gene were cloned and a recombinant protein produced for mAb production. The mAb developed can detect both the recombinant protein and the native CD34 protein on a range of pig tissues, including BM. This subset of BM cells was negative for hematopoietic lineage makers, including CD3, CD14, and CD21 and positive for other known porcine HSC markers, including CD90, CD172a, histocompatibility complex (MHC) class I, and MHC class II. Moreover, the CD34(+) BM cells were enriched for multilineage progenitor cells as determined by CFU assay. CONCLUSIONS: Similar to human and mouse CD34, pig CD34 detects a subset of BM progenitor cells. This mAb will now provide a means for isolating porcine CD34(+) cells to be further analyzed for HSC activity and to assess their potential to develop pig-to-human chimeras to induce xenograft tolerance.

Animals↗
PubMed2006

Possible antidiabetic and antihyperlipidaemic effect of fermented Parkia biglobosa (JACQ) extract in alloxan-induced diabetic rats.

1. The hypoglycaemic effect of fermented seeds of Parkia biglobosa (PB; African locust bean), a natural nutritional condiment that features frequently in some African diets as a spice, was investigated in the present study in alloxan-induced diabetic rats. Its effect was compared with that of glibenclamide (Daonil; Sanofi-Aventis, Paris, France), a reference antidiabetic drug. The effects of PB on lipid profiles were also examined. 2. In order to assess the hypoglycaemic and hypolipidaemic effects of aqueous and methanolic extracts of PB on experimental animals, fasting plasma glucose (FPG), total cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were determined. In addition, the weight of each animal was determined to assess any possible weight gain or loss in the experimental animals (diabetic rats treated with Daonil (group C), the aqueous extract of PB (group D) or the methanolic extract of PB (group E)) compared with control groups (non-diabetic (group A) and non-treated diabetic (group B)). 3. A single dose of 120 mg/kg, i.v., alloxan administered to rats resulted in significant increases in the FPG (P < 0.001) of test animals compared with controls. However, dietary supplementation with PB (6 g/kg extract for 4 weeks administered orally using an intragastric tube) ameliorated the alloxan-induced diabetes in a manner comparable with that of the reference antidiabetic drug glibenclamide. Aqueous and methanolic extracts of PB (6% w/w) elicited 69.2% and 64.4% reductions, respectively, in FPG compared with 70.4% in 0.01 mg/150 g glibenclamide-treated rats. 4. Although animals treated with the aqueous extract of PB gained weight in manner similar to normal controls, animals given the methanolic extract and glibenclamide lost weight in manner similar to non-treated diabetic rats. In addition, high levels of HDL and low LDL were observed in animals treated with the aqueous extract of PB, a pattern similar to that seen in normal controls. Low levels of HDL and high levels of LDL were observed in animals treated with the methanolic extract of PB, a pattern similar to that seen in non-treated diabetic controls. 5. The results of the present study demonstrate that both aqueous and methanolic extracts of fermented seeds of PB exert a hypoglycaemic effect; hence, PB has an antidiabetic property. However, only the aqueous extract of PB ameliorated the loss of bodyweight usually associated with diabetes. Although the aqueous extract has a favourable lipid profile, which is probably an indication of its possible anti-arteriogenic property (hypertension and ischaemic heart diseases being common complications in diabetes mellitus), the methanolic extract shows possible contraindication to ischaemic heart diseases.

Animals↗
PubMed2005

The relationship between sleep disturbance and pulmonary function in stable pediatric cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) is the most common inherited disease affecting northern European populations. It is characterized by a progressive clinical course that causes diurnal and nocturnal pulmonary and gastrointestinal symptoms. OBJECTIVES: To determine whether clinically stable pediatric patients with CF have lower sleep efficiency than healthy control subjects, and to examine the relationship between sleep efficiency and pulmonary function. METHODS: Forty-four CF patients and 40 control subjects completed 5 days of actigraphy recordings. Additionally, sleep questionnaires were independently completed by all study participants and their parents. Pulmonary function testing was performed in all patients with CF. Multiple regression analysis was used to measure the independent correlation between sleep variables and pulmonary function. RESULTS: CF patients had significantly lower sleep efficiency than control subjects. The FEV1 of these patients correlated positively with sleep duration and efficiency, and negatively with the number and duration of nocturnal awakenings, age, and body mass index (BMI). The independent effect of FEV1 on sleep was first examined. Age and FEV1 were the only variables that predicted sleep duration (R2 = 0.3; p = 0.0007), while FEV1 was the only variable predicting sleep efficiency (R2 = 0.28; p = 0.0002). When the independent effect of sleep on FEV1 was analyzed, sleep efficiency, BMI percentile, and gender predicted FEV1 (R2 = 0.46; p < or = 0.0001). The frequency of nocturnal cough reported by patients and their parents was an independent predictor of FEV1. CONCLUSIONS: Pediatric patients with CF and stable pulmonary function have lower sleep efficiency and more frequent nocturnal awakenings than do healthy control subjects. After adjustment for demographic characteristics, there was an independent and significant correlation between sleep parameters and FEV1, when either sleep variables or FEV1 were used as dependent variables. These findings suggest a bidirectional relationship between sleep disturbance and CF lung disease.

Adolescent↗
PubMed1996

Surveillance for foodborne-disease outbreaks--United States, 1988-1992.

PROBLEM/CONDITION: Since 1973, CDC has maintained a collaborative surveillance program for collection and periodic reporting of data concerning the occurrence and causes of foodborne-disease outbreaks (FBDOs). REPORTING PERIOD COVERED: This summary reviews data from January 1988 through December 1992. DESCRIPTION OF SYSTEM: The surveillance system reviews data concerning FBDOs--defined as the occurrence of two or more cases of a similar illness resulting from the ingestion of a common food. Before 1992, only one case of intoxication by chemical, marine toxin, or Clostridium botulinum toxin as a result of the ingestion of food was required to constitute an FBDO. Since 1992, two or more cases have been required. State and local public health departments have primary responsibility for the identifying and investigating FBDOs. State and territorial health departments report these outbreaks to CDC on a standard form. RESULTS: During 1988-1992, a total of 2,423 outbreaks of foodborne disease were reported (451 in 1988, 505 in 1989, 532 in 1990, 528 in 1991, and 407 in 1992). These outbreaks caused a reported 77,373 persons to become ill. Among outbreaks for which the etiology was determined, bacterial pathogens caused the largest percentage of outbreaks (79%) and the largest percentage of cases (90%). Salmonella serotype Enteritidis accounted for the largest number of outbreaks, cases, and deaths; most of these outbreaks were attributed to eating undercooked, infected eggs. Chemical agents caused 14% of outbreaks and 2% of cases; parasites, 2% of outbreaks and 1% of cases; and viruses, 4% of outbreaks and 6% of cases. INTERPRETATION: The number of FBDOs reported per year did not change substantially during the first 4 years but declined in 1992 as a result of the revised definition of an outbreak. During this reporting period, S. Enteritidis continued to be a major cause of morbidity and mortality. In addition, multistate outbreaks caused by contaminated produce and outbreaks caused by Escherichia coli O157:H7 became more prominent. ACTIONS TAKEN: State and local public health departments investigate FBDOs. At the regional and national level, surveillance data provide an indication of the etiologic agents, vehicles of transmission, and contributing factors associated with FBDOs and help direct public health actions.

Disease Outbreaks↗
PubMed1995

Ultrastructural studies on peptides in the dorsal horn of the rat spinal cord--IV. Effects of peripheral axotomy with special reference to neuropeptide Y and vasoactive intestinal polypeptide/peptide histidine isoleucine.

Using immunofluorescence histochemistry and pre- and post-embedding immunoelectron microscopy the rat lumbar dorsal horn was analysed in normal rats and 14 days after unilateral transection of the sciatic nerve. A marked increase in neuropeptide Y-like immunoreactivity was observed in the ipsilateral, superficial dorsal horn, especially in laminae III and IV, of the lumbar 4-5 spinal cord segments after peripheral axotomy. In the ipsilateral lamina II two types of neuropeptide Y-immunoreactive, presumably primary afferent terminals could be identified at the ultrastructural level. The first type contained many large dense-core vesicles (100-155 nm in diameter), whereas a second, more common type had only a few and smaller large dense-core vesicles (80-100 nm in diameter), plus synaptic vesicles of varying diameter (50-85 nm), large empty vesicles and tubular structures. Only occasionally were neuropeptide Y-positive terminals in lamina II involved in the formation of axonal labyrinths. In the ipsilateral lamina III, the number of neuropeptide Y-positive nerve terminals markedly increased after axotomy, with a moderate increase in lamina IV. These neuropeptide Y-positive terminals were morphologically similar to the second type of neuropeptide Y-positive terminal in lamina II, i.e. contained many synaptic vesicles (45-50 nm in diameter), a few small large dense-core vesicles (80-100 nm in diameter), electron-dense granular matrix and a few tubular structures. Fusion of synaptic vesicles with the plasma membrane was often observed at these synapses. These terminals frequently formed glomeruli but were not involved in axonal labyrinths. With regard to local neurons, neuropeptide Y-like immunoreactivity was observed in many dendrite-like profiles mostly making synaptic contacts with neuropeptide Y-negative dendrites and only rarely contacting the central terminal of the glomeruli. Neuropeptide Y-positive nerve endings were mainly seen in lamina I and the outer third of lamina II. After peripheral axotomy the number of vasoactive intestinal polypeptide/peptide histidine isoleucine immunoreactive terminals was increased in laminae I and II. They contained many large dense-core vesicles (100-120 nm in diameter), and some of them were positive for vasoactive intestinal polypeptide/peptide histidine isoleucine. Morphologically, the terminals were characterized by a granular matrix, tubular structures, empty vesicles, reduction in synaptic vesicles and absence of postsynaptic densities. Vasoactive intestinal polypeptide/peptide histidine isoleucine-like immunoreactivities were often found in association with labyrinth formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Surveillance for foodborne-disease outbreaks--United States, 1993-1997.

PROBLEM/CONDITION: Since 1973, CDC has maintained a collaborative surveillance program for collection and periodic reporting of data on the occurrence and causes of foodborne-disease outbreaks (FBDOs) in the United States. REPORTING PERIOD COVERED: This summary reviews data from January 1993 through December 1997. DESCRIPTION OF SYSTEM: The Foodborne-Disease Outbreak Surveillance System reviews data concerning FBDOs, defined as the occurrence of two or more cases of a similar illness resulting from the ingestion of a common food. State and local public health departments have primary responsibility for identifying and investigating FBDOs. State, local, and territorial health departments use a standard form to report these outbreaks to CDC. RESULTS: During 1993-1997, a total of 2,751 outbreaks of foodborne disease were reported (489 in 1993, 653 in 1994, 628 in 1995, 477 in 1996, and 504 in 1997). These outbreaks caused a reported 86,058 persons to become ill. Among outbreaks for which the etiology was determined, bacterial pathogens caused the largest percentage of outbreaks (75%) and the largest percentage of cases (86%). Salmonella serotype Enteritidis accounted for the largest number of outbreaks, cases, and deaths; most of these outbreaks were attributed to eating eggs. Chemical agents caused 17% of outbreaks and 1% of cases; viruses, 6% of outbreaks and 8% of cases; and parasites, 2% of outbreaks and 5% of cases. INTERPRETATION: The annual number of FBDOs reported to CDC did not change substantially during this period or from previous years. During this reporting period, S. Enteritidis continued to be a major cause of illness and death. In addition, multistate outbreaks caused by contaminated produce and outbreaks caused by Escherichia coli O157:H7 remained prominent. ACTIONS TAKEN: Current methods to detect FBDOs are improving, and several changes to improve the ease and timeliness of reporting FBDO data are occurring (e.g., a revised form to simplify FBDO reporting by state health departments and electronic reporting methods). State and local health departments continue to investigate and report FBDOs as part of efforts to better understand and define the epidemiology of foodborne disease in the United States. At the regional and national levels, surveillance data provide an indication of the etiologic agents, vehicles of transmission, and contributing factors associated with FBDOs and help direct public health actions to reduce illness and death caused by FBDOs.

Disease Outbreaks↗
PubMed2001

Physostigmine for Alzheimer's disease.

BACKGROUND: The main pharmacological approach for the treatment of Alzheimer's disease (AD) has been based on the use of agents potentiating cholinergic transmission, particularly by inhibiting acetylcholinesterase (AChE), the enzyme that destroys acetylcholine after it has been secreted into the synaptic clefts. Physostigmine is an AChE inhibitor originally extracted from calabar beans. It is licensed in many countries as an agent for reversing the effect of drugs and poisons causing the anticholinergic syndrome. Studies conducted more than 20 years ago suggested that physostigmine could improve memory in people with or without dementia. Investigation of this property has been limited by the very short half-life of physostigmine. Various forms of administering the drug have been tried to overcome this problem, most recently a controlled-release (CR) oral formulation, and a skin patch. It has been proposed as a potential drug for the symptomatic treatment of AD. OBJECTIVES: To determine whether there is evidence of beneficial effects for the use of physostigmine in Alzheimer's disease. To assess the incidence and severity of adverse effects. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched using the following terms: 'physostigmine', 'physostigmine salicylate', 'Synapton' and 'Antilirium' in accordance with the Cochrane Dementia and Cognitive Improvement Group's search strategy. The pharmaceutical company was contacted. SELECTION CRITERIA: All relevant unconfounded, double-blind, randomized, placebo-controlled trials in which physostigmine was administered for more than one day to patients with dementia of Alzheimer type. Trials in which the allocation to the treatment was not randomized, or in which the allocation to the treatment was not concealed were excluded. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers (JMC & JB), pooled where appropriate and possible, and the weighted or standardized mean differences or Peto odds ratios (95% CI) were estimated. Where possible, intention-to-treat analysis was used. MAIN RESULTS: Fifteen studies were included using four different methods of administration of physostigmine. Four studies, involving 29 people in total, used intravenous infusion; seven, involving 131 people, used a conventional oral form; four, involving 1456 participants, used a controlled-release oral form, and one study of 181 people used a verum skin patch. There are no usable results from the intravenous infusion trials, and the few results from the conventional oral form showed no benefit of physostigmine compared with placebo. The results from two of the four studies of the controlled-release physostigmine apply only to a group of patients identified as responders in a pre-randomization titration period. The best dose physostigmine (mean 25mg/day) was associated with a 1.75 point improvement on ADAS-Cog score (mean difference -1.75, 95% confidence interval -2.90, -0.60 on an intention-to-treat basis) and a 0.26 point improvement on the CGIC score (treated as a continuous scale) (mean difference -0.26, 95% confidence interval 0.06, 0.46 on an intention-to-treat basis) compared with placebo at 6 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial (22/183 vs 2/183)(OR 5.92, 95% confidence limits 2.59, 13.54) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, flatulence or sweating compared with placebo at 6 weeks. The best dose physostigmine (mean 27mg/day) was associated with a 2.0 point improvement on ADAS-Cog score (mean difference -2.02, 95% confidence interval -3.59, -0.45 on an intention to treat basis) compared with placebo at 12 weeks. There were statistically significantly higher numbers of patients from the physostigmine group withdrawing from the trial due to adverse events (13/83 vs 5/93)(OR 3.05, 95% confidence limits 1.15, 8.07) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, tremor, asthenia or sweating compared with placebo at 12 weeks. When no attempt was made to identify responders and all relevant patients with Alzheimer's disease were randomized, fixed dose physostigmine (mean 33 mg/day) was associated with a statistically significantly higher number withdrawing (234/358 vs 31/117)(OR 4.82, 95% confidence limits 3.17, 7.33), withdrawing due to adverse events (196/358 vs 10/117) (OR 6.54, 95%confidence limits 4.29, 9.95) and suffering at least one event of nausea, vomiting, diarhoea, anorexia, dizziness, stomach pain, dyspepsia, sweating, asthenia, dyspnoea or abnormal dreaming compared with placebo at 24 weeks. The results from the study of the verum patch physostigmine show that the double dose (delivering mean dose 12mg/day) was associated with statistically significantly higher numbers suffering at least one adverse event of vomiting, nausea or abdominal cramps compared with placebo at 24 weeks, but placebo was associated with statistically significantly greater numbers of gastrointestinal complaints at 24 weeks compared with single-dose physostigmine. REVIEWERS' CONCLUSIONS: The evidence of effectiveness of physostigmine for the symptomatic treatment of Alzheimer's disease is limited. Even in a controlled release formulation designed to overcome the short half-life, physostigmine showed no convincing benefit and adverse effects remained common leading to a high rate of withdrawal.

Alzheimer Disease↗