Short-term Prevention Research Articles

Tailoring Management Strategies for the Patient With Menstrual Migraine: Focus on Prevention and Treatment

Many women report an increased frequency of headaches around the time of menses. For some women, these headaches are more severe, of longer duration, and lead to greater disability than those occurring at other times in the menstrual cycle. A headache diary is critical to properly diagnose menstrual migraine (MM) by prospectively documenting headache days, severity of headache, and the headaches' relationship to menses. In women with diagnosed MM, acute treatment has been proven to be effective in randomized clinical trials. For those women who have predictable periods and may require preventive therapy, short-term prevention is a reasonable approach due to the predictability of MM. Although several agents (eg, naproxen sodium, magnesium, triptans) have been evaluated for prevention of MM, all but triptans have been assessed in small trials of between 20 and 35 women. Naratriptan, frovatriptan, and, most recently, zolmitriptan have been proven effective in preventing MM. Triptans are generally well tolerated, and the long-term safety of these agents is currently being evaluated. The flexibility of using acute and preventive therapy allows physicians to tailor treatment of MM and meet the needs of individual patients.

Serum Lactate Levels in Infants Exposed Peripartum to Antiretroviral Agents to Prevent Mother-to-Child Transmission of HIV: Agence Nationale de Recherches Sur le SIDA et les Hépatites Virales 1209 Study, Abidjan, Ivory Coast

Mitochondrial toxicity was described in infants exposed to long-term antiretroviral regimens containing nucleoside analogues for the prevention of mother-to-child transmission of HIV. We measured the serum lactate levels in children born to HIV-1 infected African women receiving short-term antiretroviral prevention of mother-to-child transmission of HIV regimens. A prospective study was conducted in women-child pairs from the third trimester of pregnancy to 3 months of life. The exposed group was formed by children exposed in utero to nucleoside analog antiretroviral regimens, zidovudine or zidovudine + lamivudine from 32 to 36 weeks of amenorrhea until delivery. All of these women received nevirapine single dose at the beginning of labor. The children received zidovudine during the first 7 days of life and a nevirapine single dose at day 3. The control group was formed by infants born to HIV-1-infected women who had received nevirapine single dose only and who were not exposed to nucleoside analog antiretroviral regimens. Serum lactate levels were measured at 4, 6, and 12 weeks of life by Cobas Integra 400. A total of 836 blood samples from 338 infants was collected (262 exposed and 76 controls). Median lactacidemia was 1.8 mmol/L (interquartile range: 1.2-2.7 mmol/L). Overall serum lactate levels > or = 2.5 mmol/L, defining hyperlactatemia, were observed in 39 of the 292 infants who had > or = 2 serum lactate measurements. The 3-month period prevalence of hyperlactatemia did not differ between the exposed group and the control group. All of the serum lactate levels returned to normal values in all of the subsequent samples. No case of symptomatic hyperlactatemia was detected during the study period. Increased lactate levels were identified equally in infants whose mother received short-term nucleoside analogs or nevirapine single dose for prevention of mother-to-child transmission of HIV. Although not rare, hyperlactatemia was not related to short-term exposure to nucleoside analog antiretroviral regimens.

Development of torsade de pointes caused by exacerbation of QT prolongation during clipping of cerebral artery aneurysm in a patient with subarachnoid haemorrhage

We report the case of a 79-yr-old woman with subarachnoid haemorrhage (SAH) in whom torsade de pointes (TdP) caused by worsening the QT prolongation occurred during clipping of cerebral artery aneurysm. This patient shows a potential risk of occurrence of life-threatening tachyarrhythmia, TdP by prolonging the QT interval during surgery in patients with SAH even with no additional factors that predispose to TdP. Therefore, a proper monitoring of the QT interval is necessary as a predictor of TdP. When ventricular tachyarrhythmia occurs, recognition of TdP is important because antiarrhythmic drug therapy for TdP is different from that for ventricular tachyarrhythmias that is not TdP.

Frovatriptan: clinical review and future directions

Triptan medications are selective serotonin receptor (5-HT1B/D) agonists approved for the treatment of acute migraine attacks. Among the currently available triptans, frovatriptan is unique with a long half-life (~26 h), metabolism by multiple pathways and a low side-effect profile. Clinical trial data demonstrates efficacy for frovatriptan across multiple doses, with the 2.5 mg dose selected for lower side effects. Frovatriptan is approved for use in the conventional treatment of an ongoing migraine attack, as are the other currently available triptan medications. The long half-life of frovatriptan has led to the initiation of studies of frovatriptan for the short-term prevention of menstrually related migraine attacks, during which patients are often difficult to treat. This newly investigated treatment approach for patients with predictable menstrually related migraine may, in the future, lead to treatment paradigms that benefit those patients with migraine attacks that are difficult to manage.

SHORT-TERM PREVENTION OF AMMONIA LOSS AND ODOR FROM LIME-STABILIZED BIOSOLIDS

SHORT-TERM PREVENTION OF AMMONIA LOSS AND ODOR FROM LIME-STABILIZED BIOSOLIDSOdors emanating from biosolids are typically associated with ammonia (NH3) loss. The study was conducted to develop convenient and efficient strategies for short-term control of NH3 loss and odors from biosolids. Aerobically-digested (AE) biosolids were collected from a wastewater treatment plant and lime-stabilized (AE-LS) in the laboratory. Aluminum (Al3+), calcium (Ca2+), iron (Fe3+) and...Author(s)Naomi Waissman AssadianWilliam LindemannJohn BalliewSourceProceedings of the Water Environment FederationSubjectSession 95: Management of Odors and VOCs/Disinfection: Characterizing and Understanding Odor SourcesDocument typeConference PaperPublisherWater Environment FederationPrint publication date Jan, 2005ISSN1938-6478SICI1938-6478(20050101)2005:7L.7932;1-DOI10.2175/193864705783813755Volume / Issue2005 / 7Content sourceWEFTECFirst / last page(s)7932 - 7939Copyright2005Word count302

Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 Years after Bariatric Surgery

Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk, but whether these benefits persist over time is unknown. The prospective, controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched, conventionally treated obese control subjects. We now report follow-up data for subjects (mean age, 48 years; mean body-mass index, 41) who had been enrolled for at least 2 years (4047 subjects) or 10 years (1703 subjects) before the analysis (January 1, 2004). The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years. After two years, the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group (P<0.001). After 10 years, the weight had increased by 1.6 percent and decreased by 16.1 percent, respectively (P<0.001). Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period. Two- and 10-year rates of recovery from diabetes, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, hypertension, and hyperuricemia were more favorable in the surgery group than in the control group, whereas recovery from hypercholesterolemia did not differ between the groups. The surgery group had lower 2- and 10-year incidence rates of diabetes, hypertriglyceridemia, and hyperuricemia than the control group; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable. As compared with conventional therapy, bariatric surgery appears to be a viable option for the treatment of severe obesity, resulting in long-term weight loss, improved lifestyle, and, except for hypercholesterolemia, amelioration in risk factors that were elevated at baseline.

Proton‐pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non‐steroidal anti‐inflammatory drugs

Although administration of gastroprotective drugs may reduce the risk of peptic ulcers associated with the chronic use of non-steroidal anti-inflammatory drugs or aspirin, no consensus exists as to whether this co-therapy is effective for short-term prevention, particularly in old age. To evaluate the risk of peptic ulcer associated with acute and chronic non-steroidal anti-inflammatory drugs or aspirin therapy in elderly subjects, and the influence of antisecretory treatment on this risk. The study included 676 elderly non-steroidal anti-inflammatory drugs or aspirin users and 2435 non-users who consecutively underwent upper gastrointestinal endoscopy. The use of non-steroidal anti-inflammatory drugs and/or aspirin as well as antisecretory drugs (H2-blockers and proton-pump inhibitors) was evaluated by a structured interview. Diagnosis of gastric and duodenal ulcer as well as Helicobacter pylori infection were carried out by endoscopy and histological examination of the gastric mucosa. About 47.3% of patients were acute and 52.7% chronic users of non-steroidal anti-inflammatory drugs or aspirin. The risk of peptic ulcer, adjusted for age, gender, H. pylori infection and antisecretory drug use was higher in acute (gastric ulcer: odds ratio, OR = 4.47, 95% CI: 3.19-6.26 and duodenal ulcer: OR = 2.39, 95% CI: 1.73-3.31) than chronic users (gastric ulcer: OR = 2.80, 95% CI: 1.97-3.99 and duodenal ulcer: OR = 1.68, 95% CI: 1.22-2.33). Proton-pump inhibitor treatment was associated with a reduced risk of peptic ulcer in both acute (OR = 0.70, 95% CI: 0.24-2.04) and chronic (OR = 0.32, 95% CI: 0.15-0.67) non-steroidal anti-inflammatory drugs/aspirin users. Conversely, concomitant treatment with H2-blockers was associated with a significantly higher risk of peptic ulcer both in acute (OR = 10.9, 95% CI: 3.87-30.9) and chronic (OR = 6.26, 95% CI: 2.56-15.3) non-steroidal anti-inflammatory drugs/aspirin users than non-users. Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users. These findings suggest that proton-pump inhibitor co-treatment is advisable in symptomatic elderly patients who need to be treated with non-steroidal anti-inflammatory drugs and/or aspirin for a short period of time.

Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment.

This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure.

Assessing psychiatric patients for violence.

Managing violent patients is a dilemma that every clinician faces. This article reviews the current literature and assesses the evidence on the management of violent patients in the clinical setting. Risk factors (dispositional, historical, contextual and clinical) and early warning signs of violence will be outlined. Understanding these issues will facilitate the short-term prediction and prevention of violence in clinical settings. Interventions have been categorized for use according to the urgency of the situation. This degree of urgency has been designated as either potential, imminent or emergent violence. Special considerations that may alter the management of violence will be delineated. Specifically, we will highlight issues related to gender, age and mental retardation. Aspects of professional training in regards to the management of the violent patient will be underscored as well. Finally, the review of the literature has led to a decision tree that can inform the reader in the evidence-based management of the violent patient. This decision tree is offered to the busy practitioner as a practical clinical tool for using evidence based practices in managing violent patients.

Future Challenges: Changing Health Care Delivery and Advancing Patient Care

Our current health care system involves multidisciplinary groups of practitioners who function as freestanding silos and in which a “team” approach means an awareness and tolerance of other disciplines as patients are handed from one practitioner to another. Pharmacy has advanced from clinical pharmacy through pharmaceutical care to the dawning of medication therapy management services. With each step pharmacy has become more focused on direct patient care. As technology and technicians improve the dispensing process and as electronic databases evolve, the pharmacist will increasingly be positioned to be more available and better equipped to provide direct patient care and medication therapy management services. Over the next decade, I see pharmacy and other health care providers moving to an interdisciplinary team approach in which decisions are made by consensus and through which each discipline has an equal opportunity for input.1 To accommodate such a change, I envision a new health care delivery model based on the following components: n Wellness and prevention services as the entry point into the system. n An interdisciplinary delivery model with providers having shared borders (a model in which our professional boundaries become blurred or overlap, and health care professionals share a common knowledge base, a common professional interest, and an instinct to help the patient). n “Physician extenders” providing disease and medication management services using evidenced-based medicine. n Systems that are outcomes driven and outcomes justified. n A broader acceptance and use of complementary and alternative medicine within the delivery model. All of the above components are evolving or already exist in the current environment. The challenge to the system is to integrate them into successful delivery models. The challenge to the pharmacist is to identify, embrace, Future Challenges: Changing Health Care Delivery and Advancing Patient Care and drive their evolving roles within this new health care delivery model.

Short-term prevention of thromboembolic complications in patients with atrial fibrillation with aspirin plus clopidogrel: the Clopidogrel-Aspirin Atrial Fibrillation (CLAAF) Pilot Study

Background We evaluated the short-term safety and efficacy of aspirin-plus-clopidogrel as antithrombotic therapy in nonvalvular atrial fibrillation (AF). Methods and results Thirty patients (11 women, 45 to 75 years of age) with non-high–risk permanent (n = 12) or persistent AF awaiting cardioversion (n = 18) underwent transesophageal echocardiography to exclude left heart thrombi and were then randomly assigned to receive warfarin (international normalized ratio, 2 to 3 for 3 weeks) or aspirin (100 mg/d alone for 1 week)-plus-clopidogrel (75 mg/d added to aspirin for 3 weeks). Bleeding time and serum thromboxane B2 were measured at entry and at 3 weeks. Bleeding time, not affected by warfarin, was prolonged by 71% by aspirin ( P < .05) and further, by 144%, by adding clopidogrel ( P < .01 vs aspirin alone; +319%, P < .01, vs baseline). Thromboxane B2, not affected by warfarin, was reduced by aspirin (−98%, P < .01) but not further by clopidogrel. No thrombi or dense spontaneous echo-contrast were found at the 3-week transesophageal echocardiography. Seven of 9 patients receiving warfarin and 7 of 9 patients receiving aspirin-plus-clopidogrel, undergoing electrical cardioversion, achieved sinus rhythm. No thromboembolic or hemorrhagic events occurred in both arms throughout the 3-week treatment and a further 3-month follow-up. Conclusions Aspirin-plus-clopidogrel and warfarin were equally safe and effective in preventing thromboembolism in this small group of patients with non–high-risk AF.

The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs.

Although the administration of gastroprotective drugs may reduce the risk of gastrointestinal (GI) bleeding due to intake of non-steroidal anti-inflammatory drugs (NSAIDs) and aspirin during chronic treatment, no consensus exists as to whether such co-therapy is effective in short-term prevention, particularly in old age. The aim of our study was to evaluate the risk of bleeding associated with acute and chronic NSAID or aspirin therapy in elderly subjects, and the influence of gastroprotective treatment on such a risk. The study included 467 elderly NSAID or aspirin users and 1784 non-users, who consecutively underwent upper GI endoscopy. The use of NSAIDs and/or aspirin as well as gastroprotective drugs (misoprostol, H2-blockers, proton pump inhibitors) was evaluated during a structured interview. Upper GI tract bleeding was diagnosed on the basis of symptoms and endoscopic signs of recent hemorrhage. 54.2% of patients were acute and 45.8% chronic users of NSAIDs or aspirin. The risk of bleeding was higher in acute [odds ratio (OR) 4.14, 95% CI 2.97-5.78] than chronic users (OR 1.71, 95% CI 1.1-2.67). The risk of bleeding, adjusted for age, gender, Helicobacter (H) pylori infection, and gastroprotective drug use were 7.87 (CI 4.90-12.60) in acute users and 3.97 (95% CI 2.27-6.96) in chronic users of NSAIDs and/or aspirin. The risk of bleeding was significantly associated with acute but not chronic use of regular-dose aspirin (OR 5.53, 95% CI 2.29-13.3), diclofenac (OR 4.44, 95% CI 2.21-8.93), ketorolac (OR 4.81, 95% CI 2.13-10.9), naproxen (OR 14.9, 95% CI 4.23-52.4) or nimesulide (OR 4.06, 95% CI 1.2-13.8). Piroxicam increased the risk of bleeding in both acute (OR 5.36, 95% CI 1.94-14.8) and chronic therapy (OR 5.53, 95% CI 1.23-24.9). In acute users, concomitant therapy with proton pump inhibitors reduced the risk of bleeding compared with non-users (OR 1.05, 95% CI 0.19-5.65), whereas co-treatment with H2-blockers was associated with a significantly higher risk of bleeding than in non-users (OR 3.40, 95% CI 1.28-9.02). Chronic users of NSAIDs or aspirin co-treated with proton pump inhibitors had a lower risk of bleeding (OR 1.12, 95% CI 0.21-6.07) than those treated with misoprostol (OR 1.91, 95% CI 0.33-10.9) or H2 blockers (OR 2.26, 95% CI 0.81-6.36). The risk of upper GI bleeding is significantly higher in elderly acute vs chronic users of NSAIDs or regular-dose aspirin. In acute NSAID or aspirin users, co-treatment with proton pump inhibitors, but not with H2-blockers, may reduce the risk of bleeding compared with non-users.

Study on Short-Term Prevention Efficiencies of Chemical Binders to Reduce Fugitive Dust

Chemical binders have been demonstrated to be a cost-effective measure to prrevent fugitive dust. Fugitive dust is a typical air pollution source produced by construction activities. From the engineering application point of view, an approach using dimensionless analysis with a multivariable regression method based on total suspended particulate (TSP) experimental data is worth exploring to predict the prevention efficiencies of chemical binders. This paper examines four-month prevention efficiencies of chemical binders using a comprehensive empirical framework with auxiliary theoretical analysis. A series of field-analogous experiments was carried out to measure TSP using high volume air samples in an artificial wind tunnel system for three general chemical binders. The short-term prevention efficiency was affected primarily by wind velocity, mass concentration of the chemical binder, spray intensity, silt content, and prevention duration. Correlated with these primary parameters, a useful equation is proposed to estimate the short-term prevention efficiencies that would be valid under the appropriate conditions suggested by this work.

I. Background and Introduction

The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) presents the National Cholesterol Education Program's (NCEP's) updated recommendations for cholesterol testing and management. It is similar to Adult Treatment Panel II (ATP II)1,2 in general outline and fundamental approach to therapy. It focuses on the role of the clinical approach to prevention of coronary heart disease (CHD).* This report continues to identify low-density lipoprotein (LDL) as the primary target of cholesterol-lowering therapy. Since ATP II, a number of controlled clinical trials with newer cholesterol-lowering drugs have been reported. These trials demonstrated remarkable reductions in risk for CHD, in both primary and secondary prevention. Their results enrich the evidence base upon which the new guidelines are founded. The ATP III panel extensively analyzed the results of recent clinical trials whose findings strongly influenced the development of the new guidelines. The panel's major goals were to review the literature objectively and to document and display the scientific evidence for ATP III recommendations. Prior to the appointment of the ATP III panel, the NCEP Coordinating Committee developed a list of important issues for the panel's consideration. This list was presented to the panel, discussed, and modified appropriately. The literature pertaining to each defined issue was identified by the panel members and by a MEDLINE search. Panel members produced a series of issue papers that carefully reviewed the literature; these issue papers became the foundation for writing the first draft of the report. Modifications of drafts were made following review and discussion of additional evidence arising from the literature search. ATP III contains both evidence statements and specific recommendations based on these statements. Each evidence statement is qualified according to category of evidence (A—D) and strength …

The Bech-Rafaelsen Melancholia Scale (MES) in clinical trials of therapies in depressive disorders: a 20-year review of its use as outcome measure.

To evaluate the psychometric properties of the Bech-Rafaelsen Melancholia Scale (MES) by reviewing clinical trials in which it has been used as outcome measure. The psychometric analysis included internal validity (total scores being a sufficient statistic), interobserver reliability, and external validity (responsiveness in short-term trials and relapse prevention in long-term trials). The results showed that the MES is a unidimensional scale, indicating that the total score is a sufficient statistic. The interobserver reliability of the MES has been found adequate both in unipolar and bipolar depression. External validity including both relapse, response and recurrence indicated that the MES has a high responsiveness and sensitivity. The MES has been found a valid and reliable scale for the measurement of changes in depressive states during short-term as well as long-term treatment.

Short-term prevention of osteoclastic resorption and osteopenia in ovariectomized rats treated with the H2 receptor antagonist cimetidine

Ovariectomy rapidly induces strong osteoclast differentiation, leading to a marked loss of cancellous bone in the rat appendicular skeleton. As we found that histamine inhibition prevented periosteal bone resorption in rats, we tested the hypothesis that cimetidine, an H2 receptor antagonist, prevents the osteoclastic burst and subsequent trabecular bone loss in this setting. Forty female Sprague-Dawley rats were ovariectomized (ovx) or sham-operated. Rats from each group received daily intramuscular injections of cimetidine (125 mg/kg per day) or vehicle. The animals were killed 14 days after surgery, and their femora were processed for morphometry. Cimetidine had no effect on serum estradiol levels in the control and ovx rats. BV/TV was reduced by 36% in the ovx rats, and by 10% in the cimetidine treated rats (p < 0.01). Tb.N and Tb.Wi were significantly reduced by 30% in the ovx rats and by 15% ovx-treated ones. OcS/BS did not change in the treated ovx rats, but increased 3.7-fold in the untreated ovx ones (p < 0.001). The N.Oc/TBPm increased markedly in the ovx rats (2.6-fold, p < 0.0001 vs. controls), but only slightly in the cimetidine-treated animals (+18%, p < 0.05 vs. controls), with a significant difference between the cimetidine-treated and -untreated ovx animals (p < 0.001). Cimetidine had no effect on these parameters in sham-operated animals. These results show that histamine inhibition by an H2 receptor antagonist partially prevents the consequences of castration on cancellous bone, possibly by an action on osteoclast differentiation. Interestingly, cimetidine had no effect on basal resorption along trabecular bone. Histamine inhibition by H2 blockers warrants further investigation in this model of osteopenia.

Selective estrogen receptor modulators (SERM): A new choice for postmenopausal women and physicians who worry on cancer

The postmenopausal state is characterized by the cessation of menstruation, loss of ovarian function, and a dramatic decrease in the level of circulating estrogen. This state of estrogen deficiency contributes to the acceleration of several age-related health problems in women, including cardiovascular disease, osteoporosis, and dementia. Estrogen replacement is clearly effective in the short-term and long-term treatment and prevention of postmenopausal symptoms. However, until now, the amount of HRT user is still very low. Fear of breast cancer and endometrial cancer are the most common concern in using hormone replacement therapy (HRT), although the relationship between long-term HRT and breast cancer remains controversial. For physicians or patients, who worry on cancer, the ideal drug is now available i.e. the selective estrogen receptor modulators (SERM), with the generic name raloxifine. (Med J Indones 2001; 10: 187-90)

Diethylenetriaminopentaacetic acid is unsuitable for long-term preservation of RBCs.

The addition of an appropriate metal chelator, such as diethylenetriaminopentaacetic acid (DTPA) to stored blood has been shown to be effective in a short-term (0-12 days) prevention of lipid peroxidation of stored RBCS: However, its long-term effectiveness has not been carefully evaluated. Blood was preserved in simulated blood bank conditions with or without the addition of DTPA for 4 weeks. Aliquots of stored blood were taken weekly from the storage bag and the deformability profile was determined using a custom-built laser viscodiffractometer. Malondialdehyde (MDA), an index of lipid peroxidation, and the extent of vesiculation of the stored blood were quantified concurrently. It was found that MDA values for DTPA-supplemented blood at the end of a 28-day storage period were significantly elevated compared with the DTPA-free counterpart (23.50 +/- 3.2 vs. 16.10 +/- 2.5 microM; p<0.05). In addition, DTPA-supplemented blood was more susceptible to vesiculation than its DTPA-free counterpart (31.26 +/- 4.1 vs. 10.26 +/- 1.5% of acetyl cholinesterase release, p<0.001). These data are also in accordance with the finding of the deformability profile result, indicating that DTPA-supplemented blood exhibits not only a decrease in deformability index, but also a tendency to shift the profile to a lower osmolality compared with that of controls (a dehydration phenomenon). Long-term (0-28 days) preservation of human RBCs with DTPA caused a gradual increase in MDA production, a progressive enhancement of the severity of vesiculation, and an alteration in the deformability profile. Free-radical-mediated oxidative damage is likely to be the culprit for this observed phenomenon. In addition, the direct effect of DTPA on RBC structural integrity must be considered.

Prevention of acute NSAID-related gastroduodenal damage: a meta-analysis of controlled clinical trials.

No consensus exists as to whether cotherapy is effective in the short-term prevention of severe NSAID-related gastroduodenal damage. The aim of this study was to provide a quantitative systematic review of the efficacy of gastroprotective drugs, such as misoprostol, H2-blockers, and proton pump inhibitors (PPI) in preventing the severe acute NSAID-related gastroduodenal damage. Placebo-controlled randomized clinical trials on the use of misoprostol, H2-blockers, and PPIs as preventative agents published between January 1986 and May 1999 were identified through Medline and reference lists from clinical reviews. Studies on patients or healthy subjects were considered to be eligible for data pooling if they were performed in acute NSAID users (not longer than 30 days) and with at least one endoscopic evaluation during therapy that reported results specifically for gastric and duodenal damage. Risk difference (RD), heterogeneity chi2 test, publication bias assessment and number needed to treat (NnT) were calculated for each meta-analysis by a customized program. Twenty-one trials met the inclusion criteria evaluating a total of 636 healthy subjects and 1904 patients with arthritis randomized to active drug or placebo. The baseline risk of NSAID-related gastric (68% vs 16.6%, P < 0.001) and duodenal (22% vs 8.5%, P < 0.001) damage was higher in healthy subjects compared to patients with arthritis. Meta-analysis demonstrated a significant heterogeneity between trials performed in the two populations (P < 0.0001). In healthy subjects the active drug treatment induced a significant prevention of severe gastric (misoprostol RD = 69%, 95% CI = 60.3-77.7, H2-blocker RD = 38.3%, 95% CI = 17.8-58.9 and PPI RD = 43%, 95% CI = 28.2-57.7) and duodenal damage (misoprostol RD = 22.3%, 95% CI = 13.6-31, H2-blocker RD = 13.2%, 95% CI = 5.2-21.3 and PPI RD = 17.7%, 95% CI = 3.5-31.8). NnT values were, respectively, 1, 3, and 2 for gastric and 4, 8, and 6 for duodenal damage. In patients with arthritis lower RD and higher NnT values were found compared to healthy subjects. In conclusions, cotreatment with gastroprotective drugs for short-term prevention of severe gastroduodenal NSAID-related damage was more effective in healthy subjects than in patients with arthritis; misoprostol and PPIs were more effective than H2-blockers in the prevention of both gastric and duodenal severe damage; more studies need to evaluate the role of short-term prevention in patients with arthritis who require acute NSAID treatment.

Blockade of sensitization to methylphenidate by MK-801: partial dissociation from motor effects

The role of MK-801's locomotor effect in blocking the development of sensitization to methylphenidate was investigated utilizing a computerized locomotor activity monitoring system. After 7 days of acclimation to a 12:12 light–dark cycle (lights on at 07:00), male Sprague–Dawley rats ( n=62) were housed in test cages and motor activity was recorded continuously for 16 days. The first 2 days of recording served as a baseline for each rat, and on day 3 each rat received a saline injection. On days 4 to 9 rats were randomly divided into seven groups: Rats received either six daily s.c. injections of methylphenidate (2.5 mg/kg; Group 1), or six daily i.p. injections of 0.30 mg/kg, 0.05 mg/kg MK-801 (Groups 2 and 3, respectively); two MK-801 pre-treatment groups received a single i.p. injection of 0.05, or 0.30 mg/kg MK-801 one hour prior to 2.5 mg/kg methylphenidate ( n=8 each) on day 4 followed by five daily injections of 2.5 mg/kg methylphenidate; and finally, two cotreatment groups received a challenge dose of 2.5 mg/kg methylphenidate on day 4 followed by either 0.05 or 0.30 mg/kg MK-801 i.p. one hour prior to 2.5 mg/kg methylphenidate from days 5 to 9. All groups were allowed five days of no treatment before being re-challenged on day 15 with the same treatment they received on day 4. Methylphenidate and 0.30 mg/kg MK-801 sensitized to their own locomotor effects, but 0.05 mg/kg MK-801, which had no acute motor effects, did not. The administration of MK-801 (0.30 mg/kg) prior to methylphenidate either singly on day 4, or coadministered throughout the repeated methylphenidate treatment phase, blocked the development of sensitization to methylphenidate. However, MK-801 at 0.05 mg/kg delayed the development of sensitization when co-administered on days 5 to 9, but a single injection 1 h prior to methylphenidate on day 4 did not prevent sensitization to subsequent methylphenidate administration. In conclusion, MK-801 prevents sensitization to methylphenidate; motor stimulation by MK-801 is not necessary for short-term prevention or delay of sensitization to methylphenidate but may be necessary for a persistent blockade of sensitization.