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PubMed2003

Sex differences in the acquisition of IV methamphetamine self-administration and subsequent maintenance under a progressive ratio schedule in rats.

RATIONALE: Previous work indicates that female rats initiate cocaine use sooner than male rats and reach significantly higher break points (BPs) for a single injection of cocaine under a progressive ratio (PR) schedule compared to male rats. OBJECTIVES: The present study extends previous work examining sex differences to the acquisition of methamphetamine (METH) (0.02 mg/kg) and maintenance of METH-maintained responding under a PR schedule. METHODS: An automated priming procedure that has previously been shown to be sensitive to sex differences was used for the acquisition of drug self-administration. A PR schedule that has been shown to be sensitive in detecting sex differences in maintenance levels of cocaine-reinforced responding was used for the maintenance phase of the experiment. RESULTS: A greater percentage of female rats met the acquisition criterion for METH (0.02 mg/kg) self-administration compared to male rats (55.6% versus 11.1%, respectively), and they did so at a significantly faster rate. Under stable fixed-ratio 1 (FR1) conditions (after acquisition and 5 days before the PR schedule) female rats responded for significantly more METH (0.02 mg/kg) infusions compared to males. Dose-response curves obtained under the PR schedule during maintenance indicated that female rats self-administered significantly more METH infusions compared to male rats. CONCLUSIONS: These data suggest that female rats are more vulnerable to the acquisition of METH self-administration, and they are more motivated to self-administer METH compared to male rats under a PR schedule during the maintenance phase.

Animals↗
PubMed1999

Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats.

RATIONALE: Recent studies suggest that the GABA(B) receptor agonist, baclofen, may be a useful pharmacotherapy for cocaine abuse. OBJECTIVES: To investigate further the effects of baclofen on maintenance and reinstatement of cocaine-reinforced behavior in rats. METHODS: Two groups of rats were trained to self-administer IV cocaine (0.2 or 0.4 mg/kg per infusion) during daily 7-h sessions under a fixed-ratio 1 schedule. Rats were pretreated with baclofen (1.25, 2.5 or 5 mg/kg IP) or saline before the session for 5 consecutive days. An additional group of rats was trained to self-administer IV cocaine (0.4 mg/kg per infusion) during the first 2 h of daily 7-h sessions. Cocaine was replaced by saline for the remaining 5 h of the session. Once behavior had stabilized over the 7-h period, priming injections of saline (IV), cocaine (3.2 mg/kg IV) or baclofen (1.25 or 2.5 mg/kg IP) were administered prior to hour 4. Injections of baclofen (1.25 or 2.5 mg/kg IP) or saline were also given before priming injections of cocaine. RESULTS: Pretreatment with the two higher doses of baclofen (2.5 and 5 mg/kg) decreased the number of cocaine infusions in both maintenance groups (0.2 and 0.4 mg/kg) over the 5-day treatment period. Baclofen had a greater suppressant effect on responding maintained by the lower dose of cocaine. Priming injections of baclofen (1.25 and 2.5 mg/kg) or saline did not reinstate responding. However, these same doses of baclofen dose-dependently reduced the reinstatement of responding produced by priming injections of cocaine. CONCLUSIONS: 1) The magnitude of the suppressant effects of baclofen on maintenance of cocaine self-administration depends upon the maintenance dose, 2) baclofen may be useful in preventing reinstatement of cocaine-seeking behavior, and 3) compared to maintenance, reinstatement of responding is more sensitive to the suppressant effects of baclofen.

Animals↗
PubMed2004

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗
PubMed2006

Long-term sinus rhythm maintenance after cardioversion of persistent atrial fibrillation: is the treatment's success predictable?

The aim of our study was to identify the clinical and echocardiographic predictors of long-term success of cardioversion in patients with persistent atrial fibrillation (AF). Our study comprised 104 patients (F/M 33/71; mean age 60.4 +/- 7.9 years) assigned to SR restoration and maintenance with sequentially administered antiarrhythmic drugs. Their clinical and transthoracic echocardiographic (TTE) variables were recorded prior to cardioversion and examined for correlation with sinus rhythm (SR) maintenance at 1 year. The variables under consideration included age, gender, echo parameters such as long and short left atrial (LA) axis, LA and right atrial (RA) area, fractional shortening (FS) and left ventricular end-diastolic diameter, AF duration, New York Heart Association functional class, and concomitant diseases. Generalized additive logistic regression method was used to investigate impact of the selected variables on long-term SR maintenance. At 1 year, SR was present in 63.5% of patients. Left atrium area (LA(ar)) > 28 cm (P < 0.02) and FS value >26% (P < 0.05), both measured at baseline, were significantly associated with SR maintenance after 1 year. Patients with large LA(ar) values (>28 cm(2)) presented a significant decrease (31.45 +/- 3.07 cm(2) vs 28.94 +/- 3.81 cm(2); P < 0.008) during 30 days following SR maintenance. In patients with LA(ar) >28 cm(2) we noted an atrial decrease of 2.57 +/- 3.2 cm(2) (P < 0.004) during 30 days following SR restoration, which turned out to be an independent factor related to SR presence at 1 year of follow-up (relative risk 1.83; 95% confidence interval: 1.03-2.95; P < 0.01). Of all the considered variables only LA area and FS value seem to be relatively reliable predictors of SR sustainability at 1 year after an effective cardioversion of persistent AF.

Aged↗
PubMed1999

Psychotic relapse and maintenance therapy in paranoid schizophrenia: a 15 year follow up.

In spite of numerous reports on a 1 to 2 year maintenance neuroleptic treatment of schizophrenia, there is little systematic information on decade-long maintenance therapy. We conducted a retrospective study in fifty outpatients with paranoid schizophrenia who have been seen at our clinic for a duration of 15 years or more since their first psychotic episodes. Relapse rate within 2, 5, 10, and 15 years from remission of the first psychotic episode were 52, 60, 86, and 90%, respectively. However, the incidence of relapse decreased with time. This decrease was accounted for by the decrease of relapse observed when off drug. Conversely, the incidence of relapse occurred on drug remained unchanged. The average maintenance dose 15 years after remission of the first psychotic episode was 5.41 +/- 7.28 mg/d (haloperidol equivalents: mean +/- SD). The maintenance dose correlated significantly with the number of relapses and total duration of psychotic episodes. These results suggest that maintenance treatment remained effective for decades, although it did not ameliorate the liability to relapse itself. Repeated relapse may be associated with requirement for a higher neuroleptic dose for relapse prevention.

Antipsychotic Agents↗
PubMed2001

Clonal maintenance of imprinted expression of SNRPN and IPW in normal lymphocytes: correlation with allele-specific methylation of SNRPN intron 1 but not intron 7.

DNA methylation is a heritable and reversible modification to CpG sites in the mammalian genome. Parental allele-specific methylation is hypothesized to be important in the establishment and maintenance of imprinted gene expression; however, dynamic changes in allele-specific patterns have been observed. The upstream regulatory region of the small nuclear riboprotein N gene (SNRPN) is an important imprinting control region (ICR) for establishing and maintaining the methylation imprint in the locus on 15q11-13 associated with Prader-Willi and Angelman syndromes (PWS). To compare directly the role of allele-specific methylation patterns and the maintenance of imprinted expression in the PWS region, clonal populations of normal T lymphocytes were cultured for 22-25 generations. A novel long-range semi-nested polymerase chain reaction (PCR) strategy was utilized in order to span two different methylation sites, and a polymorphism within SNRPN was used so that allele-specific methylation of both sites could be determined. Reverse transcription/PCR followed by polymorphism analysis was also performed in order to determine parental allele-specific transcription. Exclusive paternal expression at both SNRPN and IPW was maintained in all T cell clones and correlated with maternal methylation of the intron 1 NotI site. In contrast, biallelic methylation was observed in all clones at the previously described paternally methylated HpaII site in intron 7. These results demonstrate that the maintenance of paternal expression of SNRPN and IPW correlates with a strict clonal maintenance of allele-specific methylation at the CpG-dense 5' end of SNRPN. Differential maintenance of methylation sites within imprinted genes may depend on the density and chromatin organization of surrounding CpG sites.

Alleles↗
PubMed2000

Peptic ulcer recurrence during maintenance therapy with H2-receptor antagonist following first-line therapy with proton pump inhibitor.

We investigated the peptic ulcer recurrence rates during maintenance therapy with H2-receptor antagonists (H2RAs) following first-line therapy with a proton pump inhibitor (PPI). Patients with gastric ulcer (GU) or duodenal ulcer (DU) were enrolled in this study; 583 eligible patients (GU, 325; DU, 258) were administered lansoprazole (30 mg/day for 8 weeks for GU, and the same dosage for 6 weeks for DU) as first-line therapy, and a half dose of H2RA as maintenance therapy for 12 months. Endoscopic photographs were taken before administration and after 8 (GU) and 6 (DU) weeks of lansoprazole administration. Ulcer stage was evaluated using the classification of Sakita and Miwa. Endoscopic examinations were performed 6 months or 12 months after the start of maintenance therapy or when a recurrence was suspected because of the appearance of subjective symptoms. The healing rates for GU and DU patients after completion of lansoprazole therapy were 79% in both groups, while the S2-stage healing rates were 18% and 31%, respectively. At 1 year after the start of maintenance therapy, the recurrence rates were 25% for GU and 39% for DU patients. In DU patients, the recurrence rates from S1-stage and S2-stage were 49% and 20%, respectively (P = 0.004), but no significant difference was found between these rates in GU patients. The recurrence rates in H. pylori-positive patients before lansoprazole administration were 27% for GU and 43% for DU patients. We concluded that the maintenance therapy with a half-dose of H2RA following PPI therapy was insufficient to prevent recurrences of GU and DU.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1979

A simple technic for predicting daily maintenance dose of warfarin.

Warfarin anticoagulation data from forty-seven patients studied retrospectively was used to develop an algorithm for predicting daily maintenance dose of warfarin. A plot of prothrombin time versus cumulative warfarin loading dose was made for each of the forty-seven patients and the aera under the curve (AREA) measured from the baseline prothrombin time to a prothrombin time of 20 seconds. A linear correlation between the established daily maintenance dose of warfarin and AREA was derived regression analysis: Daily maintenance dose (mg/day) = 0.0465 x (AREA) + 1.5. The correlation was then used to predict daily maintenance dose in twenty-four patients studied prospectively. The mean prothrombin time for a seven day stabilization period after loading for all patients in the prospective study was 21.5 +/- 2.2 seconds and the seven day mean prothrombin time for each patient fell between 19 and 24 seconds. The results of the prospective study indicate that this technic is useful in the early, accurate prediction of a daily maintenance dose of warfarin.

Adult↗
PubMed1988

Identification of a secondary sperm receptor in the mouse egg zona pellucida: role in maintenance of binding of acrosome-reacted sperm to eggs.

During fertilization in mice, acrosome-intact sperm bind via plasma membrane overlying their head to a glycoprotein, called ZP3, present in the egg extracellular coat or zona pellucida. Bound sperm then undergo the acrosome reaction, which results in exposure of inner acrosomal membrane, penetrate through the zona pellucida, and fuse with egg plasma membrane. Thus, in the normal course of events, acrosome-reacted sperm must remain bound to eggs, despite loss of plasma membrane from the anterior region of the head and exposure of inner acrosomal membrane. Here, we examined maintenance of binding of sperm to the zona pellucida following the acrosome reaction. We found that polyclonal antisera and monoclonal antibodies directed against ZP2, another zona pellucida glycoprotein, did not affect initial binding of sperm to eggs, but inhibited maintenance of binding of sperm that had undergone the acrosome reaction on the zona pellucida. On the other hand, polyclonal antisera and monoclonal antibodies directed against ZP3 did not affect either initial binding of acrosome-intact sperm to eggs or maintenance of binding following the acrosome reaction. We also found that soybean trypsin inhibitor, a protein reported to prevent binding of mouse sperm to eggs, did not affect initial binding of sperm to eggs, but, like antibodies directed against ZP2, inhibited maintenance of binding of sperm that had undergone the acrosome reaction on the zona pellucida. These and other observations suggest that ZP2 serves as a secondary receptor for sperm during the fertilization process in mice and that maintenance of binding of acrosome-reacted sperm to eggs may involve a sperm, trypsin-like proteinase.

Acrosome↗
PubMed1989

Open-trial maintenance pharmacotherapy in late-life depression: survival analysis.

We report preliminary findings from an ongoing, open trial of maintenance nortriptyline pharmacotherapy in 27 elderly depressed patients (median trial length: 18 months). While patients were on maintenance nortriptyline (mean dose: 50 mg/day) with steady-state plasma levels in the range of 50-150 ng/ml, 58% of Q-6 monthly ratings on the Hamilton Rating Scale for Depression have been 10 or lower, Folstein Mini-Mental State ratings have remained above 27, and a minimal level of side effects with no increase over time has been observed. Four of 27 patients (14.8%) have suffered recurrences and have required rehospitalization at 6, 9, 10, and 13 months. Survival analysis showed an 85% survival rate (without recurrence) at 12 months and 81.5% at 18 months. Mean survival time without recurrence is 21.3 months to date. Although our pilot experience with maintenance nortriptyline in late-life depression appears more favorable than outcomes reported in earlier naturalistic studies (where no attempt was made to keep patients in systematic maintenance therapy), the need for controlled studies of maintenance therapies in late-life depression is nonetheless underscored by the current data and other naturalistic data from the United Kingdom.

Aged↗
PubMed1996

In vitro maintenance of Eperythrozoon suis.

In vitro maintenance of Eperythrozoon suis was attempted using a Petri dish erythrocyte culture system. In preliminary experiments, the optimal conditions for maintaining E. suis attachment to erythrocytes during incubation were anticoagulation with heparin or citrate solution, incubation with 5 or 10% CO2 at 37 degrees C, and incubation with reduced or non-reduced Eagle's minimum essential medium. Using heparin, a CO2 incubator and reduced Eagle's medium (rEM), E. suis metabolic activity was evaluated by measuring glucose consumption, and lactate and pyruvate production. Glucose consumption and lactate production were measurable while pyruvate production was not detected. Erythrocyte integrity was improved by the addition of inosine although no effect was observed on maintenance of E. suis attachment to erythrocytes or the rate of glucose consumption. To determine whether the glucose consumption observed in culture was due to E. suis glycolytic activity or enhanced erythrocyte glycolytic activity, the effect of E. suis killing by EDTA addition to medium was evaluated using rEM containing inosine (rEMI). Glucose consumption decreased proportionally with the decline in the percentage of parasitized erythrocytes induced by EDTA, indicating that glucose consumption was due to E. suis. In a subsequent experiment, the effect of different types of serum (pig or fetal calf serum) and different gaseous environments (5% CO2 incubator or candle jar) were evaluated using rEMI. Glucose consumption by E. suis was significantly increased by the addition of fetal calf serum; however, no difference in the maintenance of E. suis attachment to erythrocytes and in E. suis glycolytic activity was observed between a 5% CO2 incubator and a candle jar. Finally, the effect of medium refreshment (rEMI containing fetal calf serum) was evaluated. Maintenance of E. suis parasitism on erythrocytes and E. suis glycolytic activity were significantly improved by frequent medium refreshment. The maintenance system developed enabled successful metabolic radiolabeling of E. suis for protein/antigen analysis.

Animals↗
PubMed1978

Detoxification from methadone maintenance: double-blind comparison of two methods.

A well-rehabilitated group of 22 methadone maintenance patients were detoxified under ambulatory and double-blind conditions, over 42 days, either by decreasing the daily dose of methadone and supplementing it by propoxyphene napsylate (M--PN), or by decreasing the daily dose of methadone administered in two equal doses given 12 hours apart (M--M). All of 12 (100%) M--M and 5 of 10 (50%) M--PN subjects were able to temporarily withdraw from methadone maintenance, although two of the M--PN patients required maintenance with propoxyphene napsylate to cease methadone maintenance. In our experience both detoxification methods employed appear superior to the standard withdrawal technique of simply reducing the daily methadone maintenance dose in a step-wise fashion.

Adult↗
PubMed1980

A study of hospitalized surgical patients on methadone maintenance.

It is possible that admission to hospital of methadone maintenance clients requiring treatment for pain with narcotics may result in an increase in methadone maintenance dose and affect subsequent rehabilitation of the client. The hospital admission itself may modify the subsequent outcome of the client. Fifty clients of a Methadone Maintenance Therapy Program were retrospectively evaluated. Twenty-five had been admitted to the Surgical Service of Bellevue Hospital, New York City, for a variety of conditions and for periods ranging from 2 to 43 days; twenty-five were not admitted to the Hospital. Irrespective of whether or not large amounts of narcotic analgesics had been added to the maintenance methadone, patients were discharged on the same amounts of maintenance methadone as on admission and had eventual courses and outcomes similar to the control group when followed for a mean period of 20 months.

Adult↗
PubMed2006

The generation and maintenance of visual mental images: evidence from image type and aging.

Imagery is a multi-componential process involving different mental operations. This paper addresses whether separate processes underlie the generation, maintenance and transformation of mental images or whether these cognitive processes rely on the same mental functions. We also examine the influence of age on these mental operations for independence of components. In Experiment 1, younger (22 years) and older (69 years) adults generated and maintained general, specific, contextual and autobiographical visual mental images evoked in response to concrete nouns. The older adults had longer generation times, but there was no difference between the two groups on maintenance. Both groups had shortest generation and maintenance times for general images, whereas only the older adults took longest in generating autobiographical images. In Experiment 2, the total maintenance time and number of transformations for each type of image were compared in another group of younger and older adults. General images were less transformed and more subject to decay for both groups. The older people maintained the autobiographical mental images for longest compared to other image types. In conclusion, image generation, maintenance and transformation seem to be differently affected by type of image and aging, supporting a model of their cognitive segregation.

Adult↗
PubMed2004

Maintenance in working memory or response selection? Functions of NMDA receptors in the pigeon "prefrontal cortex".

The prefrontal cortex is involved in various aspects of working memory like stimulus maintenance and response selection functions. Neurobehavioral studies and neurocomputational models assume a role for NMDA receptors in prefrontal cortex for maintenance processes, while our previous studies on NMDA receptors in the avian prefrontal cortex-analogue, the nidopallium caudolaterale (NCL), showed them to be involved in response selection functions. Various tasks used in PFC-related research address in fact both functions, so they cannot disambiguate their separate contributions to performance. In order to investigate the role of NMDA receptors in avian NCL for stimulus maintenance and response selection, we trained pigeons in a delayed matching-to sample (DMTS) task, requiring both functions, and a simultaneous matching to sample (SMTS) task, requiring only response selection. After reaching criterion, pigeons had to perform the tasks alternately under local NMDA receptor blockade in NCL (DL-AP5) and after infusion of vehicle (saline solution). Blockade of NCL-based NMDA receptors led to significant increases in error rates in both DMTS and SMTS--compared with the same subjects' performance during training and in the control condition. However, there was no additional increase in errors due to the additional maintenance component, so the impairment appears to be due to deficits in adequate selection of responses, the function necessary for both tasks. We conclude that NMDA receptors in the pigeon NCL participate in response selection rather than stimulus maintenance in tasks requiring the processing of context information.

Animals↗
PubMed2005

An overview of systematic reviews of the effectiveness of opiate maintenance therapies: available evidence to inform clinical practice and research.

AIM: To summarize the major findings of the five Cochrane reviews on substitution maintenance treatments for opioid dependence. METHODS: We conducted a narrative and quantitative summary of systematic review findings. There were 52 studies included in the original reviews (12,075 participants, range 577-5894): methadone maintenance treatment (MMT) was compared with methadone detoxification treatment (MDT), no treatment, different dosages of MMT, buprenorphine maintenance treatment (BMT), heroin maintenance treatment (HMT), and l-alpha-acetylmethadol (LAAM) maintenance treatment (LMT). MEASUREMENTS: Outcomes considered were retention in treatment, use of heroin and other drugs during treatment, mortality, criminal activity, and quality of life. FINDINGS: Retention in treatment: MMT is more effective than MDT, no treatment, BMT, LMT, and heroin plus methadone. MMT proved to be less effective than injected heroin alone. High doses of methadone are more effective than medium and low doses. Use of heroin: MMT is more effective than waiting list, less effective than LAAM, and not different from injected heroin. No significant results were available for mortality and criminal activity. CONCLUSIONS: These findings confirm that MMT at appropriate doses is the most effective in retaining patients in treatment and suppressing heroin use but show weak evidence of effectiveness toward other relevant outcomes. Future clinical trials should collect data on a broad range of health outcomes and recruit participants from heterogeneous practice settings and social contexts to increase generalizability of results.

Buprenorphine↗
PubMed2006

A 12-month controlled trial of methadone medical maintenance integrated into an adaptive treatment model.

Methadone medical maintenance (MMM) reduces the reporting schedule for stable and well-functioning methadone maintenance patients to once a month, with counseling provided by medical staff. We report on the 12-month outcomes of 92 highly stable methadone maintenance patients randomly assigned to one of three study conditions: routine care, MMM at the methadone maintenance program, and MMM at a physician's office. Methadone medical maintenance patients received a 28-day supply of methadone, whereas routine care patients received five or six take-home methadone doses each week. All patients performed a medication recall once a month and submitted two urine samples each month. An adaptive stepped-care system of treatment intensification was used for patients who failed recall or who had drug-positive urine specimens. Seventy-seven patients completed the 12-month study period. Dropout was caused primarily by problems with handling methadone and disliking the recall frequency. There were low rates of drug use or failed medication recall. Treatment satisfaction was high in all groups, but the MMM patients initiated more new employment or family/social activities than did routine care patients over the study period. The stepped-care approach was well tolerated and matched patients to an appropriate step of service within a continuum of treatment intensity.

Adult↗
PubMed2006

Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial.

PURPOSE: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy. PATIENTS AND METHODS: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm). RESULTS: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities. CONCLUSION: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.

Adult↗