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Biomedical subjects

J A Cramer

Publications and source records attributed to J A Cramer.

At least 55 records · Page 3Linked to original sources
PubMed1996

Compliance with contraceptives and other treatments.

OBJECTIVE: To define some of the issues unique to compliance with oral contraceptives, and some comparisons with other preventive and therapeutic treatments. DATA SOURCES: Reports of compliance with medical treatment were used, with a focus on studies using microelectronic monitoring to assess compliance. Studies included the general population and a variety of demographically different groups. METHODS OF STUDY SELECTION: Twenty-nine studies of medication compliance (including surveys and clinical trials with specific interventions), across a broad range of medical disorders, were selected for comparison with reports of oral contraceptive compliance. TABULATION, INTEGRATION, AND RESULTS: Rates of compliance with contraceptive methods are low, but differ little from rates of compliance with other medical treatments. Several questions might be used to ascertain the likelihood that an individual is willing to use an oral contraceptive as prescribed (eg, willingness to take a daily pill, to return for follow-up, and to report adverse effects). CONCLUSIONS: Studies of a variety of medical disorders have shown that no consequence is so severe that all patients can be assumed to comply with the prescribed treatment plan. Inadequate compliance often diminishes treatment efficacy, which suggests the need for alternative methods that do not require daily compliance.

Adolescent↗
PubMed1996

Safe coadministration of terbinafine and terfenadine: a placebo-controlled crossover study of pharmacokinetic and pharmacodynamic interactions in healthy volunteers.

The pharmacokinetic and pharmacodynamic interactions of terbinafine (Lamisil) and terfenadine (Seldane) were assessed in 26 healthy volunteers randomized to receive either terbinafine (250 mg tablet) or its placebo (terbinafine placebo), which were administered in a double-blind manner once daily for 18 days. On days 12 through 18, terfenadine was coadministered (60 mg twice daily, unblinded). Pharmacokinetic profiles were obtained for terbinafine and its desmethyl metabolite on day 11 (in the absence of terfenadine), day 12, and day 18. Terfenadine and terfenadine acid metabolite levels were also assayed on days 12 and 18. After a 4-week washout period, subjects were crossed over to the alternate treatment (terbinafine or terbinafine placebo). Pharmacodynamic measures were electrocardiographic (ECG) rhythm abnormalities, corrected QT interval (QTc), and plasma ALT levels. Terfenadine levels were evaluated; however, only eight of 1502 samples assayed were above the limit of quantitation. No effect of terbinafine administration on pharmacokinetic parameters for the terfenadine acid metabolite was observed, except for a decrease of approximately 20% in through terbinafine concentrations (C0hr; p < 0.05) on the last day of terfenadine plus terbinafine coadministration. Pharmacokinetic parameters for terbinafine were unchanged on the first day of terfenadine coadministration, and only small increases in area under the plasma concentration versus time curve from 0 to 24 hours and peak plasma concentrations (16.1%[p < 0.01] and 6.63% [p < 0.05]) were observed on the last day of terfenadine and terbinafine coadministration. Values for C0hr were also about 20% to 25% higher (p < 0.05). Steady-state levels of the terfenadine acid metabolite were achieved after 2 days of terfenadine coadministration, and steady-state levels of terbinafine and its desmethyl metabolite were achieved after 14 days of terbinafine administration. The incidence of ECG rhythm abnormalities was not significantly higher in any treatment group; however, the incidence of prolongation of QTc > 10% above baseline was significantly higher in the groups treated with terfenadine. No QTc prolongation occurred in the absence of terfenadine treatment. Both terbinafine and terfenadine were well tolerated when coadministered during this study, as indicated by the low incidence of complaints, abnormalities, and adverse events. The results of this study indicate that terbinafine and terfenadine can be safely coadministered.

Adult↗
PubMed1996

A brief questionnaire to screen for quality of life in epilepsy: the QOLIE-10.

PURPOSE: To evaluate a brief questionnaire to screen aspects of health-related quality of life for persons with epilepsy. METHODS: A study of 304 adults with epilepsy was undertaken at 25 seizure clinics in the United States. It was used for derivation of a brief screening tool from a longer instrument (QOLIE-89). RESULTS: The 10-item questionnaire (QOLIE-10) covers general and epilepsy-specific domains, grouped into three factors: Epilepsy Effects (memory, physical effects, and mental effects of medication), Mental Health (energy, depression, overall quality of life), and Role Functioning (seizure worry, work, driving, social limits). Scale scores were significantly different among seizure groups (p = 0.003). CONCLUSIONS: The QOLIE-10 can be completed by a patient in several minutes and reviewed rapidly by the physician. This screening tool could provide potentially useful information for initial assessment or follow-up of problem areas that are not commonly evaluated during routine clinical visits with patients with epilepsy.

Adolescent↗
PubMed1996

Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group.

BACKGROUND: Two prospective observations of adults with symptomatic, localization-related (partial) epilepsy included 1,102 patients in VA multicenter studies (VA-118 and VA-264). Analyses assessed the likelihood of remaining seizure free for 12 and 24 months after initiating adequate antiepileptic drug therapy. METHODS: Patients were grouped as having only secondarily generalized tonic-clonic seizures (GTC), only complex partial seizures (CPS), or both types (MIXED) at entry. The cumulative proportion of patients remaining seizure free with standard antiepileptic drug therapy was determined by actuarial life table methods. RESULTS: At 12 months, 70% and 61% of GTC patients (VA-118 and VA-264, respectively) had no further GTC; 53% and 50% of MIXED, predominantly GTC patients had no further GTC, 21% and 28% of CPS patients had no further CPS and 98% and 91% were seizure free for GTC; 32% and 35% of MIXED, predominantly CPS patients had no further CPS, and 62% and 51% of patients with MIXED seizure types remained seizure free for CPS for 12 months after enrollment. CONCLUSIONS: The overall prognosis for control of seizures of any type for 12 months was best for those who had only GTC at entry (55% and 48%), worst for those who had only CPS at entry (23% and 26%), and intermediate for those with MIXED seizures at entry (32% and 25%) (all p < 0.0001). Prognosis can be based on the predominant seizure type in patients with multiple types.

Adult↗
PubMed1995

The relationship of neuropsychological functioning to quality of life in epilepsy.

OBJECTIVE: To examine the relationship of objectively assessed cognitive functioning to self-reported quality of life. DESIGN: Correlational, multiple regression, and factor analytic comparisons of a new self-report quality of life inventory with neuropsychological tests of cognition and mood. SUBJECTS: Two hundred fifty-seven patients with epilepsy. SETTING: Twenty-five epilepsy centers and neurology clinics across the United States. MEASURES: A recently developed self-report (ie, Quality of Life in Epilepsy-89 inventory) and objective tests of memory, verbal abilities, spatial functions, psychomotor and cognitive processing speed, cognitive flexibility, and mood. RESULTS: Factors that assessed mood, psychomotor speed, verbal memory, and language correlated significantly with selected scales of the Quality of Life in Epilepsy-89 inventory (P < .0001) and were predictive of overall quality of life (P < .002 to P < .0001). The mood factor showed the highest correlations (r = -.20 to r = -.73) and was the strongest predictor of quality of life in regression analyses (46.7% explained variance, P < .0001). CONCLUSIONS: Mood may be adversely affected by diminished quality of life, or perceived quality of life may be affected by mood disturbance. Quantitative quality of life assessments can be used in conjunction with formal neuropsychological testing of mood and cognition when evaluating patients with epilepsy.

Adult↗
PubMed1995

Optimizing long-term patient compliance.

The key elements for enhancing patient compliance when prescribing are selecting the fewest number of daily doses (taking patient's other medications into consideration), scheduling when doses are to be taken, and helping the patient select an appropriate reminder or "cue." Developing reminder cues, such as clock time, meal time, or bathroom ritual, requires only a few minutes of careful planning to mesh with the patient's lifestyle. If one type of cue is not successful, another or combinations of cues are tried over time. Asking patients about their cues at each visit not only helps patients develop personalized cuing systems, but also reminds them that their physician has a consistent interest in the way they take their medication. Unfortunately, no single specific strategy will enhance compliance in all patients. Physicians have the greatest influence on medication compliance when they provide specific suggestions that fit into the patient's lifestyle.

Cerebrovascular Disorders↗
PubMed1994

Kinetic and mechanistic studies with bovine testicular hyaluronidase.

Bovine testicular hyaluronidase exhibits hydrolase and transglycosylase activity. To assess the magnitude of each type of reaction, the time-course of hyaluronidase catalysed hyaluronic acid degradation was followed using a sensitive and specific HPLC method. The kinetic parameters Km and Vmax were calculated for purified short chain hyaluronic acid oligomers and native hyaluronic acid based on the appearance of unreactive hyaluronic acid tetrasaccharide. For hyaluronic acid oligomers, as substrate size increased Km decreased from 2.06 to 1.09 mM while Vmax remained about the same, indicating a 5-fold increase in the enzyme-substrate association constant, k1 (kcat/Km). The values of k2 (kcat), the enzyme-substrate disassociation constant, for native hyaluronic acid and hyaluronic acid decasaccharide were similar. The value of k1 for native hyaluronic acid, however, was larger by 70-fold. Kinetic degradation mechanisms for each hyaluronic acid oligomer, using chemical-reaction kinetics, were proposed and evaluated by computer curve fitting analysis of the experimental time vs. concentration data. The derived rate constants, together with mass balance calculations, revealed that transglycosylation plays a significant role in the degradation of all hyaluronic acid oligomers studied.

Animals↗
PubMed1994

A pharmacodynamic approach to the estimate of carbamazepine autoinduction.

Population-based pharmacokinetic prediction algorithms have been developed for several medications. A fundamental assumption has been that the kinetics remain constant over time. Carbamazepine (CBZ), however, induces its own metabolism in a concentration- and time-dependent manner. A Bayesian estimation program is presented that models the changing catabolic enzyme activity, linearly related to hepatic microsomal enzyme concentration, along with the serum drug concentration. An Emax model is used for enzyme formation with respect to drug concentration: elimination of enzyme activity is modeled as a first-order process. This program was tested in 22 drug-naive outpatients begun on CBZ monotherapy. The 1 week concentrations were used to prospectively predict concentrations at 1 month of therapy and were very close to actual measurements: prediction bias (mean error of prediction) = -0.1 micrograms/mL and precision (median absolute error of prediction) = 1.2 micrograms/mL. Comparison estimates, made by assuming a constant concentration/dose ratio, had bias = 2.6 micrograms/mL (p < 0.001) and precision = 2.2 micrograms/mL (p = 0.01). We conclude that (1) CBZ autoinduction is not complete after 1 week of therapy and (2) the methodology permits accurate estimation of CBZ pharmacokinetics.

Adult↗
PubMed1994

Phenytoin concentrations in the human brain: an in vivo microdialysis study.

We report the first human study of phenytoin concentration using in vivo microdialysis, which permits sampling the extracellular environment of the brain. This technique has been applied to patients undergoing intracranial electrode investigation for intractable epilepsy. By varying the rate of perfusion (from 2.5 to 0.25 microliters/min), it is possible to quantify the concentration of drug in the extracellular fluid (ECF), which reflects the concentration on the outer neuronal cell membrane. Samples were obtained from four catheters in two patients, in whom serum phenytoin (PHT) concentrations were held constant. Unbound serum concentrations were measured following ultrafiltration at 37 degrees C. In one patient, with left and right hippocampal probes, steady state ECF/unbound serum ratios were 87 and 84% respectively. In the second patient, with hippocampal and frontal probes, ECF/unbound serum ratios were 87 and 85% respectively. Flow rate for 50% maximal recovery averaged 1.65 microliters/min (1.5-1.7 microliters/min). We found that steady state ECF PHT concentrations corresponded closely to unbound serum concentrations. No differences are observed between different sites within the brain. Flow rates needed for equilibration of dialysate with the extracellular space were slower than reported for carbamazepine, but faster than those we found for carbamazepine-epoxide and valproate.

Brain↗
PubMed1994

Measurement of carbamazepine and carbamazepine epoxide in the human brain using in vivo microdialysis.

We report the first study of carbamazepine and carbamazepine-10,11-epoxide concentrations determined by using intracerebral microdialysis in three patients undergoing depth electrode studies for the evaluation of medically intractable epilepsy. Very small microdialysis catheters, affixed to and inserted with the depth electrodes, sampled drug concentration in the extracellular environment. We perfused artificial extracellular fluid continuously, and varied the perfusion rate to permit estimation of the absolute drug concentration in the extracellular space. Serum samples were obtained simultaneously. The relation between dialysate and extracellular concentration (recovery fraction) depended, in vivo but not in vitro, on the relative lipophilicity of the compounds, suggesting that diffusion of the drug within the brain is a major determinant of microdialysate drug concentration. When this is taken into account, the steady-state extracellular concentrations of these compounds closely mirror their unbound serum concentrations.

Brain Chemistry↗
PubMed1994

Quality of life for people with epilepsy.

The diversity and impact of problems related to epilepsy require each patient to develop a concept of what issues are most important, and seek to address these issues as a personal priority. Domains to be considered include physical, psychological, social, and epilepsy-specific issues. Level of independence is also an important concern. Quality of life instrument scores are a new measure of overall patient function. Use of well constructed, validated instruments specific for disease or general function will enhance the ability of health care providers to understand changes in patients that are not readily discernible without an extensive interview.

Epilepsy↗
PubMed1993

A clinimetric approach to assessing quality of life in epilepsy.

Clinimetrics is a concept involving the use of rating scales for clinical phenomena ranging from physical examinations to functional performance. Clinimetric or rating scales can be used for defining patient status and changes that occur during long-term observation. The scores derived from such scales can be used as guidelines for intervention, treatment, or prediction of outcome. In epilepsy, clinimetric scales have been developed for assessing seizure frequency, seizure severity, adverse effects related to antiepileptic drugs (AEDs), and quality of life after surgery for epilepsy. The VA Epilepsy Cooperative Study seizure rating scale combines frequency and severity in a weighted scoring system for simple and complex partial and generalized tonic-clonic seizures, summing all items in a total seizure score. Similarly, the rating scales for systemic toxicity and neurotoxicity use scores weighted for severity for assessing specific adverse effects typically related to AEDs. A composite score, obtained by adding the scores for seizures, systemic toxicity, and neurotoxicity, represents the overall status of the patient at a given time. The Chalfont Seizure Severity Scale also applies scores relative to the impact of a given item on the patient, without factoring in seizure frequency. The Liverpool Seizure Severity Scale is a patient questionnaire covering perceived seizure severity and the impact of ictal and postictal events. The UCLA Epilepsy Surgery Inventory (ESI-55) assesses quality of life for patients who have undergone surgery for epilepsy using generic health status instruments with additional epilepsy-specific items.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticonvulsants↗
PubMed1992

A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group.

BACKGROUND: Valproate is approved for use primarily in patients with absence seizures, but the drug has a broad spectrum of activity against seizures of all types. Partial or secondarily generalized tonic-clonic seizures are often difficult to control adequately with standard treatment, usually carbamazepine or phenytoin. METHODS: We conducted a multicenter, double-blind trial that compared valproate with carbamazepine in the treatment of 480 adults with complex partial seizures (206 patients) or secondarily generalized tonic-clonic seizures (274 patients). The patients were randomly assigned to treatment with carbamazepine or divalproex sodium (valproate) at doses adjusted to achieve blood levels in the middle of the therapeutic range. Patients were followed for one to five years or until seizures became uncontrollable, treatment had unacceptable adverse effects, or both these events occurred. RESULTS: For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively). For complex partial seizures, four of five outcome measures favored carbamazepine (100 patients) over valproate (106 patients): the total number of seizures (2.7 vs. 7.6, P = 0.05), the number of seizures per month (0.9 vs. 2.2, P = 0.01), the time to the first seizure (P less than 0.02), and the seizure-rating score (P = 0.04). Carbamazepine was also superior according to a composite score that combined scores for the control of seizures and for adverse effects (P less than 0.001). Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001). Rash was more often associated with carbamazepine (11 percent vs. 1 percent, P less than 0.001). CONCLUSIONS: Valproate is as effective as carbamazepine for the treatment of generalized tonic-clonic seizures, but carbamazepine provides better control of complex partial seizures and has fewer long-term adverse effects.

Adolescent↗
PubMed1991

A reversed-phase ion-pair high-performance liquid chromatography method for bovine testicular hyaluronidase digests using postcolumn derivatization with 2-cyanoacetamide and ultraviolet detection.

A reversed-phase ion-pair HPLC method for separating hyaluronic acid oligomers, using a polymeric C18 column at alkaline pH, is described. As the concentration of the ion-pairing agent tetrabutylammonium hydroxide increased, over the range of 0.01 to 0.06M, the capacity factors (k') of tetra- to dodecasaccharide decreased. The change in k', for each increment in pairing agent, increased with oligomer molecular weight. When changing mobile phase pH from 7 to 8, k' dramatically decreased and remained unchanged from pH 8 to 11. The isocratic separation was optimized to resolve tetrato dodecasaccharide at pH 9.0 in under 19 min. The postcolumn derivatizing agent 2-cyanoacetamide reacted with the reducing N-acetylglucosamine end groups of hyaluronic acid oligomers to yield reaction products that were monitored at 27 nm. In a series of control experiments using decasaccharide and N-acetylglucosamine, it was found that maximum product formation took place at pH 9 and was greatly influenced by borate buffer concentration. The optimum concentration for 2-cyanoacetamide was 0.33% and a temperature of 100 degrees C gave the best signal to noise ratio for the postcolumn reaction. The method is linear and reproducible, and has a lower limit of detection for tetrasaccharide of 20 ng (25 pmol). This system is suitable for studying the degradation kinetics of purified hyaluronic acid oligomers by bovine testicular hyaluronidase. Extension of the method to fluorescent and electrochemical detection and its applicability to other glycosaminoglycans is discussed.

Acetonitriles↗