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Biomedical subjects

J A Cramer

Publications and source records attributed to J A Cramer.

At least 19 recordsLinked to original sources
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↗
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↗
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↗
PubMed1991

Reproductive function in epilepsy.

The hypothalamic-pituitary-gonadal axis is a complex system within which both positive and negative feedback occur among its elements and higher brain systems. The occurrence of seizures and changes in the secretion of pituitary hormones can affect the feedback loop. Both seizures and antiepileptic drugs can affect the hypothalamic-pituitary-gonadal axis of males and females and cause changes in hormones and sexuality. Reproductive dysfunction has a social impact because of reduced fertility. Once conception occurs, live birth rates are not diminished. Prospective studies of men and women with epilepsy are needed.

Anticonvulsants↗
PubMed1990

In vivo determination of valproate binding constants during sole and multi-drug therapy.

Valproate (VPA) is present in humans and is largely bound to protein. Only free drug is metabolized, and antiepileptic and toxic effects are probably related to free concentrations. By measuring serial free and total serum VPA levels after routine oral doses, we have determined individual in vivo protein binding parameters for 37 patients after a total of 49 separate drug administrations. Binding site concentrations and dissociation constants were fitted using a nonlinear algorithm. On sole VPA (n = 28) the mean dissociation constant was 91 mumol/L, and the mean concentration of binding sites was 1,176 mumol/L. Evidence suggests a second, nonsaturable binding site. Fraction of unbound VPA ranged from 5.4% at low levels up to 38.7%, rising with increasing total concentration. Concurrent therapy with phenytoin (n = 7) or carbamazepine (n = 8) did not cause displacement of VPA. Changes in free fraction were consistently observed during the interdose interval. The data demonstrate that the binding changes are not a factor in decreased VPA levels during coadministration of other antiepileptic drugs.

Binding, Competitive↗
PubMed1990

Compliance declines between clinic visits.

Adherence to prescribed drug dosing regimens declined substantially during the interval between clinic visits and drug level tests. Using microelectronic monitors to observe pill-taking habits, 20 patients averaged 88% compliance before and 86% compliance after the visit, but this dropped to 67% compliance a month later. These data indicate that spot drug levels do not represent long-term "steady-state" drug serum concentrations.

Anticonvulsants↗
PubMed1989

How often is medication taken as prescribed? A novel assessment technique.

The evaluation of the efficacy of medication is confounded when patients do not adhere to prescribed regimens. Overdosing, underdosing, and erratic dosing intervals can diminish drug action or cause adverse effects. Using a new method with epilepsy as a model, we assessed compliance with long-term medications among newly treated and long-term patients. Medication Event Monitor Systems (Aprex Corporation, Fremont, Calif) are standard pill bottles with micro-processors in the cap to record every bottle opening as a presumptive dose. Compliance rates averaged 76% during 3428 days observed: 87% of the once daily, 81% of the twice daily, 77% of the three times a day, and 39% of the four times a day dosages were taken as prescribed. Coefficients of variation of drug serum concentrations had no significant relationship to compliance rates. Pill counts overestimated compliance increasingly as compliance with the prescribed regimen declined. Neither drug serum concentrations nor pill counts would have identified the frequency of missed doses that were revealed with continuous dose observations.

Adult↗
PubMed1989

Barbiturate-related connective tissue disorders.

Development of Dupuytren's contractures, frozen shoulder, Ledderhose's syndrome, Peyronie's disease, fibromas, and general joint pain has been linked in retrospective studies and case reports to the use of antiepileptic drugs. We undertook a prospective survey of the incidence of connective tissue disorders in 622 patients newly treated with carbamazepine, phenobarbital, phenytoin sodium, or primidone. Ten of the 406 patients who were treated for 6 months or more developed connective tissue disorders. All affected patients were taking a barbiturate (primidone, 4 patients; phenobarbital, 6 patients). Seven of the 10 problems occurred during the first year of treatment. These data are prospective evidence of a statistically significant relationship between barbiturate use and the development of connective tissue disorders, and timing of appearance.

Adult↗
PubMed1988

Crossover from polytherapy to monotherapy in primary generalized epilepsy.

Patients with primary generalized tonic-clonic seizures can obtain equal or superior seizure control and fewer side effects when managed with valproate than when taking multiple antiepileptic drugs. The conversion from polytherapy to valproate monotherapy must be done carefully if side effects and seizure exacerbation are to be avoided. A gradual crossover, often requiring several months, is usually necessary. A well-developed plan and understanding by the patient, coupled with close follow-up, are essential. The major improvement in quality of life that results for the majority of patients after completing such a conversion fully warrants the extra time and effort required.

Adult↗
PubMed1988

Can categorization of patient background problems be used to determine early termination in a clinical trial?

Many patients entering a long-term clinical study are unable to remain active in the trial (taking medication as prescribed and attending clinic as scheduled) for up to 6 years. We studied a group of 622 patients entering an antiepileptic drug study with maximum possible follow-up period of 6 years. A centralized case validation system was used in this VA Epilepsy Cooperative Study to note problems in patients entering the study. The categories established for pre-entry case status were associated with events occurring during the course of the study that led to noncompletion of the study. The data were reviewed to determine whether pre-entry status can be used to suggest the likelihood that an individual patient will remain in the study to completion or become a non-drug-related loss. Over one-half of all losses were related to failure to return to clinic. Medical problems (18%), medication noncompliance (14%), and psychiatric problems (12%) accounted for the remainder of losses. Pre-entry issues often were the same reason for early loss. However, many patients with problems known at entry were maintained in the study when targeted for extra support. We found some groups of patients had considerably more early terminations whereas others had less loss to the trial than we predicted originally. Thus, case categorization at entry can be used to estimate the likelihood of early termination from a clinical trial.

Actuarial Analysis↗
PubMed1988

Compliance in epilepsy. Strategies to enhance adherence to a medical regimen.

Treatment of medical disorders and prevention of disease are hampered by the all too frequent lack of adherence with the prescribed regimen. Delivery of health care to a broad-based population at reasonable cost and with high quality can be enhanced by use of multiple strategies to aid compliance. No single technique is best for all patients. Education, dose planning, appointment scheduling and monitoring coupled with communication between patient and physician or staff are basic strategies for development of immediate and long-term adherence behavior.

Anticonvulsants↗
PubMed1988

Aspects of compliance: taking drugs and keeping clinic appointments.

Treatment of epilepsy depends on adherence to a drug regimen as prescribed and periodic assessment of progress. Typical problems of compliance to medication and adherence to follow-up in long-term epilepsy treatment in a clinical trial were analyzed. Zero drug levels, subtherapeutic levels, variable levels and delayed dose were measures of non-compliance to the drug regimen. Missed visits and non-drug-related dropouts from the study marked non-adherence. Data from 622 patients participating in a multicenter evaluation of the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin and primidone, showed generally good compliance. Only 5% of patients had zero drug levels or greater than or equal to 24 h since prior dose at 2 or more visits. Good adherence to the protocol was demonstrated by 93% attendance as scheduled. The support structure of the study and the availability of a study assistant helped many patients to prevent potential problems and convert patients into excellent adherers.

Adolescent↗