Biomedical subjects

J Cramer

Publications and source records attributed to J Cramer.

At least 19 recordsLinked to original sources

PubMed2001

STR primer concordance study.

Over 1500 population database samples comprising African Americans, Caucasians, Hispanics, Native Americans, Chamorros and Filipinos were typed using the PowerPlex 16 and the Profiler Plus/COfiler kits. Except for the D8S1179 locus in Chamorros and Filipinos from Guam, there were eight examples in which a typing difference due to allele dropout was observed. At the D8S1179 locus in the population samples from Guam, there were 13 examples of allele dropout observed when using the Profiler Plus kit. The data support that the primers used in the PowerPlex 16, Profiler Plus, and COfiler kits are reliable for typing reference samples that are for use in CODIS. In addition, allele frequency databases have been established for the STR loci Penta D and Penta E. Both loci are highly polymorphic.

Alleles↗

PubMed2001

A systematic review of the associations between dose regimens and medication compliance.

BACKGROUND: Previous reviews of the literature on medication compliance have confirmed the inverse relationship between number of daily doses and rate of compliance. However, compliance in most of these studies was based on patient self-report, blood-level monitoring, prescription refills, or pill count data, none of which are as accurate as electronic monitoring (EM). OBJECTIVE: In this paper, we review studies in which compliance was measured with an EM device to determine the associations between dose frequency and medication compliance. METHODS: Articles included in this review were identified through literature searches of MEDLINE, PsychInfo, HealthStar, Health & Psychosocial Instruments, and the Cochrane Library using the search terms patient compliance, patient adherence, electronic monitoring, and MEMS (medication event monitoring systems). The review was limited to studies reporting compliance measured by EM devices, the most accurate compliance assessment method to date. Because EM was introduced only in 1986, the literature search was restricted to the years 1986 to 2000. In the identified studies, data were pooled to calculate mean compliance with once-daily, twice-daily, 3-times-daily, and 4-times-daily dosing regimens. Because of heterogeneity in definitions of compliance, 2 major categories of compliance rates were defined: dose-taking (taking the prescribed number of pills each day) and dose-timing (taking pills within the prescribed time frame). RESULTS: A total of 76 studies were identified. Mean dose-taking compliance was 71% +/- 17% (range, 34%-97%) and declined as the number of daily doses increased: 1 dose = 79% +/- 14%, 2 doses = 69% +/- 15%, 3 doses = 65% +/- 16%, 4 doses = 51% +/- 20% (P < 0.001 among dose schedules). Compliance was significantly higher for once-daily versus 3-times-daily (P = 0.008), once-daily versus 4-times-daily (P < 0.001), and twice-daily versus 4-times-daily regimens (P = 0.001); however, there were no significant differences in compliance between once-daily and twice-daily regimens or between twice-daily and 3-times-daily regimens. In the subset of 14 studies that reported dose-timing results, mean dose-timing compliance was 59% +/- 24%; more frequent dosing was associated with lower compliance rates. CONCLUSIONS: A review of studies that measured compliance using EM confirmed that the prescribed number of doses per day is inversely related to compliance. Simpler, less frequent dosing regimens resulted in better compliance across a variety of therapeutic classes.

Drug Administration Schedule↗

PubMed2001

The short-term impact of adjunctive tiagabine on health-related quality of life.

Combinations of tiagabine (TGB), carbamazepine (CBZ), and phenytoin (PHT) were compared for their impact on health-related quality of life (HRQOL) and adverse effects related to treatment efficacy for people with frequent complex partial seizures. Two independent, randomized, double-blind clinical trials for efficacy and safety were conducted simultaneously with treatment groups: CBZ+PHT versus CBZ+TGB, and PHT+CBZ versus PHT+TGB. Treatment was initiated at week 0 and continued through week 16. HRQOL was evaluated with the QOLIE-89. Treatment success was defined as > or =50% reduction in complex partial seizures. Among patients who achieved a > or =50% reduction in seizures, addition of TGB to baseline PHT enhanced patient perceptions of attention/concentration (13%; p = 0.002), memory (17%; p = 0.042), and language subscales (22%; p = 0.004). Addition of CBZ to PHT led to positive change in the work/driving/social relations subscale (14%; p = 0.004). These improvements were significantly different only between visits, not between the two treatment groups. Seizure worry subscale scores showed improvement among all treatment groups and was probably related to participation in the clinical trial. These exploratory analyses suggest a possible early positive effect of TGB on patient-perceived cognitive domains using the QOLIE-89. These findings are limited by the small sample size and could be related to reduction in seizures.

Adult↗

PubMed2001

Detecting improvement in quality of life and symptomatology in schizophrenia.

Instrument-based scores are often used as outcome measures. However, little is known about what changes in scores mean in terms of a clinical assessment of improvement or deterioration. The purpose of this report was to determine how much change in standard instrument scores represents a clinically detectable improvement or deterioration. The Veterans Affairs (VA) Cooperative Study of Clozapine in Refractory Schizophrenia evaluated 423 patients on clozapine or haloperidol. Symptoms and quality of life scales were completed at baseline; 6 weeks; and 3, 6, and 12 months. Among patients judged as "improved" by clinicians, the average percentage changes were a 21 percent decrease in Positive and Negative Syndrome Scale (PANSS) scores and a 26 percent increase in Quality of Life Scale (QLS) scores across all followup periods. The change in mean seven-point item scores were -0.46 (PANSS) and 0.23 (QLS). A major gain in clinically assessed improvement to "much better" was associated with a 45 percent decline in PANSS scores and 50 percent increase in QLS scores (change in mean seven-point item scores -0.88 and 0.92, respectively). Thus, modest changes in psychometric scales assessing symptoms and quality of life reflect clinically detectable improvement.

Adult↗

PubMed2001

Refill patterns of atypical and conventional antipsychotic medications at a national retail pharmacy chain.

This study examined whether patients who received prescriptions for conventional and atypical antipsychotics in routine outpatient care continued medication therapy. Prescription refill records of more than 25,000 patients from a national retail pharmacy chain were surveyed during a full eight-month period. At the start of the ninth month, 48 percent of the patients taking conventional agents were continuing therapy. The overall rate for those taking atypical agents was 44 percent; however, the rate for those taking clozapine was 71 percent. Atypical agents, despite their improved side effect profile, were not associated with higher rates of continued treatment. A highly supervised medication administration process, frequent patient-provider contact, and favorable patient selection may help explain the higher rate among patients taking clozapine.

Antipsychotic Agents↗

PubMed2001

[Knee joint endoprosthesis].

Total knee replacement is increasing in number due to increased life expectancy and improved implants. [figure: see text] Degenerative changes (arthritis) and joint destruction based on polyarthritis and posttraumatic deformities are the common indications. There are basically four modes for knee replacement: Unicompartimental prosthesis, non-constrained, semi-constrained (posterior stabilized) and constrained total knee arthroplasty. Of major importance in knee alloarthoplasty are restitution of the correct limb axis, sufficient lateral ligaments and the restoration of the patellofemoral joint. Therefore particularly in cases with deformities an extensive soft tissue release is mandatory. A meticulous operative technique and versatile implants lead to good clinical outcome. Possible complications are still septic and aseptic implant loosening as well as wound infections.

Arthroplasty, Replacement, Knee↗

PubMed2001

[The infected endoprosthesis with the example of the hip joint endoprosthesis. An increasing danger to patient and society].

Because of demographic factors there is an increase in the numbers of total joint replacement operations each year. Deep infection after joint replacement remains one of the major complications in orthopedic surgery. The economic consequences for society are enormous. The treatment of such infections usually means a long and difficult course for the patient. In most cases multiple operations, including removal or exchange of the prosthesis are required. Concepts of treatment are very different and vary from debridement and keeping the prosthesis, resection arthroplasty to one- and second-stage exchange procedures. It is essential to know the special advantages and disadvantages of each concept to be able to choose the right strategy of treatment. Even getting the right diagnosis may be difficult since only about 2/3 of all cases go along with a positive microbiology. By the example of the infected hip prosthesis, the aim of the article is to give recommendations on the bases of current literature and our own experience. The strategy of treatment of infections used in our hospital is reported.

Arthroplasty, Replacement, Hip↗

PubMed2000

Synthesis and conformational analysis of apamin analogues with natural and non-natural cystine/selenocystine connectivities.

By replacing two cysteine residues in apamin with selenocysteine, the three possible isomers related to the side-chain connectivities of a bis-cystinyl-peptide were synthesized in regioselective manner exploiting the low redox potential of the diselenide bond. Nuclear magnetic resonance conformational analysis of monoselenocystine analogue apamin with the natural diselenide/disulfide network confirmed the highly isomorphous character of the sulfur replacement with selenium despite its slightly larger atomic radius and increased bond lengths. The comparative conformational analysis of the apamin analogues containing the non-natural side-chain links with wild type apamin clearly revealed retention of the main structural fold and thus the high propensity of these small molecules to adopt the secondary structure elements present in natural apamin. These findings offered interesting hints for a better understanding of the oxidative refolding pathway of the bis-cystinyl peptide that leads exclusively to the correct natural isomer.

Amino Acid Sequence↗

PubMed2000

Photomodulation of conformational states. II. Mono- and bicyclic peptides with (4-aminomethyl)phenylazobenzoic acid as backbone constituent.

It has been reported that backbone cyclization of octapeptides with the photoresponsive (4-aminomethyl)phenylazobenzoic acid imparts sufficient restraints to induce and stabilize ordered conformations of the peptide backbone in both the cis- and trans-azo-isomers (L. Ulysse, J. Cubillos, and J. Chmielewski, Journal of the American Chemical Society, 1995, Vol. 117, pp. 8466-8467). Correspondingly, the active-site octapeptide fragment H-Ala-Cys-Ala-Thr-Cys-Asp-Gly-Phe-OH [134-141] of thioredoxin reductase, with its high preference for a 3(10)-helix turn conformation centered on the Thr-Cys sequence, was backbone cyclized with this azobenzene moiety in the attempt to design a photoresponsive system where the conformational states of the peptide backbone are dictated by the configuration of the azobenzene and can be further modulated by the disulfide bridge. Nuclear magnetic resonance conformational analysis of the monocyclic compound clearly revealed the presence of two conformational families in both the cis- and trans-azo configuration. Of the higher populated conformational families, the structure of the trans-isomer seems like a pretzel-like folding, while the cis-isomer relaxes into a significantly less defined conformational state that does not exhibit any regular structural elements. Further restrictions imparted by disulfide bridging of the peptide moiety leads to an even better defined conformation for the trans-azo-isomer, whereas the cis-isomer can be described as a frustrated system without pronounced energy minima and thus with little conformational preferences. Our findings would suggest that this photoresponsive peptide template may not be of general usefulness for light-induced conformational transitions between two well-defined conformational states at least under the experimental conditions employed, even in the bicyclic form. However, trans --> cis isomerization of the bicyclic peptide is accompanied by a switch from a well-defined conformation to an ensemble of possible conformations.

Aminobenzoates↗

PubMed2000

Effect of creatine loading on neuromuscular fatigue threshold.

The purpose of this investigation was to determine the effect of creatine (Cr) loading on the onset of neuromuscular fatigue by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at the fatigue threshold (PWC(FT)) test. Using a double-blind random design, 15 women athletes [mean age 19.0 +/- 2.0 (SD) yr] from the university crew team received a placebo (n = 8; 20 g glucose) or Cr (n = 7; 5 g Cr monohydrate + 20 g glucose) four times per day for 5 consecutive days. Analysis of covariance was used to analyze the data (covaried for presupplementation PWC(FT) values). The adjusted mean postsupplementation PWC(FT) value for the Cr group (mean = 186 W) was significantly (P < 0.05) higher than that of the placebo group (mean = 155 W). These findings suggest that Cr loading may delay the onset of neuromuscular fatigue.

Adolescent↗

PubMed2000

Clinical and psychopharmacologic factors influencing family burden in refractory schizophrenia. The Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: This study compares the effect of clozapine and haloperidol and identifies other factors related to family burden as experienced by relatives of patients with refractory schizophrenia (DSM-III-R). METHOD: Of 423 patients participating in a multisite randomized clinical trial, 221 identified a family member who was actively involved in their care and who agreed to complete a standardized measure of family burden at 6 weeks and 3, 6, 9, and 12 months after randomization, simultaneous with comprehensive patient assessments. RESULTS: Patient factors most consistently correlated with greater family burden were symptom severity, days living in the community (i.e., not in the hospital), and frequency of family contact. Among family members, clozapine was associated with significantly (p = .048) greater reduction in feelings of dissatisfaction related to providing support to the patient, but not in objective measures of support, amount of worry the patient engendered, or days of missed employment or household activity. Although clozapine reduces symptoms, thus lowering family burden, it also increases days living in the community, which tends to increase family burden, perhaps canceling out the benefit to families of reduced symptoms. CONCLUSION: Clozapine has a small but significant effect on the experience of families of patients. This is the first study to demonstrate that effective pharmacotherapy may be of some benefit to families as well as to patients.

Adult↗

PubMed2000

A phase I and pharmacokinetic study of the mitochondrial-specific rhodacyanine dye analog MKT 077.

This Phase I study was performed to evaluate the tolerability and pharmacokinetic behavior of MKT-077, a water soluble rhodacyanine dye analogue, which partitions into tumor cell mitochondria where it is thought to act as a metabolic poison, leading to G1 arrest and apoptosis. Thirteen patients with advanced solid malignancies were treated with MKT-077 administered as a 30-min i.v. infusion weekly for 4 weeks every 6 weeks at doses ranging from 42 to 126 mg/m2/week. The principal toxicity was renal magnesium wasting, which was dose-limiting (grade 3) in one patient at each of the 84- and 126-mg/m2 dose levels. The other three patients at the 126-mg/m2 dose level developed grade 2 hypomagnesemia, which was cumulative in nature, improved with i.v. magnesium supplementation, and was controlled in two patients by the administration of prophylactic magnesium before and after treatment with MKT-077. Given the requirement for extensive monitoring of serum magnesium levels, dose escalation >126 mg/m2 was not considered feasible. Thus, the recommended dose for disease-oriented studies with this schedule of MKT-077 is 126 mg/m2/week. Pharmacokinetic studies revealed a prolonged terminal half-life (37 +/- 17 h) and a large volume of distribution (685 +/- 430 liters/m2). Clearance averaged 39 +/- 13 liters/h/m2. Peak MKT-077 plasma concentrations (1.2 +/-0.31 to 6.3 +/- 5.3 microg/ml) exceeded the IC50 concentrations required for human CX-1 colon, MCF-breast, CRL-1420 pancreas, EJ bladder, and LOX melanoma tumor cell lines in vitro (0.15-0.5 microg/ml). These results indicate that at the recommended dose level of 126 mg/m2/week of MKT-077, the toxicity profile was consistent with the preferential accumulation of the agent within tumor cell mitochondria, and biologically relevant plasma concentrations were achieved.

Adult↗

PubMed2000

Medication continuation and compliance: a comparison of patients treated with clozapine and haloperidol.

BACKGROUND: This study compares medication continuation and regimen compliance with the atypical antipsychotic medication clozapine versus the conventional antipsychotic haloperidol. METHOD: Data from a 15-site double-blind, randomized clinical trial (N = 423) were used to compare patients with DSM-III-R schizophrenia assigned to clozapine or haloperidol in terms of duration of participation while taking the randomly assigned study drug (continuation) and the proportion of prescribed pills that were taken (compliance). Multiple regression analysis was used to determine the relationship of baseline characteristics and measures of clinical change to continuation for the entire sample and for patients assigned to each medication. RESULTS: Patients assigned to clozapine continued taking the study drug for a mean of 35.5 weeks as compared with only 27.2 among patients assigned to haloperidol (F = 4.45, df = 1,422; p = .0001). No differences were found between the groups in the proportion of prescribed pills that were returned at any timepoint. Among patients assigned to haloperidol, poorer continuation was associated with being older and greater continuation with receiving public support. Among patients on clozapine treatment, continuation was poorer among African American patients and greater among patients who showed reduced clinical symptoms and akathisia. Continuation with clozapine was greater even after adjusting for these factors. CONCLUSION: Continuation with medication is greater with clozapine than haloperidol and is partly explained by greater symptom improvement and reduced side effects. No differences were found in regimen compliance.

Adult↗

PubMed2000

Safety and efficacy of standard and new antiepileptic drugs.

Knowledge about the comparative safety and efficacy of standard and new antiepileptic drugs (AEDs) is limited. Medications are selected on the basis of seizure type and epilepsy syndrome, adverse effect profiles, and cost. However, there are few data comparing the efficacy of the new AEDs for the treatment of recent-onset versus refractory partial seizures, simple versus complex partial seizures, frontal versus temporal lobe seizures, or other relevant clinical types. Few studies compare new AEDs. The next best approach has been the use of meta-analyses and compilation of data from clinical trials, which allow interstudy comparisons to define broad and rough comparative estimates. These analyses, however, do not define clear differences in the safety and efficacy of the new AEDs because of differences in study populations. The new AEDs have expanded our arsenal against seizures. As a group, they have favorable safety and efficacy profiles. The challenge is to define the differences in terms of clinical significance.

Anticonvulsants↗

PubMed1999

Preferred conformation of endomorphin-1 in aqueous and membrane-mimetic environments.

The newly discovered endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) are potent opioid peptides with the highest affinity and selectivity for the mu receptor among all known endogenous ligands. To investigate a possible correlation between these biological properties and the conformational preferences of the small peptides, a comparative structural analysis was performed of endomorphin-1 in aqueous buffer and in membrane-mimicking SDS and AOT normal and reverse micelles by the use of CD, FT-IR, fluorescence and(1)H-NMR spectroscopy. It is well established for opioid peptides that, independently of the receptor selectivity, the Tyr1 residue plays the role of the primary pharmacophore and that the orientation of the second aromatic pharmacophore relative to the tyrosine side-chain dictates the mu or delta-receptor selectivity. By varying the environment of endomorphin-1 from water to the amphipathic SDS micelles and even more efficiently to the AOT reverse micelles, the display of the aromatic side-chains changes from an interaction of the Tyr1 and Phe4 residues to a switch of the Trp3 indole group into close contact with the phenolic moiety to prevent this type of interaction and to force an orientation of the Phe4 side-chain into the opposite direction. This conformational switch is accompanied by a stabilization of the cis -Pro2 isomer and the resulting spatial array of the pharmacophoric groups correlate well with the structural model of mu receptor-bound opioid peptides. The results indicate that AOT reverse micelles with a woof 10, where almost exclusively ordered water is secluded in the cavity, constitute with their electrostatic and hydrophobic potential an excellent mimetic of amphipathic surfaces as present on lipid bilayers and on ligand-recognition and ligand-binding sites of proteins.

Circular Dichroism↗

PubMed1999

Cost-effectiveness of clozapine in patients with high and low levels of hospital use. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: This study examined the relationship between pretreatment hospital use and the cost-effectiveness of clozapine in the treatment of refractory schizophrenia. METHODS: Data from a 15-site randomized clinical trial were used to compare clozapine with haloperidol in hospitalized Veterans Affairs patients with refractory schizophrenia (n = 423). Outcomes were compared among those with many days in the hospital use (hereafter, high hospital users) (n = 141; mean = 215 psychiatric hospital days in the year prior to study entry) and those with few days in the hospital use (hereafter, low hospital users) (n = 282; mean = 58 hospital days). Analyses were conducted with the full intention-to-treat sample (n = 423) and with crossovers excluded (n = 291). RESULTS: Clozapine treatment resulted in greater reduction in hospital use among high hospital users (35 days less than controls, P = .02) than among low users (21 days less than controls, P = .05). Patients taking clozapine also had lower health care costs; after including the costs of both medications and other health services, costs were $7134 less than for controls among high hospital users (P = .14) but only $759 less than for controls among low hospital users (P = .82). Clinical improvement in the domains of symptoms, quality of life, extrapyramidal symptoms, and a synthetic measure of multiple outcomes favored clozapine in both high and low hospital user groups. CONCLUSIONS: Substantial 1-year cost savings with clozapine are observed only among patients with very high hospital use prior to initiation of treatment while clinical benefits are more similar across groups. Cost-effectiveness evaluations, and particularly studies of expensive treatments, cannot be generalized across type of use groups.

Adult↗

PubMed1999

Interrater reliability levels of multiple clinical examiners in the evaluation of a schizophrenic patient: quality of life, level of functioning, and neuropsychological symptomatology.

Sir Ronald Fisher used a single-subject design to derive the concepts of appropriate research design, randomization, sensitivity, and tests of statistical significance. The seminal work of Broca demonstrated that valid and generalizable findings can and have emerged from studies of a single patient in neuropsychology. In order to assess the reliability and/or validity of any clinical phenomena that derive from single subject research, it becomes necessary to apply appropriate biostatistical methodology. The authors develop just such an approach and apply it successfully to the evaluation of the functioning, quality of life, and neuropsychological symptomatology of a single schizophrenic patient.

Activities of Daily Living↗

PubMed1999

How long to wait for a response to clozapine: a comparison of time course of response to clozapine and conventional antipsychotic medication in refractory schizophrenia.

This study compared the time course to clinical improvement with clozapine and with conventional antipsychotic medications. A double-blind trial compared clozapine and haloperidol in patients with schizophrenia who were refractory to conventional antipsychotic medication and were hospitalized for 30 to 364 days at 15 Veteran Affairs medical centers during the year before study entry. Patients in the original study were randomly assigned to haloperidol or clozapine and followed for 12 months, at maximum tolerable doses. Patients who completed a full year of treatment with clozapine (n = 122), or with either haloperidol or another conventional antipsychotic medication (n = 123) and who also completed the 9- or 12-month assessment were included. Response to treatment was defined as 20 percent improvement on standard scales of symptoms and quality of life at the latter of the 9- or 12-month interviews. More patients assigned to clozapine achieved 20 percent improvement in symptoms at each followup. Among patients who did not improve at 6 weeks, 3 months, or 6 months, there were no significant differences between clozapine and comparison patients in outcomes at 1 year. Among patients who did improve, maintenance of that improvement also did not differ between the groups at 1 year on symptom measures. Maintenance of improvement in quality of life at 1 year was significantly greater for clozapine patients who had improved at 6 months (p < 0.04). Significant differential symptom response to clozapine occurred exclusively during the first 6 weeks of treatment.

Adult↗