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Biomedical subjects

J Cramer

Publications and source records attributed to J Cramer.

At least 37 records · Page 2Linked to original sources
PubMed1999

The disulfide-coupled folding pathway of apamin as derived from diselenide-quenched analogs and intermediates.

The sequence of apamin, an 18 residue bee venom toxin, encloses all the information required for the correct disulfide-coupled folding into the cystine-stabilized alpha-helical motif. Three apamin analogs, each containing a pair of selenocysteine residues replacing the related cysteines, were synthesized to mimic the three possible apamin isomers with two crossed, parallel, or consecutive disulfides, respectively. Refolding experiments clearly revealed that the redox potential of selenocysteine prevails over the sequence encoded structural information for proper folding of apamin. Thus, selenocysteine can be used as a new device to generate productive and nonproductive folding intermediates of peptides and proteins. In fact, disulfides are selectively reduced in presence of the diselenide and the conformational features derived from these intermediates as well as from the three-dimensional (3D) structures of the selenocysteine-containing analogs with their nonnatural networks of diselenide/disulfide bridges allowed to gain further insight into the subtle driving forces for the correct folding of apamin that mainly derive from local conformational preferences.

Amino Acid Sequence↗
PubMed1999

Risk factors for poor health-related quality of life in adolescents with epilepsy.

PURPOSE: To examine potential risk factors for poor health-related quality of life (HRQOL) among adolescents with epilepsy by using the newly developed QOLIE-AD-48. Risk factors were derived from sociodemographic, social, academic, and epilepsy- and health-related domains. METHODS: The QOLIE-AD-48 was administered to 197 English-speaking adolescents (age 11-17 years from >20 sites in the United States and in Canada). The self-report instrument yields an overall HRQOL score and eight subscale scores. Other data were obtained from family interviews, physician reports, and health records. Multiple regression analyses were conducted to study risk factors for impairment of HRQOL. RESULTS: Older adolescents (age 14-17 years), those with more severe epilepsy and more symptoms of neurotoxicity, and those living in households with lower socioeconomic status were more likely to report poor overall HRQOL. Risk factors in the eight HRQOL domains were found as follows: (a) Epilepsy Impact: older age in adolescence, more severe epilepsy and neurotoxicity, more hospitalizations during the past year, and fewer hours of extracurricular activities; (b) Memory and Concentration: longer duration of epilepsy, special education classes, and history of repeating a grade in school; (c) Attitude Toward Illness: older age, female gender, and more severe epilepsy and neurotoxicity; (d) Social Support: younger age, male gender, and fewer hospitalizations in the last year; (e) Stigma: lower socioeconomic status and special-education classes; and (f) Health Perceptions: older age, female gender, and lower socioeconomic status. None of the factors examined was significantly associated with HRQOL in (g) Physical Functioning or (h) School Behavior subscales. CONCLUSIONS: We identified several risk factors for poor HRQOL outcomes in adolescents with epilepsy. Age, increased seizure severity, and neurotoxicity were most consistently associated with poor HRQOL across domains. Older adolescents, independent of epilepsy severity, reported worse overall HRQOL than did their younger counterparts. Older adolescents also were more likely to perceive a greater negative impact on life and general health, and had more negative attitudes toward epilepsy. Adolescent boys and girls may show different sensitivities to various quality-of-life domains.

Achievement↗
PubMed1999

Impact of clozapine on negative symptoms and on the deficit syndrome in refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

OBJECTIVE: This study compared the effect of clozapine and haloperidol on positive and negative symptoms of schizophrenia and in patients with high levels of negative symptoms or the deficit syndrome. METHOD: Patients were participants in a 15-site double-blind, random-assignment Veterans Administration trial comparing clozapine (N=205) and haloperidol (N=217) in hospitalized patients with refractory schizophrenia. Analysis of covariance examining change at 6 weeks, 3 months, and 1 year evaluated 1) clozapine's effect on positive and negative syndromes; 2) clozapine's effect on each syndrome, statistically controlling for the other; and 3) the interaction of clozapine treatment and the presence or absence of high levels of negative symptoms at baseline and the deficit syndrome. RESULTS: Patients treated with clozapine showed significantly greater improvement than control subjects on positive symptoms at all time points and on negative symptoms at 3 months. Clozapine had no independent effect on negative symptoms at any time after control for positive symptoms, but its effects on positive symptoms persisted after control for negative symptoms at 6 weeks only. There were no significant differences in response to clozapine between patients with high and low levels of negative symptoms at baseline or between patients with and without the deficit syndrome. CONCLUSIONS: The greater effectiveness of clozapine as compared to conventional medications in refractory schizophrenia is not specific to either negative clinical symptoms or clinical subtypes defined by prominent negative symptoms or evidence of the deficit syndrome.

Analysis of Variance↗
PubMed1998

Predictors of differential response to clozapine and haloperidol. Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: We sought to identify baseline predictors of response to clozapine. METHODS: Data were from a 15-site randomized clinical trial comparing clozapine and haloperidol in hospitalized patients with refractory schizophrenia (n = 423). Three-month outcomes were analyzed with the full sample (n = 368 due to attrition). Because of crossovers, analyses of 12-month outcomes were conducted with crossovers excluded (n = 291). Clinical predictors included age, race, diagnosis (current substance abuse, paranoid subtype of schizophrenia, or depressive syndrome), severity of symptoms, quality of life, age at onset of schizophrenia, extrapyramidal symptoms, and VA compensation payment. Multiple regression analysis was used to examine the interaction of treatment condition and each of these variables in predicting outcomes for symptoms, quality of life, side effects, and days hospitalized. RESULTS: Patients with higher quality of life at baseline (p = .04) and higher symptoms (p = .02) had relatively smaller declines in hospital days at 6 months. In the 12-month sample patients with higher levels of symptoms had greater symptom reductions at 12 months (p = .03) and greater improvement in quality of life (p = .004). CONCLUSIONS: Although high levels of symptoms were associated with greater improvement on clozapine, these findings are not robust enough to suggest that any specific, clinically defined subgroup of refractory patients should be preferentially targeted for clozapine treatment.

Adult↗
PubMed1998

Does participation in psychosocial treatment augment the benefit of clozapine? Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: This study examines the role of participation in psychosocial treatment as a mediator of the clinical effectiveness of clozapine. METHODS: Subjects participated in a 12-month double-blind random-assignment trial comparing clozapine and haloperidol in patients hospitalized 30 to 364 days for refractory schizophrenia at 15 Department of Veterans Affairs medical centers. A broker-advocate case management intervention was used to facilitate participation in psychosocial treatments and to document such participation. RESULTS: Between those who continued receiving clozapine (n=122) or a conventional antipsychotic drug (n=169) for 12 months, those receiving clozapine were more likely to participate in psychosocial rehabilitation treatment. Although they were no more likely to receive clinical recommendations for such treatments, they were more likely to both verbally accept recommendations and to act on them. Structural equation modeling shows that participation in psychosocial treatment did not play a mediating role in clozapine's effect on outcomes at 6 months, but was associated with both reduced symptoms and improved quality of life at 12 months. CONCLUSIONS: Clozapine facilitates participation in psychosocial treatment, and such enhanced participation is associated with improved quality-of-life and symptom outcomes. Psychosocial rehabilitation should be offered concomitantly with clozapine.

Adult↗
PubMed1998

Multiple outcome assessment in a study of the cost-effectiveness of clozapine in the treatment of refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

OBJECTIVE: To develop new methods for combining results from multiple outcome domains and to demonstrate their application in a study of the cost-effectiveness of clozapine in treating hospitalized patients with refractory schizophrenia. DATA SOURCES/STUDY SETTING: Interview assessments, and administrative utilization and cost data, concerning 423 patients with refractory schizophrenia who had been hospitalized for 30-364 days during the year before study entry, at 15 VA medical centers. STUDY DESIGN: A 12-month double-blind trial compared clozapine (n = 205) and haloperidol (n = 218) in the treatment of refractory schizophrenia. DATA COLLECTION/EXTRACTION METHODS: Data from standard assessment instruments, gathered at baseline and at 6 weeks, and at 3, 6, 9, and 12 months, were used to develop a Composite Health Index for Schizophrenia, a measure that addresses outcome in six domains, weighted by patient or provider preferences. Cumulative improvement was estimated by computing the area under the improvement curve. This measure was then combined with cost data, reflecting consumption of societal resources to estimate incremental cost-effectiveness ratios. PRINCIPAL FINDINGS: Clozapine was significantly more effective than haloperidol on measures of symptoms (p = .02) and side effects (p < .0001), with nonsignificant trends in the positive direction on community role functioning (p = .06), family relationships (p = .23), social relationships (p = .30), and daily activities (p = .20). Clozapine was also more effective than haloperidol on the one-year cumulative Composite Health Index for Schizophrenia (p < .0001 for all weighting schemes). After converting this measure to a 0-1 Worst Health-Good Health Scale analogous to Quality Adjusted Life Years, clozapine was found to yield a small improvement of .049 Worst Health-Good Health Units as compared to an improvement of only .027 Units for haloperidol (p < .0001). Average annual costs were $2,733 lower for clozapine (95% C.I. = -$9,220 to $3,754). Although clozapine was significantly more effective than haloperidol, the summary cost-effectiveness ratio had a wide 95 percent confidence interval ranging from -$431,585 to $177,352. CONCLUSIONS: Methods demonstrate an approach to using conventional disease-specific measures to evaluate the cumulative effectiveness of novel treatments for psychotic disorders and for expressing their economic effect as cost-effectiveness ratios. Among high hospital users with refractory schizophrenia, clozapine is more cost-effective than standard treatment, although the magnitude of its effect is small and there is considerable uncertainty about the cost estimates.

Clozapine↗
PubMed1997

[Excision and open wound treatment of pilonidal sinus. Rate of recurrence and duration of work incapacity].

BACKGROUND AND OBJECTIVE: There is controversy whether open or closed operative treatment of pilonidal sinuses is better, especially with regard to postoperative recurrence rate and duration of work incapacity in these mostly young patients. Having performed radical excision with subsequent open wound healing, we have analysed recurrence rate, duration of sickness certification, amount of pain and general impairment in our group of patients. PATIENTS AND METHODS: All 103 patients operated on for pilonidal sinus between January 1992 and December 1994 (84 men, 19 women, mean age 28.1 [16-68] years) were sent a questionnaire to record any recurrence, duration of certified incapacity to work, amount of pain and general satisfaction of the operation, using visual analogue scales. Complete answers were obtained from 86 patients (83.5%). RESULTS: The follow-up period ranged from 12 to 47 months postoperatively. The recurrence rate was 12.8%, median duration of work incapacity was 4 weeks, longer for the employed and manual workers than for self-employed. Postoperative pain (scale of 0-6) averaged 3.3 and 2.3, respectively, for the in-hospital and post-hospital periods. CONCLUSION: Taking into account duration of incapacity, general patient satisfaction and recurrence rate, the radical excision method with subsequent open wound granulation provides a reasonable alternative to closed methods. But a definitive assessment of the advantages of the open method with respect to these criteria must await the results of prospective randomized series.

Adolescent↗
PubMed1997

A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.

BACKGROUND: Clozapine, a relatively expensive antipsychotic drug, is widely used to treat patients with refractory schizophrenia. It has a low incidence of extrapyramidal side effects but may cause agranulocytosis. There have been no long-term assessments of its effect on symptoms, social functioning, and the use and cost of health care. METHODS: We conducted a randomized, one-year, double-blind comparative study of clozapine (in 205 patients) and haloperidol (in 218 patients) at 15 Veterans Affairs medical centers. All participants had refractory schizophrenia and had been hospitalized for the disease for 30 to 364 days in the previous year. All patients received case-management and social-rehabilitation services, as clinically indicated. RESULTS: In the clozapine group, 117 patients (57 percent) continued their assigned treatment for the entire year, as compared with 61 (28 percent) of the patients in the haloperidol group (P<0.001). As judged according to the Positive and Negative Syndrome Scale of Schizophrenia, patients in the clozapine group had 5.4 percent lower symptom levels than those in the haloperidol group at all follow-up evaluations (mean score, 79.1 vs. 83.6; P=0.02). The differences on a quality-of-life scale were not significant in the intention-to-treat analysis, but they were significant among patients who did not cross over to the other treatment (P=0.003). Over a one-year period, patients assigned to clozapine had fewer mean days of hospitalization for psychiatric reasons than patients assigned to haloperidol (143.8 vs. 168.1 days, P=0.03) and used more outpatient services (133.6 vs. 97.9 units of service, P=0.03). The total per capita costs to society were high -- $58,151 in the clozapine group and $60,885 in the haloperidol group (P=0.41). The per capita costs of antipsychotic drugs were $3,199 in the clozapine group and $367 in the haloperidol group (P<0.001). Patients assigned to clozapine had less tardive dyskinesia and fewer extrapyramidal side effects. Agranulocytosis developed in three patients in the clozapine group; all recovered fully. CONCLUSIONS: For patients with refractory schizophrenia and high levels of hospital use, clozapine was somewhat more effective than haloperidol and had fewer side effects and similar overall costs.

Adult↗
PubMed1996

A comparison of health-related quality of life in patients with epilepsy, diabetes and multiple sclerosis.

The purpose of this investigation was to compare self-reported health-related quality of life (HRQOL) in epilepsy compared to another neurological condition or a non-neurological chronic illness. Patients with epilepsy (N = 271), multiple sclerosis (N = 85) and diabetes (N = 555) completed a generic measure of HRQOL (RAND 36-Item Health Survey 1.0 (SF-36)), and the eight SF-36 scale scores were compared across groups, adjusting for differences in sociodemographic characteristics and co-morbid medical conditions. Patients with multiple sclerosis reported significantly worse HRQOL compared to both the epilepsy and diabetes groups (who did not differ from one another) on the Physical Functioning, Role Limitations-Physical, Energy, and Social Function scales. Patients with epilepsy and multiple sclerosis did not differ from one another but reported significantly lower HRQOL scores than the diabetes group on the Emotional Well-Being and Role Limitations-Emotional scales. However, the epilepsy group reported better health perceptions compared to the diabetes and multiple sclerosis patients. Generic measures of HRQOL appear useful in identifying some effects of neurological disease, but disease-targeted supplements may be required to more clearly identify the impact of epilepsy on quality of life.

Adult↗
PubMed1996

Distant entry pneumothorax in a competitive fencer.

An elite level fencer sustained a penetrating wound to the upper arm after his opponent's blade broke. Standard care for a deep puncture wound was given but it was some time before the athlete presented symptoms of a pneumothorax, which was confirmed by radiograph. Although resolution of this case was unremarkable, the possibility of penetrating thoracic injury, even when the point of entry is well outside the thorax and the athlete is not immediately symptomatic, should be born in mind by medical personnel working with fencers.

Arm Injuries↗
PubMed1995

Agreement between self reports and proxy reports of quality of life in epilepsy patients.

Agreement between self reports and proxy reports of quality of life was examined in a sample of 292 patients with epilepsy and their designated proxies. Patients and proxies completed an 89-item Quality of Life Inventory (QOLIE-89), with the items rephrased for the proxy. Results reveal moderate correlations (product-moment r ranging from 0.29 to 0.56 for 17 multi-item scales) between self reports and proxy reports. Agreement was good for measures of function that are directly observable and relatively poor for more subjective measures. Mean scale scores were significantly different between patients and proxies for only five of 17 multi-item scales. Proxy respondents systematically reported better functioning than did patients in three scales assessing cognitive functioning (all p < 0.001). By contrast, patients reported more positive health perceptions and less seizure distress than proxies. Patient educational attainment correlated inversely with degree of disagreement between patient and proxy reports for six of the 17 QOL scales and for the overall score. In addition, proxy educational attainment correlated positively with agreement for four scales. This study indicates that for group level comparisons, proxy respondents can be substituted for adults with epilepsy having low to moderate seizure frequency. However, for individual level assessments proxies should be used with caution.

Adolescent↗
PubMed1995

Development of the quality of life in epilepsy inventory.

We developed an instrument to measure health-related quality of life (HRQOL) in epilepsy. A 99-item inventory was constructed from the RAND 36-Item Health Survey (generic core), with 9 additional generic items, 48 epilepsy-targeted items, and 6 other items concerning attitudes toward epilepsy and self-esteem. We administered the 99-item inventory to 304 adults with epilepsy at 25 epilepsy centers. Patients and patient-designated proxies completed the inventory and were retested 1-91 days later. A multitrait scaling analysis of these data led to retention of 86 items distributed in 17 multiitem scales (Cronbach's alpha ranged from 0.78 to 0.92). Factor analysis of the 17 multiitem scales yielded four underlying dimensions of health: an epilepsy-targeted dimension, a cognitive factor, mental health, and physical health. Construct validity was supported by significant patient-proxy correlations for all scales and correlations between neuropsychologic tests and self-reported emotional and cognitive function (all p values < 0.05). There were significant negative correlations between the four factor scores derived from the HRQOL scales and neurotoxicity, systemic toxicity, and health care utilization (except for the correlation between mental health factor and health care utilization; all p values < 0.05). Patients who were seizure-free in the preceding year reported better HRQOL for the overall score, three of the four factor scores, and 8 of the 17 scale scores than did patients with a high frequency of seizures. Relative validity analysis showed that the epilepsy-targeted factor and three of its four component scales were more sensitive to categorization of patients by severity of seizure frequency and type than scales tapping physical health, mental health, or cognitive function. These cross-sectional data support the reliability and validity of this measure of HRQOL in epilepsy. The addition of an epilepsy-targeted supplement to the generic core improved the sensitivity to severity of epilepsy. The 86 items included in the field testing were supplemented by three additional items to form the Quality of Life in Epilepsy (QOLIE-89) inventory.

Adolescent↗
PubMed1995

Dose frequency and dose interval compliance with multiple antiepileptic medications during a controlled clinical trial.

Compliance with medication regimens and clinical trial schedules was evaluated during a study of vigabatrin (VGB), an antiepileptic drug (AED). Medication Event Monitors (MEMS, Aprex Corp., Fremont, CA, U.S.A.) were provided to monitor use of VGB and other AEDs administered to 111 patients at 10 sites. MEMS reports showed the number of doses administered daily, times of doses, and intervals between doses. The 66 patients whose data were evaluable took VGB as prescribed (twice daily, b.i.d.) on 89 +/- 7% of days in the clinical trial (mean 189 +/- 63 days). However, only 66 +/- 24% of doses were taken within the 9-15-h dose interval window for twice-daily dosing, a lower rate than that for dose frequency compliance (p < 0.001). Concomitant medications prescribed b.i.d. (n = 66) (86 +/- 11% dose frequency compliance) were taken at lower rates than VGB (p < 0.02). Interval compliance also was lower for concomitant b.i.d. medications (59 +/- 26%) than for VGB (p < 0.01). Dose frequency compliance for thrice-daily (t.i.d.) medications (n = 36) was 80 +/- 18 and 40 +/- 19% for interval compliance (6-10 h) (both p < 0.0001 vs. VGB). Dose frequency compliance for four times daily (q.i.d.) medications (n = 23) was 80 +/- 23 and 33 +/- 18% for interval compliance (4-8 h) (both p < 0.0001 vs. VGB). Patients at eight sites did not use MEMS properly, often for practical reasons, voiding including of data for 93 medications (32%) because of noncompliance with the study design to monitor compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Ultrasonographic monitoring of conservative-functional treatment of rupture of the Achilles tendon].

Rupture of the Achilles tendon has become more common in recent years. Operative repair is the treatment generally used but non-surgical therapy is being accepted by an increasing number of surgeons because of the reports of good results with conservative treatment. Ultrasonographic examination not only allows an exact diagnosis to be made in muscle and tendon injuries, but also observation of the healing processes. Therefore, conservative functional treatment of rupture of the Achilles tendon can be used with more success, which is a very comfortable concept for these patients. We present a series of 22 subcutaneous ruptures of the Achilles tendon treated non-operatively to emphasize the value of conservative functional therapy with ultrasonographic monitoring. After immobilization of the lower leg by a walking cast in the equinus position for 3-6 weeks, the functional treatment follows using a decreasing heel lift and physiotherapy. Ultrasound examinations were performed frequently to recognize new diastasis early. We observed complete healing in all patients, absence of complications and excellent functional results. The morbidity of the patients was lower than with operative treatment and no hospital stay was needed. In conclusion, in our opinion ultrasound-controlled conservative functional treatment of rupture of the Achilles tendon should be used more frequently in future.

Achilles Tendon↗
PubMed1988

Kinetics of the inhibition by plasminogen activator inhibitor 2 of urokinase isolated from human urine and recombinant microorganisms. Further evidence for correct tertiary structure of recombinant urokinase.

The specific plasminogen activator inhibitor 2 (PAI-2) from human placenta was used to compare the kinetics of inactivation of recombinant urokinase and urokinase from human urine. The inactivation of the enzymes proceeded with identical second order rate constants. The result is considered a further indication of corresponding 3-dimensional structures of urokinases from human urine and of recombinant origin.

Glycoproteins↗