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Biomedical subjects

B Bender

Publications and source records attributed to B Bender.

At least 19 recordsLinked to original sources
PubMed2000

Brain morphology in Klinefelter syndrome: extra X chromosome and testosterone supplementation.

OBJECTIVE: This study focuses on variation in brain morphology associated with supernumerary X chromosome and Klinefelter syndrome (KS). Using an unselected birth cohort of KS subjects and high-resolution MRI, the authors investigated the neuroanatomic consequences of the 47,XXY karyotype in the presence and absence of exogenous testosterone supplementation. METHODS: Regional brain volumes were measured in 10 subjects with KS and 10 age-matched control men. Five of the KS subjects had received testosterone supplementation since puberty (KS+T) and five had not (KS-T). RESULTS: KS subjects showed significant (p < 0.01) reduction in left temporal lobe gray matter volumes compared with normal control subjects. Differences in left temporal gray volumes were also significant between the KS+T and KS-T groups (p < 0.01). Verbal fluency scores were significantly different between the KS+T and KS-T groups as well. CONCLUSION: Supernumerary X chromosome material in men is associated with a reduction in left temporal lobe gray matter, a finding that is consistent with the verbal and language deficits associated with KS. Also, relative preservation of gray matter in the left temporal region is associated with exposure to exogenous androgen during development. A history of testosterone supplementation also appears to be associated with increased verbal fluency scores in KS patients.

Adult↗
PubMed2000

Comprehensive allelotype and genetic anaysis of 466 human nervous system tumors.

Brain tumors pose a particular challenge to molecular oncology. Many different tumor entities develop in the nervous system and some of them appear to follow distinct pathogenic routes. Molecular genetic alterations have increasingly been reported in nervous system neoplasms. However, a considerable number of affected genes remain to be identified. We present here a comprehensive allelotype analysis of 466 nervous system tumors based on loss of heterozygosity (LOH) studies with 129 microsatellite markers that span the genome. Specific alterations of the EGFR, CDK4, CDKN2A, TP53, DMBT1, NF2, and PTEN genes were analyzed in addition. Our data point to several novel genetic loci associated with brain tumor development, demonstrate relationships between molecular changes and histopathological features, and further expand the concept of molecular tumor variants in neuro-oncology. This catalogue may provide a valuable framework for future studies to delineate molecular pathways in many types of human central nervous system tumors.

Alleles↗
PubMed2000

Ablation of atypical atrial flutter guided by the use of concealed entrainment in patients without prior cardiac surgery.

INTRODUCTION: Mapping techniques have not been systematically evaluated with respect to atypical atrial flutter (AF) not involving the inferior vena cava isthmus. The purpose of this study was to assess prospectively the use of concealed entrainment (CE) in mapping of AF and to assess the clinical benefit of ablation of clinically relevant atypical AF. METHODS AND RESULTS: In seven consecutive patients without prior cardiac surgery presenting with atypical AF, mapping was performed in the right and, if necessary, left atrium. At sites with CE, radiofrequency energy was delivered. In a posthoc analysis, the endocardial activation time, stimulus-flutter wave (F) interval, presence of split potentials and diastolic potentials, and postpacing interval were assessed, and effective sites were compared to ineffective sites. A total of 22 forms of atypical AF either could be induced or were present at the time of the study. Eleven of the 13 targeted atypical AFs (85%) were successfully ablated. The positive predictive value of CE increased from 45% to 75% in the presence of matching electrogram-F and stimulus-F intervals or if flutter terminated during entrainment pacing, and to 88% in the presence of split atrial electrograms or diastolic potentials. During short-term clinical follow-up, none of the patients had recurrence of the ablated AF. However, the majority of patients required either medication for atrial fibrillation or repeated interventions for new forms of AF. CONCLUSION: Mapping and ablation of atypical AF is feasible if sites with CE can be identified. However, the clinical benefit of successful ablations in patients with atypical flutter appears to be limited.

Adult↗
PubMed2000

Location of the lower turnaround point in typical AV nodal reentrant tachycardia: a quantitative model.

INTRODUCTION: Recent observations suggest that the circuit of AV nodal reentrant tachycardia (AVNRT) may extend down to the His bundle. The purpose of this study was to develop a quantitative model indicating the location of the lower turnaround point in AVNRT. METHODS AND RESULTS: Slow pathway modification was performed in 70 patients with typical AVNRT. During sinus rhythm, ventricular pacing was performed with the AVNRT cycle length. During AVNRT, the HinitAinit interval was measured from initial His to the initial atrial deflection recorded in the His-bundle lead. During ventricular pacing, the HendAinit interval was measured from end of the His to the beginning of the atrial deflection. It was hypothesized that x reflects conduction time from the lower turnaround point to Ainit, whereas y reflects conduction time from the lower turnaround point to Hinit. Anterograde conduction during AVNRT and retrograde conduction during ventricular pacing were assumed to be identical if there was 1:1 retrograde conduction at the AVNRT cycle length. The following formulas describe the relation of the measured parameters: x - y = HinitAinit; and x + y = HendAinit. Resolving both formulas yields the unknown x and y: y = (HendAinit - HinitAinit)/2, x = (HendAinit + HinitAinit)/2. These criteria were present in 52 of 70 patients. The mean cycle length of AVNRT was 355 +/- 42 msec, mean HinitAinit was 54 +/- 27 msec, and mean HendAinit was 60 +/- 29 msec. Accordingly, in 20 of 52 patients, the lower turnaround point was located within the His bundle (y = -15.4 +/- 16.1 msec), in 3 of 52 it was in the nodal-His junctional area (y = 0), and in 29 of 52 it was above the His bundle (y = +12.7 +/- 10.3 msec). The HinitAinit interval was significantly longer (66 +/- 32 msec vs 47 +/- 20 msec; P = 0.02) and the HendAinit interval was significantly shorter (45 +/- 30 msec vs 69 +/- 24 msec; P = 0.004) when the first group was compared with the others. CONCLUSION: In about 1 of 3 of patients with typical AVNRT, the lower turnaround point of the circuit is within the His bundle; in more than half of the patients it is above the His bundle. These data do not support the concept that all AVNRTs have an intranodal circuit, but are in accordance with the finding of longitudinal dissociation of the His bundle.

Adult↗
PubMed2000

Pharmacological management of atrial fibrillation: an update.

Therapy of atrial fibrillation remains difficult in many patients. There is increasing awareness that antiarrhythmic drug therapy instituted to maintain sinus rhythm after successful cardioversion of atrial fibrillation may pose a substantial risk to the patient. Therefore, results of prospective randomized trials are needed to allow a more evidence-based approach to the treatment of this common arrhythmia. Two recently published studies have shown superiority of amiodarone over conventional antiarrhythmic drugs in maintaining sinus rhythm. The largest such study published today, the Canadian Trial in Atrial Fibrillation (CTAF), has randomized 403 patients to amiodarone or to sotalol or propafenone. At the end of the observation period, amiodarone-treated patients were significantly more likely to remain in sinus rhythm than conventionally treated patients. A number of new antiarrhythmic drugs, mainly class III substances, are currently developed for the treatment of atrial fibrillation or atrial flutter. Ibutilide has recently been released for intravenous administration, attempting pharmacological cardioversion of atrial fibrillation/atrial flutter. It has been evaluated in a number of prospective trials, which showed a higher conversion rate in patients with atrial flutter. Dofetilide is another new compound developed mainly for maintenance of sinus rhythm after restoration of sinus rhythm. It has been evaluated in two prospective, randomized, placebo-controlled trials; moreover, analysis of the DIAMOND trials showed effectiveness of dofetilide in maintaining sinus rhythm in patients with depressed left ventricular function without increased mortality when compared with placebo. Finally, several ongoing studies compare the therapeutic strategy of controlling ventricular rate in atrial fibrillation compared with the strategy of maintaining sinus rhythm. These trials will help to optimize therapy in atrial fibrillation, the most commonly encountered arrhythmia.

Anti-Arrhythmia Agents↗
PubMed2000

[Microvolt level T wave alternans: a new marker for noninvasive risk stratification].

Prospective identification of patients with structural heart disease who could profit from prophylactic ICD therapy is hampered by the low predictive power of the currently available risk stratification parameters. Microvolt T wave alternans measured noninvasively is a new promising parameter to assess impaired ventricular repolarization which has been associated with an increased incidence of ventricular tachyarrhythmias. T wave alternans is rate-dependent; to induce alternans, heart rate may be increased by atrial stimulation during invasive EP testing or noninvasively by exercise stress testing. The first clinical validation with respect to prediction of inducibility of ventricular tachyarrhythmias and of arrhythmic events during follow-up in patients undergoing invasive EP testing was reported in 1994. Subsequently, a good concordance between the results of invasive and noninvasive assessment of T wave alternans was demonstrated by our group. The first prospective evaluation of the noninvasive alternans measurement using submaximal exercise testing was performed in patients surviving prehospital ventricular fibrillation or sustained ventricular tachycardia referred to our institution. The occurrence of T wave alternans in this patient population was predictive of future tachyarrhythmic events with subsequent appropriate ICD therapy. The results of the currently performed prospective trials in various patient populations will help to establish the utility of T wave alternans assessment as a risk stratifier in clinical practice.

Action Potentials↗
PubMed1999

Pharmacological therapy of atrial fibrillation.

Pharmacological treatment of atrial fibrillation aims at reducing symptoms and possible complications of this frequently encountered arrhythmia. Prevention of embolic events by means of oral vitamin K antagonists is therefore mandatory in most patients presenting with atrial fibrillation. Whereas in paroxysmal atrial fibrillation reduction in frequency and duration of episodes is the treatment goal, symptomatic relief of persistent atrial fibrillation can be achieved by two treatment strategies: 1) restoration of sinus rhythm, referred to as rhythm control, and 2) limitation of the average and maximal ventricular heart rate, referred to as rate control. This review provides data from relevant clinical studies addressing the effectiveness and limitations of currently available drug therapy according to the two treatment approaches.

Anti-Arrhythmia Agents↗
PubMed1998

Effects of normobaric oxygen on ciliary beat frequency of human respiratory epithelium.

Respiratory infection is a major cause of morbidity after general anaesthesia. Impairment of respiratory ciliary beat frequency (CBF) by different stress factors causes a decrease in mucus transport rate (MTR). We have tested the effect of different concentrations of oxygen on CBF of human respiratory epithelium in a prospective, randomized, in vitro study. Samples of superficial mucosa of the inferior nasal turbinates of 20 non-smoking healthy volunteers were harvested and exposed to three different oxygen environments (group I = 21% oxygen, group II = 60% oxygen and group III = 95% oxygen) for 2 h. In 50% of the samples, exposure time was prolonged. At 30, 60, 90, 120 and 240 min, light microscopic images of cilia activity were videotaped and CBF was later assessed in slow motion. Compared with baseline, group I showed no difference in CBF throughout the study. CBF was increased in group II from mean 9.7 (SD 0.4) to 11.2 (0.4) Hz (16%, P < 0.001) and in group III from 9.5 (0.6) to 12.1 (0.5) Hz (28%, P < 0.001) at 120 min. After 240 min of exposure to 95% oxygen, the CBF trend in group III was reduced to 11.8 (0.6) Hz but still remained above baseline. We conclude that oxygen appeared to have a dose- and time-dependent accelerating effect on CBF. Prolonged exposure to high oxygen concentrations reversed this trend. Direct oxygen toxicity ("oxygen stress") is a possible explanation for this effect. These changes may result in impaired MTR.

Cilia↗
PubMed1998

Psychological factors associated with medication nonadherence in asthmatic children.

Adherence with inhaled beta-agonists and corticosteroids in 24 asthmatic children was tracked over 3 months utilizing the metered-dose inhaler chronolog (MDIC). Patients seldom took all of their medications as prescribed, and failed to take any inhaled corticosteroid doses on a median of 41.8% of days or inhaled beta-agonists on 28.1% of days despite prescribed daily use. Medication nonadherence was correlated with lower levels of asthma knowledge (Asthma Knowledge Questionnaire) and family dysfunction (Family Assessment Device), but not child behavior disorder (Child Behavior Checklist). Patients tended to dramatically over-report medication use. Improved identification of the markers of nonadherence can directly facilitate more efficient targeting of behavioral interventions, resulting in improved adherence, better illness control, and less requirement of urgent medication intervention.

Anti-Asthmatic Agents↗
PubMed1997

Nonadherence in asthmatic patients: is there a solution to the problem?

LEARNING OBJECTIVES: Reading this article will reinforce the reader's awareness of the relationship between adherence and treatment outcome, of the causes of nonadherence, of methods of measurement, and of steps toward successful intervention. DATA SOURCES: Articles on adherence to asthma therapy were reviewed. A MEDLINE database using subject keywords was searched from 1990 through 1997. STUDY SELECTION: Pertinent articles were chosen, with preferential presentation of results from controlled studies. RESULTS: There is no evidence of recent improvement in the rates of nonadherence, and patients continue on average to take about 50% of prescribed medication. Nonadherence assessment is most accurate when it can be measured objectively, and relies neither on patient report nor physician estimate. The consequences of nonadherence are measured in patient suffering, financial cost, and serious compromise of clinical trial outcomes. Underlying causes of nonadherence are traced to characteristics of the disease, treatment, patient, and caregiver system. CONCLUSION: Improved adherence will lead to improved disease control, but only if medical care systems encourage and support the allocation of sufficient resources to allow barriers to self-management to be discussed and solutions negotiated. Attempts to improve adherence outside of the caregiver-patient relationship are less likely to succeed. Special programs for difficult-to-manage patients are necessary to change behavior, although significant illness improvement and cost savings are likely to result.

Asthma↗
PubMed1997

Adverse effects of medications for rhinitis.

LEARNING OBJECTIVES: Reading this article will reinforce the reader's awareness of the adverse effects of medications used for the treatment of rhinitis. DATA SOURCES: Articles on therapy of rhinitis and reports of associated side effects were reviewed. A MEDLINE database using subject keywords was searched from 1992 through 1997. STUDY SELECTION: Pertinent articles were chosen. A distinction was made in the text between controlled studies and case reports. RESULTS: Antihistamines, decongestants, anticholinergic agents, and corticosteroids, alone or in combination are used in the treatment of rhinitis. Reported side effects include sedation, psychosis, impaired learning and memory, and cardiac arrhythmias. CONCLUSION: Rhinitis and its complications are important medical conditions. Adverse reactions are often difficult to diagnose and assess. Side effects may arise from the use of individual drugs or from drug combinations. There is insufficient cause to abandon these medications, but physicians must be mindful of the inherent risks of the drugs that they prescribe and of others that their patients may be taking without the physicians' knowledge or approval.

Adrenal Cortex Hormones↗
PubMed1997

Nonadherence to asthma treatment and failure of therapy.

Adherence to clinical regimens is paramount in determining their effectiveness. Asthma is a chronic illness that requires consistent, anti-inflammatory therapy. A "high risk" profile for fatal or near-fatal asthma has emerged that includes suboptimal pharmacotherapy in conjunction with severe disease, psychologic dysfunction, black race or Hispanic-American ethnicity, and residence in an urban area with a high concentration of poverty. Collaboration between physicians and patients is necessary to allow individuals to make choices informed by medical facts and the physician's experience. Objective monitoring of adherence and pulmonary function and acceptance by the clinicians of the National Asthma Education and Prevention Program guidelines to control airway inflammation are essential in order to reduce the unacceptable rates of morbidity and mortality associated with asthma.

Asthma↗
PubMed1997

Purge system for rotary blood pumps.

Purge liquid has been supplied successfully to lubricate the bearings and wash the seals of rotary blood pumps to minimize hemolysis and thrombosis, extending their operating endurance. Although encouraging results have been obtained and development is proceeding for pumps with blood lubricated bearings, their validation and clinical use will occur some time in the future. For rotary blood pumps with purged bearings, a miniature purge liquid pump weighing 80 g has been successfully developed to meet the design point of 1 ml/h at 1,000 mm Hg (required by an existing rotary blood pump) with a motor power of 4 mW. The novel device maintains the flow rate for a sufficient time to service or replace the pump without flow interruption. A preliminary design has been made for a wearable purge delivery unit comprising a purge liquid pump, an electronic control, a purge liquid reservoir, and a battery.

Biomechanical Phenomena↗
PubMed1996

Noncompliance and treatment failure in children with asthma.

BACKGROUND: Accurate and reliable information about children's use of inhaled medications is needed because of the growing reliance on these drugs in the treatment of asthma and the excessive morbidity and mortality attributable to this disease. OBJECTIVE: This study was designed to evaluate the adherence of children with asthma to regimens of inhaled corticosteroids and beta-agonists. METHODS: Data collected electronically by metered-dose inhaler monitors were compared with data recorded by patients on traditional diary cards. A volunteer sample of 24 children, between 8 and 12 years old, who had asthma for which they were receiving both inhaled corticosteroids and beta-agonists, participated over a 13-week period. Each child was accompanied by a parent to all study visits. The main outcome measures were the use of medication as reported by diary card entries and recorded by electronic monitoring and disease exacerbation, as indicated by requirement for oral corticosteroids. RESULTS: The median use of inhaled corticosteroids reported by patients on their diaries was 95.4%, whereas the median actual use was 58.4%. More than 90% of patients exaggerated their use of inhaled steroids, and diary entries of even the least compliant subjects reflected a high level of adherence. The children who experienced exacerbation of disease sufficient to require a burst of oral corticosteroids differed markedly from the others in their adherence to prescribed therapy as recorded by the electronic monitors. The median compliance with inhaled corticosteroids was 13.7% for those who experienced exacerbations and 68.2% for those who did not. CONCLUSIONS: Electronic monitoring demonstrated much lower adherence to prescribed therapy than was reported by patients on diary cards. Low rates of compliance with prescribed inhaled corticosteroids were associated with exacerbation of disease. Poor control of asthma should alert the physician to the possibility of noncompliance.

Administration, Inhalation↗
PubMed1996

Monogenetic hypertension and pheochromocytoma.

Hypertension attributable to pheochromocytoma is a very attractive model for the elucidation of the pathogenesis of hypertension. Sixteen different point mutations in the RET proto-oncogene and 30 mutations in the Von Hippel-Lindau (VHL) tumor suppressor gene have been identified so far associated with expression of pheochromocytoma. Each of these mutations initiates either the syndrome of multiple endocrine neoplasia type 2 (MEN 2) (MEN 2A and MEN 2B) or the VHL disease. Certain mutations in both genes are associated with the presence of pheochromocytoma. In general, these pheochromocytomas produce catecholamines that result in hypertension. Therefore, analysis for germline mutations in these genes are of practical value, because susceptibility to these diseases can be predicted in as yet clinically unaffected relatives.

Genes, Tumor Suppressor↗
PubMed1996

Low-dose fluconazole as primary prophylaxis for cryptococcal infection in AIDS patients with CD4 cell counts of < or = 100/mm3: demonstration of efficacy in a positive, multicenter trial.

The efficacy of low-dose fluconazole (200 mg orally administered thrice weekly) as primary prophylaxis for cryptococcal infection was prospectively assessed in a multicenter trial involving 218 patients who were infected with human immunodeficiency virus (HIV) and who had CD4 cell counts of < or = 100/mm3. The median CD4 cell count at baseline was 39/mm3, 58% of the patients had an AIDS-defining illness or infection prior to enrollment. Cryptococcal meningitis occurred in 0.4% (1) of the 218 patients. The breakthrough isolate was susceptible to fluconazole, and the fluconazole kinetic study demonstrated adequate drug absorption and serum fluconazole levels; noncompliance could not be excluded in this case. Mucocutaneous and/or esophageal candidiasis developed in 18% (40) of the patients. Noncompliance with fluconazole therapy was the only variable independently associated with breakthrough candidiasis in the study patients (P = .00002). Thus, fluconazole (200 mg thrice weekly) given to HIV-infected patients with CD4 cell counts of < or = 100/mm3 was efficacious as primary prophylaxis for cryptococcosis, with notably lower costs and increased convenience for patients in comparison with daily administration of the drug.

AIDS-Related Opportunistic Infections↗