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Biomedical subjects

L Benson

Publications and source records attributed to L Benson.

At least 55 records · Page 3Linked to original sources

Polyethylene glycolated interleukin-2 as maintenance therapy for acute myelogenous leukemia in second remission.

Seven patients in second complete remission of acute myeloid leukemia (AML) aged 19-65 years were treated with polyethylene glycolated interleukin-2 (PEG IL-2), 1 x 10(6) U/M2 IV weekly as the sole postremission therapy. Second remission duration was in the range of 4-49+ months, and three patients had a second remission duration substantially longer than their first (6, 21+, and 42+ months). The results suggest that PEG IL-2 may prolong second remission duration in AML and that a prospective randomized study designed to test that idea is warranted.

Adult↗

Heparin therapy in pediatric patients: a prospective cohort study.

Current guidelines for heparin therapy in pediatric patients have been extrapolated from trials in adult patients without rigorous evaluation of efficacy and safety. We prospectively monitored consecutive pediatric patients receiving systemic doses of heparin over 10 mo at one institution using a predetermined nomogram to monitor maintenance therapy. Sixty-five consecutive children; 38 males and 27 females, received systemic doses of heparin. Thirty children had deep venous thrombosis and/or pulmonary embolism; 11 had arterial thrombi, most frequently after diagnostic angiography; and the remaining 24 received heparin prophylactically, for congenital heart disease. Twenty-nine (45%) of the 65 patients were less than 1 y of age and 22 (34%) were 10 y or older. Congenital heart disease was the predominant diagnosis under 1 y and deep venous thrombosis in older children. After a bolus dose of 50 U/kg, 39% of children (n = 30) achieved a minimal level activated partial thromboplastin time (APTT). Sixty-eight percent of children achieved a minimal level APTT by 24 h and 81% by 48 h. For all 65 children, APTT values were within the therapeutic range 43% of the time. APTT values outside the therapeutic range were twice as likely to be low as high. The average amount of heparin required to maintain therapeutic APTT values for children was 22 U/kg/h: 28 U/kg/h for infants < 1 y and 20 U/kg/h for the rest. Bleeding was rare (2%) and mild. Documented recurrent thrombotic disease was more common (7%) with associated morbidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Maternally inherited hypertrophic cardiomyopathy due to a novel T-to-C transition at nucleotide 9997 in the mitochondrial tRNA(glycine) gene.

We report a unique heteroplasmic T-to-C transition at nucleotide 9997 in the mitochondrial tRNA(glycine) gene in a multiplex family who manifested nonobstructive cardiomyopathy. The degree of mtDNA heteroplasmy generally correlated with the severity of the symptoms. This T-to-C transition disrupts hydrogen bonding in the region adjacent to the acceptor stem of the tRNA molecule. The thymine residue at position 9997 is highly conserved in mammals, as well as in various vertebrates and invertebrates. A PCR diagnostic test for the presence of the 9997 T-to-C transition revealed that the base change was always present in high proportion in affected family members, not present in unaffected family members, and never present in control subjects from various ethnic groups (25 groups sampled, 42 individuals), thus ruling out the possibility that this change represents a polymorphic variant in the general population. The degree of heteroplasmy in lymphoblast cultures also correlated with the level of enzyme activity present for cytochrome c oxidase (complex IV) and succinate cytochrome c oxidoreductase (complexes II and III). The absence of previously reported mtDNA mutations associated with hypertrophic cardiomyopathy was verified by both PCR diagnostic procedures and sequence analysis. All mitochondrial tRNA genes, as well as genes encoding ATPase subunits 6 and 8, were sequenced and found not to possess base changes consistent with the clinical profile. More detailed biochemical and molecular biological investigations are discussed.

Adenosine Triphosphatases↗

Phase I clinical and pharmacokinetic study of menogaril (7-con-O-methylnogarol) in previously treated patients with acute leukemia.

Fifteen patients with relapsed or refractory acute leukemia were treated in this phase I study of menogaril (7-con-O-methylnogarol), a nogalamycin anthracycline derivative. Doses ranged from 50 mg/m2/day to 130 mg/m2/day, administered daily for 5 days. Pharmacokinetic studies were performed at each dose level and confirmed the findings of pharmacokinetic data derived from previous studies in patients with solid tumors. All patients experienced grade 4 hematologic toxicity and the dose limiting toxicity was mucositis. Two patients, one with acute myeloid leukemia and one with acute lymphoid leukemia, achieved complete responses. The AML complete response lasted 10 months and the ALL patient died in CR at 2+ months. Both patients were treated at a dose of 100 mg/m2/day for five days. At this dose, a second induction or consolidation course could be given without severe mucositis, and this is the dose recommended for further phase II studies in leukemia using this schedule.

Acute Disease↗

Tumour-like localized amyloid of the brain is derived from immunoglobulin light chain.

A patient is presented in whom the amyloid component of an intracerebral 'amyloidoma' has been purified and characterized by amino acid sequence analysis. The material originated from an autopsy of a 76-year-old man who 15 years earlier had been operated for an intracerebral 'amyloid tumour'. The tumour had recurred and grown to an almost walnut-sized mass in the right cerebral hemisphere. It was located in the parietal lobe close to the lateral ventricle and had a close connection to the choroid plexus. Histological examination showed large masses of amyloid surrounded by some plasma cells and a few macrophages of the foreign body type. Amino acid sequence analysis of a major fibril subunit protein showed homology with the variable region of a monoclonal lambda immunoglobulin light chain, subgroup III or IV. This shows that the amyloid in the 'tumour' was of AL type and presumably derived from local synthesis by plasma cells.

Aged↗

Long-term follow-up of treatment and potential cure of adult acute lymphocytic leukemia with MOAD: a non-anthracycline containing regimen.

A total of 55 previously untreated adults with acute lymphocytic leukemia (ALL), median age 38 years (range 15-73 years), were treated with MOAD (methotrexate, vincristine, L-asparaginase, and dexamethasone). This regimen includes five phases--induction, consolidation, cytoreduction, maintenance, and central nervous system (CNS) prophylaxis with parenteral high-dose methotrexate. Of the 55 evaluable patients, 42 achieved complete remission 76%), with a median CR duration of 12+ months (range 0.5-195+ months). The median survival in remission is 22+ months (range 1-198+ months), with 33% of remitters continuing in long-term remissions (> 5 years). Two out of four patients who developed CNS leukemia did so without marrow relapse, were successfully treated for that complication, and continue in total complete remission at 8+ and 16+ years. Another patient with extramedullary relapse (breast) was treated with radiation to that site and remains in total CR at 16+ years. Expected toxicities included myelosuppression during the induction phase of treatment, with 65% of patients requiring intravenous antibiotics. Mucositis was the next most frequent toxicity and required dose-reduction in seven patients. Minimal toxicity was seen during the post-remission phases of treatment. L-Asparaginase toxicity was more prominent during intravenous administration (24 patients) than when the intramuscular route of administration (30 patients) was used. The remission rate and long-term survivorship achieved with this regimen, without the use of an anthracycline, is comparable to that of other regimens for adult ALL. MOAD was well-tolerated by young and old adults with ALL. Aseptic necrosis of bone, successfully treated in each instance, occurred in four long-term disease-free survivors. The effect of this complication and its treatment on quality of life has been negligible.

Adolescent↗

Percutaneous pericardial catheter drainage in childhood.

The clinical course of 41 consecutive pediatric patients (mean age 7.6 +/- 5.8 years, weight 27 +/- 22 kg) who underwent percutaneous pericardial drain placement during a 3-year period were reviewed. The most common diagnoses were malignancy (20%), postpericardiotomy syndrome (17%), aseptic pericarditis (12%), and patients recovering from a Fontan type of operation (12%). Indications for drainage included increasing effusion size determined by 2-dimensional echocardiogram (48%), clinical deterioration (33%) and echocardiographic evidence of hemodynamic compromise (12%). Only 3 (7%) patients had clinical evidence of cardiac tamponade. Drainage catheter placement was accomplished percutaneously from the subxiphoid approach. Insertion was successful in all but 1 patient (98%) and successful evacuation of the pericardial space was achieved in 93% of patients. There was 1 death in a critically ill 2-week-old infant and 4 complications, 3 of which occurred in patients aged less than 2 years. Drainage catheters remained in position from 1 to 18 days (mean 3 +/- 3 days) with no late complications. There were 3 instances (7%) of drainage catheter occlusion. These data support the notion that placement of a percutaneous pericardial catheter is safe and effective in providing definitive drainage of the pericardial space in the pediatric age group. Children younger than age 2 years may be at increased risk for complications.

Catheters, Indwelling↗

Obesity among Navajo adolescents. Relationship to dietary intake and blood pressure.

We evaluated anthropometric measurements, blood pressures, dietary intakes, and self-perceived body image of 352 Navajo Indian adolescents. Thirty-three percent of the girls and 25% of the boys were obese according to a body mass index criterion. Navajo youth tended to have larger skinfolds than their white (National Health and Nutrition Examination Survey II) and Mexican American (Hispanic Health and Nutrition Examination Survey) counterparts, with the greater difference in the subscapular skinfolds indicating a greater amount of truncal rather than peripheral fat. When divided into lower, middle, and upper thirds of body mass index, systolic and diastolic blood pressures were positively related with increasing body mass index for girls, and systolic blood pressure and body mass index were related among boys. The high prevalence of obese adolescents and the apparent effect of the increased weight on blood pressure in this population indicate the need for interventions aimed at improving dietary habits and fitness levels.

Adolescent↗

Balloon atrial septostomy under transesophageal echocardiographic guidance.

Balloon atrial septostomy is an established method of palliation for several forms of congenital heart disease. Previously performed under fluoroscopic x-ray control, recent reports have demonstrated the utility of transthoracic echocardiographic monitoring. We report the first application of uniplane transesophageal echocardiography (TEE) (6.7-mm probe) as an alternative imaging modality for control of balloon atrial septostomy on neonates in the intensive care unit.

Catheterization↗

A phase II trial of CI-921 in advanced malignancies.

CI-921, (9-[[2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino]- N,5-dimethyl-4-acridinecarboxamide 2-hydroxyethanesulfonate (1:1)), an anilinoacridine derivative with activity in experimental solid tumors was studied in a multicenter phase II trial in patients with solid tumors. Eligible tumor types included cancers of the breast, stomach, pancreas, nonsmall cell lung, small cell lung, colon, head and neck area, and melanoma. Prestudy requirements included an ECOG performance status of < or = 2, no CNS metastases, and measurable disease. CI-921 was administered intravenously over 1-2 hours on days 1, 8, and 15 of a 35-day course at an initial dose of 270 mg/M2, with modification in subsequent courses based upon tolerance. Principal toxicities included leukopenia, marked phlebitis, and mild nausea and vomiting. One hundred fifty patients were entered of whom 132 were evaluable for response. There was one complete and one partial response among 19 patients with breast cancer, and two partial responses, one each among 14 head and neck and 36 nonsmall cell lung cancer patients.

Adult↗

Ambulatory blood pressure monitoring and left ventricular mass and function after successful surgical repair of coarctation of the aorta.

Late cardiovascular morbidity and mortality remain significant despite apparently successful surgical repair of aortic coarctation. Alterations in cardiac function have been reported in normotensive patients who have had successful repair, the reasons for which remain unclear. This study addresses the relation between ambulatory blood pressure measurements and alterations in left ventricular performance in 20 patients with normotension at rest after successful repair of aortic coarctation. Exercise testing, ambulatory blood pressure monitoring and two-dimensional echocardiographic studies in 13 boys and 7 girls (mean age 14.2 +/- 2.31 and 14.7 +/- 3 years, respectively) who had no evidence of recoarctation were compared with the findings in 20 matched control subjects. No difference was found in systolic blood pressure at rest or peak exercise between patients and control subjects. Male patients developed a significant arm/leg gradient at peak exercise. Systolic ambulatory blood pressure was higher throughout the day in the male group. In the female group, systolic blood pressure was higher only during sleep. No difference was found in diastolic blood pressure or heart rate. The transverse aortic arch was smaller and the left ventricular mass greater in all patients. The relation of wall stress to rate-corrected velocity of shortening was 2 SD above normal in 8 of the 20 patients, suggesting that some have enhanced contractility. The E/A ratio on the atrial echocardiogram was significantly reduced in the patient group. Successfully treated patients who are normotensive at rest after operation are still at risk for developing end organ damage, which is probably explained by incipient mild hypertension documented by ambulatory blood pressure monitoring.

Adolescent↗

Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Childrens Cancer Study Group.

The anthracycline antibiotics, daunorubicin, doxorubicin, and the newer derivatives, are important components of many antineoplastic chemotherapeutic regimens. Their usefulness is limited by their cardiotoxicity. Sequential monitoring of cardiac function of patients undergoing chemotherapy allows identification of subclinical cardiotoxicity. In many patients monitoring can thus guide the modification of the chemotherapy to minimize cumulative cardiotoxicity, reducing acute and long-term clinical and subclinical sequelae. Such monitoring also aids in the comparison of cardiotoxicity produced by different drugs and different methods and schedules of drug administration. The considerable variability of monitoring regimens between institutions and in the literature has detracted from its usefulness. The Cardiology Committee of the Childrens Cancer Study Group has, therefore, reviewed the field and has formulated recommendations for standardized noninvasive monitoring of children during and immediately after chemotherapy and for the modification of the chemotherapy where indicated.

Antibiotics, Antineoplastic↗

Scale models.

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Community Health Services↗

Determination of the anatomical size of ventricular septal defects on the basis of hemodynamic data and noninvasive assessment of pulmonary to systemic vascular resistance ratio Rp/Rs by Doppler-echocardiography.

The pulmonary and systemic flow (Qp/Qs) and resistance ratios (RP/Rs) were determined in children with isolated ventricular septal defects (VSD) to derive an "effective defect resistance" (Rd/Rs) representing the ratios of the resistance of the defect to the systemic vascular resistance. The defect size (expressed as the ratio of the area of the defect to the cross-sectional area of the ascending aorta) was related to the calculated "effective defect resistance," where a significant (non-linear) correlation was found. The effective resistance of the defect is a useful aid for estimation of the anatomical size of a ventricular septal defect. The close correlation between anatomical size and the hemodynamic parameter Rd/Rs allows one to calculate the ratio Rp/Rs with this concept using noninvasive Doppler-ultrasound and echocardiography. This was performed in 21 children with VSD who underwent cardiac catheterisation. The noninvasive calculated flow ratio Qp/Qs and the resistance ratio Rp/Rs showed a close correlation to the values measured at cardiac catheterisation.

Cardiac Catheterization↗

Factors influencing the persistence of shunting within 24 hours of catheter occlusion of the ductus arteriosus.

Catheter occlusion of the persistent ductus arteriosus recently became clinically available with a Rashkind (USCI Bellerica, Massachusetts, USA) umbrella occluder system. A few patients, however, had residual left to right shunting after the procedure. The impact of soaking the foam of the device in a thrombin solution to enhance clotting and of using a device with a diameter of 12 or 17 mm was assessed in 117 consecutive patients undergoing catheter closure. The frequency of residual shunting detected by colour flow Doppler 24 hours after the procedure was the same whether or not thrombin was used.

Cardiac Catheterization↗