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Biomedical subjects

K Blake

Publications and source records attributed to K Blake.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effect of nedocromil sodium on childhood asthma during the viral season.

Viral-induced symptomatic respiratory infections (SRI) frequently cause exacerbations of asthma in children. This study investigated the protective effects of 0.5% nedocromil sodium nebulizer solution given three times a day in preventing asthma exacerbations associated with SRI. Ninety-three mild-moderate asthmatic children (6 to 12 yr of age) received either 0.5% nedocromil sodium or placebo for 24 wk during the viral season. The nedocromil sodium group was symptom-free 58% of the days, and the placebo-treated patients were symptom-free 45% of the days (p = 0.027). During Weeks 1-12, significant differences favored nedocromil sodium for asthma summary score (means: nedocromil sodium = 0.61, placebo = 0.92; p = 0.026), and daytime asthma (nedocromil sodium = 0.78, placebo = 1.22; p = 0.03). Significant differences were noted during monthly intervals for cough (Weeks 1-4: nedocromil sodium = 0.61, placebo = 0.92, p = 0.027) and peak expiratory flow rate (PEFR) (nedocromil sodium 262, placebo = 254 L/min, p = 0.041 Weeks 9-12). Patients in the active treatment group reduced their need for rescue inhaled beta 2-agonist by 10%, whereas patients treated with placebo demonstrated a 24% increase. There was a strong correlation between asthma symptoms and SRI symptoms (r = 0.47; p < 0.001). During SRIs, patients in the nedocromil sodium group demonstrated more rapid resolution of asthma symptoms immediately following infection (p = 0.033 summary score, p = 0.039 sleep difficulty). No serious adverse events were noted. Nedocromil sodium did not prevent the infection or exacerbation of asthma symptoms during SRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Asthmatic Agents↗
PubMed1994

Bioequivalence of a generic slow-release theophylline tablet in children.

OBJECTIVE: To determine whether a generic slow-release theophylline tablet (manufactured by Sidmak Laboratories, Inc.) is therapeutically equivalent to a proprietary theophylline tablet, Theo-Dur, in children. DESIGN: Prospective, randomized, double-blind, crossover trial. SETTING: Multicenter clinics. PATIENTS: 38 children, 6 to 16 years of age, with asthma. INTERVENTIONS: Individualized doses of Theo-Dur or generic tablet every 12 hours for 5 days. MEASUREMENTS AND MAIN RESULTS: During the last 24 hours of each regimen, theophylline serum concentrations were measured serially and a standardized exercise stress test was performed at 24 hours (trough serum concentration). Neither formulation effectively blocked the response to exercise; the maximum decrease in forced expiratory volume in the first second was 26.1% +/- 18.9% with Theo-Dur and 24.8% +/- 19.7% with the generic product (p = 0.68; beta = 0.08). The mean +/- SD peak serum concentrations were 18.0 +/- 3.0 micrograms/ml with Theo-Dur and 18.7 +/- 3.7 micrograms/ml with the generic tablet; the trough serum concentration was < 10 micrograms/ml in 15 subjects after administration of Theo-Dur and in 20 subjects after administration of the generic product. There were no significant differences in relative extent of absorption or the time to reach peak serum concentration. CONCLUSIONS: This generic formulation and Theo-Dur are bioequivalent in children. However, these results cannot be extrapolated to slow-release theophylline formulations that have not been approved by the U.S. Food and Drug Administration as equivalent to Theo-Dur.

Adolescent↗
PubMed1993

Monoclonal antibody-purged bone marrow transplantation therapy for multiple myeloma.

Forty patients with plasma cell dyscrasias underwent high-dose chemoradiotherapy and either anti-B-cell monoclonal antibody (MoAb)-treated autologous, anti-T-cell MoAb-treated HLA-matched sibling allogeneic or syngeneic bone marrow transplantation (BMT). The majority of patients had advanced Durie-Salmon stage myeloma at diagnosis, all were pretreated with chemotherapy, and 17 had received prior radiotherapy. At the time of BMT, all patients demonstrated good performance status with Karnofsky score of 80% or greater and had less than 10% marrow tumor cells; 34 patients had residual monoclonal marrow plasma cells and 38 patients had paraprotein. Following high-dose chemoradiotherapy, there were 18 complete responses (CR), 18 partial responses, one non-responder, and three toxic deaths. Granulocytes greater than 500/microL and untransfused platelets greater than 20,000/microL were noted at a median of 23 (range, 12 to 46) and 25 (range, 10 to 175) days posttransplant (PT), respectively, in 24 of the 26 patients who underwent autografting. In the 14 patients who received allogeneic or syngeneic grafts, granulocytes greater than 500/microL and untransfused platelets greater than 20,000/microL were noted at a median of 19 (range, 12 to 24) and 16 (range, 5 to 32) days PT, respectively. With 24 months median follow-up for survival after autologous BMT, 16 of 26 patients are alive free from progression at 2+ to 55+ months PT; of these, 5 patients remain in CR at 6+ to 55+ months PT. With 24 months median follow-up for survival after allogeneic and syngeneic BMT, 8 of 14 patients are alive free from progression at 8+ to 34+ months PT; of these, 5 patients remain in CR at 8+ to 34+ months PT. This therapy has achieved high response rates and prolonged progression-free survival in some patients and proven to have acceptable toxicity. However, relapses post-BMT, coupled with slow engraftment post-BMT in heavily pretreated patients, suggest that such treatment strategies should be used earlier in the disease course. To define the role of BMT in the treatment of myeloma, its efficacy should be compared with that of conventional chemotherapy in a randomized trial.

Adult↗
PubMed1993

Congenital heart disease in CHARGE association.

This study reviews the spectrum of congenital heart disease and associated anomalies in 59 patients with the CHARGE association. We have analyzed our clinical experience in managing the cardiovascular anomalies and have reviewed outcome and risk factors for mortality. This study also highlights problems of cardiac management in children born with multiple system involvement. Twenty patients have died; actuarial survival was 78% at 1 year and 60% at 10 years. In only four of the nonsurvivors could their demise be ascribed to their underlying congenital heart disease. We found the outlook for survival was poor if more than one of the following three features were present; cyanotic cardiac lesions, bilateral posterior choanal atresia, or tracheoesophageal fistula. However, mortality was largely due not to the structural heart or choanal abnormalities, but instead reflected the underlying pharyngeal and laryngeal incoordination which resulted in aspiration of secretions. Furthermore, outcome is likely to be improved if collaboration between specialist surgical teams allows necessary procedures to be performed using the minimum of anesthetics. Examination of both the short- and long-term management of these children has stressed the importance of a multidisciplinary approach to their care. The pattern of cardiac defects was not random; lesions within the Fallot spectrum accounted for 33% of their congenital heart disease. Atrioventricular septal defects were also overrepresented. Not all cardiovascular defects could be explained by hypothesizing a neural crest etiology.

Abnormalities, Multiple↗
PubMed1993

Growth in CHARGE association.

Growth data is shown from 44 children (aged 0.5-18 years; 27 boys, 17 girls) with CHARGE association. Children had a normal birth weight and length, but in infancy there was a fall in centiles. Children remained small and there was pubertal delay in boys. Close monitoring of growth with early detection and intervention is recommended.

Abnormalities, Multiple↗
PubMed1992

CHARGE and esophageal atresia.

CHARGE association was diagnosed in 61 infants, 20 of whom died, mainly during the first 2 years of life. Esophageal atresia and/or tracheoesophageal fistula were present in 10 neonates. Axial skeletal anomalies occurred in 7 of the 10, but none had preaxial limb defects typical of the VATER association. All had major cardiac anomalies, predominantly tetralogy of Fallot. The majority of patients had primary repair of the esophagus. The postoperative course was stormy in all patients, with a high incidence of complications and 70% died. The recognition of features of the CHARGE association is important because it has major prognostic and therapeutic implications.

Abnormalities, Multiple↗
PubMed1992

JC virus associated meningoencephalitis in an immunocompetent girl.

JC virus is most commonly acquired during childhood, and no clinical illness has been associated with primary infection, which is assumed to be asymptomatic. The only disease associated with JC virus to date is progressive multifocal leucoencephalopathy (PML), which is usually caused by viral reactivation in immunocompromised adults. A chronic meningoencephalitis associated with an active JC virus infection in an immunocompetent 13 year old girl is described.

Adolescent↗
PubMed1991

All advanced stage non-Hodgkin's lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment.

Polymerase chain reaction (PCR) of bcl-2 provides an extremely sensitive method to detect minimal disease in approximately 50% of patients with non-Hodgkin's lymphomas (NHL). In an attempt to determine the clinical usefulness of this technique, we examined the bone marrow (BM) of 152 patients with advanced-stage NHL at the time of evaluation and after induction or salvage chemotherapy before autologous BM transplantation. The BM proved to be an accessible and reproducible tissue source to determine PCR positivity because all of the 102 patients examined had the same PCR-amplifiable breakpoint in their BM and lymph node. At the time of evaluation, PCR analysis in advanced-stage NHL patients added little additional information to morphologic analysis because each technique identified BM infiltration in approximately 70% of patients. PCR was significantly more useful in determining BM infiltration after induction or salvage therapy. At that time, approximately 50% of patients had morphologically normal BM, whereas PCR analysis remained positive in 100% of those with an amplifiable breakpoint. These observations were confirmed in a clinical trial attempting to induce remission in previously untreated low-grade advanced-stage NHL patients. In this series, PCR was positive in all patients after treatment although the BM was histologically uninvolved in 50% of cases, showing that conventional therapy did not eradicate bcl-2-positive cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Autologous bone marrow transplantation in 69 patients with a history of low-grade B-cell non-Hodgkin's lymphoma.

Sixty-nine patients with a history of low-grade B-cell non-Hodgkin's lymphoma (NHL) in sensitive relapse or incomplete first remission underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-treated autologous bone marrow transplantation (ABMT). At ABMT, 51 patients had low-grade histology and 18 patients had a history of low-grade NHL that had undergone histologic transformation to a higher-grade NHL. Before ABMT, only 20 of the 51 low-grade patients and 10 of the 18 patients with transformed histologies were in complete remission. Moreover, at the time of marrow harvest, 24 of the low-grade and eight of the transformed histology patients had histologic evidence of lymphoma cells infiltrating the marrow. Following high-dose therapy, only one acute, in-hospital death was observed. There was no significant difference in the disease-free survival (DFS) between patients with low-grade and patients with transformed histologies. Among patients with low-grade NHL, the patients in complete remission before ABMT experienced significantly longer DFS than those in partial remission (P less than .05). This preliminary study suggests that some patients with relapsed low-grade NHL may experience prolonged DFS following high-dose ablative therapy.

Adult↗
PubMed1990

Autologous bone marrow transplantation in B-cell non-Hodgkin's lymphoma: very low treatment-related mortality in 100 patients in sensitive relapse.

One hundred patients with B-cell non-Hodgkin's lymphoma (NHL) in sensitive relapse or incomplete first remission underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MAb)-treated autologous bone marrow transplantation (ABMT). These patients demonstrated good performance status with a Karnofsky score of 80% or greater. The majority of these patients had one or more adverse prognostic features including a failure to achieve a complete remission (CR) with conventional combination chemotherapy (37 patients), bone marrow infiltration (69 patients), a history of extranodal disease other than bone marrow infiltration (42 patients), and histologic conversion (18 patients). At the time of ABMT, only 52 patients were in CR; however, all patients achieved a minimal disease state following conventional intensive therapy. Moreover, at the time of marrow harvest, 37 of these patients had histologic evidence of lymphoma cells infiltrating the marrow. Following high-dose ablative therapy, two acute in-hospital treatment-related deaths were observed. Two late deaths were observed, not due to recurrent lymphoma. Of the remaining 96 patients, 61 are in unmaintained CR with a median follow-up of 13 months. Kaplan-Meier actuarial analysis predicts 50% probability of disease-free survival (DFS) at 37.8 months. This very low treatment-related mortality provides the rationale to apply high-dose therapy and ABMT as consolidative therapy for patients in first remission who are at high risk for relapse following conventional therapy.

Actuarial Analysis↗
PubMed1989

The postnatal expression of acetylcholinesterase in somatostatin-positive cells of mouse hippocampus.

The neuroanatomical distributions of acetylcholinesterase (AChE) staining and somatostatin-like immunoreactivity (SOMLI) of neurons intrinsic to the mouse hippocampal formation have been evaluated during postnatal development. Besides the progressive development of neuropil staining for AChE, as a consequence of the septohippocampal innervation, intense AChE staining was also expressed in a subpopulation of neurons intrinsic to the stratum oriens and the hilus of dentate gyrus. In the stratum oriens, the number of AChE-positive cells increased between postnatal day (PND) 3 and PND 10 and declined slightly after PND 21. In the hilus of the dentate gyrus, the number of AChE-stained cell bodies increased progressively until PND 21 when the adult complement was achieved. The AChE-positive neurons of strata radiatum and lacunosum-moleculare, which were few and scattered, increased progressively from PND 7 until adulthood. SOMLI-positive neurons were present in the hippocampal formation by PND 3, and their density showed initial increases followed by decreases in the second to third postnatal week. SOMLI cell distribution on the other hand did not change remarkably during subsequent maturation. Because of the similar developmental time course and localization of AChE and SOMLI neurons, co-localization was assessed by a double-staining method. A large percentage of the neurons staining for one of these markers also stained for the other. In the stratum oriens, from PND 3 to PND 10, the number of SOMLI neurons expressing AChE was increased while a slight decrease from the PND 21 to adulthood was evident. Virtually all SOMLI-positive neurons in the dentate gyrus stained for AChE from PND 7 through adulthood, although the intensity of AChE reactivity declined with maturation.

Acetylcholinesterase↗
PubMed1989

Angina and vasospasm at rest in a patient with an anomalous left coronary system.

An anomalous left main coronary artery with passage between the right ventricular infundibulum and aortic root has been incriminated as the causation of sudden death in a small number of individuals, many of whom are quite young. Mechanical features such as angulation and compression are most often incriminated. A 59-year-old man with such a coronary anomaly who had chest pain at rest, ST segment elevation, and ventricular tachycardia, but who had no evidence of effort-related myocardial ischemia, is reported. Improvement in the degree of coronary tone in the anomalous left main coronary with intracoronary nitroglycerin administration was demonstrated. This represents the first report of an individual with an anomalous left main coronary system with ventricular tachycardia/ventricular fibrillation and documented vasospasm in the anomalous artery.

Angina Pectoris↗
PubMed1989

Complement-independent neutralising monoclonal antibody with differential reactivity for strains of human cytomegalovirus.

A mouse monoclonal antibody with complement-independent neutralising activity against cytomegalovirus (CMV) and reactive with the 86 kilodalton (kDa) viral glycoprotein H is described. Neutralisation tests against a range of different strains of CMV showed significant crossreactivity, but clear differences were evident between the two prototype viruses AD169 and Davis, and particularly between AD169 and several low-passage recent clinical isolates; CMV present in urine was neutralised weakly if at all.

Animals↗