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Biomedical subjects

J Manning

Publications and source records attributed to J Manning.

At least 19 recordsLinked to original sources
PubMed1992

Prognostic value of proliferating cell nuclear antigen expression in chronic lymphoid leukemia.

Chronic lymphocytic leukemia (CLL) is a usually indolent disease that can assume an aggressive clinical course in some patients. To develop assays that would be predictive of how a particular patient's disease would evolve, we studied the expression of proliferating cell nuclear antigen (PCNA) by Western blotting in 40 patients with CLL. The concentration of PCNA, a cofactor for delta DNA-dependent DNA polymerase, is indicative of the proliferative state of the cell. Significantly lower PCNA levels were observed in earlier stage CLL when compared with more advanced disease. The leukemic cell proliferative rate, assessed by lymphocyte doubling time and flow cytometry, also correlated significantly with the level of PCNA expression. These results suggest that a high level of PCNA in the cells of CLL patients at presentation identifies a subgroup of patients whose CLL cells have a higher proliferative activity and who may, therefore, have a potentially shorter survival.

Actins↗
PubMed1991

Cytomorphologic, immunocytochemical, and nucleic acid flow cytometric study of 50 lymph nodes by fine-needle aspiration. Comparison with results obtained by subsequent excisional biopsy.

Fifty patients with clinically suspected or previous diagnosis of lymphoma underwent fine-needle aspiration (FNA) and subsequent excisional biopsy of their lymph nodes. Results of cytologic diagnosis made from the direct smears in conjunction with immunocytochemical study of cytospin preparations and nucleic acid flow cytometric study (FCM) were compared with the results obtained from histologic sections, cryostat-immunohistochemical study, and nucleic acid FCM performed on resected lymph nodes. This study demonstrates (1) results of immunocytochemical and DNA-FCM analysis of FNA-derived material are comparable in the majority of cases to those obtained from surgical specimens, (2) immunostaining of cytospin preparations for immunoglobulin (Ig) gives less background staining and in certain cases is easier to interpret than when performed on frozen sections, and (3) monotypia in FNA in conjunction with cytomorphologic study is 100% specific for lymphoma, and polytypic staining for Ig does not exclude HD, T-cell lymphoma, or B-cell malignancy focally involving a lymph node.

Adult↗
PubMed1991

Pharmacokinetics, safety, and pharmacologic effects of fosinopril sodium, an angiotensin-converting enzyme inhibitor in healthy subjects.

The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five subjects each. Serum aldosterone levels, ACE activity, and sitting blood pressure were determined, as were pharmacokinetic parameters of fosinoprilat, the active diacid of fosinopril. In a dose-tolerance study (study II), 80 and 160 mg of the drug were administered in doses of 40 mg bid and 80 mg bid for 2 weeks. Pharmacokinetics were determined on days 1 and 14, and blood pressure and ACE activity were measured daily. One hour after all doses of fosinopril, serum ACE activity was undetectable. Peak blood levels of fosinoprilat occurred at about 3 hours after dosing, and linear kinetics of the diacid were observed. ACE activity remained undetectable for more than 24 hours after the treatment was stopped in study II. Serum aldosterone levels were decreased by 50% of baseline values in both studies. In study I, maximal reductions in mean blood pressure occurred approximately 6 hours postdose; once-daily doses of 20 mg or greater achieved reductions of 11.3 to 21.6% (P less than or equal to .05, compared with placebo reductions). Fosinopril was well tolerated. Subjects reported only mild gastrointestinal complications at doses of 80 mg/day or higher. These data show that fosinopril is a safe and effective inhibitor of ACE with a long duration of action on serum ACE activity.

Adolescent↗
PubMed1989

Differential expression of the c-erbB-2 gene in human small cell and non-small cell lung cancer.

We studied non-small cell lung cancers (NSCLC) from 60 patients for abnormalities in the c-erbB-2 gene. Eleven human lung cancer cell lines, including four derived from small cell lung cancer (SCLC) and seven derived from NSCLC were also examined for altered c-erbB-2 gene expression. Southern blot analysis of paired tumor and normal lung samples demonstrated that amplification of the c-erbB-2 gene is rare in NSCLC (2/60) and not restricted to adenocarcinomas. One patient showed an EcoRI restriction fragment length polymorphism for the c-erbB-2 locus. Four of four SCLC cell lines demonstrated minimal or nondetectable expression of c-erbB-2 mRNA compared to high levels of expression by seven of seven NSCLC lines. The highest expression levels were seen in four of four adenocarcinomas. We conclude that c-erbB-2 expression is different in SCLC compared to NSCLC and high expression of c-erbB-2 is consistently present in lung adenocarcinomas.

Blotting, Northern↗
PubMed1989

Isolation and characterization of paraflagellar proteins from Trypanosoma cruzi.

Two different Trypanosoma cruzi polypeptides, with masses of 70 and 68 kDa were purified and characterized in this work. These two polypeptides designated PAR 1 and PAR 2, respectively, co-purified during each step of the isolation procedure and were found to be located exclusively in T. cruzi flagella by indirect immunofluorescence. A pre-embedding immunoelectron microscopy procedure, with a gold-tagged secondary antibody, permitted direct identification of PAR 2 as a component of the T. cruzi paraflagellar rod. PAR 1 and PAR 2 were found to be immunologically distinct and showed no cross-reactivity with actin, tubulin, intermediate filament proteins, or other proteins present in mammalian cells. The results presented indicate that PAR 1 and PAR 2 are the major components of T. cruzi paraflagellar filaments, and that these filaments have no counterpart in mammalian cells.

Animals↗
PubMed1989

Hodgkin disease in a patient with common variable immunodeficiency.

Extensive extralymphatic Hodgkin disease developed in a young man with common variable immunodeficiency manifested by hypogammaglobulinemia, recurrent sinopulmonary infections, and multiple autoimmune phenomena. Both humoral and cell-mediated immune dysfunction were present prior to treatment. After two cycles of chemotherapy, irreversible shock developed, and death occurred secondary to overwhelming infection in spite of prophylactic gammaglobulin replacement. The unusual features of this patient's case of extralymphatic Hodgkin disease in association with a primary immunodeficiency disorder have not been previously reported.

Adult↗
PubMed1989

Polysemy and the subjective lexicon: semantic relatedness and the salience of intraword senses.

Subjective perceptions of the senses of polysemous English words are collected in questionnaire studies and the effects of variability in semantic distances among these senses are examined in an experiment. In the first of two questionnaire studies, native speakers produce meanings for 175 polysemous words; from their responses, the most frequently produced meaning for each word is identified as its dominant sense. In a second questionnaire, independent subjects rate the semantic relatedness between the dominant meaning and the other senses generated for each word in the first study. Relatedness measures vary, raising the possibility that polysemous words vary in terms of the salience of their different senses in different contexts. This is confirmed in an experiment showing that salience ratings are influenced by the interacting factors of sentential context, extent of relatedness of the senses, and the dominance status of the senses.

Adolescent↗
PubMed1988

Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma.

Fresh tumor samples from 27 patients with large cell lymphoma, either previously untreated (26 patients) or minimally treated (one patient), were processed for cytogenetic studies. Cytogenetic abnormalities were observed in all patients, most commonly in chromosomes 1, 3, 7, 12, 14, 17, and 18. Nine chromosomal breakpoints appeared frequently: 14q32 in 14 instances; 18q21 in seven; 9p13-21, 17p11-13, and 3q21-23 in six each; 1p11-21 in five instances; 1p36 in four; and 2p21-23 in three. The most common structural abnormalities were t(14;18)(q32;q21) in seven patients (26%) and 17p- in six (22%). The presence of 17p- was associated with a significantly higher proliferative capacity as manifested by the percentage of S phase = 22% versus 11% for cases without 17p-(P less than 0.05). Trisomy 12, typical of small lymphocytic lymphoma, was seen in five patients in this series, all of whom had diffuse large cell lymphoma; frequently, it appeared simultaneously with t(14;18). The two patients with immunoblastic lymphoma of B-cell type had an abnormality involving chromosome 2p21-23. Deletions in the long arm of chromosome 6, previously described as typical of diffuse large cell lymphoma and B-cell immunoblastic lymphoma were observed infrequently in this series. However, this abnormality has been present in 50% of patients with large cell lymphoma previously exposed to therapy, suggesting that it may be related to effects of chemotherapy or to clonal evolution.

Chromosome Aberrations↗
PubMed1988

Extended aortoplasty to relieve supravalvular aortic stenosis.

An extended aortoplasty was used to relieve severe supravalvular aortic stenosis in 5 patients whose preoperative left ventricular-aortic gradient ranged from 85 to 140 mm Hg (median, 120 mm Hg). The stenotic ring above the commissures was divided in two places by an inverted U incision extending into the right and noncoronary sinuses. A distal vertical incision in the ascending aorta converted this into an inverted Y. The ridge above the left coronary sinus was excised. The aortic incision was repaired with an inverted Y-shaped Dacron gusset. The postoperative gradient ranged from 0 to 30 mm Hg (median, 15 mm Hg). The extended aortoplasty provides excellent relief of supravalvular aortic stenosis and, in addition, restores the aortic root geometry to a much more anatomical configuration than is achieved with the simple patch technique.

Adolescent↗
PubMed1988

Long-term palliation with the classic Blalock-Taussig shunt.

Eighty-five patients received a classic Blalock-Taussig shunt between 1973 and 1986. Their age range was 1 day to 9.3 years and their median age was 4 months. Forty-one percent (35/85) were less than 1 month of age. The basic operative technique was unchanged throughout the time period. The subclavian artery opposite the side of the arch was used in 89% (79/88) of the patients. All anastomoses were done with monofilament suture and there was a tendency toward smaller suture material (7-0) in the latter years. All anastomoses except one were done with an interrupted suture technique. The operative mortality rate was 4.7% (4/85) and was not statistically related to age, diagnosis, or year of operation. Palliation was considered to be satisfactory until either a second shunt or a premature corrective operation were necessary. Seven patients required a second shunt and three, a premature corrective operation. The mean time between the initial shunt and the second procedure, either a second shunt or a corrective operation, was 2.9 years and 2.4 years, respectively. Twenty-five patients have had an elective corrective operation and the mean interval to that procedure was 3.9 years. Two years after the operation, 97% of patients older than 1 month of age at operation remain in well-palliated condition, as do 87% of those less than 1 month of age. At 4 years, 87% of those older than 1 month and 54% of those less than 1 month of age continue to be in well-palliated condition. The classic Blalock-Taussig shunt provides excellent palliation at a low operative mortality for virtually all patients for a minimum of 2 years. It will provide adequate pulmonary blood flow for most patients for an extended period of time beyond 2 years.

Anastomosis, Surgical↗
PubMed1987

Monosomy 21, partial duplication of chromosome 11, and structural abnormality of chromosome 1q21 in a case of lymphoma developing in a transplant recipient: characteristic abnormalities of secondary lymphoma?

Cytogenetic analysis by QFQ-banding of direct preparation of a testicular mass from a patient with secondary lymphoma revealed a modal chromosome number of 45,XY, including structural and numerical anomalies. The most consistent anomalies were the monosomy 21, duplication of the long arm of #11, and structural anomaly associated with chromosome #1 in band q21.

Adult↗
PubMed1987

Partial atrioventricular canal defect: the early and late results of operation.

Thirty-five patients underwent repair of a partial atrioventricular canal defect and have been followed for a mean of 8 years. Seventeen patients had either moderate or severe mitral incompetence prior to operation. The mitral valve was treated as a bileaflet structure. The cleft in its anterior leaflet was closed in each patient in whom the valve was incompetent. The septal defect was closed with pericardium, and the coronary sinus was left on the right atrium. Two patients required reoperation, 1 to close a recurrent septal defect and 1 to replace a mitral valve that had been competent for the first several years after the initial repair. All 33 survivors remain in New York Heart Association Functional Class I. Nineteen patients have no mitral incompetence, and the remaining 14 have only mild incompetence. These data demonstrate that excellent late results from repair of partial atrioventricular canal are possible when the mitral valve is managed as a bileaflet structure.

Adolescent↗
PubMed1987

The long-term risk of warfarin sodium therapy and the incidence of thromboembolism in children after prosthetic cardiac valve replacement.

Thirty children less than 18 years of age underwent cardiac valve replacement with a prosthetic valve between 1967 and 1984 and have been followed up for a mean of 6 years (range 1 to 17 years). Their mean age at the time of operation was 13 years (range 6 to 17 years). All patients were begun on a regimen of warfarin before hospital discharge. One major and four minor bleeding episodes occurred in 211 patient-years of warfarin therapy, an incidence of 2.3 per 100 patient-years. Three of those five episodes occurred in patients who were receiving excessively anticoagulation or who were participating in physical activities inappropriate for a patient on warfarin therapy. Thus, the majority of the bleeding episodes were preventable. There were five thromboembolic events in 211 patient-years, an incidence of 2.3 per 100 patient-years. Three of those five patients had intentionally stopped their warfarin therapy. The majority of thromboembolic episodes, like the bleeding episodes, were preventable. Eight teenage patients were noncompliant with the warfarin therapy. More than one third of that group experienced a thromboembolic event, an incidence of 5.5 per 100 patient-years (55 patient-years). Twenty-two patients adhered to the warfarin regimen and only two (9%) of them had a thromboembolic event, an incidence of 1.3 per 100 patient-years (156 patient-years). Warfarin therapy presented no greater risk of serious bleeding to this pediatric age group than it does to an adult age group. The incidence of thromboembolism among these patients was less than that which is generally reported for adult patients. Discontinuation of or noncompliance with warfarin therapy substantially increased the risk of thromboembolism. Continuous warfarin therapy is recommended for every child after prosthetic valve replacement.

Adolescent↗
PubMed1986

Late results of the Mustard procedure in transposition of the great arteries.

Thirty-five patients were discharged from the hospital after a Mustard procedure and have been followed a mean of 4.5 years. Thirty remain in a stable atrial or sinus rhythm, 3 have required hospitalization and medication to control atrial dysrhythmias, 1 is in a junctional rhythm, and 1 requires a pacemaker. In no patient has there been clinical evidence of systemic or pulmonary venous baffle obstruction. Twenty-two patients have had an elective postoperative cardiac catheterization, which has confirmed the absence of baffle obstruction. We attribute the lack of baffle obstruction and the low incidence of atrial dysrhythmias to several technical points in the operation including: direct high cannulation of the superior vena cava, aggressive resection of the atrial septum except in the region of the atrioventricular node, an extremely large pericardial baffle trimmed in the manner of Brom, sharp divergence of the upper and lower limbs of the inferior suture line away from one another and toward the caval orifices once they enter the right atrium, and very superficial endocardial bites of the baffle suture line in the region of the sinoatrial and atrioventricular nodes.

Arrhythmias, Cardiac↗
PubMed1986

The midterm and long-term results of the Mustard operation in patients with transposition of the great vessels and dynamic left ventricular outflow tract obstruction.

Eight of 43 patients with transposition of the great vessels (TGV) and either an intact ventricular septum or very small ventricular septal defect were found to have dynamic left ventricular outflow tract obstruction (LVOTO). The preoperative left ventricle-pulmonary artery (LV-PA) pressure gradient ranged between 14 and 60 mm Hg. In 3 patients the pulmonary artery could not be catheterized. They had a left ventricular pressure of 43, 45, and 62 mm Hg, respectively, no evidence of pulmonary vascular disease, and either echocardiographic or angiocardiographic demonstration of LVOTO. The outflow tract was explored in 3 patients at the time of the Mustard operation. Exposure of the LVOT was difficult, particularly in patients less than 6 months of age. A shallow septal myectomy was performed in 1 patient; a thin fibrous endocardial scar was resected in 2; and no procedure was performed in the third. All 8 patients survived and remain asymptomatic 1 to 11 years (mean, 5 years) after operation. The LV-PA pressure gradient has either remained the same or has increased in every patient except 1 in whom there was a slight reduction in the gradient. We conclude that dynamic LVOTO persists after the Mustard operation and is not amenable to direct surgical relief. However, an excellent clinical result can be obtained for up to 11 years after operation.

Child, Preschool↗