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Biomedical subjects

P T Campbell

Publications and source records attributed to P T Campbell.

At least 19 recordsLinked to original sources
PubMed2001

Stability of adiposity phenotypes from childhood and adolescence into young adulthood with contribution of parental measures.

OBJECTIVE: The stability of several indicators of body composition and adipose tissue distribution over 12 years was quantified. RESEARCH METHODS AND PROCEDURES: The participants were 77 boys and 76 girls who were evaluated along with their parents at baseline as children and adolescents (8 to 18 years of age) and remeasured as young adults 12 years later. Indicators of body composition included the body mass index, fat mass, fat free mass, percentage of body fat, sum of six skinfolds (SF6), and the first principal component of six age-adjusted skinfold residuals. Relative adipose tissue distribution was represented by the second principal component of skinfold residuals and a trunk-to-extremity skinfold ratio, adjusted for SF6. RESULTS: Partial interage correlations, controlling for initial age and length of follow-up, were 0.65 and 0.59 for the body mass index, 0.59 and 0.64 for fat mass, 0.65 and 0.57 for fat free mass, 0.50 and 0.57 for percentage of body fat, 0.66 and 0.44 for SF6, 0.64 and 0.42 for the first principal component of six age-adjusted skinfold residuals, 0.19 and 0.31 for the second principal component of skinfold residuals, and 0.41 and 0.47 for trunk-to-extremity skinfold ratio, adjusted for SF6, in men and women, respectively. Multiple regression analyses indicated that the significant partial R(2) values of parental measurements on the prediction of their offspring in young adulthood ranged from 2% to 9%. DISCUSSION: The results indicate moderately high stability of indicators of body composition and somewhat lower stability of measures of adipose tissue distribution. Overall, parental measures offer less predictive value than do measures of childhood and adolescent body composition and adipose tissue distribution.

Adipose Tissue↗
PubMed1999

Changing nursing practice through research utilization: consistent support for breastfeeding mothers.

This research utilization project was designed to increase staff nurse support for four early postpartum breastfeeding practices: initiation in the delivery room, high frequency feedings, unlimited suckling time, and no supplementation. Research links these practices with lower neonatal bilirubin values and an earlier onset of lactation. An organizational approach to research utilization was taken to encourage nurses to support mothers in the desired breastfeeding practices. A before and after design was used to evaluate the extent to which the intended patient outcomes were achieved with the practice changes. The percent of infants having bilirubin tests decreased significantly. No significant differences were observed in mean bilirubin levels, incidence of hyperbilirubinemia, or lactation onset. The project promoted state-of-the-science nursing care and helped our nurses become more adept in using research to guide practice.

Breast Feeding↗
PubMed1995

Cytomegalovirus pericarditis: a case series and review of the literature.

Cytomegalovirus (CMV) commonly infects both normal and immunocompromised hosts. Although it usually produces an asymptomatic infection to mild illness, CMV has the potential to significantly injure many different organs. Reports of CMV causing pericardial disease, however, are limited and documentation of infection by growth of the virus from tissue or fluid is rare. As part of a prospective trial of subxiphoid pericardial biopsy in 57 adult patients with large pericardial effusions, three culture-proven cases and one serologically confirmed case of CMV pericardial disease were discovered. Subsequently, CMV was grown from the pericardium of an infant with congenital heart disease. A review of the documented cases of CMV pericarditis is provided along with a discussion of the pathogenesis and significance of this perhaps not so uncommon disease.

Adult↗
PubMed1993

Etiology of large pericardial effusions.

PURPOSE: To determine the effectiveness of the preoperative evaluation and overall diagnostic efficacy of subxiphoid pericardial biopsy with fluid drainage in patients with new, large pericardial effusions. DESIGN: A prospective interventional case series of consecutive patients admitted with new, large pericardial effusions. PATIENTS AND METHODS: Fifty-seven of 75 consecutive patients admitted to a university tertiary-care center and a university-affiliated Veterans Administration Medical Center with new, large pericardial effusions were studied over a 20-month period. Each patient was assessed by a comprehensive preoperative evaluation followed by subxiphoid pericardiotomy. The patients' tissue and fluid samples were studied pathologically and cultured for aerobic and anaerobic bacteria, fungi, mycobacteria, mycoplasmas, and viruses. RESULTS: A diagnosis was made in 53 (93%) patients. The principle diagnoses consisted of malignancy in 13 (23%) patients; viral infection in 8 (14%) patients; radiation-induced inflammation in 8 (14%) patients; collagen-vascular disease in 7 (12%) patients; and uremia in 7 (12%) patients. No diagnosis was made in four (7%) patients. A variety of unexpected organisms were cultured from either pericardial fluid or tissue: cytomegalovirus (three), Mycoplasma pneumoniae (two), herpes simplex virus (one), Mycobacterium avium-intracellulare (one), and Mycobacterium chelonei (one). The pericardial fluid yielded a diagnosis in 15 (26%) patients, 11 of whom had malignant effusions. The examination of pericardial tissue was useful in the diagnosis of 13 (23%) patients, 8 of whom had an infectious agent cultured. Of the 57 patients undergoing surgery, the combined diagnostic yield from both fluid and tissue was 19 patients (33%). CONCLUSIONS: A systematic preoperative evaluation in conjunction with fluid and tissue analysis following subxiphoid pericardiotomy yields a diagnosis in the majority of patients with large pericardial effusions. This approach may also result in the culturing of "unusual" infectious organisms from pericardial tissue and fluid.

Biopsy↗
PubMed1993

Mycoplasmal pericarditis: evidence of invasive disease.

Although the pathogenic mycoplasmas usually infect the respiratory and urogenital tracts, these organisms also can cause disease in remote sites. Such infections are difficult to diagnose because of both the fastidious nature of the mycoplasmas and the failure to consider their presence. Pericarditis is an uncommonly diagnosed and rarely confirmed example of invasive mycoplasmal infection. As part of a prospective study of large pericardial effusions, we discovered two cases with Mycoplasma pneumoniae infection. Subsequently, two cases of pericarditis due to Mycoplasma hominis and one due to Ureaplasma urealyticum were diagnosed. For all five patients, cultures of pericardial tissue and/or fluid were positive. In addition, four of the five patients either were immunocompromised or had undergone cardiac surgery previously. Appropriate antibiotic therapy was uniformly effective. We report here our experience with mycoplasmal pericarditis, provide evidence of an invasive pathogenesis for this syndrome, and suggest that pericardial disease caused by these organisms may not be an uncommon finding when sought in an aggressive manner.

Adult↗
PubMed1993

A prospective trial of subxiphoid pericardiotomy in the diagnosis and treatment of large pericardial effusion. A follow-up report.

OBJECTIVE: This study was designed to determine the cause of large pericardial effusions and evaluate the efficacy of subxiphoid pericardiotomy. SUMMARY BACKGROUND DATA: Despite great advances in the techniques used to diagnose pericardial effusions, much controversy remains concerning their cause and the optimal treatment of these effusions. METHODS: In a prospective consecutive case series, 57 patients underwent a thorough preoperative evaluation followed by a subxiphoid pericardiotomy. All tissue and fluid was exhaustively evaluated. Postoperatively, all patients were followed for a least 1 year. RESULTS: Surgery was performed under local anesthesia in 77% of patients, and the complications of surgery were minimal. Pericardial tissue and fluid established or aided in establishing a diagnosis in 81% of patients. Infection and malignancy were the leading causes; the condition in only 4 patients remained undiagnosed. Follow-up revealed recurrent effusion in nine (16%) patients, but only five (9%) required further surgery. The mortality rate at 30 days was 12%, and at 1 year, it was 37%. Fourteen of the 21 deaths occurred in patients with malignancies. CONCLUSIONS: These data show that the cause of most large pericardial effusions can be determined by a thorough evaluation accompanied by subxiphoid pericardiotomy. In addition, subxiphoid pericardial biopsy and window creation is safe and effective in the treatment of these effusions.

Biopsy↗
PubMed1992

Diagnosis and management (by subxiphoid pericardiotomy) of large pericardial effusions causing cardiac tamponade.

To determine the clinical features, course and outcome of patients with cardiac tamponade, 57 consecutive patients with new, large pericardial effusions were prospectively studied. Twenty-five patients (44%) developed cardiac tamponade with venous hypertension and a pulsus paradoxus greater than 10 mm Hg. Electrocardiography, radiographic studies and echocardiography did not differentiate patients with and without tamponade. All 57 patients underwent thorough diagnostic evaluation followed by subxiphoid pericardial biopsy and drainage. A diagnosis was obtained in 53 patients (93%). Collagen vascular disease was significantly more frequent in the 25 patients with than in the 32 without cardiac tamponade (24 vs 3%; p less than 0.05). The frequency of malignant and uremic effusions was equal in both groups, whereas radiation-induced effusions seldom produced tamponade. At 1-year follow-up, 3 patients (12%) with tamponade had recurrent effusions, and 1 needed reoperation. This was not significantly different from the 32 patients without tamponade. Twelve-month mortality was also similar in both groups (36 vs 44%). This prospective series disclosed several unexpected findings: (1) Cardiac tamponade occurred in almost 50% of patients with new large pericardial effusions; (2) both malignancy and collagen vascular disease occurred with equal frequency as etiologies, whereas radiation-induced tamponade was unusual; (3) thorough clinical evaluation resulted in few idiopathic etiologies; and (4) subxiphoid pericardiotomy was effective for both diagnosis and therapy of tamponade.

Cardiac Tamponade↗
PubMed1992

Subxiphoid pericardiotomy in the diagnosis and management of large pericardial effusions associated with malignancy.

To determine the safety, diagnostic value, and clinical outcome of patients with malignancy undergoing subxiphoid pericardiotomy for large pericardial effusions, we prospectively studied 25 consecutive patients with malignancy and new, large pericardial effusions diagnosed by echocardiography. Twenty-two of the 25 operations were done under local anesthesia, and no patient died at surgery. Pericardial fluid cytology revealed malignant cells in 11 patients (44 percent), while tumor was seen in only five (45 percent) of these 11 patients on pathologic examination. The remaining 14 patients showed no evidence of pericardial invasion with tumor. Evidence of intrathoracic disease by CT or MRI scanning, tamponade, a sanguineous pericardial fluid character, and an elevated serum and pericardial fluid lactate dehydrogenase level all were suggestive of malignant invasion of the pericardium. All 25 patients were followed at least 12 months postoperatively. Effusions recurred in three patients (12 percent), and one patient required reoperation. Overall mortality was 72 percent with a 91 percent (10 of 11) mortality for those with malignant effusions and a 57 percent (8 of 14) mortality for those with nonmalignant effusions. Diagnostically, subxiphoid pericardiotomy has little advantage over examination of pericardial fluid alone in this group of patients. Therapeutically, however, it is a low morbidity procedure which is safe and effective in treating patients with malignancy and large pericardial effusions.

Cardiac Tamponade↗
PubMed1991

Comparative rates of desensitization of beta-adrenergic receptors by the beta-adrenergic receptor kinase and the cyclic AMP-dependent protein kinase.

Three separate processes may contribute to rapid beta-adrenergic receptor desensitization: functional uncoupling from the stimulatory guanine nucleotide-binding protein Gs, mediated by phosphorylation of the receptors by two distinct kinases, the specific beta-adrenergic receptor kinase (beta ARK) and the cyclic AMP-dependent protein kinase A (PKA), as well as a spatial uncoupling via sequestration of the receptors away from the cell surface. To evaluate the relative importance and potential role of the various processes in different physiological situations, a kinetic analysis of these three mechanisms was performed in permeabilized A431 epidermoid carcinoma cells. To allow a separate analysis of each mechanism, inhibitors of the various desensitization mechanisms were used: heparin to inhibit beta ARK, the PKA inhibitor peptide PKI to inhibit PKA, and concanavalin A treatment to prevent sequestration. Isoproterenol-induced phosphorylation of beta 2 receptors in these cells by beta ARK occurred with a t1/2 of less than 20 sec, whereas phosphorylation by PKA had a t1/2 of about 2 min. Similarly, beta ARK-mediated desensitization of the receptors proceeded with a t1/2 of less than 15 sec, and PKA-mediated desensitization with a t1/2 of about 3.5 min. Maximal desensitization mediated by the two kinases corresponded to a reduction of the signal-transduction capacity of the receptor/adenylyl cyclase system by about 60% in the case of beta ARK and by about 40% in the case of PKA. Receptor sequestration was much slower (t1/2 of about 10 min) and involved no more than 30% of the cell surface receptors. It is concluded that beta ARK-mediated phosphorylation is the most rapid and quantitatively most important factor contributing to the rapid desensitization. This rapidity of the beta ARK-mediated mechanism makes it particularly well suited to regulate beta-adrenergic receptor function in rapidly changing environments such as the synaptic cleft.

Carcinoma, Squamous Cell↗
PubMed1991

A small region of the beta-adrenergic receptor is selectively involved in its rapid regulation.

Plasma membrane receptors that couple to guanine nucleotide-binding regulatory proteins (G proteins) undergo a variety of rapid (minutes) and longer term (hours) regulatory processes induced by ligands. For the beta 2-adrenergic receptor (beta 2AR), the rapid processes include functional desensitization, mediated by phosphorylation of the receptor by the cAMP-dependent protein kinase and the beta-adrenergic receptor kinase, as well as a loss of hydrophilic ligand binding proposed to represent sequestration of receptors into a cellular compartment distinct from the plasma membrane. The slower processes include beta 2AR down-regulation (i.e., a decrease in the total cellular complement of receptors). It is not yet known whether beta 2AR phosphorylation and/or sequestration are prerequisites for down-regulation of the receptor. Like other G protein-coupled receptors, the beta 2AR molecule spans the plasma membrane seven times, and the cytoplasmic carboxyl-terminal domain has been proposed to contain molecular determinants for each of these regulatory processes. We replaced four serine and threonine residues located within a 10-amino acid segment of this domain of beta 2AR and thereby prevented agonist-promoted phosphorylation, sequestration, and rapid desensitization of the adenylyl cyclase response. In contrast, these mutations did not affect functional coupling to the stimulatory G protein Gs or long-term down-regulation. These findings thus define a small, hitherto unappreciated region of the receptor molecule that may selectively subserve its rapid regulation. In addition, with the demonstration that beta 2AR does not have to be phosphorylated or sequestered in order to enter the down-regulation pathway, the results suggest that the classical receptor endocytosis model may not be appropriate for beta 2AR regulation.

Adenylyl Cyclases↗
PubMed1991

Mutations of the human beta 2-adrenergic receptor that impair coupling to Gs interfere with receptor down-regulation but not sequestration.

The integrity of coupling of the beta 2-adrenergic receptor (beta 2AR) to its guanine nucleotide-binding protein, Gs, and phosphorylation events on the receptor molecule have been proposed to be important determinants in the processes of receptor sequestration and down-regulation. However, little is known about the molecular mechanisms underlying these processes, and the regions of the receptor molecule that specifically subserve sequestration and down-regulation have yet to be delineated. To address these questions, we stably transfected eight mutant beta 2AR genes into Chinese hamster fibroblasts and evaluated the coupling, sequestration, and down-regulation properties of the mutated receptors. These mutant receptors have been previously demonstrated either to exhibit abnormal coupling to Gs or to lack functionally important phosphorylation sites for either the cAMP-dependent protein kinase or the agonist-dependent beta-adrenergic receptor kinase. All eight mutants exhibited receptor sequestration equivalent in extent to that of the beta 2AR, regardless of their coupling or phosphorylation status. However, four mutants that exhibited various degrees of impairment in coupling to Gs showed blunted receptor down-regulation patterns. Simultaneous treatment with isoproterenol and dibutyryl-cAMP did not improve the abilities of the mutant receptors to undergo down-regulation. These findings demonstrate that a variety of mutant beta 2AR with impaired coupling to Gs are, nevertheless, able to be sequestered normally. In contrast, agonist-induced down-regulation appears to require coupling of the beta 2AR to Gs but is largely independent of the generation of cAMP. Our results also suggest that molecular determinants of the beta 2AR involved in receptor sequestration are distinct from those participating in the down-regulation process.

Amino Acid Sequence↗
PubMed1989

Two distinct pathways for cAMP-mediated down-regulation of the beta 2-adrenergic receptor. Phosphorylation of the receptor and regulation of its mRNA level.

We have studied cyclic AMP-mediated regulation of the beta 2-adrenergic receptor (beta 2AR). The effects of cAMP were assessed in Chinese hamster fibroblast (CHW) cells expressing either the wild type human beta 2AR receptor (CH-beta 2) or mutated forms of the receptor lacking the consensus sequences for phosphorylation by the cAMP-dependent protein kinase. Treatment of the CH-beta 2 cells with the cAMP analogue dibutyryl cAMP (Bt2cAMP) induces a time-dependent "down-regulation" of the number of beta 2AR. This down-regulation of the receptors is accompanied by a decline in the steady state level of beta 2AR mRNA. Moreover, the treatment with Bt2cAMP induces an increase in the phosphorylation level of the membrane-associated beta 2AR. Both the reduction in beta 2AR mRNA and the enhanced phosphorylation of the receptor are rapid and precede the loss of receptor. The down-regulation of beta 2AR induced by Bt2cAMP is concentration-dependent and mimicked by the other biologically active cyclic nucleotide analogue, 8-Br-cAMP, by forskolin, and by the phosphodiesterase inhibitor, isobutylmethylxanthine. In the CHW cell lines expressing receptors lacking the putative protein kinase A phosphorylation sites, the Bt2cAMP-induced phosphorylation of beta 2AR is completely abolished. In these cells the down-regulation of beta 2AR receptor number produced by cAMP is significantly slowed, whereas the reduction in beta 2AR mRNA level is equivalent to that observed in CH-beta 2 cells. These data indicate that there are at least two pathways by which cAMP may decrease the number of beta 2ARs in cells: one involves phosphorylation of the receptor by the cAMP-dependent protein kinase and the other leads to a reduction in steady state beta 2AR mRNA levels.

1-Methyl-3-isobutylxanthine↗
PubMed1976

Folate analogues altered in the C9-N10 bridge region. 10-Oxafolic acid and 10-oxaaminopterin.

The unambiguous synthesis of two folate analogues, in which the 10-amino group of folic acid was replaced with oxygen, is described. The synthetic sequence employed commercially available methyl p-hydroxybenzoate and n-(2,3-epoxypropyl)phthalimide as starting materials. The use of cesium bicarbonate as a coreactant in the nucleophilic displacement reaction between bromo ketone 3 and the nucleophile 4 was found to be unique in character. The aminoacetonyl oxime 7 obtained by the hydrazinolysis of 6 was used as a common intermediate for the synthesis of both compounds. The generality of the use of the TFA-HCL mixture to deprotect the carbonyl group of both 10 and 12 reductions involving sodium hydrosulfite in aqueous dmf were further substantiated by conversions of 11 and 13 to 14 and 15 quickly and efficiently without employing catalytic hydrogenations. Subsequent cyclizations, oxidations, and hydrolysis of these reduction products to the pteroate analogues 17 and 19 were carried out efficiently as described for the synthesis of the sulfur analogues. Activation of the carboxyl group of 19 by way of the mixed anhydride 22 and subsequent coupling to glutamic acid was carried out using the solid-phase coupling procedure. However, compound 17 required trifluoroacetylation to 20 prior to the coupling reaction due to solubility problems. Both 10-oxafolic acid (1) and 10-oxaaminopterin (2) showed potent antifolate activity when tested against two folate-requiring organisms. Compound 2 was a very powerful inhibitor of DCM-resistant lactobacillus casei dihydrofolate reductase. The activity was comparable to that of methotrexate while the 4-hydroxy analogue did not show inhibition. 7,8-Dihydro-10-oxafolic acid failed to show any substrate activity to this enzyme and did not inhibit the enzymatic reaction when used with an equimolar concentration of the natural substrate.

Aminopterin↗
PubMedDate not supplied

Prediction of physical activity and physical work capacity (PWC150) in young adulthood from childhood and adolescence with consideration of parental measures.

The 12-year prediction of physical activity level and submaximal aerobic fitness observed during young adulthood was quantified from childhood and parental measures. The sample consisted of 153 children and adolescents of the Quebec Family Study who were evaluated at baseline and reassessed 12 years later, as young adults. Physical work capacity at a heart rate of 150 beats x min(-1) (PWC150) was measured using cycle ergometry. A 3-day activity record was used to estimate daily energy expenditure (DEE), inactive time (IA), and time spent in moderate-to-vigorous activity (MVPA). Spearman partial inter-age correlations, controlling for length of follow-up and age at baseline, indicated better tracking for PWC150 (0.24 and 0.46, males and females, respectively) than for indicators of physical activity (0.07 < or = r < or = 0.25, males; 0.06 < or = r < or = 0.22, females). Multiple regression analyses indicated that parental measurements of activity and PWC150 did not add any predictive value, with the exception of paternal DEE, which accounted for 8% of the variance in males. There is moderately high stability of submaximal work capacity and lower tracking of physical activity from childhood and adolescence into young adulthood.

Adolescent↗