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Clinical Protocols↗
Biomedical subjects
C Campbell
Publications and source records attributed to C Campbell.
Hepatitis B virus DNA in peripheral-blood mononuclear cells in chronic hepatitis B after HBsAg clearance.
In this study, peripheral-blood mononuclear cells from patients with chronic hepatitis B and spontaneous or therapy-induced disappearance of HBsAg were examined for HBV DNA. Samples were evaluated by in situ hybridization and polymerase chain reaction both before and after clearance of HBsAg. By in situ hybridization, positive signals were observed in 2 of 13 samples collected after HBsAg loss, in 8 of 15 samples before HBsAg loss and in 0 of 4 control patients without serological markers of active or prior HBV infection. When polymerase chain reaction analyses were performed, HBV DNA was detected in 5 of 12 HBsAg-negative samples and 10 of 15 HBsAg-positive samples from the study group. Testing of mononuclear cells after disappearance of HBsAg revealed that two of eight patients were HBV DNA positive by in situ hybridization and by polymerase chain reaction, whereas two additional patients were positive by polymerase chain reaction alone. Mononuclear cell-associated HBV DNA was detected between 2 and 9 mo after the disappearance of circulating HBsAg by in situ hybridization and as long as 4 yr later by polymerase chain reaction. These data indicate that patients who have undergone HBsAg seroconversion may nonetheless harbor HBV DNA in their peripheral-blood mononuclear cells for prolonged periods.
Adult↗
Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen.
Polymerase chain reaction (PCR) was used to detect hepatitis B virus DNA in the sera and livers of nine patients with chronic hepatitis B after treatment-induced or spontaneous loss of serum hepatitis B surface antigen. Patients were evaluated at intervals ranging from 3 to 67 months after disappearance of hepatitis B surface antigen. PCR was performed using primer pairs from the surface and core gene regions, and surface gene products were quantitated. Liver tissue was also evaluated by in situ hybridization to assess viral transcription. Five of the nine patients had viral DNA detectable in serum by PCR. Quantitation of polymerase chain reaction products in serum and liver showed that the DNA levels tended to decline progressively after antiviral therapy. Six of seven surface antigen-negative patients tested had detectable viral DNA in the liver, and four of the six DNA-positive patients were negative for DNA in serum by PCR. None had surface gene messenger RNA. Thus, it is concluded that hepatitis B virus DNA may be detectable by PCR in liver tissue years after the disappearance of hepatitis B surface antigen, even in the absence of detectable hepatitis B virus DNA in serum.
Alanine Transaminase↗
Transition program from pediatric to adult care for cystic fibrosis patients.
A survey of adolescents and young adults with cystic fibrosis (CF) attending an adult CF center was conducted to evaluate a transition program as a means of transferring care from pediatric to adult setting. A total of 40 patients completed a self-administered questionnaire of whom 13 (32.5%) went through the transition program, and 21 (52.5%) received their care at the University of Michigan Cystic Fibrosis Center. Fourteen patients (35.0%) were cared for at other pediatric CF centers, and five (12.5%) were first diagnosed as adults. All those in the transition program approved of having the visit with the internal medicine physician in the pediatric clinic. Most thought that the transition program made the change from pediatric to adult care easier. All patients were comfortable leaving the pediatric clinic after the transition period. Of the 40 patients, 17 (42%) recommended that other patients go through the transition program, although 9 of these 17 patients did not themselves go through the transition program. Twenty-six patients (65%) preferred the adult program. These findings suggest that adolescents with CF should be encouraged to transfer their medical care to an adult CF Center once they have reached an agreed-upon age. This process should be smooth and should occur as part of the regular CF care. This is possible through a well-structured and well-organized transition program with committed pediatric and adult staff.
Adolescent↗
Altered glomerular extracellular matrix synthesis in experimental membranous nephropathy.
Chronic progressive membranous nephropathy (MN) in humans is characterized by thickening of the glomerular basement membrane (GBM) with formation of spikes which contain laminin and other extracellular matrix (ECM) proteins. We have utilized two models of MN in the rat (active and passive Heymann nephritis, AICN, PHN) to define the sequential changes in composition of GBM as they relate to changes in glomerular gene expression for ECM components, altered permeability and morphological changes. Renal biopsies obtained during the course of AICN and PHN were immunostained for various ECM proteins and total glomerular RNA was hybridized with cDNA probes specific for laminin B2-chain, s-laminin, and types I and IV collagen. In addition, the ability of anti-glomerular epithelial cell (GEC) antibody and complement on rat GEC in culture to induce laminin release or laminin and s-laminin mRNA expression was determined. The results demonstrate that at weeks 12, 16, and 20 of AICN, immunostaining for laminin, s-laminin, fibronectin, entactin, and heparan sulfate proteoglycan increased in the GBM in a spike-like pattern. Concomitantly, glomerular mRNA levels of laminin B2-chain and of s-laminin increased. Type IV collagen protein and gene expression remained unchanged or decreased. No glomerular immunostaining for type I collagen occurred during AICN despite increased expression of mRNA for this collagen type. In contrast to AICN, in PHN no pronounced changes of the glomerular ECM occurred, except for transient expression of type I collagen mRNA in whole glomerular RNA and type I collagen protein the GEC cytoplasm. Stimulation of GEC in culture with anti-GEC antibody and complement also failed to induce transcription of laminin or s-laminin mRNA or the release of laminin protein. These findings suggest that the polyantigenic expansion of GBM which occurs in chronic experimental MN may be stimulated by factors different from the C5b-9 mediated processes that cause the initial proteinuria.
Animals↗
Re: Nuclear medicine and diagnostic radiologists.
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Clinical Competence↗
Developmental expression of insulin-regulatable glucose transporter GLUT-4.
The insulin-regulatable glucose transporter (GLUT-4) is expressed in adipose tissue and in cardiac and skeletal muscle (D. E. James, R. Brown, J. Navarro, and P. F. Pilch. Nature Lond. 333: 183-185, 1988). We examined GLUT-4 development between postnatal days 1 and 41 (P1-P41) in male and female rats in these tissues by quantitative immunoblotting. GLUT-4 was detectable in each tissue at comparable levels at P1. However, the subsequent patterns of GLUT-4 development were distinctive. GLUT-4 increased in the diaphragm after P7, peaked at P20, and then declined. GLUT-4 expression in the heart increased rapidly after P7 to plateau on P41 at levels four times greater than the diaphragm. In sharp contrast, adipose tissue expression was highest between P3 and P5 but declined to a nadir at P20 before rebounding at P34. These patterns were observed for both sexes within each tissue, but female GLUT-4 expression was higher in diaphragm and heart and lower in adipose tissue. The expression of GLUT-4 appears to be regulated in a tissue-specific manner by a developmental program that may coordinate the expression of other proteins of metabolic importance.
Adipose Tissue↗
Lung oxidant changes after zymosan peritonitis: relationship between physiologic and biochemical changes.
Our purpose was to determine the effect of non-bacteria-dependent systemic inflammation on the degree and time course of lung oxidant activity and antioxidant defenses, comparing these changes with lung, physiologic, and histologic alterations. Adult male rats were given intraperitoneal zymosan (0.7 mg/g body weight) and were fluid resuscitated. Oxidant changes were measured as lung tissue oxidized glutathione (GSSG) and malondialdehyde (MDA) content, antioxidant defenses as tissue reduced glutathione (GSH), and catalase. Animals were killed at 4, 12, and 24 h, and at 5, 10, and 30 days. Lung data were compared with that found in liver. We noted a 45% mortality in the first 18 to 36 h with all remaining animals surviving. In the first 24 h, we noted a doubling of lung MDA and an 80% conversion of tissue GSH to GSSG compared with less than 5% in control animals, indicating a severe oxidant stress. These findings corresponded with marked increase in lung neutrophils. Arterial pressure (PaO2) was significantly decreased from a control of 95 +/- 4 mm Hg to 80 +/- 5 mm Hg and 75 +/- 4 mm Hg at Days 5 and 10, respectively, but returned toward control by 30 days. Lung GSSG and MDA remained significantly increased for the 30-day period, whereas amounts of the antioxidants, catalase, and GSH returned to control after 24 h. The ongoing oxidant stress corresponded with marked mononuclear cell infiltration and interstitial thickening, which persisted over the 30-day period even after peritonitis had completely resolved.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Insulation of heated wire circuits.
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Anesthesiology↗
Glomerular epithelial cells secrete a glomerular basement membrane-degrading metalloproteinase.
Cultured rat glomerular epithelial cells (GEC) were examined for their ability to release extracellular matrix-degrading proteinases with [3H]gelatin as substrate. GEC-conditioned media, under serum-free conditions, contained modest amounts of gelatinase activity (1 to 10 U/mg of protein); the activity was maximal at neutral pH, was inhibited by zinc chelators, was not inhibited by tissue inhibitor of metalloproteinase-2, and could not be further activated by trypsin or organomercurials. Gelatin substrate sodium dodecyl sulfate-polyacrylamide gels of GEC-conditioned medium revealed several zones of lysis, with molecular sizes of 150 kd (major band), and 220, 86 to 93, and 52 to 54 kd (minor bands). Northern blot analysis demonstrated that the GEC metalloproteinase(s) were distinct from the 68- to 72-kd type IV collagenase/gelatinase present in mesangial cells or the 92-kd type IV collagenase present in neutrophils. The GEC gelatinolytic activity also degraded insoluble type IV collagen in glomerular basement membrane in a dose-dependent manner. The major metalloproteinase activity responsible for the type IV collagen degradation has a molecular size of 150 kd with a type IV collagen substrate gel. Thus, GEC produce several neutral metalloproteinases, which, by virtue of their substrate specificity, may play an important role in glomerular basement membrane remodeling and in glomerular diseases characterized by alterations in basement membrane permeability.
Animals↗
Minimizing diagnostic blood loss in critically ill patients.
BACKGROUND: Blood loss from diagnostic procedures in critically ill patients needs to be minimized. Traditionally, when drawing blood from arterial lines, the initial sample used to clear the line has been discarded (open method). Use of a temporary reservoir enables this discard sample to be returned to the patient (closed method). METHODS: Critically ill surgical patients were prospectively randomized to the open or closed method of drawing blood from arterial lines. Blood loss to diagnostic sampling was measured in both groups. RESULTS: A comparison study (n = 1657) of these two methods revealed that blood loss to the patient was significantly decreased (P << .01) using the closed method. Mean blood loss per patient per day was 69 mL in the open group (n = 873) vs 35 mL in the closed group (n = 784). CONCLUSIONS: Use of the closed method when drawing blood from arterial lines results in a significant decrease in blood lost to diagnostic procedures.
Adult↗
Coordinate expression of Wilms' tumor genes correlates with Wilms' tumor phenotypes.
The cloning and molecular characterization of two putative tumor genes, WT1 and WIT1, from the chromosome 11p13 region has provided a means of evaluating their role in the generation of Wilms' tumor heterogeneity. A series of 29 tumors were analyzed for WT1 and WIT1 expression by Northern blot or RNase protection analyses, and results were compared with tumor histopathology. Tumors were scored for the percentage of mesenchymal and epithelial derived tissue components. Homotypic tumors comprised blastema, tubular epithelium, and a fibroblast-like mesenchyme. In addition to these tissue components, the group of tumors designated as heterotypic also contained ectopic cell phenotypes such as muscle and squamous epithelium. The analyses suggest that heterotypic differentiation patterns occur when WT1 and WIT1 expression is low relative to normal fetal kidney. In situ hybridization using antisense RNA probes showed that WT1 and WIT1 were concordantly expressed in normal fetal kidney and in the blastema of tumors. The ratio of WT1:WIT1 expression remained relatively constant in homotypic tumors but deviated significantly in heterotypic tumors. These results suggest that expression patterns of the WT1 and WIT1 genes can be closely correlated to Wilms' tumor histopathology.
Blotting, Northern↗
[Guidance to parent of black babies with a cleft lip and palate].
There are indications that the parents of babies with a cleft lip and palate often require more information regarding their baby's birth defect than what is given to them. In South Africa shortcomings exist in the literature covering the specific requirements of parents of black cleft lip and palate babies. In this study the unique requirements of parents of black cleft lip and palate babies was determined and, based on these results, an information pamphlet was prepared for this population group. Based on the results obtained with the help of fifteen participants it was established, firstly, that the needs of black South-African parents of children with a cleft lip and palate are similar to the needs of parents of babies with the same birth defect world-wide. Secondly, it was established that the information pamphlet which was compiled as part of the study made a positive contribution to parent guidance conducted with the participants. Important therapeutic implications were also reflected by the results.
Black or African American↗
Intraoperative radiation therapy.
1. Local and regional recurrence of disease is a major problem in cancer management. Intraoperative radiation therapy (IORT) combines surgery with irradiation to treat any disease remaining after surgery and to decrease the local recurrence rates for certain cancers. 2. The development of an IORT treatment program is often undertaken by groups and institutions with expertise in multidisciplinary oncology, particularly surgical and radiation oncology. The program uses multiple resources, requiring cooperation and teamwork to achieve an efficient procedure with maximum patient outcome. 3. The process should be reviewed and modified each time it is performed. There is no "standard" way to use IORT, and every program will have variations that adapt to the circumstances existing in each specific facility.
Combined Modality Therapy↗
Low level and bystander exposure to lead among factory workers.
A clinical field survey of 36 workers employed in the manufacturing of leaded products used in radiologic safety was conducted. Although the principal source of lead exposure was limited to an area where two individuals mixed lead oxide and vinyl liquid, increased lead absorption was found in other workers employed in adjacent areas. The mean lead concentration of the plant workers was 29.3 micrograms/dL (SD +/- 9.0), and four workers had blood lead levels of 40 micrograms/dL or higher. A statistically significant correlation was noted between blood lead and serum creatinine; linear regression analysis demonstrated that cigarette smoking was a significant factor in predicting the blood lead level. The exposure encountered in this plant may be typical of lead exposure in many similar industrial settings. It calls attention to the risk of excessive exposure among workers who are not working at the primary source of exposure, and should be considered in the design of medical surveillance programs for workers employed in small manufacturing plants.
Adult↗
C2 rotation and spinous process deviation in migraine: cause or effect or coincidence?
Previous reports have shown an association between the side of C2 spinous process deviation or asymmetrical prominence, or vertebral rotation, and the side of the headache in unilateral migraine. However, this study has found that such C2 appearances were present as frequently in the controls as in the migraine patients, and that there was no association between the side of the anomaly and the lateralisation of the headache. The results were comparable for the different sub-groups of migraine.
Cervical Vertebrae↗
Increased synthesis of extracellular matrix in mesangial proliferative nephritis.
Extracellular matrix expansion is frequently noted in mesangioproliferative renal diseases. This study investigates the role of immunologic factors in glomerular matrix accumulation. The gene expression of type I and IV collagen, laminin and s-laminin was examined in the rat model of mesangial proliferative glomerulonephritis induced with anti-Thy 1.1 antibody. Northern analysis was performed on glomerular RNA isolated one, three and five days after disease induction and at day 3 following prior complement depletion. Tissue was immunostained for the protein products of these genes as well as for heparan sulfate proteoglycan, entactin and PCNA (a marker of cell proliferation) at days 1, 3, 5, 14, 21 and 42. A seven- to ten-fold increase of collagen IV and laminin mRNA as well as de novo expression of collagen I mRNA occurred at days 3 and 5 corresponding to the time of maximal proliferation. S-laminin mRNA levels only increased three-fold. With the exception of s-laminin, mesangial staining for all examined matrix proteins increased to a maximum at day 5 and decreased thereafter. Focal alterations of the glomerular architecture and matrix persisted at day 42. Complement depletion prevented the histological abnormalities as well as the increased expression of matrix proteins at day 3. These findings indicate that immunologic injury in the mesangium may result in overproduction of extracellular matrix components and may ultimately contribute to the development of glomerulosclerosis.
Animals↗