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Biomedical subjects

W G Campbell

Publications and source records attributed to W G Campbell.

At least 19 recordsLinked to original sources
PubMed1999

Brain SPECT imaging and neuropsychological testing in coronary artery bypass patients: single photon emission computed tomography.

BACKGROUND: Cognitive deficits appear frequently after cardiac operation. While the etiology remains unclear, alterations in cerebral perfusion during cardiopulmonary bypass may be causative. Single photon emission computed tomography (SPECT) scanning utilizes a radiopharmaceutical to provide images of cerebral perfusion. We proposed to study the cerebral circulation of patients during coronary artery bypass operation employing cardiopulmonary bypass. METHODS: Thirty-five neurologically normal patients underwent preoperative SPECT brain scanning and neuropsychological testing. A second SPECT brain perfusion scan was obtained by administering the radioisotope during cardiopulmonary bypass, with subsequent scanning upon completion of the procedure. Postoperative neuropsychological testing was performed prior to discharge. RESULTS: Fourteen (40%) of patients demonstrated significant neuropsychological decline. Patients who suffered cognitive impairment were no different in demographic, general health, or surgical variables. Patients who demonstrated neuropsychological decline had significantly poorer cerebral perfusion both at baseline and during operation. CONCLUSIONS: Impaired cerebral perfusion at baseline may identify patients at risk for cognitive injury after cardiac operation. Alterations in cerebral perfusion during cardiopulmonary bypass is common, and may be a factor in neuropsychological deficits seen after cardiac operation.

Aged↗
PubMed1999

H-K-ATPase in the RCCT-28A rabbit cortical collecting duct cell line.

In the present study, we demonstrate that the rabbit cortical collecting duct cell line RCCT-28A possesses three distinct H-K-ATPase catalytic subunits (HKalpha). Intracellular measurements of RCCT-28A cells using the pH-sensitive dye 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) indicated that the mechanism accounting for recovery from an acid load exhibited both K+ dependence and sensitivity to Sch-28080 characteristic of H-K-ATPases. Recovery rates were 0.022 +/- 0.005 pH units/min in the presence of K+, 0.004 +/- 0.002 in the absence of K+, and 0.002 +/- 0.002 in the presence of Sch-28080. The mRNAs encoding the HKalpha1 subunit and the H-K-ATPase beta-subunit (HKbeta) were detected by RT-PCR. In addition, two HKalpha2 species were found by RT-PCR and 5' rapid amplification of cDNA ends (5'-RACE) in the rabbit renal cortex. One was homologous to HKalpha2 cDNAs generated from other species, and the second was novel. The latter, referred to as HKalpha2c, encoded an apparent 61-residue amino-terminal extension that bore no homology to reported sequences. Antipeptide antibodies were designed on the basis of this extension, and these antibodies recognized a protein of the appropriate mass in both rabbit renal tissue samples and RCCT-28A cells. Such findings constitute very strong evidence for expression of the HKalpha2c subunit in vivo. The results suggest that the rabbit kidney and RCCT-28A cells express at least three distinct H-K-ATPases.

Animals↗
PubMed1999

Molecular identification of the renal H+,K+-ATPases.

The pharmacological properties of H+,K+-ATPase activity described in the kidney were not necessarily consistent with the properties of the well-characterized gastric H+,K+-ATPase. Recent molecular biology experiments suggest that renal H+,K+-ATPase activity may be the product of several closely related P-type ATPases. At least 3 different pumps containing the HKalpha1, HKalpha2a, and HKalpha2c subunits have been detected in rabbit kidney. The current view is that these HKalpha subunits arose through gene duplication early in evolution and the proteins evolved their differing activities over time. The HKbeta protein associates with HKalpha1 in gastric tissues and is the likely mate for the HKalpha1 subunit in renal tissues. Three distinct beta subunits have been implicated as possible partners for the HKalpha2 subunits, but it remains to be determined which beta subunit predominantly associates with the HKalpha2 subunits in vivo. Sequence analysis suggests the beta subunit was constrained by size and shape of the protein rather than specific amino acid content during the course of evolution. Multiple H+,K+-ATPases in the kidney may be an important adaptation providing redundancy for the essential physiological function of maintaining ionic balance.

Amino Acid Sequence↗
PubMed1998

Carvedilol prevents severe hypertensive cardiomyopathy and remodeling.

BACKGROUND: Carvedilol (Coreg/Kredex) is an unselective vasodilating beta-blocker with potent antioxidant activity used in the treatment of hypertension, angina, and congestive heart failure. In previous studies, carvedilol has been demonstrated to confer significant cardiac protection in acute ischemic paradigms and reduction of left ventricle hypertrophy in spontaneously hypertensive rats. OBJECTIVE: To examine the effects of carvedilol on discrete histopathologic changes in the heart induced by severe hypertension in stroke-prone spontaneously hypertensive rats. DESIGN: Three groups of stroke-prone spontaneously hypertensive rats were maintained on 1% NaCl drinking solution and a high-fat (24.5%) diet (salt-fat diet). Two of these groups had their salt-fat diet supplemented by 1200 or 2400 ppm carvedilol. The third group had the same diet but it was not supplemented with drug and this group served as a control. We fed a fourth group of stroke-prone spontaneously hypertensive rats a normal diet and used this group to define cardiac changes induced by salt-fat diet. METHODS: In total, 33 stroke-prone spontaneously hypertensive rats from these four groups (n = 7-9 in each group) survived for 18 weeks under these treatment regimens and were evaluated in terms of cardiovascular parameters and several quantitative and semiquantitative histopathologic indices that we developed to identify and compare cardiac muscle and vascular pathology/remodeling. RESULTS: Administration of carvedilol had no effect on systolic blood pressure (range for all salt-fat diet groups 288 +/- 8 to 294 +/- 6 mmHg compared with the value for the normal diet group of 228 +/- 12 mmHg) whereas heart rate was slightly reduced (by 10-18%; P<0.05). Administration of carvedilol produced a significant (P<0.01) dose-related decrease in total cardiac histologic damage (i.e. the sum of several histopathologic indices) induced by the salt-fat diet (i.e. it reduced damage by 54 and 82% at low and high doses, respectively). Specifically, administration of carvedilol produced dose-dependent reductions in histopathologic indices of coronary artery hypertrophy (by up to 88%), hyperplasia (by up to 89%), degeneration of myofiber (by up to 91%), myocardial inflammation (by up to 100%), cardiac fibrosis (by up to 67%), arterial microthrombosis (by up to 95%), and myocardial microinfarction (by up to 100%; all P<0.01). Salt-fat diet induced an increase in total cardiac mass and left ventricle-intraventricular septum cross-sectional area that was completely eliminated by administration of carvedilol (P<0.01). CONCLUSIONS: These data indicate that carvedilol provides remarkable cardioprotection, by suppressing severe hypertension-induced cardiac remodeling and myopathies at doses that do not reduce systemic blood pressure.

Administration, Oral↗
PubMed1998

Use of silicone oil in the treatment of complicated retinal detachment: results from 1981 to 1994.

PURPOSE: To evaluate the advantages and disadvantages of the retention and removal of silicone oil in the treatment of complicated retinal detachments. METHODS: The records of 344 patients (348 eyes) that underwent vitrectomy and silicone oil injection for complicated retinal detachments were abstracted and analysed. The anatomical and functional results, complications and influencing factors are discussed. The outcome in eyes after removal of the silicone oil was compared with the outcome in a comparable group of eyes in which the silicone oil was retained. RESULTS: The overall retinal reattachment rate was 63% (220/348). The final vision of 5/300 or better was 52% (115/220) in those eyes with totally attached retinas. The silicone oil-related complications included keratopathy (23%) and secondary glaucoma (11%). Comparing removal of silicone oil with retention of silicone oil, we found: (i) there was no statistical difference in the redetachment rate (19 vs 17%); (ii) oil-removed eyes had a better final vision (P < 0.05); and (ii) keratopathy (13 vs 23%), secondary glaucoma (11 vs 25%) and optic nerve atrophy (4 vs 18%) were significantly lower in oil-removed eyes. CONCLUSION: Silicone oil injection is useful in the treatment of complicated retinal detachments. For reducing the incidence of complications, early removal of silicone oil is recommended in those cases in which the retina is attached, all breaks adequately closed and traction relieved.

Adolescent↗
PubMed1997

Autoimmune hypothesis of acquired subglottic stenosis: lack of support at time of surgical repair in children.

Numerous mechanisms have been suggested for the development of subglottic stenosis. This study sought serum antibody and cricoid cartilage immunohistologic evidence of an autoimmune process. The autoimmune hypothesis is that subglottic inflammation may extend into the cricoid cartilage, degrade the extracellular matrix and expose normally-sequestered type II collagen to the afferent arm of the immune system. The resultant anti-collagen antibodies are hypothesized to contribute to further injury and scarring. Specimens were obtained from 10 patients. Immunofluorescent stains for antibodies in histologic specimens, and serum antibodies to type II and type IX collagen were sought. No evidence for an autoimmune process was found in these specimens with the techniques used. The negative findings may be attributable to the autoimmune process being inactive at the mature stage of the disease in the patients studied.

Adolescent↗
PubMed1997

Is self-organized criticality relevant to alcoholism?

The concept of self-organized criticality suggests that large interactive (dynamic) systems move toward a critical state. Seen throughout nature these systems follow a power law where the amount of energy involved in a change is related to the number of events that have occurred such that N is proportional to one over E to the power b (N alpha 1/Eb), where N is the number of events, E is the energy of the event and b is a constant for the system. A pilot series of 316 individuals reporting alcohol problems were studies and the number of individuals (N) reporting number of detoxifications (DN) was found to be related such that N was proportional to one over DN to the power k (N alpha 1/DNk), where k varies with the parameters of the population studies (i.e., gender, time sober). It is hypothesized that the "disease of alcoholism" can be conceptualized to be related to the energy of effort required to move from one "attractor" (drinking) to another (non-drinking) as a power law. The results suggest that alcoholics are "attracted" to the critical state of intoxication independent of clinical presentation or initial conditions.

Adult↗
PubMed1997

Evaluation of a residential program using the Addiction Severity Index and stages of change.

Fifty six individuals admitted to Recovery Acres (a thirty five bed male residential recovery program/half way house) were evaluated using the Addiction Severity Index (ASI) and Socrates, an instrument designed to measure stage of change. Composite scores obtained from the ASI indicated that major problems were present in the areas of employment, alcohol, family/social, and emotional functioning. Stages of Change revealed 27% to be in preparation, 67% action, and 6% in maintenance. Patients left Recovery Acres either through relapse, or to follow a non-residential program. Follow-up of 26 cases revealed that residents showed statistically significant improvement in areas of alcohol, drug, family/social and emotional problems. Employment, medical, and legal problems as identified by the ASI composite score were significant indicators of negative outcome. Employment still remained a problem three months after admission for most residents. Stage of Change did not predict outcome in terms of abstinence or residential status.

Adult↗
PubMed1996

Plasma and renal prorenin/renin, renin mRNA, and blood pressure in Dahl salt-sensitive and salt-resistant rats.

We measured plasma prorenin and renin levels, renal renin mRNA, renal anti-renin and anti-prorenin-prosequence immunoreactivity, and blood pressure in maturing Brookhaven Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats during 14 days of low (0%), medium (0.4%), or high 4%) NaCl diets. Blood pressure was higher in Dahl S rats and did not increase with high NaCl. Seven-week-old Dahl R rats had twofold and sixfold higher levels of plasma prorenin and renal prosequence immunoreactivity, respectively, which by 9 weeks were the same as in Dahl S rats. The anti-renin antiserum, BR1-5, was found to detect prorenin better than renin; Dahl S rats had suppressed renal anti-renin immunoreactivity relative to Dahl-R rats. Dahl R rats were unresponsive to high NaCl, whereas in Dahl S rats, plasma renin and renal prosequence immunoreactivity fell by 90% (P < .01), renal anti-renin immunoreactivity and renal renin MRNA fell by 35% (P < .05 for both), and plasma prorenin fell by 30% (P = NS). NaCl depletion increased prorenin/renin parameters similarly in both strains. There were direct relationships among all of the prorenin/renin parameters. Between low and high salt diets in Dahl S rats, plasma renin increased 20-fold, plasma total renin (renin plus prorenin) and renal renin mRNA both increased threefold, and plasma prorenin increased twofold. The results indicate that under steady-state conditions, plasma and renal renin/prorenin parameters change concordantly and that plasma total renin (renin plus prorenin) reflects changes in renal renin mRNA. The lower blood pressure of Dahl R rats is associated with later maturation-related declines in plasma and renal prorenin. Suppression of plasma renin may delay the salt-induced blood pressure rise in Dahl S rats. Finally, the renin system and blood pressure of Dahl R rats have remarkable disregard for a high salt diet.

Animals↗
PubMed1996

Morphogenesis of inclusion bodies of urothelial carcinoma: a case study.

The morphogenesis of inclusions of urothelial carcinoma (K. Donhuijsen et al.: Hum Pathol 23:860, 1992) is described in a case of a 51-year-old man with poorly differentiated urothelial carcinoma. Peritoneal fluid preparations contained numerous dyscohesive, large, anaplastic cells with abundant dense amphophilic cytoplasm often compartmentalized into multiple, variably sized, intracytoplasmic lumina, each containing "bull's eye"-like inclusions, with a periodic acid Schiff-positive refractile central core and an alcian blue/mucicarmine-positive rim. Ultrastructurally, the progression of osmiophilic substance from membrane-bound exocrine-type secretory granules, via exocytosis, to a presence in both intracytoplasmic lumina and extracellular space has been documented. Immunohistochemically, the periodic acid Schiff-positive refractile cores, as well as the minute periodic acid Schiff-positive granules in the cytoplasm, stained positively for secretory component and peanut agglutinins, whereas the alcian blue-positive mucinous material, which coated the refractile cores as well as the lining of the intracytoplasmic lumina, stained strongly for epithelial membrane antigen and leu M1. Ultrastructurally, protein A-gold probes, immunolabeled for peanut agglutinin and secretory component, were localized to the osmiophilic substance.

Carcinoma, Transitional Cell↗
PubMed1996

Chronic carvedilol reduces mortality and renal damage in hypertensive stroke-prone rats.

The effects of carvedilol, a novel vasodilating beta-blocker and antioxidant, and propranolol on survival, neurobehavioral deficits, cardiovascular parameters, plasma renin, plasma aldosterone levels and renal pathology were determined in stroke-prone spontaneously hypertensive rats. Stroke-prone spontaneously hypertensive rats were allowed access to 1% NaCl as the drinking solution and a high fat diet supplemented with carvedilol (1200 or 2400 ppm) or propranolol (2400 ppm). The control group consisted of stroke-prone spontaneously hypertensive rats placed on the same diet with no drug supplement. Animals fed propranolol had a blood level of 864 +/- 68 ng/ml, whereas carvedilol-fed animals had blood levels of 24 +/- 4 ng/ml at 1200 ppm and 471 +/- 145 ng/ml at 2400 ppm. Carvedilol and propranolol treatment resulted in significant beta adrenoceptor blockade. Both compounds reduced heart rate, but had no significant effects on systolic arterial blood pressure. Carvedilol- and propranolol-treated animals also exhibited significant, prolonged protection from neurobehavioral deficits and mortality (P < .01). Elevated plasma renin activity and aldosterone levels seen in untreated controls were significantly decreased by propranolol (P < .05), and to a considerably greater extent by the same dose of carvedilol (P < .01). Carvedilol decreased renal histopathological damage and cardiac hypertrophy to a greater extent (P < .01) than propranolol (at equal doses). Both carvedilol (P < .01)- and propranolol (P < .01)-treated animals had considerably reduced renal damage at 18 weeks of treatment. Carvedilol reduced renal damage more than propranolol (P < .05). In addition, the lower (1200 ppm) dose of carvedilol, which decreased neurobehavioral deficits and mortality, had no significant effects on organ mass or renal function, but significantly (P < .01) reduced renal damage. These data indicate that both beta adrenoceptor blockers, especially carvedilol to a considerably greater degree, convey significant protection in a genetic model of severe hypertension that results in renal and cardiovascular organ pathology, neurobehavioral deficits and premature death.

Adrenergic beta-Antagonists↗
PubMed1995

Renal expression of the gene encoding the gastric H(+)-K(+)-ATPase beta-subunit.

The gastric mucosal parietal cells and cells of the renal collecting duct both possess H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) activities. In the stomach, the H(+)-K(+)-ATPase (EC 3.6.1.3) is responsible for acidification of luminal contents. The kidney H(+)-K(+)-ATPase protein(s) contribute to potassium reabsorption and secretion of hydrogen ions to maintain potassium and acid-base homeostasis. The stomach H(+)-K(+)-ATPase is well defined and consists of an alpha-catalytic subunit of apparent molecular mass of 95 kDa and a highly glycosylated beta-subunit of 60-90 kDa. The molecular identity of the protein that mediates the H(+)-K(+)-ATPase activity in the kidney has been addressed in this paper. A combination of RNA hybridizations, polymerase chain reaction analysis of kidney RNA, and sequence analysis of cDNAs indicated that gastric H(+)-K(+)-ATPase beta-subunit mRNA is present in kidney. Immunoblotting with antibodies specific for the gastric H(+)-K(+)-ATPase beta-subunit detected proteins, which, after deglycosylation, had the same molecular mass as the gastric beta-subunit in membrane protein preparations from rabbit, pig, rat, and mouse kidneys. Furthermore, we have used transgenic mice to demonstrate that the gastric H(+)-K(+)-ATPase beta-subunit gene contains cis-acting regulatory sequences that are active in both gastric parietal cells and the renal collecting ducts. Overall, these data indicate that the gastric H(+)-K(+)-ATPase beta-subunit is found in the kidney and probably associates with the gastric H(+)-K(+)-ATPase alpha-subunit and/or other P-type ATPase alpha-subunits, thus contributing to acid-base and potassium homeostasis.

Animals↗
PubMed1995

In situ hybridization of H-K-ATPase beta-subunit mRNA in rat and rabbit kidney.

Through a variety of techniques, several investigators have demonstrated the presence of an H-K-adenosinetriphosphatase (H-K-ATPase) enzyme in the renal collecting duct, suggesting that this enzyme serves an important physiological role in the regulation of acid-base balance and potassium excretion by the kidney. The present study was designed to localize cells expressing H-K-ATPase beta-subunit mRNA in rat and rabbit kidney by nonradioactive in situ hybridization. A 570-bp DNA fragment of rabbit renal H-K-ATPase beta-subunit was used to produce digoxigenin-labeled riboprobes by in vitro transcription. Northern blot hybridization demonstrated transcripts in rat gastric oxyntic mucosa and kidney. In situ hybridization on kidney tissue sections demonstrated H-K-ATPase beta-subunit mRNA localization in epithelial cells, including intercalated cells in the connecting segment and cortical and medullary collecting duct, principal cells in the inner stripe of the outer medullary collecting duct, and inner medullary collecting duct cells in both the rat and the rabbit. These observations provide evidence that H-K-ATPase beta-subunit mRNA is present throughout the collecting duct of the kidney. The distribution of this message is consistent with a role for H-K-ATPase in bicarbonate absorption in both the outer and inner medullary collecting duct.

Animals↗
PubMed1994

Pituitary-specific transcription factor (Pit-1) binding site in the human renin gene 5'-flanking DNA stimulates promoter activity in placental cell primary cultures and pituitary lactosomatotropic cell lines.

Renin gene expression is limited to a number of specific tissues, including the kidney, adrenal glands, reproductive organs (of particular relevance to this study, the placenta), and the pituitary gland. In the present study, we investigated the human renin (hRen) 5'-flanking DNA sequences required to drive the expression of a luciferase reporter gene in placental and pituitary cells and in two cell lines, 293 and JEG-3, which have been proposed as model systems with which to study transcriptional regulation of renin genes. The activities of specific sequences in the hRen 5'-flanking DNA sequences in human placental cell primary cultures were very similar to those that we previously reported in pituitary cells, suggesting the involvement of common promoter elements and related transcription factors. Accordingly, the binding site for the pituitary-specific transcription factor (Pit-1) was the major determinant of renin promoter activity in both pituitary and placental cells. Gel mobility shift analysis showed a placental nuclear factor with a gel mobility different from that of Pit-1. However, Northern blot analysis failed to demonstrate abundant Pit-1-related mRNAs in renin-expressing cultures of chorionic and decidual cells, suggesting that the placental factor is not closely related to Pit-1. Although a factor from 293 cells also bound to the Pit-1 site, it had gel mobility shift characteristics different from Pit-1 and the placental factor. Moreover, the low promoter activity in 293 cells was independent of this site or, indeed, of sequences upstream from the TATA box. In JEG-3 cells, renin 5'-flanking DNA sequences showed virtually no transcriptional activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1994

The concurrence of duodenal epithelioid stromal sarcoma, pulmonary chondromatous hamartoma, and nonfunctioning pancreatic islet cell tumor. A possible analogue of Carney's triad?

A 63-year-old man with non-insulin-dependent diabetes mellitus and peripheral vascular disease presented with acute pulmonary edema and ascites. He died after a brief illness. Coincidence of duodenal epithelioid stromal sarcoma, pulmonary chondromatous hamartoma, and pancreatic islet cell tumor was found at autopsy. This rare concurrence of three uncommon neoplasms may be a pathogenetic variant or an analogue of Carney's triad in an elderly individual. Since all three tumors expressed markers for neural differentiation, the coincidence of tumors with these features may represent a form of neurocristopathy.

Adenoma, Islet Cell↗
PubMed1993

Control of blood pressure and end-organ damage in maturing salt-loaded stroke-prone spontaneously hypertensive rats by oral angiotensin II receptor blockade.

OBJECTIVE: To study the effects of renin-angiotensin system blockade by a novel non-peptide angiotensin II receptor antagonist, losartan, on development of hypertension and acceleration of end-organ damage in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). DESIGN AND METHODS: One hundred and eighty-one male SHRSP were fed a 4% sodium diet from 6 to 18 weeks of age. Seventy-eight SHRSP were treated orally with losartan, 30 mg/kg per day. One hundred and three rats constituted untreated controls. Blood pressure, plasma renin activity (PRA), renal function and end-organ damage were monitored during the transition to malignant hypertension. RESULTS: Losartan prevented a blood pressure rise during the first 4 weeks of salt loading. Thereafter, blood pressure rose slowly in losartan-treated rats; however, at each time-point studied blood pressure was significantly lower in losartan-treated rats than in control rats. Losartan treatment increased PRA during the first 4 weeks, but this effect was not sustained. Thereafter, PRA decreased to control (week 0) levels. In contrast, 2 weeks after high-sodium feeding started, untreated SHRSP failed to suppress PRA appropriately; thereafter, PRA rose significantly. Losartan affected renal pathophysiology by blunting the decline in glomerular filtration rate, controlling proteinuria and preventing or delaying the appearance of malignant nephrosclerosis. Losartan treatment significantly increased survival and completely prevented cerebrovascular infarcts. CONCLUSIONS: The results indicate that angiotensin II blockade markedly reduces both hypertension and end-organ damage in chronically salt-loaded SHRSP and that the renin-angiotensin system may play an important role in the development of hypertensive cardiovascular disease in SHRSP.

Angiotensin II↗
PubMed1993

Needle drainage of subretinal fluid. A randomized clinical trial.

Needle drainage of subretinal fluid with simultaneous observation using the indirect ophthalmoscope has been reported to have a very low complication rate. The technique was evaluated by a prospective clinical trial. The study group consisted of 100 patients undergoing scleral buckling for rhegmatogenous retinal detachment who were randomly assigned to groups treated with needle drainage or conventional two-stage drainage. At 1 month, the retina was anatomically flat in 88% of all cases. Subretinal hemorrhage occurred in 10 of 45 patients (22.2%) after needle drainage and in 7 of 55 patients (12.7%) after conventional drainage. The difference was not statistically significant. Retinal puncture occurred during conventional drainage in one case and in no cases during needle drainage. There were no cases of retinal incarceration. The results showed that subretinal hemorrhage was more common after needle drainage, but a larger study would be required to show whether this difference was statistically significant. The fear that the retina would be damaged by placement of a needle in the subretinal space throughout the drainage procedure was unfounded.

Aged↗