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Biomedical subjects

J Wiggins

Publications and source records attributed to J Wiggins.

At least 19 recordsLinked to original sources
PubMed2001

Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat.

BACKGROUND: Podocytes are highly differentiated glomerular epithelial cells with limited potential to divide. They are responsible for maintaining and supporting the glomerular basement membrane so as to facilitate efficient filtration. The hypothesis tested was whether the development of glomerulosclerosis in the puromycin aminonucleoside (PAN)-treated rat could be attributed to podocyte depletion. METHODS: PAN was injected in Sprague-Dawley rats once, twice, or three times at 30-day intervals. Podocytes were counted in glomeruli using immunoperoxidase histochemistry and antibodies to both GLEPP1 (PTPRO) and WT-1. Podocytes were assayed in urine using reverse transcription-quantitative polymerase chain reaction (RT-QPCR). Glomerular areas were measured by computerized morphometry. RESULTS: In a preliminary experiment, a single injection of PAN caused a reduction in the glomerular podocyte count by 25%. Additional independent confirmation that podocytes were lost from glomeruli after PAN injection was obtained identifying detached podocytes in Bowman's space, measurement of nephrin and GLEPP1 mRNAs in urine, ultrastructural analysis of glomeruli, and identification of TUNEL-positive apoptotic podocytes in glomeruli. In a second experiment, sequential podocyte depletion by 15, 31, and 53% was achieved by the administration of one, two, or three injections of PAN at 30-day intervals. The region of the glomerulus devoid of podocytes developed glomerulosclerosis, and this area progressively increased as podocytes were progressively depleted. The correlation coefficient (r(2)) value for the relationship between percent podocyte depletion and glomerulosclerotic area was 0.99. The Y intercept of this plot showed that glomerulosclerosis was initiated when only 10 to 20% of podocytes were lost. CONCLUSION: This report supports the growing body of data linking glomerulosclerosis directly to a reduction in relative podocyte number [increased glomerular area per podocyte (GAPP)]. It raises important questions related to the mechanisms of podocyte loss, strategies for prevention of podocyte depletion, and the prevention of progression of glomerular diseases.

Animals↗
PubMed1995

Utilization of advanced practice nurses in healthcare systems and multispecialty group practice.

Cost-effective strategies for delivering primary care require the appropriate mix of healthcare providers. The authors define the scope of practice for the advanced practice nurse. Results of a nationwide survey of 26 large healthcare systems and multispecialty group practices are presented. Findings from these practice settings are contrasted with those previously reported in the literature. Implications for the future are discussed.

Cost-Benefit Analysis↗
PubMed1995

Familial cryptogenic fibrosing pleuritis with Fanconi's syndrome (renal tubular acidosis). A new syndrome.

We describe two siblings with a progressive unrelenting and unique syndrome of bilateral fibrosing pleuritis of unknown cause occurring in association with Fanconi's syndrome (renal tubular acidosis). The parents of the siblings were second cousins. Both siblings had identical pleural histologic characteristics and identical urinary metabolic defects. This condition resulted in the development of severe respiratory failure in both patients and ultimately the death of the older sibling at the age of 21 years.

Acidosis, Renal Tubular↗
PubMed1993

Continuous veno-venous haemofiltration following cardio-pulmonary bypass. Indications and outcome in 35 patients.

OBJECTIVE: To study the impact of continuous veno-venous haemofiltration on survival in patients with acute renal failure (ARF) following cardio-pulmonary bypass (CPB) surgery. DESIGN: A retrospective study of all patients requiring haemofiltration after CPB over a 2 year period. SETTING: A 20 bedded, adult cardothoracic intensive care unit in a postgraduate teaching hospital. PATIENTS: 35 patients (26 male, age range 24-74 years) required haemofiltration (2.7% of the total number of patients undergoing CPB). MAIN RESULTS: Cardiovascular failure post CPB was the commonest causes of ARF (n = 16). Indications for haemofiltration were uremia (21), oligo-anuria (11), volume overload (2) and hyperkalaemia (1). Mean time from CPB to the initiation of haemofiltration was 8 days (range 0-15 days). Mean urea was 30 mmol/l and creatinine 362 mumol/l immediately prior to treatment. Urea was well-controlled in all patients, although 2 needed haemodiafiltration. Twenty-six patients died during their admission to the ICU (74% mortality). A further 3 patients died during their hospital admission, following discharge from ICU. Outcome was particularly poor in patients with cardiovascular failure following CPB (16 cases, 0 survivors). Survivors tended to commence filtration earlier (mean of 4 vs 7 days for non-survivors) and required treatment for a mean period of 8 days (range 1-26 days). Survival was determined by the number of failed organ systems at the start of haemofiltration. Thus, 100% of patients with single system failure survived, compared to only 10% with 3 or more system failure. CONCLUSIONS: Despite the theoretical advantages of haemofiltration and the effective control of uraemia the mortality associated with ARF following CPB remains high and is probably determined by the number of failed organs systems.

Acute Kidney Injury↗
PubMed1992

Production, purification, and characterization of human recombinant IL-8 from the eucaryotic vector expression system baculovirus.

The cDNA for the human chemotactic interleukin, IL-8, was subcloned from a bacterial source into the eucaryotic vector expression system baculovirus. Recombinant human IL-8 (rhIL-8) was synthesized and secreted from Sf9 cells derived from Spodoptera frugiperda following infection of a recombinant virus harboring the full-length IL-8 structural gene. Infected Sf9 cells produced rhIL-8 in a range from 0.5 to 2.0 mg of rhIL-8/liter of postinfection cell culture media. The recombinant interleukin was purified (greater than 600-fold) to homogeneity using preparative HPLC. rhIL-8 retained all of the physical, immunological, and biochemical properties observed for the natural product, monocyte-derived IL-8. rhIL-8 was assessed for biological efficacy by three criteria: (a) ability to induce chemotaxis in human neutrophils, (b) ability to induce oxygen burst metabolism, and (c) ability to be recognized by purified rabbit antibody generated against monocyte-derived IL-8. Antibody generated against monocyte-derived IL-8 recognized rhIL-8 isolated during all stages of the purification protocol. rhIL-8 was strongly chemotactic for human neutrophils and exhibited a chemotactic index comparable to that reported for other strong chemotactic peptides. rhIL-8 was identified following sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single silver-stained band having an estimated molecular weight of 9.2 kDa and displayed amino acid residue molar abundance homology predicted for the mature form of the interleukin. Baculovirus vector expression coupled to preparative HPLC proved to be a very efficient method for large-scale recombinant interleukin production.

Amino Acids↗
PubMed1991

Detection of bronchiectasis by high-resolution computed tomography in the yellow nail syndrome.

High resolution computed tomography of the lungs was performed in three patients with the yellow nail syndrome to detect bronchiectasis. Standard CT was performed in a fourth patient. Evidence of bronchiectasis with bronchial wall thickening and bronchial dilatation was observed in all four patients. High resolution CT is a non-invasive method for detecting and assessing the extent of airway disease in the yellow nail syndrome.

Aged↗
PubMed1991

Steroid trials in the assessment of reversibility of air flow limitation: a survey of current clinical practice of chest physicians.

To evaluate how steroid trials are currently used in the assessment of reversibility of air flow limitation, a postal questionnaire was sent to 355 consultant members of the British Thoracic Society working in England and Wales; 253 questionnaires were returned (71% response rate). Two respondents did not undertake steroid trials; of the remaining 251, 75% prescribed 30-40 mg oral prednisolone, with the commonest treatment period being 2 weeks. A high dose steroid inhaler was sometimes used as an alternative by 31% of respondents. Although 71% of respondents made lung function measurements on several occasions before starting steroids and 76% made measurements during treatment, 78% assessed patients on only one occasion at the end of the trials to ascertain its outcome. Weight, blood pressure and glycosuria were measured less frequently after the steroid treatment compared to the pre-trial period. Blood glucose and serum electrolytes were infrequently measured both before and after treatment. Wide variations exist in steroid trial regimens and current practice may neither provide definitive evidence of treatment benefit nor an adequate safeguard for patients against potential side-effects.

Chronic Disease↗
PubMed1991

A comparison of several agents with two delivery systems for the prevention of airway narrowing induced by nebulised pentamidine isethionate.

Bronchial narrowing is the major side effect of inhaled nebulised pentamidine isethionate, used for the prophylaxis and treatment of Pneumocystis carinii pneumonia. Several agents and delivery systems were assessed for prophylaxis of bronchial narrowing in HIV-positive males receiving regular nebulised pentamidine isethionate. In a previous study we found the mean maximum fall in FEV1 with nebulised pentamidine alone to be 21%. FEV1 was measured before and after inhaling nebulised pentamidine, preceded by one of the following bronchodilator/immunoregulatory agents: Terbutaline metered dose inhaler (500 micrograms), nebulised salbutamol (5 mg), nebulised ipratropium bromide (500 micrograms), nebulised sodium cromoglycate (20 mg), and nedocromil sodium metered dose inhaler (4 mg). Each agent was administered once only to ten different subjects. Nebulised salbutamol gave most effective prophylaxis against bronchial narrowing induced by nebulised pentamidine (mean maximum fall in FEV1 = 5% vs. 21%, P less than 0.001). Terbutaline given by metered dose inhaler was significantly less effective than high dose terbutaline (10 mg) given by nebuliser, demonstrated in the previous study (mean maximum fall in FEV1 = 14% vs. 6%, P less than 0.05). Mean maximum falls in FEV1 for ipratropium bromide, sodium cromoglycate and nedocromil sodium were 16, 17 and 16%, respectively. High dose beta 2-agonists administered by nebuliser give more effective prophylaxis against nebulised pentamidine-induced bronchial narrowing than either lower doses given by metered dose inhaler, anticholinergics or immunoregulatory drugs.

Adult↗
PubMed1991

Novel compounds possessing potent cAMP and cGMP phosphodiesterase inhibitory activity. Synthesis and cardiovascular effects of a series of imidazo[1,2-a]quinoxalinones and imidazo[1,5-a]quinoxalinones and their aza analogues.

A series of novel imidazoquinoxalinones and their aza analogues were prepared by the cyclization of o-amino(1H-imidazol-1-yl)aryls and heteroaryls with carbonyldiimidazole. The compounds were screened for inhibition of Type I and Type IV phosphodiesterases (PDE's) and evaluated for their vasorelaxant and positive inotropic activities in vitro. In general, compounds having potent PDE inhibitory activity also possessed good inotropic and vasodilator activity, although linear correlations between these activities could not be established.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Absence of interferon in sera of patients with Kawasaki syndrome.

We measured serum interferon concentrations in 42 patients with Kawasaki syndrome. The children ranged in age from 7 months to 6 years. All acute sera were obtained within 12 days of the onset of fever. Convalescent sera (illness day 19 to 56) were available from 25 of 42 patients. Sera were also obtained from 40 controls ranging in age from 2 months to 12 years. Control sera included healthy children (n = 14), children with bacterial infection (n = 10) and children with viral infection (n = 16). Sera were coded and interferon concentrations were measured blindly using human diploid fibroblast cell monolayers challenged with 10(4) plaque-forming units of vesicular stomatitis virus. Specimens from 10 of 16 patients with viral infection were positive for interferon. Three of 10 patients with bacterial infection had detectable serum interferon. No interferon was detected in specimens from the 14 healthy control children or the 42 children with Kawasaki syndrome. Despite the use of a sensitive assay we were unable to detect interferon in the sera of patients with Kawasaki syndrome.

Bacterial Infections↗