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Biomedical subjects

R Cade

Publications and source records attributed to R Cade.

At least 19 recordsLinked to original sources
PubMed2006

AAV delivery of mineralocorticoid receptor shRNA prevents progression of cold-induced hypertension and attenuates renal damage.

UNLABELLED: The aim of this study was to determine the effect of RNA interference inhibition of mineralocorticoid receptor (MR) on cold-induced hypertension (CIH) and renal damage. Recombinant adeno-associated virus (AAV) carrying short hairpin small interference (si)RNA for MR (AAV.MR-shRNA) was constructed and tested for the ability to inhibit renal MR and to control CIH. Three groups of rats with CIH received AAV.MR-shRNA (1.25 x 10(9) particles/rat, intravenous), AAV carrying scrambled shRNA (AAV.Control-shRNA) (1.25 x 10(9) particles/rat, intravenous) and phosphate buffer solution (PBS), respectively. All rats were kept in a cold chamber (6.7 degrees C) throughout the experiment. Adeno-associated virus delivery of MR-shRNA prevented progression of CIH. Blood pressure (BP) of the AAV.MR-shRNA-treated group did not increase and remained at 145+/-3 mm Hg, whereas BP of the AAV.Control-shRNA-treated and PBS-treated group increased to 167+/-4 and 161+/-3 mm Hg, respectively, at 3 weeks after gene delivery. Thus, the antihypertensive effect of a single injection of AAV.MR-shRNA lasted for at least 3 weeks (length of the study). Adeno-associated virus carrying short hairpin siRNA for MR significantly increased urinary sodium excretion and decreased proteinuria. It also decreased serum creatinine and blood urea nitrogen, suggesting enhanced renal function. Both Western blot and immunohistochemical analysis showed that MR expression was decreased significantly in the kidney in the AAV.MR-shRNA-treated rats, confirming that renal MR is effectively inhibited by AAV.MR-shRNA. Adeno-associated virus carrying short hairpin siRNA for MR also significantly attenuated renal hypertrophy. In addition, AAV delivery of MR-shRNA prevented atrophy and dilation of renal tubules and abolished tubular deposition of proteinaceous material seen in CIH rats. CONCLUSIONS: (1) AAV delivery of MR-shRNA effectively silenced MR in vivo. (2) RNA interference inhibition of MR may open a new avenue for the long-term control of hypertension and renal damage.

Animals↗
PubMed2001

NIM1 overexpression in Arabidopsis potentiates plant disease resistance and results in enhanced effectiveness of fungicides.

The NIM1 (for noninducible immunity, also known as NPR1) gene is required for the biological and chemical activation of systemic acquired resistance (SAR) in Arabidopsis. Overexpression of NIM1 in wild-type plants (hereafter referred to as NIM1 plants or lines) results in varying degrees of resistance to different pathogens. Experiments were performed to address the basis of the enhanced disease resistance responses seen in the NIM1 plants. The increased resistance observed in the NIM1 lines correlated with increased NIM1 protein levels and rapid induction of PR1 gene expression, a marker for SAR induction in Arabidopsis, following pathogen inoculation. Levels of salicylic acid (SA), an endogenous signaling molecule required for SAR induction, were not significantly increased compared with wild-type plants. SA was required for the enhanced resistance in NIM1 plants, however, suggesting that the effect of NIM1 overexpression is that plants are more responsive to SA or a SA-dependent signal. This hypothesis is supported by the heightened responsiveness that NIM1 lines exhibited to the SAR-inducing compound benzo(1,2,3)-thiadiazole-7-car-bothioic acid S-methyl ester. Furthermore, the increased efficacy of three fungicides was observed in the NIM1 plants, suggesting that a combination of transgenic and chemical approaches may lead to effective and durable disease-control strategies.

Arabidopsis↗
PubMed2000

Heller's myotomy: thoracoscopic or laparoscopic?

Cardiomyotomy is now usually performed using a minimally invasive approach. A consecutive series of 18 patients with an intention to treat thoracoscopically were followed by the same number of patients treated laparoscopically. Both groups have been followed prospectively for a minimum of 2 years. The groups were well matched for age, symptom duration, preoperative lower esophageal sphincter pressure, and number having undergone balloon dilatation. There was one conversion from a thoracoscopic to a laparoscopic approach so that, for the purpose of analysis, there are 17 in the thoracoscopic group and 19 in the laparoscopic group. There was no difference in the average operating time, rate of conversion to open operation, mucosal breaches, or length of hospitalization. Nor was there any difference in dysphagia symptoms, with 14/17 having a satisfactory result after thoracoscopic myotomy and 18/19 after laparoscopic myotomy. Frequency of reflux symptoms was similar and, although mild reflux was common, only two patients required treatment with a proton pump blocker. In the treatment of achalasia, thoracoscopic and laparoscopic myotomy without fundoplication are equally effective in relieving dysphagia and have a similar safety profile.

Cardia↗
PubMed1999

Induced plant defence responses: scientific and commercial development possibilities.

Recent work has demonstrated that plants have endogenous defence mechanisms that can be induced as a response to attack by insects and pathogens. There are two well-studied examples of these induced defence responses. Systemic acquired resistance (SAR) results in increased resistance to a broad spectrum of pathogens throughout a plant in response to localized necrosis caused by pathogen infection. The second example is the systemic induction of proteinase inhibitors to deter feeding by herbivores following an initial event of feeding. In addition, there is now preliminary evidence for other induced defence response pathways. By understanding the breadth of induced defence responses and the mechanisms used to control these pathways, novel plant protection strategies may be developed for use in agronomic settings. Rather than reducing crop losses caused by pests or pathogens by using chemicals that are designed to kill the offending organism, the plant's own defence mechanisms can be used to limit damage due to pests. Novel crop protection strategies based on genetic or chemical regulation of these induced responses show great potential. The first example of a crop protection product that acts by inducing an endogenous defence response pathway is now on the market. Bion reduces the level of pathogen infection in plants by activating SAR.

Agriculture↗
PubMed1998

The major trauma management study: an analysis of the efficacy of current trauma care.

BACKGROUND: An audit of the management and outcome of major trauma patients was carried out to determine ways in which the system of care may be improved. METHODS: The Major Trauma Management Study (MTMS) collected data prospectively on all consecutively admitted major trauma patients at eight major hospitals during a 12-month period. Outcome was studied using trauma and injury severity score (TRISS) and a severity characterization of trauma (ASCOT) analyses, as well as a preventable outcome analysis, which looked at survivors with complications or with a Glasgow Coma Score < 15 on discharge from hospital, as well as studying deaths. RESULTS: The group of 859 patients was more severely injured than most described previously, with a mortality of 14.8% and a mean injury severity score of 19.8. Formal ASCOT analysis indicated 2.25% fewer survivors than would be predicted by Major Trauma Outcome Study norms. Extrapolating the TRISS and ASCOT process to include those patients with missing data, and then comparing groups of matched severity with the norms, gave no statistically different outcome in the MTMS group of patients. Preventable outcome analysis revealed rates of preventable and potentially preventable (P/PP) outcomes of 32% among deaths and 8% among survivors. The types of management deficiencies responsible for P/PP outcomes are identified. CONCLUSIONS: The points of deficiency in a system of care have been identified, and the development of an integrated trauma system in Victoria, based upon these facts, is recommended. Children, the elderly, patients with head injuries and patients being transferred between hospitals would benefit from improvements to the system of care. The calculation of efficacy rate (0.95 for the MTMS patients) is recommended to accurately assess the system of care. Preventable Outcome Analysis is more relevant to auditing a system of trauma care in detail, than is ASCOT or TRISS. The MTMS has refined and defined the process so that it is reproducible in further comparative studies.

Critical Pathways↗
PubMed1993

Bile duct injury during laparoscopic cholecystectomy: a report of the Standards Sub-committee of the Victorian State Committee of the Royal Australasian College of Surgeons.

A survey of Victorian surgeons performing laparoscopic cholecystectomy was carried out. This report discusses the bile duct injuries identified in the survey. Twelve injuries were recorded, a rate of 0.2%. Three of the 12 required formal repair, the other 9 being treated by T-tube alone. Possible mechanisms of these injuries, the experience of the surgeon, the role of operative cholangiography and delays in recognition of the injury are discussed.

Bile Ducts↗
PubMed1993

Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases.

Protein phosphorylation plays an important role in pheromone-induced differentiation processes of haploid yeast cells. Among the components necessary for signal transduction are the STE7 and STE11 kinases and either one of the redundant FUS3 and KSS1 kinases. FUS3 and presumably KSS1 are phosphorylated and activated during pheromone induction by a STE7-dependent mechanism. Pheromone also induces the accumulation of STE7 in a hyperphosphorylated form. This modification of STE7 requires the STE11 kinase, which is proposed to act before STE7 during signal transmission. Surprisingly, STE7 hyperphosphorylation also requires a functional FUS3 (or KSS1) kinase. Using in vitro assays for FUS3 phosphorylation, we show that pheromone activates STE7 even in the absence of FUS3 and KSS1. Therefore, STE7 activation must precede modification of FUS3 (and KSS1). These findings suggest that STE7 hyperphosphorylation is a consequence of its activation but not the determining event.

Amino Acid Sequence↗
PubMed1992

Marathon running: physiological and chemical changes accompanying late-race functional deterioration.

Twenty-one experienced runners were studied before, during and immediately after a marathon race to ascertain whether either depletion of energy substrate or rise in body temperature, or both, contribute to late-race slowing of running pace. Seven runners drank a glucose/electrolyte (GE) solution ad libitum (Na+ 21 mmol l-1, K+ 2.5 mmol l-1, Cl- 17 mmol l-1, PO4(2-) 6 mmol l-1, glucose 28 mmol l-1) throughout the race; 6 drank water and 8 drank the GE solution diluted 1:1 with water. Although average running speeds for the three groups were not significantly different during the first two-thirds (29 km) of the race, rectal temperature was significantly higher (P < 0.05) and reduction of plasma volume was greater (P < 0.05) in runners who replaced sweat losses with water. During the last one-third of the race, the average running pace of the water-replacement group slowed by 37.2%; the pace slowed by 27.9% in the 8 runners who replaced their sweat loss with GE diluted 1:1 with water (1/2 GE) and 18.2% in runners who replaced fluid loss with full-strength solution (GE). Eleven runners (5 in the water group, 4 in the 1/2 GE group and 2 in the GE group) lapsed into a walk/run/walk pace during the last 6 miles of the race. Ten of these had a rectal temperature of 39 degrees C or greater after 29 km of running, and plasma volume in these runners was reduced by more than 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Fibrovascular polyp of the oesophagus.

Fibrovascular polyps of the oesophagus are rare. Despite this, they provoke considerable interest because of their often dramatic presentation, and their potential for lethal complications. When the diagnosis is entertained, endoscopic or radiological confirmation is usually easily obtained and local excision is curative. An adult patient is described who presented after partial regurgitation of a 10 cm polyp. In view of the size of the lesion and its proximal attachment, endoscopic polypectomy was undertaken. The diagnostic pitfalls and therapeutic options in this unusual condition are discussed.

Esophageal Neoplasms↗
PubMed1988

Prevention of recurrent urinary tract infections in postmenopausal women.

Twelve postmenopausal women who experienced frequent urinary tract infections were found to have atrophic vaginitis. Four of them who were taking sulfonamide preparations chronically also had an interstitial nephritis manifest by decreasing glomerular filtration rate and eosinophiluria. Treatment consisted of a Betadine douche daily for 1 week, administration of an appropriate nonsulfonamide antibiotic, and institution of estrogen therapy to restore glycogen deposition in the vaginal epithelium and promote return of a normal vaginal pH and bacterial flora. Prior to estrogen therapy, the frequency of infection was four per patient per year. During a follow-up observation period ranging from 2 to 8 years, there have been only four infections in the entire group. When sulfonamides were discontinued in the 4 patients with manifestations of interstitial nephritis, the eosinophiluria cleared, and the glomerular filtration rate increased significantly.

Estrogens↗
PubMed1987

Hepatorenal syndrome. Studies of the effect of vascular volume and intraperitoneal pressure on renal and hepatic function.

Eleven patients with well-documented hepatorenal syndrome were studied by measurement of blood volume, glomerular filtration rate, renal plasma flow, plasma aldosterone concentration, renin substrate concentration, and plasma renin activity. They were then given 750 ml of stored plasma, 750 ml of fresh frozen plasma, and then an infusion of angiotensin II, in random order on successive days. Infusion of fresh frozen plasma improved function more than did stored plasma and in addition returned a very low filtration fraction toward normal. Angiotensin II infusion increased filtration fraction, but decreased glomerular filtration rate, renal plasma flow, and urine flow sharply. Patients were then given a daily infusion of 1,000 ml of fresh frozen plasma for seven to 18 days to expand the blood volume to supranormal levels as assayed by serial measurement of blood volume. Plasma aldosterone levels decreased to a normal range, glomerular filtration rate and renal plasma flow both increased, and urinary excretion of sodium and potassium both returned toward normal. The effect of intraperitoneal pressure was then studied by measuring glomerular filtration rate, renal plasma flow, pressure in the vena cava, hepatic vein free flow, and hepatic vein wedged pressure before, during, and after paracentesis to reduce the intraperitoneal pressure from 30 to 40 cm H2O to 12 to 17 cm H2O. Venous pressures moved parallel to ascitic fluid pressures, and glomerular filtration rate, renal plasma flow, and urine flow all improved sharply; then, as ascitic fluid continued to form, reducing vascular volume, urine flow, glomerular filtration rate, and renal plasma flow all decreased slowly. Six patients then underwent placement of a LeVeen shunt. Improvement in glomerular filtration rate and renal plasma flow and clinical condition was dramatic. During postoperative observation of up to two years, progressive improvement in hepatic function has occurred.

Angiotensin II↗
PubMed1986

Effect of long-term azathioprine administration in adults with minimal-change glomerulonephritis and nephrotic syndrome resistant to corticosteroids.

Thirteen adult patients with nephrotic syndrome resistant to corticosteroid administration were treated with azathioprine daily for four years. Progressive improvement occurred in all 13 patients so that they were in complete remission after one to three years. The onset of apparent improvement was earlier and the rate of progressive improvement more rapid in patients who had selective proteinuria before therapy than in those whose proteinuria was nonselective. One patient who stopped therapy after 20 months suffered relapse but again responded when azathioprine treatment was restarted. Observation after the four-year therapeutic period ranges from three to 15 years; there have been no relapses during this time.

Adolescent↗
PubMed1984

Schizophrenia, hemodialysis, and the placebo effect. Results and issues.

This report presents the results of a double-blind study that examines the impact of hemodialysis on patients with chronic schizophrenia. Twelve patients were randomly assigned to sham and 12 patients to active dialysis. All patients experienced a drug washout period and were then followed up over an eight-week period. A statistically significant condition by weeks interaction was found, with patients in the sham group improving and patients in the active dialysis group decompensating over the last weeks of the trial. This complex finding fails to support the hypothesized efficacy of hemodialysis in the treatment of schizophrenia but also fails to support a simple placebo explanation for positive results reported in earlier open studies. The methodologic complications are reviewed, and a possible direction for future research is presented.

Adult↗
PubMed1984

Effect of aerobic exercise training on patients with systemic arterial hypertension.

One hundred five patients with established diastolic hypertension were enrolled in an exercise program to examine the effect of aerobic conditioning on blood pressure. In four patients, the decrease in mean blood pressure was less than 5 mm Hg; in all others, there was a significant decline in arterial blood pressure. In 58 patients who were not taking drug medication in the pre-exercise period, mean blood pressure decreased by 15 mm Hg. Of 47 patients receiving drug therapy during the pre-exercise period, 24 were able to discontinue all medication. Mean blood pressure in this group fell from 116.9 +/- 6.5 mm Hg to 97.2 +/- 9.2 mm Hg as a result of exercise. In patients still taking antihypertensive drugs, mean pressure decreased from 120.9 +/- 28.8 mm Hg to 104.4 +/- 17.9 mm Hg after three months of exercise. It is concluded that in patients physically and emotionally able to exercise, a significant decline in blood pressure can be achieved.

Adult↗
PubMed1984

Effects of phosphate loading on 2,3-diphosphoglycerate and maximal oxygen uptake.

Increased concentration of red blood cell 2,3-diphosphoglycerate (RBC 2,3-DPG) shifts the hemoglobin-oxygen dissociation curve to the right, thus theoretically allowing better oxygenation of tissues. To determine whether such a shift is physiologically significant, we investigated the effects of oral phosphate loading on several parameters including plasma phosphate concentration, RBC 2,3-DPG, hematocrit and hemoglobin concentration, maximal oxygen uptake (VO2max), and degree of lactic acidemia in 10 well-trained distance runners. After control determinations were made, either a phosphate load or a placebo was given for 3 d before the athlete was restudied. A placebo and two phosphate-loading studies were performed at weekly intervals, followed by 2 wk of rest and another post-intervention control study. Blood samples for control values were drawn before and after a standard warm-up period, after treadmill exercise at a 10% grade, and at the completion of the VO2 determination. After oral phosphate loading there was a significant increase in serum phosphate and RBC 2,3-DPG. Maximal oxygen uptake was significantly increased and correlated with the rise in RBC 2,3-DPG (r = 0.81). The increase in blood lactate after exercise on the 10% grade was attenuated during sessions which followed phosphate loading.

2,3-Diphosphoglycerate↗
PubMed1983

Effectiveness of hemodialysis in chronic schizophrenic patients: a double-blind study.

Twenty-four chronic schizophrenic patients were treated with active or sham hemodialysis in a double-blind, randomized-group design. Treatment outcomes, as measured by the Schedule for Affective Disorders and Schizophrenia (version PD), are presented. Patients in both active and sham conditions responded to the dialysis process. The research design may have prevented the separation of these groups of responders. Further research is needed to evaluate the effectiveness of hemodialysis on a selected group of schizophrenic patients.

Adult↗