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C Jacobs

Publications and source records attributed to C Jacobs.

At least 109 records · Page 6Linked to original sources
PubMed1996

Chronic effects of endothelin-3 on blood pressure and renal haemodynamics in rats.

BACKGROUND: Renal vasoconstriction and systemic hypertension are well-known effects of bolus or short-term endothelin administration. However, the role of endothelin as a circulating hormone remains largely unknown. METHODS: The present study explores the effects of endothelin-3 (ET-3) on renal haemodynamics and systemic blood pressure during a 3-h and a 3-day intravenous infusion in rats. Male Sprague-Dawley (SD) rats were infused with vehicle (group 1) or ET-3 (group 2), 10 ng/kg per min; group 3, 50 ng/kg per min) delivered via osmotic minipumps into the right jugular vein for 3 days. On day 3 after pump implantation, rats were anaesthetized with Inactin and surgically prepared for assessment of mean arterial blood pressure (MABP), renal plasma flow (RPF), glomerular filtration rate (GFR), and renal vascular resistance (RVR). The same parameters were assessed during a 3-h ET-3 infusion study in SD rats (group 4, vehicle; group 5, ET-3, 10 ng/kg per min; group 6, ET-3, 50 ng/kg per min). RESULTS: In 3-day infused rats, ET-3 induced a significant decrease in RPF (-22+/-7% and -26+/-8% for group 2 and group 3 respectively, P<0.05 vs group 1) and an increase in RVR (+40+/-11% for groups 2 and 3; P<0.05 vs group 1); 50 ng/kg per min ET-3 significantly decreased GFR (-17%, P<0.05 vs group 1). MABP was not significantly affected by endothelin infusion. In acute infusion studies a decrease of the same magnitude was seen for the renal haemodynamics values. 50 ng/kg per min ET-3 increased MABP; a systemic effect that disappeared after the 3-day infusion. CONCLUSIONS: This study suggests that intravenously administered ET-3 in the rat has only a transient effect on systemic blood pressure, whereas it induces alterations in renal haemodynamics after both acute and chronic perfusions.

Animals↗
PubMed1996

cis Elements and trans factors are both important in strain-specific regulation of the leukotoxin gene in Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans, the etiologic agent of localized juvenile periodontitis, produces a potent leukotoxin that kills human neutrophils. The production of leukotoxin RNA can vary more than 50-fold among isolates of A. actinomycetemcomitans, and strains expressing high levels of leukotoxin RNA are most often found at sites of periodontal disease. To assess the relative contributions of transcription factors and promoter sequences in setting the disparate levels of leukotoxin RNA found, we have undertaken classical cis/trans analyses. First, the leukotoxin promoter regions from moderately leukotoxic (Y4) and minimally leukotoxic (ATCC 33384) strains of A. actinomycetemcomitans were cloned, sequenced, and compared with the previously sequences leukotoxin promoter region of the high-producer strain JP2. The Y4 and ATCC 33384 promoter regions each contain a 528-bp segment that is absent from JP2. Interestingly, the analysis of various deletion constructs in A. actinomycetemcomitans indicated that Y4, despite the large insertion, initiates leukotoxin RNA synthesis at the same promoter as JP2 does. To perform cis/trans analyses, these three leukotoxin promoter regions were cloned into a plasmid upstream of the reporter gene beta-galactosidase. Each plasmid was transformed into JP2, Y4, and ATCC 33384, and the beta-galactosidase levels were determined. The results indicated that the sequences responsible for down-regulating leukotoxin RNA levels in Y4 relative to JP2 are found within the transcribed region of the Y4 leukotoxin operon. Importantly, in ATCC 33384, strain-specific trans factors and promoter sequence differences are equally significant in determining the lower levels of leukotoxin RNA. We hypothesize that either strain ATCC 33384 has a negative regulatory protein (which is missing or mutated in JP2/Y4) or that JP2 and Y4 carry an activator that is missing or mutated in ATCC 33384.

Aggregatibacter actinomycetemcomitans↗
PubMed1996

Clinical and magnetic resonance imaging features of L-2-hydroxyglutaric acidemia: report of three cases in comparison with Canavan disease.

We report three cases of L-2-hydroxyglutaric acidemia and three cases of Canavan disease. The L-2-hydroxyglutaric acidemia cases are the first biochemically proven Turkish cases. Magnetic resonance imaging findings in the cases and similarities between the two diseases are emphasized. Both diseases are characterized by predominant subcortical white-matter involvement and dentate nuclei lesions with variable basal ganglia involvement. Canavan disease differs from L-2-hydroxyglutaric acidemia by the presence of typical brainstem involvement.

Canavan Disease↗
PubMed1996

Transplantation of CD34+ hematopoietic progenitor cells.

We have developed an avidin-biotin immunoadsorption technique in conjunction with a monoclonal anti-CD34 antibody that is capable of selecting CD34+ progenitor cells from marrow and mobilized peripheral blood. Clinical studies with these CD34+ selected cells have shown that the cells are capable of rapid and durable engraftment. In addition, there is significantly less infusional toxicity to the patient because the volume in which the CD34+ selected cells are contained is much less than that of a typical marrow or apheresis buffy coat. Selection of CD34+ progenitor cells also offers other potential advantages, including T-cell depletion of allografts and tumor cell depletion of autografts. CD34+ selection can also be used to facilitate other manipulations of marrow and peripheral blood, including gene transfection, ex vivo stem cell expansion, tumor purging, and progenitor cell banking. Future graft engineering studies are expected to clarify these relationships and enable refinement of the graft to the point at which GVHD can be minimized, graft survival maximized, and relapse-free survival prolonged.

Antigens, CD34↗
PubMed1996

Prevention of cyclosporin nephrotoxicity with a platelet-activating factor (PAF) antagonist.

BACKGROUND: Cyclosporin (CsA) is a potent immunosuppressive drug whose main side-effect is nephrotoxicity. In the kidney, CsA induces vasoconstriction with a decrease in renal blood flow (RBF) and glomerular filtration rate (GFR) and a significant increase in renal vascular resistance (RVR). CsA enhances platelet-activating factor (PAF) synthesis in mesangial cells in vitro. PAF, a secondary mediator of anaphylaxis and inflammation, exhibits vasoactive properties in the kidney similar to those of CsA. METHODS: The in situ autoperfused rat kidney model was used to investigate whether PAF plays a role in the haemodynamic injury induced by CsA. RESULTS: In this model, CsA (40 mg/kg and 20 mg/kg i.v.) induced a significant decrease in RBF and in GFR and an increase in RVR. BN 52021, a potent and specific PAF antagonist (20 mg/kg i.v. bolus dose) induced a significant increase in GFR (137 +/- 32% of initial value, P < 0.05). BN 52021 (20 and 10 mg/kg) also significantly prevented the decline in RBF and GFR induced by CsA. CONCLUSIONS: We have demonstrated that the PAF antagonist BN 52021 can minimize the alteration of renal function induced by CsA.

Animals↗
PubMed1996

[Treatment of cardiac failure with angiotensin-converting enzyme inhibitors and diuretics].

Congestive cardiac failure is characterised by redistribution of blood flow to the brain and the heart at the expense of the kidneys. The prognosis of this condition at its most advanced stage (stage IV) is poor with a mortality of about 50% at 5 years. The reduction of renal perfusion will lead to stimulation of all vasoconstrictor and anti-natiuretic mechanisms, and to a parallel activation of vasodilator and natiuretic systems. There is, therefore, a clear conflict of interest between the heart, which attempts to preserve its perfusion and function, and the kidneys which aggravate the haemodynamic disturbances by salt and water overload and the risk of arrhythmias due to hypokalaemia and hypomagnesaemia. The diuretics and ACE inhibitors are essential therapeutic classes for the treatment of congestive cardiac failure. The prevention of the secondary effects of diuretics and ACE inhibitors on renal function, serum sodium, potassium and magnesium concentrations, is based on an initial low dose prescription, the detection and correction of risk factors and strict clinical and biological surveillance. In order to avoid the risks of hyperkalaemia during the association of ACE inhibitor and diuretic therapy with a potassium sparing agent, the initial dose of these two drugs should be as low as possible.

Aged↗
PubMed1996

Age and gender-related incidence of chronic renal failure in a French urban area: a prospective epidemiologic study.

OBJECTIVE: To determine the age- and gender-related incidence of chronic renal failure in a French urban area. METHODS: Prospective study of adult patients newly identified as having established, chronic renal failure defined by serum creatinine (Scr) > or = 200 mumol/l, with the cooperation of all nephrology and dialysis units in the Ile de France district (10,660,000 inhabitants) during a 1-year period. RESULTS: 2775 patients (1780 males, 995 females) were referred with Scr > or = 200 mumol/l between July 1991 and June 1992, an overall incidence of 260/million population. 847 had advanced renal failure (Scr > or = 500 mumol/l) and 541 patients (19.5%) were > or = 75 years of age. The age-related incidence was 92, 264, 523 and 619/million population in the age groups 20-39, 40-59, 60-74 and > or = 75 years old, respectively. The annual incidence was twice as high in males than in females up to 75 years and three times as high in patients > or = 75 years (1124 vs 356/million population). Based on the proportion of patients reaching end-stage renal failure within one year of referral, the minimal estimation of the need for supportive therapy is 81/million/year. CONCLUSIONS: This epidemiological study in a large French urban area indicates an incidence of 260 patients per million population annually referred to nephrology units for chronic renal failure defined by Scr > or = 200 mumol/l, with a marked preponderance of males and a dramatic increase of incidence with age in both genders.

Adult↗
PubMed1996

[Demography and effects of chronic renal insufficiency in Ile-de-France].

In order to assess the incidence of chronic renal failure (CRF) and the demographic characteristics of affected patients, a prospective, multicenter epidemiologic study was conducted with the cooperation of all nephrology and dialysis units in the Ile-de-France district, the total population of which is 10660000 inhabitants (source: national census, march 1990). Included were patients with a plasma creatinine (Pcr) concentration > or = 200 mumol/l referred during the one-year period from July 1, 1991 until June 30, 1992. The overall response rate was 98.5%. A total of 2775 adult patients were recorded, including 1780 males (64%) with a mean (+/- SD) age of 58.1 +/- 16.3 years and a mean Pcr of 447 +/- 214 mumol/l, and 995 females (36%) with a mean age of 59.2 +/- 16.4 years and a mean Pcr of 425 +/- 185 mumol/l. Age of patients was < 40 in 16%, 40-59 in 31%, 60-74 in 34% and > or = 75 years in 19%. Pcr was 200-399 mumol/l in 54%, 400-599 mumol/l in 25%, 600-799 mumol/l in 12% and > or = 800 mumol/l in 9%. The overall incidence of CRF was 260/million population/year, twice higher in males than in females (348 vs 179/10(6)/year, p < 0.001). Incidence of CRF dramatically rose with age in both genders, with figures as high as 1124 and 356/10(6)/year respectively in male and female patients aged > or = 75 years, vs 288 and 151/10(6)/year in patients aged < 40 years. A sequential evaluation was performed in a representative sample of 251 patients with initial Pcr > or = 300 mumol/l. End-stage renal failure (ESRF) was reached within one year in 99% of patients with PCr > 600, 49% with Pcr 500-599, 24% with PCr 400-499 and 11% with PCr 300-399 mumol/l. Based on these figures, the predicted incidence of ESRF within one year of referral was 864 out of the 2775 patients, an estimated annual incidence of 81 patients per million population. In conclusion, this prospective study affords the first direct information on the incidence of chronic renal failure and the demographic characteristics of patients with CRF in the Ile-de-France district. Due to the design of the study conducted only in nephrology units, the estimated figure of 81 new patients per million population per year reaching ESRF is a minimal evaluation. In view of the relentless aging of population in France, an incidence of at least 100 ESRF patients per million population per year is to be expected in the next future.

Adult↗
PubMed1995

[Terminal chronic kidney failure: treatment by dialysis. Confirmations and controversies after 35 years of experience].

There are currently more than 500,000 people on long-term renal dialysis throughout the world, some have been treated for more than 20 years. Despite this major success in the treatment of chronic renal failure, many unsolved problems remain, often leading to controversial debate. Should dialysis be "adequate" or "optimal"? To answer this question results are evaluated on the basis of mid-term and long-term survival rates, morbidity and quality of life criteria including psychological tolerance. While the need for a reliable vascular access and an appropriate dialysis system is obvious for haemodialysis, debate has focused on the optimal dialysis time; total weekly duration under 10-11 hours is sometimes advocated. Nephrologists have emphasized that peritoneal dialysis frees patients from the risk of vascular puncture and the need for anticoagulation while providing better haemodynamic stability. The higher morbidity and risk of infectious complications are however major drawbacks of peritoneal dialysis. Both techniques may require use of recombinant human erythropoietin and daily protein intake of about 1.2 g/kg body weight is mandatory. Despite all the progress made in dialysis concepts and technical applications, several factors may lead to "inadequate" dialysis in some patients. Some, such as insufficient blood flow, are subject to corrective measures, others are cost-related. What is the optimal duration of a dialysis session? How often should dialysers be reused? Are bio-compatible membranes or systems for producing sterile haemodialysis fluid cost-effective? Finally, our understanding of the uraemic toxicity syndrome is still insufficient for a totally satisfactory treatment of renal failure. Further advances in technology and in our understanding of the pathophysiology of renal function and dialysis are needed to reduce morbidity of patients treated for end-stage chronic renal failure and improve their quality of life.

Humans↗
PubMed1995

Renal replacement therapy for end-stage renal failure in France: current status and evolutive trends over the last decade.

Between 1982 and 1992, the number of new patients taken yearly onto renal replacement therapy (RRT) increased from 42 to 62 per million population. By December 1992, approximately 22,800 patients (401 per million population) were alive under some mode of RRT. The number of patients aged 15 to 34 years starting RRT slumped from 20% to 11%, whereas that of patients aged > or = 75 years tripled (5% to 15%). The proportion of patients with primary glomerulopathy decreased (25% to 19%) whereas that of patients with vascular diseases or diabetic nephropathy increased notably (14% to 21% and 7% to 13%, respectively). An ever increasing proportion of patients were treated with in-center or limited-care hemodialysis, whereas home hemodialysis steadily declined and continuous ambulatory peritoneal dialysis (CAPD) was applied to 7% of patients in 1991. The average number of weekly hemodialysis hours tended to decrease, particularly for patients aged > or = 75 years. At best, in 1991, approximately 2,000 renal transplants (36 per million population) were performed yearly, but unfortunately, this figure is steadily declining. Five- and 10-year overall survival rates were similar in young patients who were treated with center or home hemodialysis and those who underwent transplantation. Overall survival is rather poor in diabetic patients, 38% and 17% at 5 and 10 years, respectively, but best in those with a functioning first kidney transplant (69% at 10 years). Cardiac causes accounted for one third of all deaths in hemodialysis patients, vascular causes for 15% to 18%, and infectious causes for 10%. Deaths of cardiac or infectious origin were highest in diabetic patients when compared with those recorded in patients with standard (nonsystemic) and vascular renal diseases.

Adolescent↗
PubMed1995

Effects on renal haemodynamics and tubular function of the contrast medium Ioxaglate in renal transplant patients.

The aim of this study was to evaluate the effects of Ioxaglate on renal haemodynamics and tubular function in renal transplant patients at increased risk of nephrotoxicity. 21 patients undergoing either intravenous pyelography or arteriography with Ioxaglate were studied. Renal clearance studies were carried out 1 day before and 1 day after administration of Ioxaglate (173 +/- 37 ml) injected into each patient. None experienced any adverse reaction. Mean serum creatinine, glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and urinary NAG excretion were unaltered by ioxaglate. No patient suffered a nephrotoxic reaction or acute oliguria that required dialysis as a result of the administration of contrast material. In the subset of seven patients receiving cyclosporine the same results were observed. In the subset of 10 patients with a GFR lower than 60 ml/min before injection of Ioxaglate were also observed no significant change in mean GFR, ERPF and urinary NAG excretion. Only two patients had a transient decrease of GFR of between 10 and 20%. The results of this study show that the ionic, low osmolar contrast medium ioxaglate may be used safely in patients with a renal transplant thus extending previous data obtained in patients with chronic renal failure.

Acetylglucosaminidase↗