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Biomedical subjects

A Hertig

Publications and source records attributed to A Hertig.

12 recordsLinked to original sources
PubMed2001

Prognostic value of plasminogen activator inhibitor type 1 mRNA in microdissected glomeruli from transplanted kidneys.

BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) exerts antifibrinolytic and profibrotic activities. Inside the glomerulus, PAI-1 is mainly synthesized by mesangial cells. We hypothesized that thrombin, via its receptor protease activated receptor type 1 (PAR-1), present on the membrane of glomerular cells, is an important mediator of PAI-1 synthesis. METHODS: Using the technique of Peten et al., we microdissected the glomeruli of 23 kidney transplanted patients admitted in our department from 1993 to 1997, and we followed-up these patients for up to 5 years, with sometimes iterative renal biopsies. With this technique, we also microdissected the glomeruli of three patients who have had a nephrectomy for cancer (control patients). We investigated mRNA expression of the PAI-1, the thrombin receptor PAR-1, the alpha2 chain of type IV (alpha2 IV) collagen, and of a housekeeping gene (cyclophilin) by reverse transcription-polymerase chain reaction. The results were correlated with the renal function and the histological findings classified into acute rejection (9 biopsies), chronic rejection (22 biopsies), or normal (8 biopsies). RESULTS: A significant up-regulation of PAI-1 and alpha2 IV collagen mRNA was observed in acute rejection (P<0.05) when compared to normal kidneys. A positive correlation exists between alpha2 IV collagen mRNA level and the degree of cellular infiltration. A negative correlation was found between the level of mRNA of PAR-1 and the degree of vascular thrombosis (P=0.005) and glomerulosclerosis (P=0.04). A positive correlation was found between the degradation of renal function and the mRNA level of PAI-1 at the time of the renal biopsy (P<0.05). CONCLUSIONS: These results suggest that glomerular PAI-1 mRNA may be predictive of the long-term renal graft function.

Adolescent↗
PubMed2001

[Plasminogen activator inhibitor type 1: physiology and role in renal physiopathology].

Plasminogen activator inhibitor type 1 plays a prominent part in the regulation of extra and intra-vascular fibrinolysis through the inhibition of plasmin formation. In addition to its role in the resolution of blood clots, PAI-1 is involved in a variety of other biological processes including extracellular remodeling, cellular mobility, embryo implantation, development and tumoral proliferation. Moreover, PAI-1 is also implicated in various pathological processes such as thromboembolic diseases, atherosclerosis and fibrosis formation, particularly in the kidney and the lung. Inhibition of PAI-1 activity or of PAI-1 synthesis by specific antibodies, peptidic antagonists, antisens oligonucleotides or decoy oligonucleotides has been obtained in vitro but need to be evaluated in vivo. All these findings may have new therapeutical implications, explaining the importance of studies on PAI-1 production and regulation.

Aldosterone↗
PubMed2000

[Familial benign hypercalcemia revealed by renal colic].

BACKGROUND: Diagnosis of familial benign hypercalcemia can be challenged by the association with a urinary lithiasis, which, in the presence of hypercalcemia, will most frequently lead to affirm primary hyperparathyroidism. CASE REPORTS: We report the case of a 23 year-old patient who presented with a left ureteral stone composed of calcium oxalate. His serum total calcium value was 2.92 mmol/l. Serum PTH value was inappropriately in the normal range (32 ng/l, normal values 10 to 58 ng/l). Hypercalcemia persisted despite a subtotal parathyroidectomy and new investigation biochemical revealed familial benign hypercalcemia. CONCLUSION: This diagnosis is usually made fortuitously, since most patients have few, if any, symptoms. A past familial history of hypercalcemia and several biochemical features (such as a reduced fractional excretion of calcium, mild hypermagnesemia, and a normal serum inorganic phosphorus level) are helpful dues to the diagnosis of familial benign hypercalcemia. In some cases, however, searching for an inactivating mutation of the extracellular calcium-sensing receptor gene is necessary to distinguish this autosomal dominant disease from primary hyperparathyroidism.

Adult↗
PubMed2000

Acute renal failure in patients over 80 years old: 25-years' experience.

OBJECTIVE: To determine the epidemiological trends, spectrum of etiologies, morbidity and mortality of acute renal failure (ARF) in patients over 80 years old. DESIGN: Historical cohort analysis. SETTING: Intensive care unit (ICU) of nephrology, Tenon Hospital, Paris. PATIENTS AND PARTICIPANTS: The criteria of inclusion was ARF, defined on the basis of a creatinine value over 120 mumol/l, in patients over 80 years of age admitted between October 1971 and September 1996. When moderate chronic nephropathy was pre-existing, ARF was defined by the increase of at least 50% over the basal creatininemia. MEASUREMENTS AND RESULTS: Three hundred and eighty-one patients over 80 years of age were included. The etiology and mechanism of ARF are detailed. 29% of the patients received dialysis. Global mortality at the hospital was 40%. Factors significantly associated with a poor prognosis are identified. Mean survival after hospitalization was 19 months. CONCLUSION: The frequency of admission to ICUs for ARF in patients older than 80 years seems to be on the increase. Mortality is less severe than expected. These patients could benefit from the renal replacement therapy of modern intensive care medicine.

Acute Kidney Injury↗
PubMed2000

Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis.

Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis. The progression of renal lesions to fibrosis involves several mechanisms, among which the inhibition of extracellular matrix (ECM) degradation appears to play an important role. Two interrelated proteolytic systems are involved in matrix degradation: the plasminogen activation system and the matrix metalloproteinase system. The plasminogen activator inhibitor type 1 (PAI-1), as the main inhibitor of plasminogen activation, regulates fibrinolysis and the plasmin-mediated matrix metalloproteinase activation. PAI-1 is also a component of the ECM, where it binds to vitronectin. PAI-1 is not expressed in the normal human kidney but is strongly induced in various forms of kidney diseases, leading to renal fibrosis and terminal renal failure. Thrombin, angiotensin II, and transforming growth factor-beta are potent in vitro and in vivo agonists in increasing PAI-1 synthesis. Several experimental and clinical studies support a role for PAI-1 in the renal fibrogenic process occurring in chronic glomerulonephritis, diabetic nephropathy, focal segmental glomerulosclerosis, and other fibrotic renal diseases. Experimental models of renal diseases in PAI-1-deficient animals are in progress, and preliminary results indicate a role for PAI-1 in renal fibrogenesis. Inhibition of PAI-1 activity or of PAI-1 synthesis by specific antibodies, peptidic antagonists, antisense oligonucleotides, or decoy oligonucleotides has been obtained in vitro, but needs to be evaluated in vivo for the prevention or the treatment of renal fibrosis.

Animals↗
PubMed2000

[Primary hyperparathyroidism].

Primary hyperparathyroidism is the third most frequent endocrine disorder. The condition required for diagnosis is inappropriately elevated secretion of parathyroid hormone (PTH) with respect to calcemia. Most often, the disease is due to a parathyroid adenoma, i.e. a monoclonal benign parathyroid tumor, less often to a parathyroid hyperplasia. The main tumorogenic mechanisms currently proposed are a DNA rearrangement in the PTH locus (transposition of the PTH promoter upstream to Cyclin D1/PRAD 1 gene) and a mutation of the gene responsible for multiple endocrine neoplasia type I. The clinical presentation has strikingly evolved towards a milder, asymptomatic form, frequently diagnosed on systematic screenings. Though the mechanism of hypercalcemia is better understood, several hypothesis are still being considered about the regulation of tumoral PTH secretion: the role of the expression of calcium-receptor in parathyroid gland cells, vitamin D receptor and estrogen receptor polymorphisms, etc. Surgery is still advised for symptomatic forms of the disease, either because of a bone involvement, or because of an evolutive nephrolithiasis. In the near future, the new calcium-receptor agonists could be a relevant therapeutic approach.

Humans↗
PubMed1997

[Extrapulmonary and disseminated pneumocystosis in AIDS. A review of the literature].

We present a literature review about extrapulmonary and disseminated pneumocystosis in AIDS. The prevalence of such infections seems low but is probably under-estimated. Disseminated pneumocystosis occurs in patients with profound immunosuppression, who do not receive prophylaxis against Pneumocystis carinii pneumonia or are treated with aerolized pentamidine. The lack of specificity of symptoms may delay the diagnosis. Most organs may be involved. Three different presentations may be individualized: disseminated pneumocystosis, intra-thoracic only disseminated pneumocystosis, in an intra-thoracic localization alone, and localized extrapulmonary pneumocystosis. The mortality from disseminated disease is high, especially in the presence of low serum albumin level.

AIDS-Related Opportunistic Infections↗
PubMed1994

[Quality assurance in nursing: nursing standard. Nausea, gagging and vomiting during emetogenic cytostatic therapies. Report of research into the development and introduction of nursing standards].

This report documents the introduction of standard-setting in the haemato-oncological reverse-isolation unit of the Kanton hospital, Basle. The topic is the prevention or reduction of nausea, choking and vomiting, and the treatment of patients who are receiving prolonged chemotherapy. The objective was quality assurance in nursing care. The definition of the desired outcome was the well-being and safety of patients. In addition the wish of the staff to increase their security in dealing with antiemetics was taken into consideration. The authors describe the basic problems they encountered in their strategies and actions for standard setting. By extensive use of measurement and evaluation it was possible, in cooperation with medical leadership, to develop instructional leaflets and checklists. Approximation to the intended outcome was achieved. The well being of patients and satisfaction of the safety-needs of staff and patients reached a high level. The report shows that the introduction of nursing standards requires great effort and a high level of commitment of the entire team. It also shows that the effort is worthwhile for patients and staff.

Antineoplastic Agents↗