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Biomedical subjects

G Keusch

Publications and source records attributed to G Keusch.

At least 55 records · Page 3Linked to original sources

[Thrombocytosis following pancreas transplantation].

Thrombosis of the pancreas transplant is one of the main causes for the lower success rate of this procedure compared with that of other organ transplantations. Approximately one quarter of the pancreas transplantations discussed in this study are unsuccessful for this reason. This work is a retrospective study focusing on the postoperative blood platelet counts from 19 patients with a combined pancreas and kidney transplant, functioning well for at least 1.5 months. 19 patients with only a kidney transplantation with similar distribution of sex, age and postoperative immunosuppressive treatment were observed as a control group. After pancreas transplantation the platelet counts increased considerably and were found to be far above the normal level. There are no proven pathophysiological explanations for this thrombocytosis. Because of an increased risk of thrombosis, we recommend to use platelet inhibitors during the first two postoperative months.

Adult↗

[Frequent problems of non-steroidal antirheumatic agents in old age].

The relationship between nonsteroidal antiinflammatory drugs (NSAID) and peptic lesions in the upper gastrointestinal tract remains unclear in many respects. Nevertheless, there is increasing evidence that the risk in patients over 65 years of age and particularly in women is higher than in younger individuals. Data suggest that compounds with long elimination half life increase the risk further. In patients at risk it is therefore advisable to start treatment with the lowest potentially effective dosage and to avoid compounds with long half lives as first line treatment. NSAID are today the most frequent cause of drug induced renal damage. The renal function disturbances induced by NSAID are largely due to inhibition of renal prostaglandin synthesis. In patients with underlying risk factors NSAID can cause acute renal failure, salt and water retention and hyperkalemia. Because of a progressive decline in renal function and alterations in water and electrolyte homeostasis with aging, elderly patients taking NSAID are particularly at risk of developing renal disease.

Aged↗

[Kaposi's sarcoma following kidney transplantation: remission following reduction of immunosuppression and consequent HIV infection].

Kaposi's sarcoma (KS) in renal allograft recipients is a rare though serious complication of immunosuppressive treatment. Therapeutic procedures such as surgical excision and local irradiation are inappropriate, since the endothelial-originated tumor is often multicentric. However, systemic treatment such as chemotherapy entails further immunosuppression. We observed a patient with renal allograft who developed disseminated KS of legs and trunk while receiving azathioprine, cyclosporin and prednisone after intensive rejection therapy with high dose corticosteroids, antithymocyte globulin and transplant irradiation. At that time the immunological status was similar to that of an AIDS patient, though HIV serology was negative. Azathioprine was withdrawn while cyclosporin and prednisone were continued. KS disappeared shortly after without a decrease in allograft function, and immunological parameters tended to normalize. When KS had disappeared almost completely the patient became infected with HIV. Complete remission was not hampered, nor was there recurrence of KS. The late appearance of HIV-antigenemia with seroconversion in the course of the tumor makes HIV unlikely as a causative factor. The predisposing factors for KS after renal transplantation are discussed: 1. Amplification of immunosuppression due to rejection therapy, 2. Genetic predisposition such as HLA DR5 antigen, 3. Cytomegalovirus infections. For therapy of iatrogenic KS we propose reduction of immunosuppressive therapy before additional chemotherapy is initiated.

Acquired Immunodeficiency Syndrome↗

[Are cephalosporins more active than penicillin G in poisoning with the deadly Amanita?].

High dose penicillin-G has been found empirically to be effective against liver cell damage in amanita mushroom poisoning. We have recently found that betalactam antibiotics inhibit eukaryotic DNA polymerase-alpha, penicillins being more active than cephalosporins, and this may explain the antagonistic effect of penicillin-G against amanitin toxicity. Preliminary experiments in liver cell cultures and in mice are summarized, as well as first clinical experience pointing to the possibility that cephalosporins may be more effective against amanita mushroom toxicity than penicillin-G.

Animals↗

Synthetic peptides of Shiga toxin B subunit induce antibodies which neutralize its biological activity.

Shiga toxin B chain, the binding subunit of Shiga toxin, was recently purified; and the amino acid sequence of this 7,716-dalton polypeptide was determined (N.G. Seidah, A. Donohue-Rolfe, C. Lazure, F. Auclair, G. T. Keusch, and M. Chretien, J. Biol. Chem. 261:13928-13931, 1986). In the present study, synthetic peptides corresponding to three overlapping sequences from the N-terminal region of this subunit were prepared. The peptides synthesized consisted of residues 5 to 18, 13 to 26, and 7 to 26. This region coincides with the major peak of hydrophilicity and surface area residues predicted from a computer analysis. For the purpose of immunization, the peptides either were conjugated with a protein or synthetic carrier or were polymerized with glutaraldehyde. Antisera against these peptide derivatives raised in rabbits reacted not only with the respective homologous peptide but also to a comparable extent with the intact Shiga toxin. The anti-peptide antisera effectively neutralized the various biological activities of the Shiga toxin, namely, cytotoxicity to HeLa cells, enterotoxic activity (the fluid secretion into ligated ileal loops in rats), and neurotoxicity in mice. Furthermore, active immunization with the peptide conjugates was found to protect mice against the lethal effect of Shiga toxin.

Amino Acid Sequence↗

[Essential cryoglobulinemia with glomerulonephritis as a variant of the purpura-arthralgia-nephritis syndrome].

The syndrome of mixed cryoglobulinemia is clinically characterized by the findings of purpura, arthralgia and glomerulonephritis, the latter developing in up to 50% of the cases. The cryoglobulins have rheumatoid factor activity and serum levels of complement factor C4 are significantly reduced. A report is presented on seven patients with a typical purpura-arthralgia-nephritis syndrome and two patients with essential cryoglobulinemia, rheumatoid factor activity and glomerulonephritis without extrarenal manifestations of vasculitis. Based on these observations, measurement of rheumatoid factor activity is recommended in serum of patients with unclassified glomerulonephritis.

Complement C3↗

Catheter-related complications during continuous ambulatory peritoneal dialysis (CAPD): a retrospective study on sixty-two double-cuff Tenckhoff catheters.

From May 1980 to April 1985, a total of 62 double-cuff Tenckhoff catheters were surgically implanted in 54 patients through a low medial laparotomy. The follow-up on continuous ambulatory peritoneal dialysis accounted for 1,029 patient-monthly. The patients who used a detachable double-bag system developed a total of four exit-site infections, one tunnel infection, three outer cuff erosions, four catheter dislocations, and two dialysate leaks. In five patients, the catheter had to be removed (one exit-site infection, two catheter breaks, and two catheter dislocations). Cumulative catheter survival using the method of life-time analysis was 81% and 70% after 1 and 2 years, respectively, considering all catheters implanted, and 92% and 92%, respectively, when peritonitis-related removal was excluded.

Catheterization↗

[Microangiopathic hemolytic anemias. Clinical pattern, therapy and clinical course in 14 patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome].

Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) have in common a microangiopathic hemolytic anemia involving disseminated platelet aggregation and endothelial damage of the microvasculature mainly of the brain (TTP) and kidney (HUS). The underlying pathomechanism still remains unclear. The disease takes an acute, dramatic and frequently fatal course. Unfortunately a broadly approved therapeutic regimen is still lacking since the rarity of TTP and HUS makes study of a large group of patients impossible. We have observed and treated 14 patients with TTP and HUS during a period of 9 years. Most of the cases have been triggered by infectious diseases and pregnancy. Diagnostic cornerstones were hemolytic anemia, schistocytes on peripheral blood smears and consumption thrombocytopenia. Renal and cerebral symptoms were observed regularly, whereas lesions of the pancreas, liver and heart were much less frequent. The treatment included plasma transfusion (47%), plasma exchange (42%), high dose corticosteroids (74%), antiplatelet agents (53%), vitamin E (32%) and vincristin (11%). The outcome of 19 episodes of TTP or HUS was as follows: in 78% complete recovery, in 11% persistence of impaired renal function, and in 11% death. From analysis of our cases it is concluded that plasma transfusions and high dose corticosteroids improve the prognosis of TTP and HUS significantly.

Adolescent↗

[Severe electrolyte disorders during the therapy of heart failure with the therapy of heart failure with the ACE-inhibitor enalapril].

Angiotensin I converting enzyme inhibition by captopril and enalapril may influence sodium and potassium homeostasis. In patients without cardiac failure and with normal renal function significant electrolyte disturbances rarely occur. We report on four patients who developed life-threatening electrolyte disturbances following treatment with enalapril for severe cardiac failure (NYHA-class II-IV). There were important concomitant factors in all four cases: in one case under additional medication with a thiazide diuretic and a nonsteroidal antiinflammatory, hyponatremia of 107 mmol/l occurred. In two further cases severe hyperkalemia of 7.4 and 7.3 mmol/l was observed in the presence of acute renal failure due to enalapril-induced hypotension and concomitant therapy with a nonsteroidal antiinflammatory drug respectively. In a fourth case the combination of enalapril with a potassium-sparing diuretic provoked severe hyperkalemia of 7.9 mmol/l.

Acute Disease↗

[Management of cardiac tamponade in uremic pericarditis].

Pericarditis with tamponade is known to occur in patients with chronic renal failure. It is an acute life-threatening emergency which requires immediate intervention. 6 patients with cardiac tamponade complicating uremic pericarditis who were treated at our institution from 1975 to 1984 are described. The diagnosis of pericardial tamponade was made by 2 D-echocardiography in the presence of jugular vein distension and pulsus paradoxus. Drainage by a percutaneously inserted pigtail catheter after subxiphoidal puncture was performed. Initial drainage of 707 (200-1660) ml fluid resulted in rapid improvement of the hemodynamic findings: the systolic blood pressure increased from 118 +/- 18 (SD) mm Hg to 157 +/- 16 mm Hg, the pulse pressure from 45 +/- 9 mm Hg to 79 +/- 11 mm Hg and the central venous pressure decreased from 21 +/- 6 cm H2O to 14 +/- 4. The catheters were left in place for a mean 61 (23-90) hours until no further fluid accumulated. As supportive measures, non-absorbable steroids were instilled via the percardial catheters and dialysis treatment was intensified. No complications were observed and no recurrence of effusion or development of constriction was noted for 9 to 35 months. In conclusion, subxiphoidal pericardiostomy with prolonged drainage and local steroid instillation has been found to be an effective and safe method which provides immediate and lasting relief.

Cardiac Catheterization↗

[Metastatic pulmonary calcification in patients with chronic renal insufficiency].

Case reports on two patients with metastatic pulmonary calcification are presented. Both suffered from long standing chronic renal failure and received immunosuppressive therapy for a (non-functioning) renal transplant. Laboratory tests disclosed hyperphosphatemia and secondary hyperparathyroidism. In the first patient, who presented with "pulmonary edema", the course was rapidly fatal. Diffuse pulmonary calcification was diagnosed only post mortem. Transbronchial biopsy was diagnostic for calcification in the second patient, who had exertional dyspnea and bilateral, asymmetric, interstitial infiltrations on chest X-ray. In patients with chronic renal failure, metastatic calcifications are due not only to disturbances of calcium-phosphate homeostasis but also to other, mostly unknown factors. Diagnostic procedures include biopsy and 99m-technetium-diphosphonate scintigraphy. Prophylaxis of pulmonary calcifications through normalization of serum phosphate and, if indicated, subtotal parathyroidectomy is of the utmost importance as regression of established calcifications rarely occurs.

Calcinosis↗

[Continuous arteriovenous hemofiltration for the treatment of acute kidney failure].

Continuous arterio-venous haemofiltration (CAVH), a simple technique not employing pumps, was used for treatment of acute renal failure in 25 intensive care patients (mean age 52 +/- 16 [SD] years). Acute renal failure was due to trauma in 9 patients, occurred after surgery in 7 patients and was related to septicaemia in 5 patients, peritonitis in 2 patients and pancreatitis in one patient; in one patient acute renal failure developed during pregnancy after preexisting renal disease. Seventeen patients were oliguric and 8 patients were non-oliguric, with a mean daily urine output of 507 +/- 407 ml. At the start of CAVH the serum creatinine level was 511 +/- 198 mumol/l. The duration of treatment with CAVH was 1 to 36 days (average 9.3 days). Access to the circulation was by cannulation of the femoral artery and vein in 23 patients and by Scribner shunt in 2 patients. After an initial systemic dose of 2000 IU heparin, a continuous infusion of 250-1000 IU/hr into the arterial blood line was administered, adjusted to a partial thrombin time of 58 +/- 28 sec. With this heparin regimen a single haemofilter could be used for an average time of 2.6 +/- 1.2 days. The mean spontaneous filtration rate was 6 +/- 2 ml/min, resulting in the following serum levels: creatinine 490 +/- 187 mumol/l; urea 39 +/- 12.5 mmol/l; potassium 4.5 +/- 0.5 mmol/l. Nine catheter-associated complications occurred in 5 patients. The most important aspect of CAVH was its simplicity, optimal control of fluid balance and the possibility of unlimited parenteral nutrition. Uremia was adequately and continuously controlled. Prognosis of ARF was related to the patients' underlying illness.

Acute Kidney Injury↗

Antegrade pyelography, percutaneous nephrostomy and ureteral perfusion (Whitaker test) for the renal transplant recipient.

Ureteral obstruction is a serious complication in renal transplant recipients. The diagnosis may be difficult with standard methods of investigation, and definite treatment may, therefore, be delayed. This paper describes the indications, the technique, and the experience with antegrade pyelography, ureteral perfusion and percutaneous drainage in 18 patients with suspected urinary obstruction. Though invasive, these methods proved to be a safe, fast and accurate means for evaluating the location and significance of ureteral obstruction. For initial treatment in obstruction, percutaneous nephrostomy is the method of choice. Surgery should be delayed until recovery of renal function with decreasing serum creatinine is demonstrated. Patients with persistent or rising serum creatinine (greater than 250 mumol./l.) did not benefit from surgical relief of obstruction.

Adolescent↗

[Ergometrically determined work capacity in chronic hemodialysis treatment].

To evaluate the degree of physical activity in hemodialysis patients, working capacity was assessed by bicycle ergometry in 16 hemodialysis patients (mean age 47 +/- 12 [SD] years). The mean length of dialysis treatment was 21 +/- 17 months. The laboratory and clinical findings were as follows (mean values +/- SD): urea 34 +/- 6 mmol/l; creatinine 1127 +/- 169 mumol/l; potassium 5.7 +/- 0.63 mmol/l; calcium 2.25 +/- 0.22 mmol/l; phosphate 1.76 +/- 0.54 mmol/l; hemoglobin 8.54 +/- 1.02 g/dl; hematocrit 26.1 +/- 2.9%; blood pressure 140 +/- 18/86 +/- 9 mm Hg; nerve conduction velocity 39.5 +/- 6.5 m/sec. Mean working capacity was 58 +/- 31 W (41 +/- 24% of normal values) and the specific working capacity (watts/kg body weight) was 0.79 +/- 0.54. The duration of exercise testing was 4.9 +/- 2 min. The ergometry had to be discontinued because of the following reasons: leg fatigue (10 patients); general fatigue (3); dyspnea (1); attainment of maximal heart rate (2). The maximal blood pressure during exercise testing was 149 +/- 21/86 +/- 14 mm Hg and the maximal increase in heart rate 117 +/- 34 beats/min. In patients treated with a beta-blocker agent for hypertension, maximal increase in blood pressure was comparable to normotensive patients. There was a negative correlation between working capacity and the age of the patients (r = 0.77; p less than 0.01). A positive correlation was found between working capacity and the serum creatinine level (r = 0.52; p less than 0.05).

Age Factors↗