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Biomedical subjects

G Grimm

Publications and source records attributed to G Grimm.

At least 73 records · Page 4Linked to original sources

Improvement of brain function in hemodialysis patients treated with erythropoietin.

To evaluate the effects of recombinant human erythropoietin (rHuEPO) on brain function, 15 chronic hemodialysis patients were studied by event-related P300, stimulus-related evoked potentials, and trailmaking before (hematocrit 22.7%) and after rHuEPO (hematocrit 30.6%). P300 peak latency elicited by a tone discrimination paradigm improved (391 before vs. 366 ms after; Cz = vertex; P less than 0.01) confirming beneficial effects on cerebral cognitive processing. P300 amplitude (13.6 vs. 15.8 microV; P = 0.06) and trailmaking tended to improve (55 vs. 43 s). P300 measures were influenced by low hemoglobin levels before rHuEPO (P less than 0.01), suggesting that severe anemia may contribute to uremic brain dysfunction. Furthermore, decrease of stimulus-related auditory brainstem I-V interpeak latency (4.28 before vs. 4.17 ms after; P less than 0.05) and increase of somatosensory N20/P25 amplitude (4.8 vs. 7.0 microV; P less than 0.05) pointed to improvement of sensory pathways by mechanisms unrelated to cognition. Brain dysfunction in chronic hemodialysis patients may, beside other factors, in part be caused by severe anemia and can be improved by rHuEPO treatment.

Anemia↗

Increased plasma histamine levels in uraemic pruritus.

1. We determined plasma levels of histamine in uraemic patients and examined their correlation with the presence of pruritus. 2. In 27 patients with chronic renal failure, plasma histamine levels were analysed by radioimmunoassay and were compared with those of 40 healthy adult subjects. The control population showed plasma histamine concentrations of 185 +/- 33 pg/ml, which were significantly lower than those of the patients with renal insufficiency. The highest levels (552 +/- 116 pg of histamine/ml) were found in 16 patients with chronic renal failure (mean serum creatinine 5.1 +/- 1.0 mg/dl) and severe itching. 3. Twelve patients with pronounced pruritus who were on maintenance haemodialysis (serum creatinine 9.2 +/- 1.2 mg/dl) had a mean plasma histamine concentration of 515 +/- 81 pg/ml. Fifteen patients on regular haemodialysis (serum creatinine 9.0 +/- 1.5 mg/dl) and who experienced itching had plasma histamine levels (322 +/- 40 pg/ml) which were significantly lower (P less than 0.01) than those of the patients with pruritus but which were elevated compared with those of the control population (P less than 0.01). 4. No correlation could be found between increased plasma histamine levels and the type of dialysis membrane used or the method of sterilization of the membrane. 5. Haemodialysis alone did not reduce plasma histamine concentrations, although high concentrations could be detected in the ultrafiltrate. In six patients a rapid decrease in plasma histamine concentration from 565 +/- 134 pg/ml to within the normal range could be detected after 60 min of combined haemodialysis and haemoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Energy metabolism in acute and chronic renal failure.

Energy metabolism was measured by indirect calorimetry in 86 patients with various forms of renal failure and in 24 control subjects. In patients with acute renal failure with sepsis, oxygen consumption, carbon dioxide production, and resting energy expenditure were increased (P less than 0.05). In other groups with renal failure (acute renal failure without sepsis, chronic renal failure with conservative treatment or hemodialysis, and severe untreated azotemia) these indices were not different from those of control subjects. Urea nitrogen appearance was decreased in patients with chronic renal failure undergoing conservative treatment, in those with severe untreated azotemia, and in hemodialysis patients (P less than 0.05). We conclude that renal failure has no influence on energy expenditure as long as septicemia is absent. Reduced urea nitrogen appearance rates in chronic renal failure are due to a reduced energy and protein intake. Wasting is a consequence of decreased food intake but not of hypermetabolism in chronic renal failure.

Acute Kidney Injury↗

Successful treatment of hemodialysis-related porphyria cutanea tarda with deferoxamine.

End-stage renal failure and long-term hemodialysis treatment promote the development of genetically conditioned porphyria cutanea tarda (PCT). The clinical manifestation is triggered off by unknown factors coexisting with renal insufficiency and hemodialysis. Iron overload is often associated with the disease and is thought to play a key role in its pathogenesis. Iron removal by deferoxamine infusions is regarded as the treatment of choice for patients who cannot undergo repeated phlebotomy procedures and has been successfully used in patients with normal renal function. We report a case of hemodialysis-related PCT and iron overload in whom repeated venesections were contraindicated on account of severe anemia and treatment with deferoxamine led to a striking improvement of symptoms.

Deferoxamine↗

Dopamine infusion in patients with hepatic encephalopathy: plasma levels and haemodynamic changes.

During a constant infusion of dopamine (DA 4.5 micrograms/kg/min), the plasma levels of DA reached at 30 min of infusion were 81 +/- 6.9 ng/ml and 71.6 +/- 14.8 ng/ml in patients with hepatic encephalopathy (HE) and control patients, respectively. In both groups of patients, the plasma levels of DA did not change between 30 and 60 min of continuous DA infusion. The DA infusion was associated with an increase of arterial blood pressure, heart rate and cardiac index. In the patients with HE, the increase in cardiac index was directly correlated with the plasma level of DA (r = 0.843, p less than 0.01). The present results clearly demonstrate that in HE circulating DA does not accumulate during continuous infusion of DA. They further provide evidence that the increase in circulating catecholamines in HE reflects increased release from the sympatho-adrenal system.

Adult↗

[Administration of a new fat emulsion in intensive care].

A new lipid emulsion for parenteral nutrition, Elolipid, was evaluated for in vitro stability as a component of an all-in-one nutrition solution and, in an open prospective investigation, for clinical tolerance and utilisation in intensive care patients with a broad spectrum of underlying diseases and organ dysfunctions. In vitro stability was determined by photon correlation spectroscopy (mean particle diameter) and Coulter Counter cell sizing (particle size distribution) after 0, 24, 48, 96 h of storage at temperatures of 4 degrees C and 25 degrees C. Mean particle diameter of 330 nm was not altered at any storage time or temperature. The portion of particles with an diameter of greater than 1,000 nm increased mildly during storage of 96 h at room temperature. 31 critically ill patients (mean age 55 +/- 3 years) entered the clinical study: 23 subjects were on artificial ventilation, 15 acquired septicemia, 9 renal insufficiency, and 7 acute or chronic hepatic failure. Fat was given as a component of an all-in-one solution at a rate of 1 g/kg b.w./day for a mean duration of 10 +/- 2 days. Plasma triglycerice concentrations rose mildly between days 3 and 5 only, but in none of the patients the infusion had to be stopped. Lipid-related disturbances of glucose or electrolyte metabolism, hepatic function, cholestasis, induction of disseminated coagulation, impairment of pulmonary gas exchange or renal function were not seen. 7 of 31 patients (22%) died. Side effects of complications attributable to the fat infusion could not be identified. It is concluded that the new lipid emulsion Elolipid is stable as a component of an all-in-one parenteral nutrition solution, is free of side effects and is well-tolerated and utilized even in critically ill patients with multiple organ dysfunctions.

Adolescent↗

Fatal encephalitis in a patient with chronic graft-versus-host disease.

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.

Adult↗

Prevention of upper gastrointestinal bleeding in long-term ventilated patients. Sucralfate versus ranitidine.

Thirty-two long-term ventilated patients were randomly selected for a study of the efficacy of sucralfate (1 g six times per day via gastric tube) versus ranitidine (six 50-mg to six 100-mg doses per day intravenously) for the prevention of upper gastrointestinal bleeding. The patients of the two treatment groups (each 16) were comparable with respect to diseases precipitating acute respiratory failure and risk factors of bleeding, e.g., renal failure, thrombopenia, coagulopathy, and anticoagulant treatment. Mean duration of mechanical ventilation was 7.4 in sucralfate- and 7.7 days in ranitidine-treated patients. During mechanical ventilation, macroscopically visible bleeding developed in three of the sucralfate-treated (18.7 percent) and seven of the ranitidine-treated (43.7 percent) patients. Until the end of the study, only three of the sucralfate-treated but nine of the ranitidine-treated (56.2 percent) patients bled; the difference between the two treatment groups was at all times significant (p less than 0.05). Packed red blood cells had to be administered to the three bleeding patients in the sucralfate group and to seven bleeding in the ranitidine group. Therefore it seems that sucralfate prevented mostly minor bleeding. The high bleeding rate during ranitidine treatment was presumably due to the high number of pH-nonresponders, as almost 30 percent of the gastric aspirates of this group had a pH less than 5. During treatment no difference was found in positive blood culture specimens and bronchial secretions between the two groups. However, nosocomial pneumonia developed in two ranitidine-treated patients, whereas that complication developed in none of the sucralfate-treated patients. In long-term ventilated patients, sucralfate prevented minor upper gastrointestinal bleeding significantly better than ranitidine. However, this does not imply that major upper gastrointestinal bleeding can be prevented by either sucralfate or ranitidine in these patients.

Adolescent↗

Recombinant human colony stimulating factor-granulocyte/macrophage and -granulocyte, but not macrophage induce the development of a respiratory burst in primary human myeloid leukemic cells in vitro.

Respiratory burst develops in myeloid blast cells if they differentiate functionally along the monocytic or granulocytic lineage. Using the nitroblue tetrazolium (NBT) assay we studied the effects of recombinant human granulocyte/macrophage colony stimulating factor (rhuGM-CSF), rhuG-CSF and rhuM-CSF on development of respiratory burst activity in primary blast cells from patients with myeloid leukemia. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (AML, n = 13) or myeloid-blast crisis (myBC) of chronic myeloid leukemia (CML, n = 5) it was found that the percentage of NBT positive cells was increased by at least 20% as compared to control cultures by rhuGM-CSF in 6/17 cases, by rhuG-CSF in 7/17 cases and by rhuM-CSF in 0/16 cases, representing in 'responders' a mean increase of 267% and 270% in the absolute number of NBT positive cells by rhuGM-CSF and rhuG-CSF, respectively. Morphological examination of cultured cells from 'responders', as compared to controls, showed decreased blast cell content but generally no evidence of terminal differentiation. The demonstration of Auer rods in NBT positive cells indicates that respiratory burst developed in a leukemic clone. These findings may be of physiological, pathophysiological and clinical relevance.

Cell Differentiation↗

Successful long-term treatment of portal-systemic encephalopathy by the benzodiazepine antagonist flumazenil.

A patient with portal-systemic encephalopathy refractory to standard therapy (40-g protein diet, oral neomycin and lactulose, supplementation of diet with branched chain amino acids) following extensive liver resection and construction of a portacaval shunt was treated with 25 mg of flumazenil twice daily by mouth. Before treatment with flumazenil she was encephalopathic and experienced 12 attacks of coma within 2 yr. When treated with flumazenil all signs of encephalopathy abated in spite of an unrestricted dietary intake of protein. Two days after discontinuation of flumazenil treatment she became comatose again. She remained chronically encephalopathic and had four further episodes of coma during the subsequent 3 mo. Since reinstitution of flumazenil treatment she has been well for 14 mo during follow-up without any signs of encephalopathy while on an unrestricted protein diet. Furthermore, flumazenil therapy reversed abnormalities of recordings of multimodality evoked potentials that were associated with hepatic encephalopathy. The striking remission of encephalopathy by treatment with flumazenil suggests that this benzodiazepine antagonist may be valuable in the long-term management of portal-systemic encephalopathy.

Adult↗

Assessment of oxygen-consumption by use of reverse Fick-principle and indirect calorimetry in critically ill patients.

Oxygen consumption was measured simultaneously by the reverse Fick-principle (V02FICK) and by indirect calorimetry ("Metabolic Measurement Cart Horizon") (V02MMC) in 31 critically ill patients; 24 men and 7 women. Seventeen patients were breathing spontaneously, 14 patients were on mechanical ventilation. The fractional inspiratory oxygen concentration (FI02) in ventilated patients ranged from 0.21 to 0.4 (mean 0.302). Total oxygen consumption as measured by indirect calorimetry was 286.7 +/- 59.7 ml/min (mean +/- SD), and measured by reverse Fick-principle 258.9 +/- 52.2 ml/min (mean +/- SD). The coefficient of correlation between the two methods was r = 0.873. The absolute difference of oxygen consumption between reverse Fick-method and indirect calorimetry was 11.3%. Regression analysis according to Theil revealed a similar regression between spontaneously breathing and mechanically ventilated patients for the studied FI02 values below 0.4. It is concluded that indirect calorimetry is a reliable method for measuring oxygen consumption in spontaneously breathing as well as mechanically ventilated critically ill patients.

Journal Article↗

Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis.

In nine patients with decompensated alcoholic cirrhosis of the liver and impaired renal function the effect of 8-ornithin vasopressin (ornipressin) on renal function and haemodynamic parameters was studied. Ornipressin was infused at a dose of 6 IU/h over a period of four hours. During ornipressin infusion an improvement of renal function was achieved as indicated by an increase of creatinine clearance (76 (15)%; p less than 0.01), urine volume (108 (29)%; p less than 0.05) and sodium excretion (168 (30)%; p less than 0.05). The hyperdynamic circulation of hepatic failure, as characterised by increased cardiac index and heart rate as well as decreased systemic vascular resistance was reversed to a nearly normal circulatory state during ornipressin infusion. The raised noradrenaline plasma concentration (1.74 (0.31) ng/ml) and plasma renin activity (13.5 (3.9) ng/ml/h) were lowered during ornipressin infusion to 0.87 (0.21) ng/ml and 5.9 (2.1) ng/ml/h, respectively (p less than 0.01). The efficacy of a vasoconstrictor agent in reverting a hyperdynamic state and improving renal function provides evidence for the substantial role of accumulation of vasodilator substances and subsequent activation of sympathetic nervous system and renin-angiotensin-axis in the pathogenesis of renal dysfunction in hepatic failure. Values are expressed as mean (SE).

Female↗

[Benzodiazepine antagonists in the treatment of heptic encephalopathy].

For the first time a causal treatment of hepatic encephalopathy may be possible by the benzodiazepine antagonist flumazenil. In contrast to all other treatments used so far by flumazenil hepatic encephalopathy improves within minutes. Flumazenil is the first benzodiazepine antagonist which can be used in humans and is a well established for treatment of benzodiazepine overdose. For treatment of hepatic encephalopathy development of a new antagonist with a longer half-life is desirable. However, ut should be stressed that the current experience with flumazenil is limited and that the effects of flumazenil on hepatic encephalopathy is not proven by randomized controlled studies. Therefore, this drug should only be used in clinical studies.

Animals↗

Improvement of hepatic encephalopathy treated with flumazenil.

The effects of the benzodiazepine antagonist flumazenil were studied in 20 episodes of hepatic encephalopathy (HE) in 17 patients with acute (n = 9) or chronic (n = 8) liver failure who had not responded to conventional therapy. Patients with a history of benzodiazepine intake were excluded. Changes in HE stage, in Glasgow coma scale, and in somatosensory evoked potentials were measured. In 12 of 20 episodes HE stage improved. The response to treatment occurred rapidly (within 3-60 min). In 8 of these 12 episodes HE worsened 0.5-4 h after treatment. In 5 of the 8 episodes that did not respond to flumazenil patients had clinical evidence of brain oedema. Flumazenil may be valuable in the treatment of HE in acute and chronic liver failure.

Acute Disease↗

[Prevention of stress hemorrhage in an internal medicine intensive care station: sucralfate versus ranitidine].

Stress ulcer bleeding is a serious complication of critical illness and is associated with increased morbidity and mortality. For the prophylaxis of stress ulcers, antacids, H2-blockers, or sucralfate are prescribed. While H2-blockers inhibit the secretion of gastric acid, sucralfate appears to provide protection without reducing levels of gastric acid. Inhibition of acid secretion increases gastric pH, allowing bacterial overgrowth of the stomach by Gram negative bacteria, which colonize the pharynx and trachea and increase the risk of nosocomial pneumonia. For this reason, H2 blockers appear disadvantageous, though they offer adequate prophylaxis for stress ulcer bleeding. As it does not increase gastric pH, sucralfate provides adequate protection against Gram negative gastric overgrowth, however its prophylactic efficacy is not generally accepted. Therefore, we compared the H2-blocker ranitidine to sucralfate in the prophylactic treatment of stress ulcer bleeding and studied the incidence of positive bacteriological findings in the blood and bronchial secretions of the two groups. In a randomized study, 84 patients undergoing general intensive care received either ranitidine (6 x 50 to 6 x 100 mg daily i.v.) or sucralfate (6 x 1 g via gastric tube or per os). Both groups were comparable with respect to age, underlying disorders, and factors predisposing to the development of stress ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Energy metabolism in patients with severe heart failure].

Resting energy expenditure was measured by indirect calorimetry in 11 patients (8 men, 3 women) with severe heart failure. The study was done after an over night fast (10-12 h). 5 patients suffered from idiopathic cardiomyopathy, 5 patients from coronary heart disease and 1 patient from congestive heart failure following from viral myocarditis. The cardiac index was 2.09 +/- 0.5 l/min/m2, the pulmonary capillary wedge pressure 24.6 +/- 8.0 mm Hg. Resting energy expenditure was 1.175 +/- 0.176 kcal/min/1.73 m2. The basal energy expenditure calculated according to Harris and Benedict was 1.008 +/- 0.055 kcal/min/1.73 m2. The difference was statistically significant (p less than 0.05). Respiratory quotient was 0.775 +/- 0.06 as a result of a high oxidation rate for fat (64.8% of total energy expenditure). These results show that after an overnight fast the caloric requirements of patients with severe heart failure are increased. This increased energy expenditure could be an explanation for the malnutrition often found in patients with severe chronic heart failure.

Adult↗