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Biomedical subjects

J Link

Publications and source records attributed to J Link.

At least 163 records · Page 9Linked to original sources

Clearance of ceftriaxone in critical care patients with acute renal failure.

Serum concentrations of ceftriaxone (RocephinTM), a third generation cephalosporin, were monitored in 5 operative intensive care patients suffering from acute renal failure (ARF) and compared to those of 7 patients without renal disturbance. For a period of 7 days, a fixed dose of 2 g/day was given by a 15 min infusion. Pharmacokinetic parameters were calculated by fitting all serum and urine data measured over the period of treatment. Ceftriaxone free fraction was measured on days 2 and 7. There was no evidence for an intraindividual change in ceftriaxone-clearance during the observation period. Ceftriaxone renal clearance was closely dependent on creatinine clearance according to a linear regression expressed by Clren = 0.14 Clcrea + 2.2 (r = 0.951, p less than 0.0001). Total clearance was also associated with creatinine clearance: Cltot = 0.19 Clcrea + 8.2 (r = 0.964, p less than 0.0001). Related to the free fraction, renal clearance was in the range of the glomerular filtration rate. Non-renal clearance was strongly decreased when related to the free fraction indicating that biliary excretion is also impaired in patients with acute renal failure. Obviously no compensatory increase in hepatic ceftriaxone clearance takes place. It is concluded that elimination of ceftriaxone may be strongly impaired during acute renal failure in surgical intensive care patients and that dosage should be restricted according to degree of the impairment of creatinine clearance.

Acute Kidney Injury↗

Intrahospital transport of critically ill patients.

Severe complications sometimes occur in critically ill patients during intrahospital transport. Possible causes may be inadequate ventilation, insufficient monitoring, interrupted application of vasoactive drugs, or disconnections and accidental extubation. We constructed a transport unit equipped with a respirator; capnometer; monitor to measure ECG, arterial and intracranial pressures, and temperature; and two syringe pumps that can be connected easily to the patient's bed. Gas is supplied by cylinders with oxygen and air. Electrical power is supplied by two accumulators connected to recharger and transformer devices that deliver 220 V (110 V). Since this transfer unit was introduced, we have had no unanticipated problems during intrahospital ICU patient transport.

Critical Care↗

[Preservation of homeostasis following the onset of brain death].

One of the main problems faced by transplantation medicine is the lack of suitable donor organs. The success of organ transplantation depends on the quality of the organ to be transplanted. The initial function of the transplant depends on the quality of preparation. The aim of efforts after brain death is to maintain the morphological and functional integrity of the donor organ in situ. At our clinic, all potential organ donors undergo direct arterial pressure measurement and many receive a Swan-Ganz catheter. Catecholamine administration--varied on the basis of the hemodynamic parameters--is not associated with an impairment of organ function. Electrolyte determinations at 2-hour intervals and close laboratory controls are obligatory. These intensive-care measures are necessary because of the occurrence of severe metabolic and hemodynamic imbalances. A partly transient diabetes insipidus is the most frequent homeostatic disorder. In addition, severe electrolyte imbalances, disturbed glucose utilization and hypotension may be observed. Our investigations on the plasma concentration course of thyroid hormones, ACTH and cortisol after the onset of brain death suggest that the secretion of pituitary hormones is maintained until total necrosis of the pituitary gland occurs 30 to 40 hours later. The detection of circulating ADH up to 24 hours after the onset of brain death, despite the angiographically confirmed cessation of cerebral circulation, suggests that there may be a residual perfusion of hypothalamus and pituitary. The blood levels of epinephrine, norepinephrine and dopamine measured in brain-dead patients not receiving catecholamines were in part considerably above the reference level. Our data suggest that vigorous intensive care management increases the number and quality of organs suitable for transplantation and reduces to a minimum the incidence of premature organ losses.

Brain Death↗

Utilization of labeled thymidine in DNA synthesis: studies for PET.

Carbon-111-thymidine and positron emission tomography (PET) have the potential for noninvasively measuring DNA synthesis in tumors and tissues. In order to validate this potential, one needs to construct accurate biochemical models that reflect the metabolism of thymidine, including its uptake and degradation as well as its incorporation into DNA. Our studies employed thymidine labeled in the methyl position using 11C, 14C, and 3H. Studies with rapidly proliferating tissues of mice demonstrated that most of the activity, 60 min after injection of labeled thymidine, was present in DNA, with smaller amounts found in metabolites. Studies in dogs, however, reveal that more activity was present in metabolites, rather than in the DNA of tumors and spleen tissue. HPLC analysis of canine blood after the injection of thymidine revealed rapid conversion of thymidine to thymine and other metabolites. We have found significant differences in the metabolism of [3H]thymidine versus thymidine labeled with radioactive carbon. These differences, which were not found when comparing 14C and 11C, indicate that [3H]thymidine is not an appropriate standard for comparison with PET studies employing [11C] thymidine. To accurately interpret images of [11C]thymidine as representations of DNA synthesis we are developing kinetic models that take into account the metabolism of thymidine and the contribution of degradation products to the 11C images.

Animals↗

Ehrlichiosis in a dog with seizures and nonregenerative anemia.

Ehrlichia canis infection was diagnosed in a dog with a history of seizures and nonregenerative anemia. Serologic titer to E canis was greater than 1:100. Evaluation of CSF revealed a high cell count, high protein concentration, and a positive Pandy test result. Several mononuclear leukocytes in the CSF contained E canis morulae. Central nervous system lesions are commonly found on postmortem examination of animals with ehrlichiosis, although clinical reports of neurologic signs attributable to this disease are less common. Ehrlichiosis should be included in the differential diagnosis of CNS disease in dogs from enzootic areas.

Anemia↗

Injury and recovery of the liver from preservation assessed by 31P NMR spectroscopy: the contrast between preservation with Collins' solution and Ringer's lactate solution.

The biochemistry of hepatic injury and recovery from preservation for transplantation was studied in rat liver perfused in vitro with erythrocytes. ATP and its metabolites, inorganic phosphate (Pi) and pH were quantitated as often as every 2.5 min by 31P NMR spectroscopy during preservation and recovery. Release of the hepatocellular enzymes, lactate dehydrogenase V (LDV) and aspartate aminotransferase (AST) were also measured. The duration of preservation with Collins' solution, the standard clinical preservative, affected the rate of recovery of ATP and monophosphate esters (MP), which include AMP + IMP, and the final recovery of Pi, but not of ATP. The difference between Collins' and Ringer's lactate solution, a poor preservative, became more apparent as preservation time increased. The differences included (1) pH at the end of preservative infusion; (2) pH between 0 and 2.5 min of reperfusion; (3) the MP increase (AMP + IMP) at the end of 13 h of preservation; (4) rate of recovery of ATP after preservation; (5) final ATP recovery during reperfusion; (6) LDV after 13h of preservation. These biochemical differences between good and poor preservation form a rational basis for prediction of liver failure after transplantation and for tests of the quality of new preservatives.

Animals↗

[Faulty functioning of the expiration valve of the Dräger circle system].

We observed, that under controlled ventilation the expiration valve of the circle system "8 ISO" did not close and rebreathing occurred, as the spirometer run counterclockwise. In such potentially dangerous events only a capnometer which measures inspiratory CO2 would give alarm. Dräger is informed of the above and until the problem is resolved, every anaesthesist should watch the expiration valve and spirometer carefully.

Anesthesiology↗

[Is cerebral panangiography unnecessary in determining brain death?].

UNLABELLED: The diagnosis of brain death, i.e. death of cortex and brainstem, can be established by neurologic examination only if there is no intoxication, sedative therapy, or hypothermia. In the latter cases, until now only cerebral panangiography can establish the diagnosis. We investigated, whether in these cases cerebral perfusion scintigraphy (CPS) in combination with brainstem auditory evoked potential (BAEP) can replace CPA for establishing the diagnosis. METHODS: 40 patients, treated in our interdisciplinary ICU because of primary or secondary brain lesions and in whom determination of brain death by neurological examination was contraindicated, were subjected to the following procedure: When coma was diagnosed, brainstem reflexes were examined. If negative, an atropine-test was done and this being negative, apnea-testing was performed. If apnea was positive, BAEP, CPS and CPA were performed. The results of BAEP and CPS were compared with the results of CPA. RESULTS: In 38 patients with suspected brain death the first examination showed complete correspondence between BAEP and CPS on one hand and CPA on the other hand (Table 3). In patient No. 39, CPS as well as CPA showed minimal supratentorial circulation, whereas BAEP were negative as was circulation in the fossa posterior. In patient No. 40 as well CPS and CPA showed minimal supratentorial circulation. Brainstem testing with BAEP was negative although CPA showed minimal brainstem perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

[Incorrect placement of a vena cava catheter and its prevention by intra-atrial ECG].

Up to now, radiological position control was obligatory due to the frequent complications arising from false cava catheter positioning. Apart from the radiological control, which is time consuming and expensive and involves the danger of allergic reactions due to contrast media, intraatrial ECG-recording can be applied to achieve correct positioning of the catheter tip. By this method exact placement of the catheter tip in the superior vena cava was possible in 98 of 100 cases examined. Only 2 catheters could not be placed: one was placed intra-arterially, and the other could not pass a venous valve. The method proved to be inexpensive, time saving and could even be applied in emergency situations (intraoperatively). Important prerequisites for the success of the procedure are a disturbance-free ECG-derivation, a sinus rhythm, and sufficient practical experience on the part of the examiner with regard to the assessment of intra-atrial ECG-alterations.

Catheterization, Central Venous↗

[Auditory evoked potentials in determining brain death].

Until now, in hypothermic patients, patients under barbiturate therapy etc. brain death can only unequivocally be determined by cerebral panangiography. We evaluated in 41 patients, whether panangiography can be substituted by recording of brain stem auditory evoked potentials in combination with cerebral perfusion scintigraphy. Our results demonstrate, that even if no potential except wave I can be recorded, a minimal intracranial perfusion may exist, so that by definition the patient is not dead. During the course of our investigations we found one patient, in whom disappeared auditory evoked potentials recovered. So we conclude, that the recording of auditory evoked potentials is only an adjunct in determination of brain death, not an objective method as is cerebral panangiography. But recording of auditory evoked potentials is helpful in excluding brain death in certain patients.

Brain Death↗

Stable expression of recombinant factor VIII molecules using a bovine papillomavirus vector.

The bleeding disorder in hemophilia A results from a deficiency or abnormality of Factor VIII (FVIII), a member of the coagulation cascade. FVIII is a large glycoprotein (approximately 350,000 daltons) that is activated by a series of proteolytic cleavages. During activation, a large internal domain (B domain) is removed, resulting in an active complex comprised of the amino and carboxyl subunits of the parental molecule. Using a bovine papillomavirus expression vector system, we have established stable, genetically engineered cell lines harboring either full-length FVIII cDNA or variant FVIII cDNA (delta FVIII), the latter containing an extensive deletion in the region encoding the B domain. We demonstrate that the two recombinant FVIII molecules manifest the biological attributes of native FVIII. Relative to full-length FVIII transformants, cells harboring delta FVIII cDNA are five to eight times more efficient in expressing coagulant activity. This difference is due to a post-transcriptional event.

Bovine papillomavirus 1↗

Changes in intracranial pressure associated with extradural anaesthesia.

The intracranial pressure (ICP) response to the lumbar extradural injection of bupivacaine hydrochloride was measured in two patients on a total of 29 occasions. In the first patient, mean ICP increased from an average figure of 18.8 mm Hg to 39.5 mm Hg after the injection of 10 ml of solution. This increase was maintained for an average of 4.5 min. Both the magnitude and the duration of the increase were less when 5 ml was injected. The second patient had a normal baseline ICP, but the injection of bupivacaine 10 ml produced an increase from a mean of 9.3 mm Hg to 15.6 mm Hg. Injection of the same volumes of physiological saline in the second patient induced increases in ICP similar to those obtained with bupivacaine. There was a good correlation between baseline ICP and the increase produced by the extradural injection. It is concluded that extradural anaesthesia must be used with extreme caution in patients with reduced intracranial compliance, and should not be used at all in a patient with intracranial hypertension or a space-occupying lesion.

Adult↗

The structure of 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone, an effective analog of colchicine.

-Methoxy-5-(2',3',4'-trimethoxyphenyl) tropone is an active analog of colchicine, a mitotic spindle inhibitor, which is missing the middle "B" ring. This compound crystallizes in the triclinic system, space group P1, with Z = 2; a = 10.135(2), b = 10.166 (4), and c = 7.863(2) A; alpha = 82.15(3), beta = 103.49(3), and gamma = 107.16(2); degrees and V = 750.7(4) A. The structure was solved by direct methods and refined by full-matrix least-squares to a final R = 0.063, using 2503 observed reflections and 271 parameters. Despite the absence of the middle ring, the conformation of the molecule is similar to that of colchicine, isocolchicine , and their derivatives. The troponoid ring is dissimilar to the phenyl ring in that it is not aromatic and does have alternating short and long bond lengths. The dihedral angle between the least-squares planes of the two rings is -57.4 degrees. Van der Waals surface representations of the analog and colchicine are presented to demonstrate the similarity and differences of these two molecules . The structural information of the analog is consistent with the interpretation of thermodynamic parameters which govern the interactions between brain tubulin and the analog.

Chemical Phenomena↗

Changes in plasma renin activity and haemodynamics during vasodilator therapy in conscious dogs with myocardial infarction or chronic volume overload.

The aim of the study was to compare the changes in plasma renin activity induced by a vasodilator in normal dogs and in dogs with an impaired cardiac reserve. In normal conscious dogs, a 60-min nitroprusside infusion increased plasma renin activity from 1.05 +/- 0.26 to 8.35 +/- 1.20 ng, angiotensin I ml-1 h-1 (P less than 0.002) and heart rate from 83 +/- 6 to 149 +/- 15 beats/min (P less than 0.002). In five dogs in which a aortocaval fistula had been created 4 weeks earlier, the same infusion still increased plasma renin activity but significantly less than in normal dogs (0.90 +/- 0.29 to 4.44 +/- 0.64 ng ml-1 h-1; P less than 0.01) and the heart rate was unchanged (134 +/- 4 to 139 +/- 7 beats/min; NS). Similarly, in five dogs with a previous myocardial infarction, the heart rats response to nitroprusside was blunted (108 to 107 beats/min;NS) and plasma renin activity increased less than in normal dogs. Plasma renin activity also increased acutely after hydralazine administration in dogs which myocardial infarction (1.05 +/- 0.26 to 8.99 +/- 0.79 ng ml-1 h-1; P less than 0.05); after 1 week of hydralazine, plasma volume had increased from 54.9 +/- 0.9 ml kg-1 to 74.5 +/- 4.9 ml kg-1 (P less than 0.05) and plasma renin activity remained higher than control (4.66 +/- 0.66 ng ml-1 h-1; P less than 0.01). In conclusion, vasodilator therapy rapidly activates vasoconstrictor forces and fluid retention even in dogs with limited cardiac reserve. Although the regulation of plasma renin secretion appears altered in these models of heart disease, the renin response remains sufficient to seriously limit the beneficial effects of vasodilator therapy.

Animals↗

[Effect of therapeutic hyperventilation on blood lactate concentration].

The increase of blood lactate is a well known side effect of active and passive hyperventilation. In 22 patients who underwent controlled respiration after head injury or elective neurosurgical operations, we measured lactate, pyruvate, pH, and bicarbonate in central venous blood and investigated their interference by hypocapnia. The level of ventilation was between pCO2 equal 25 mmHg and pCO2 equal 45 mmHg, measured in the central venous blood. With decreasing pCO2, pH showed an increasing (from 7.40 +/- 0.015 to 7.50 +/- 0.068) and bicarbonate a decreasing tendency (from 25.46 +/- 1.32 mMol/l to 23.28 +/- 3.76 mMol/l). Lactate and pyruvate remained within the normal range down to a central venous pCO2 of 31 mmHg. But then with increasing hypocapnia both increased significantly (lactate 2.001 +/- 1.08 mMol/l, 0.098 +/- 0.068 mMol/l). At a pCO2-range of 25-27 mmHg (central venous) lactate continued increasing to 2.212 +/- 0.995 mMol/l whereas pyruvate dropped to 0.087 +/- 0.05 mMol/l. Therefore the possibility of hypocapnia-induced lacticemia seems to arise at a ventilation level less than 30 mmHg (pCO2 central venous). Production of excess-lactate may begin at a central venous pCO2 of 27 mmHg.

Adult↗