Hypothesis of insufficient efforts in respect to organ donation in some European regions.
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Europe↗
Biomedical subjects
H Lange
Publications and source records attributed to H Lange.
[Selective percutaneous transluminal thrombolytic therapy with rt-PA in central retinal artery occlusion].
UNLABELLED: In central retinal arterial occlusion systemic fibrinolytic therapy can involve a variety of serious complications. The local application of a fibrinolytic agent close to the embolus by means of a femoral catheter should reduce the rate of complications. We therefore present the results of a preliminary study of nine consecutive patients treated with rt-PA via transcutaneous femoral catheter. PATIENTS: From October 1993 to January 1994, nine patients ranging in age from 50 to 83 years who had central retinal occlusion were treated with rt-PA. The latency from the onset of the symptoms to the beginning of the therapy was 10-37 h. A catheter was placed via the femoral artery, the tip being located either at the common carotid artery or at the internal carotid artery or at the internal carotid artery. A continuous infusion containing 10 micrograms (ACTILYSE (rt-PA) was given over 2 h. Thereafter, each patient received 7000 IU heparin sulfate 4 times daily for 3 days and 1200 micrograms pentoxifylline i.v. daily for 10 days. On discharge, permanent therapy with salicylic acid (100 micrograms) was prescribed. The patients have been followed up for up to 18 months so far. RESULTS: In five of eight patients an improvement of central visual acuity was observed. It changed from perception of hand movement only to 12/20 in three patients. In two of these patients visual acuity had continued to improve after 6-9 months, to 16/20 and 20/20. In one patient visual acuity fell to 6/20 because of progression of ischemic ophthalmopathy. In our patients visual acuity could still be improved even 27 h after arterial occlusion. CONCLUSION: A low incidence of complications and the good effect on thrombolysis support the local rt-PA therapy. Good interdisciplinary cooperation is required. Patients must be referred for this therapy as early as possible.
Aged↗
The influence of the immunosuppressants OKT3 and ATG on immunological parameters.
Cytokines play an important role in the immune response induced by organ grafting, particularly during episodes of rejection. We tested the influence of monoclonal and polyclonal antibodies upon levels of mediators of the immune system. In 29 patients various cytokines and mediators were serially analyzed following transplantation. Thirteen patients received polyclonal antibodies (ATG) and 7 monoclonal (OKT3). Both OKT3 and ATG induced a rise in body temperature. Mean serum levels of amyloid A, neopterin, plasma levels of TNF alpha, interleukin 2 receptor (IL-2R) and urine levels of interleukin 6 (IL-6) and IL-2R were elevated when antibodies were employed. Interestingly, urine and plasma TNF-alpha as well as urine IL-6 and IL-2R remained elevated following ATG but not OKT3 and did not rise in case of basic treatment. In summary, antibody therapy increased levels of immune mediators. These mediators remained elevated following the discontinuation of treatment in case of ATG but not OKT3.
Acute Disease↗
The effect of erythropoietin on lactate, pyruvate and excess lactate under physical exercise in dialysis patients.
To investigate EPO-induced increase of hemoglobin on energy metabolism plasma concentrations of lactate (L), pyruvate (P) and excess lactate (XL) were determined in ten dialysis patients at rest, immediately after 6 minutes of ergometric exercise as well as after recovery for 15 and 30 min. The investigations were performed before EPO-therapy at a mean Hb = 7.5 +/- 0.9 g/dl and under EPO-therapy at a mean Hb = 10.0 +/- 0.6 g/dl and at a mean Hb = 11.9 +/- 0.8 g/dl. Ten healthy subjects were subjected to the same investigation at Hb = 14.7 +/- 1.1 g/dl. There was a significant rise of L and XL in all patient groups under ergometric exercise. The increase of hemoglobin from 7.5 g/dl to 10.0 g/dl led to significantly (p < 0.01) lower L and XL concentrations immediately after exercise (L = 4.62 vs 3.23 mmol/l, XL = 2.37 vs 1.38 mmol/l). The further decrease of the mean L and XL values (L = 2.88 mmol/l, XL = 1.05 mmol/l) associated with the rise of hemoglobin to 11.9 g/dl could not be confirmed statistically. In contrast to all patient groups, there was no significant rise in XL in the healthy control subjects under physical exercise. The present results make it evident that patients with renal anemia react even to light physical exercise with pronounced tissue hypoxia in contrast to healthy subjects. The increase of the hemoglobin content under the EPO-therapy leads to a marked reduction of the tissue hypoxia and consequently of anaerobic energy production. A further rise of the hemoglobin content above and beyond 10.5 g/dl will have an additional positive effect on oxygen supply only in occasional cases. The comparison with healthy subjects shows that despite a very large degree of normalization of the hemoglobin content, no normalization of energy metabolism can be attained.
Anaerobic Threshold↗
Development of new ricin A-chain immunotoxins with potent anti-tumor effects against human Hodgkin cells in vitro and disseminated Hodgkin tumors in SCID mice using high-affinity monoclonal antibodies directed against the CD30 antigen.
The lymphocyte activation marker CD30 has been shown to be an excellent target for the immunotherapy of human Hodgkin's lymphoma. In order to develop new potent immunotoxins (ITs) against CD30, we chemically linked 6 recently described monoclonal antibodies (MAbs) via SMPT to deglycosylated ricin A-chain (dgA). Cross-blocking experiments demonstrated that these MAbs, termed Ki-2 to Ki-7, recognize 3 different clusters on the CD30 antigen: Ki-2, Ki-4, Ki-5 and Ki-7 recognize cluster A; Ki-6 recognizes cluster B; Ki-3 binds to cluster C. Staining of 29 sections of normal human organs revealed no major cross-reactivity of any MAbs tested. Binding to the CD30 antigen on L540Cy Hodgkin cells was assessed by flow cytometry, and demonstrated high affinities for Ki-2, Ki-3 and Ki-4. The concentration giving 50% of the mean fluorescence intensity (MFI50) was 0.58 micrograms/ml to 0.78 micrograms/l. MAbs Ki-5, Ki-6, and Ki-7 bound much more weakly. The staining intensity of the MAbs correlated with the cytotoxicity of the corresponding ITs. Ki-2.dgA, ki-3.dgA and Ki-4.dgA inhibited the protein synthesis of L540Cy cells by 50% at concentrations (IC50) of 3.5 x 10(-10)M to 4.0 x 10(-11)M. The most effective IT, Ki-4dgA, is 5-fold more potent than previously reported CD30 ricin A-chain ITs. Ki-4.dgA was subsequently used for the treatment of disseminated human Hodgkin's lymphoma in a SCID mouse model. The mean survival time (MST) of lymphoma-bearing SCID mice was extended from 42 days in untreated controls to more than 132 days when Ki-4.dgA was applied one day after tumor challenge. Ki-4.dgA is a new potent IT suitable for further evaluation against Hodgkin's lymphoma in man.
Animals↗
Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L540 is strongly inhibited by a new CD30-specific antibody (Ki-4).
The CD30-activation marker was detected as the Hodgkin-associated Ki-I antigen and is regarded as a target for the treatment of Hodgkin patients with immunotoxins. The CD30 is released from tumor cells and this soluble CD30 (sCD30) is an indicator of the disease activity. Since the shedding of sCD30 may be influenced by antibodies, we produced 6 new CD30-specific antibodies (Ki-2 to Ki-7) for the purpose of finding antibodies that might inhibit the formation of sCD30. Ki-2 to Ki-7 and the other anti-CD30 antibodies Ki-I, Ber-H2, HeFi-I, M44, M67, HRS-I, HRS-4 and C10 were employed for epitope mapping. The binding of a particular radio-labeled anti-CD30 antibody to Hodgkin's-disease-derived L540 cells was completed by addition of the various non-labeled anti-CD30 antibodies. Three non-overlapping regions, expressing different antigen-specific determinants, could be defined on the extracellular part of the CD30 molecule. Cluster A of determinants was recognized by Ki-2, Ki-4, Ki-6 and Ki-7, Ber-H2, HRS-I and HRS-4, while cluster B was detected by Ki-I, Ki-5 and M67. Cluster C, which probably contains the binding site for the CD30 ligand, was defined by Ki-3, M44, HeFi-I and C10. Co-culture experiments of L540 cells with the various antibodies followed by the isolation of sCD30 from culture supernatant fluids revealed that the release of sCD30 was most strongly increased by Ki-I and weakly enhanced by Ki-2, Ki-3, Ki-5 and HeFi-I, whereas it was almost completely inhibited by Ki-4 and to a slightly lesser extent by Ber-H2.
Animals↗
A simplified procedure of direct calorimetry for bedside monitoring of the resting metabolic rate.
A simplified procedure of direct calorimetry (SPDC) for determination of resting metabolic rate of respiratory uncompromised subjects in a supine position is presented. This procedure was based on computer-assisted measurements of heat losses due to evaporation, radiation, conduction, and convection. The subject's total loss of mass was recorded hydraulically with a beam scale and afterwards transformed into a digital electric signal. Differences between dry bulb temperature and mean skin temperature were measured by semiconductor thermistors and also transformed into digital signals. With special software an interfaced personal computer assisted in performing SPDC and in calculating heat losses due to evaporation, radiation, and conduction. In a thermoneutral environment, six healthy volunteers were investigated to determine the mean convective heat transfer coefficient (hc) from the difference in an individual between the metabolic energy transformation (M) measured by indirect calorimetry (IC) and the sum of heat losses by radiation, conduction, and evaporation. The room-specific value of hc of 2.12 (SD 0.22) W.m-2.degrees C-1 was in good agreement with data in the literature. Compared to the results of M from a second series of IC, the total heat loss (THL) measured by SPDC in a thermoneutral environment was calculated as 100.5 (SD 6.0)%. The THL by SPDC performed three times at 3-h intervals on ten other volunteers revealed a mean difference of 0.22 (SD 1.74) W.m-2. Thus, SPDC would seem to be a valid and reproducible method under conditions of thermal neutrality.
Adult↗
Immediate metabolic effects of different nutritional regimens in critically ill medical patients.
OBJECTIVE: Metabolic effects of different caloric regimens were investigated in nonsurgical, medical patients with multiple-organ failure (MOF). DESIGN: Seven total parenteral nutrition (TPN) regimens were administered, differing in amount (14, 28, and 56 kcal/kg per day, i.e., hypo-, iso-, and hypercaloric nutrition, respectively) and distribution [carbohydrates (COH), amino acids (AA), long-chain and medium-chain triglycerides (LCT/MCT)] of calories. Each regimen was administered over 12 h. Metabolism was monitored by energy expenditure (EE), body temperature (BT), protein breakdown (PB), and blood glucose and serum lactate levels. Measurements were started within 2 days of MOF onset. SETTING: The study was conducted in a medical intensive care unit. PATIENTS: Twenty patients with MOF on mechanical ventilation (mean Apache II score x = 26) were investigated. MEASUREMENTS AND RESULTS: The mean values of the EE (x = 31 kcal/kg per day), BT (x = 38 degrees C), PB (x = 1.5 g/kg per day), and lactate (x = 2.0 mmol/l) and glucose level (x = 222 mg/dl) parameters were elevated. EE, BT, and lactate and glucose levels were significantly lower under hypocaloric nutrition than during iso- and hypercaloric nutrition (p < 0.01). Differences in the metabolic effects of LCT and MCT were not significant. PB was significantly elevated under hypercaloric nutrition (p < 0.01). Protein balance was positive under hypercaloric nutrition, and negative under iso- and hypocaloric nutrition. CONCLUSIONS: In nonsurgical, medical patients neither hypercaloric nor isocaloric nutritional support prevented protein catabolism; in contrast, they enhanced the metabolic burden measured by EE, thermogenesis, urea production rate, and glucose and lactate levels. A hypocaloric regimen is therefore recommended for these patients during the early phase of MOF.
Aged↗
Cecum of guinea pig is a reservoir and sigmoid is a high-resistance conduit.
We compared the filling responses of the cecum and the sigmoid of the guinea pig using volumes up to 60 ml and 2.5 ml, respectively. In the isolated cecum, each 1-cm increment of hydrostatic pressure above zero led to accommodation of 10 ml volume; in the sigmoid, the yield pressure (at which accommodation first occurred) was 6 cm H2O, and pressure increments up to 20 cm H2O produced volume increments of less than 0.5 ml. Resting pressure at half-maximal filling was 5.0 +/- 0.7 cm H2O for the sigmoid and 1.7 +/- 0.6 cm H2O for the cecum. K+ depolarization led to a significant upward shift in the pressure curves of both segments. Ca2+ withdrawal decreased sigmoid and cecal pressures at some volumes. Distension of the cecum triggered intermittent contractions, which began with the shortening of the teniae and were associated with low-amplitude pressures and expulsion of a 5- to 10-ml volume. Distension of the sigmoid produced propagating contractions that were associated with high-amplitude pressures and lengthening; compartmentalization in the sigmoid prevented efflux from it, and volume inflow was not affected by pressure waves. Our observations indicate that its large capacity and great distensibility make the cecum suitable for reservoir functions, whereas its narrowness and lack of distensibility make the sigmoid a high-resistance conduit.
Animals↗
[Inadvertant intracardiac entrapment of a Swan-Ganz catheter].
A 58-year-old man, admitted with one-vessel coronary disease and aortic valve insufficiency, was scheduled for cardiac surgery. He underwent single coronary bypass grafting and aorta ascendens replacement by a composite graft. During surgery he was monitored by a Swan-Ganz catheter, which had been inserted uneventfully via the right internal jugular vein. Six hours after completion of surgery we were unable to remove this catheter. Fluoroscopy showed intracardiac entrapment of the catheter. Rethoractomy was performed, revealing entrapment by a suture. The purse-string suture was released, and the catheter was withdrawn without resistance.
Catheterization, Swan-Ganz↗
The pattern of attentional deficits in Huntington's disease.
Different aspects of attention, e.g. phasic alertness, vigilance, divided attention, response flexibility, response inhibition and intermodal integration, were investigated with a computerized test-battery in a group of 20 patients with Huntington's disease and 27 healthy controls. Huntington's disease patients are not impaired in reacting to task-contingent external stimulation in the phasic alertness task, but the self-generated maintenance of attention as measured by the vigilance task, is disturbed. The simultaneous monitoring of different input-channels in the divided attention task and the ability to operate with information given to different modalities in the intermodal integration task are severely affected. The performance of Huntington's disease patients in the response flexibility task, in which internal cued shifts are required, is impaired. Huntington's disease patients are also impaired in reacting selectively to go/no-go stimuli in the response inhibition task. It is suggested that a number of 'higher' cognitive deficits described in Huntington's disease might, at least partly, be due to basic attentional disturbances.
Adult↗
[Necrosis of the ligamentum teres hepatis and the anterior abdominal wall in acute pancreatitis].
The varying sites of extrapancreatic tissue necrosis in acute pancreatitis seldom include the anterior abdominal wall. In cases of liver enlargement causing a high portal pressure, the umbilical vein serves as a vent, shunting the portal blood through the teretic hepatic ligament to the anterior abdominal wall. Corticosteroids make the tissues even more susceptible to the activated pancreatic enzymes and are thus a contributing factor to the tissue necrosis. We describe a case of necrosis of the teretic hepatic ligament and the anterior rectus abdominis muscle following acute biliary pancreatitis.
Acute Disease↗
Copper and childhood cirrhosis.
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Bottle Feeding↗
[Combined kidney and pancreas transplantation in late-stage diabetes].
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Diabetes Mellitus, Type 1↗
Cyclosporine pharmacokinetics and variability from a microemulsion formulation--a multicenter investigation in kidney transplant patients.
The steady-state pharmacokinetics and tolerability of a microemulsion formulation of cyclosporine (Sandimmune Neoral) were compared with the commercial formulation (Sandimmune) in 55 clinically stable renal allograft recipients. In study period I (2 weeks' duration), patients entered the study on a stable, individualized twice-daily dosage regimen of the commercial formulation. In period II (2 weeks), they were changed over to the microemulsion formulation at the same dose as at study entry. In period III (2 weeks), dose titration was subsequently allowed if necessary to provide comparable steady-state trough concentrations as at study entry. The commercial formulation was reinstituted during period IV (2 weeks). Safety and tolerability were assessed at weekly clinic visits, and the steady-state pharmacokinetics of cyclosporine in whole blood were characterized at the end of each study period. A milligram-to-milligram dose conversion was adequate when making the initial change between formulations in order to maintain steady-state trough concentrations in the target therapeutic range. Concomitant with this conversion, the steady-state peak concentration and area under the curve increased on average by 59% and 30%, respectively, due to absorption-related differences between the formulations. These increases were not associated with an increase in adverse experiences or changes in blood pressure or clinical laboratory parameters over the first four weeks after the change-over. Trough concentrations were more stable and were more strongly correlated with systemic exposure (area under the curve) during treatment with the microemulsion formulation. Intraindividual coefficients of variation in steady-state peak concentration, time to attain the peak, area under the curve, and percent peak-trough fluctuation ranged from 18% to 74% from the commercial formulation. Variability from the microemulsion formulation was significantly less, ranging from 10% to 22%.
Absorption↗
Maternal immunization modulates the primary immune response to 2-phenyl-oxazolone in BALB/c mice.
The development of the antibody repertoire in newborn mice is greatly influenced by idiotype network interactions. It has been demonstrated that anti-idiotypic antibodies either directly injected or transferred from the mother may alter the repertoire for life. For an elucidation of the underlying mechanisms we have analyzed the primary immune response to 2-phenyl-5-oxazolone (phOx) coupled to chicken serum albumin (CSA) in BALB/c mice after complete disappearance of maternal antibodies which originated from different stages of affinity maturation. Depending on the serum titers of the mothers after primary (1 degree mo), secondary (2 degrees mo) or tertiary (3 degrees mo) immunization, maternal anti-phOx IgG persisted in F1 mice for up to 9 months. In addition, F1 mice born to 2 degrees mo developed--even without immunization--an anti-phOx IgM titer which reached levels similar to an antigen-induced primary response. An enhancement of the early primary anti-phOx as well as anti-CSA response was seen in F1 mice born from 1 degree mo, whereas the response was delayed when born to 2 degrees mo and 3 degrees mo. The antibody titers in the latter group of mice remained at a lower level for 3 months. In contrast, mice of the F2 generation which received a smaller amount of the same collection of maternal antibodies as F1 mice from 3 degrees mo exhibited a quite different primary response: (i) They showed an earlier onset in their anti-CSA response. (ii) Whereas normally a plateau in antibody titer was reached by the 4th weak after immunization, in 55% of the F2 mice a prolonged increase of the anti-phOx and anti-CSA antibody titers was observed. At 12 weeks after antigenic challenge, titers reached plateau levels of 6 x 10(5) which were never before seen in a primary phOx or CSA response. Thus, depending on its own immunological experience, the maternal immune system induces a state of memory in the offspring which results in a faster and/or enhanced immune response in the F1 and F2 [corrected] generations.
Animals↗
[Difficult intubation due to facial malformations in a child. The laryngeal mask as an aid].
Variations in anatomy of the bony and soft-tissue structures of the neck and facial cranium due to trauma, disease, or dysmorphic syndromes may lead to severe intubation problems. These patients are admitted for mandibulofacial and otolaryngologic surgery. It is important to inspect the patient's outer and inner pharyngeal structures carefully during preoperative assessment, as suggested by Mallampati. The observer estimates the facility of intubation by inspection of the faucial pillars, soft palate, and uvula. Unfortunately, even careful examination does not predict every case of difficult intubation, so that unexpected problems may occur. There may also be difficulties in ventilating these patients with a face mask. Safe intubation is possible in these cases using the laryngeal mask airway (LMA), laryngoscopy with a rigid optical aid, and the fibreoptic bronchoscope. Case report. We report a 14-month-old girl with Goldenhar's syndrome (oculo-auricular dysplasia) who presented for soft-palate surgery. This syndrome belongs to the group of cranio-mandibular-facial malformations; the main symptoms are congenital unilateral malformations in the area of the 1st and 2nd branchial arches. The patient's jaw was hypoplastic with aplasia of the temporo-mandibular joint, which led to asymmetry of the lower face and an extremely short mandible. Additionally, we observed a large tongue in relation to the small jaw. Macrostomia is part of the syndrome, and may lead to underestimation of intubation problems.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia, Inhalation↗
Pressure-time product and work of breathing during biphasic continuous positive airway pressure and assisted spontaneous breathing.
The pressure-time product (PTP) and work of breathing (W) were measured in 19 intubated patients during weaning from mechanical ventilation after aortocoronary bypass surgery. The patients were supported by two different ventilatory modes: biphasic continuous positive airway pressure (Biphasic CPAP; a ventilatory mode that permits spontaneous breathing at two different levels of airway pressure during inspiration and during expiration) and pressure-support ventilation (denominated as assisted spontaneous breathing, ASB). Our aim was to compare the energy cost of breathing imposed by both modes. The PTP was obtained by integrating the area enclosed by the esophageal and chest-wall static recoil pressure curves. The W performed by the patient (Wp) was calculated using Campbell's diagram method, based on the esophageal pressure curve and normalized per liter of ventilation. Two comparable support levels, corresponding to a high and a low degree of mechanical support, were studied for each ventilator mode. The levels of support were generally higher than that necessary to overcome inspiratory resistance. We found significantly higher PTP values during biphasic CPAP than during ASB (p < 0.01), whereas the Wp was the same with biphasic CPAP and ASB at both support levels. We conclude that because of the higher PTP values measured during biphasic CPAP, this mode of ventilation appears to have been more exhausting for our patients. The discrepancy between PTP and Wp is probably due to the different mechanisms of support given by the two ventilatory modes and the greater patient effort is related to those respiratory cycles that are not helped by the ventilator and which represent nearly half of the breaths during biphasic.
Aged↗