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To show the equivalence of the transpulmonary thermodilution method to the direct Fick principle in children.Prospective single-centre study.A 16-bed paediatric cardiac ICU and a cardiac catheterisation laboratory at an university affiliated centre for paediatric cardiology and congenital heart disease.We consecutively investigated 18 patients (mean age 12.1 +/- 6.4 years) during cardiac catheterisation and after corrective cardiac operation.We prospectively defined limits of equivalence for cardiac index (CI) for both methods of +/- 0.25 l/min x m(2). We measured oxygen consumption for determination of CI by Fick as the clinical "gold standard" and performed a set of three transpulmonary thermodilution measurements. The mean CI(Fick) was 2.88 +/- 1.07 l/min x m(2) (range 1.10-4.62 l/min x m(2)) and CI(TPID)was 2.85 +/- 1.03 l/min x m(2)(range 1.02-4.49 l/min x m(2)). The mean difference between CI(Fick) and CI(TPID)was 0.030 +/- 0.168 l/min x m(2), and limits of agreement -0.306 to 0.366 l/min x m(2)(90% confidence interval -0.040 to 0.099 l/min x m(2)). The regression equation was : CI(Fick)=1.0244 x CI(TPID)-0.040, r(2) = 0.976, P0.0001. The intraclass coefficient of reliability for three repeated measurements of CI(TPID) was 0.97, the corresponding lower limit of the 95% confidence interval was 0.94.We demonstrated the equivalence of CI measurement by transpulmonary thermodilution and the Fick principle in children. This new method may improve hemodynamic monitoring and management in seriously ill children.

Efficient inhalation therapy depends on successful delivery of the drug to the lung. The efficacy of drug delivery is not only influenced by the characteristics of the inhalation device, but also by the patient's handling of the device and by the inspiratory maneuver achieved through the device. We analyzed the output characteristics of three different chlorofluorocarbon (CFC)-free breath-actuated inhalers for inhaled glucocorticosteroids (BUD Turbohaler, FP Diskus/Accuhaler and HFA-BDP Autohaler, respectively). Mass output and particle size distribution of drug aerosol delivered by the inhalers were determined depending on different inhalation parameters in vitro using an Andersen cascade impactor. We found that, beside the peak inspiratory flow (PIF), other factors such as flow acceleration and inhalation volume also have significant effects on aerosol generation with respect to mass output and particle size distribution. Thus, these parameters should be taken into account when a suitable device for an individual patient is to be selected. The dependency on inspiratory parameters was most pronounced for the dry powder inhalers. The Turbohaler showed by far the highest variance in particle output (fine particle fraction ranging from 3.4% to 22.1% of label claim), whereas the Diskus was less dependent on variations in inhalation (10.6% to 18.5% of label claim). The most constant aerosol output was found for the Autohaler, which also released the highest fine particle fraction (43.1% to 56.6% of label claim).

Background: Local recurrence remains a major concern after primary treatment of breast cancer and has a major impact on subsequent survival. While most studies report a poorer survival rate in patients with a local recurrence after mastectomy than after breast conservation, it remains controversial whether different risk profiles at the time of primary diagnosis may account for this difference. Method: Matched pair analysis of 134 patients with newly diagnosed locoregional recurrence of breast cancer without evidence of systemic disease. Matching criteria included the primary surgical treatment, tumor size, nodal status, and age. The significance of various prognostic parameters at the time of primary diagnosis and at the time of recurrence were evaluated, by univariate and multivariate analyses, with respect to survival after recurrence. The median follow-up was 8.4 years. Results: Risk factors at the time of presentation, such as tumor size and lymph node status, were comparable between both groups. Local recurrence occurred on an average 9 months earlier in patients after mastectomy (P=0.08). Univariate analysis showed that lymph node status (P=0.0001) and disease-free interval from primary treatment to local recurrence (P=0.0002) were the most significant single prognostic factors for subsequent survival after local recurrence. The primary surgical treatment modality was shown to be of marginal statistical influence (only P=0.05). Conclusion: Local recurrence after mastectomy seems to be associated with worse survival than after breast-conserving therapy. Early onset of chest-wall recurrence, moreover, represents the highest independent risk for cancer-associated death.

Patients with carcinoma of the cervix and histologically proven blood vessel invasion have a poor prognosis. At the I. Frauenklinik der Universität München, 34 women were enrolled for a prospective study and were alternatively treated with or without adjuvant chemotherapy (carboplatin and 5-fluorouracil). Of the 28 patients included in the follow-up (14 with/14 without chemotherapy), 12 patients died (5 with/7 without chemotherapy). The disease-free interval was 18.6 months in the group treated with chemotherapy compared to 29.3 months in the group without chemotherapy. There is no statistically significant difference in the survival of patients with blood vessel invasion in relationship to adjuvant chemotherapy following radical hysterectomy.

The practicability and efficiency of a standardized, preoperative isovolemic hemodilution was investigated during major gynecological operations (Wertheim's operation, etc.).Prospective clinical trial with a historical control group.Operating room of a gynecological university hospital.Under general anesthesia hemodilution to a hemoglobin concentration of 9 g/dl was performed in 48 patients (mean age: 53 years). Shed blood volume amounted to 900 +/- 210 ml. Transfusion of autologous or homologous blood was provided when Hb concentration decreased beyond 7 g/dl intraoperatively.Compared to a control group of 57 patients without hemodilution the total number of PRBC units transfused was significantly reduced. Moreover, in 65% of all patients the transfusion of homologous blood could completely be avoided perioperatively (control group: 21% of patients). Adverse effects did not occur.The data reflect that acute isovolemic hemodilution before major gynecological operations represents a safe, easy to handle and effective procedure to avoid transfusion of homologous blood up to a total blood loss of 1,300-1,400 ml.

Between 1963 and April 1994, 3823 women were treated both at the Universitäts-Frauenklinik Berlin-Charlottenburg as well as at the I. Frauenklinik der Universität München, for a malignant condition of the breast gland. 161 of these (4.2%) exhibited an intraductal carcinoma stage pTis, whilst 99 (61.5%) were axillary lymphadenectomised. During the observation time-span of up to 24 years, 9 patients (5.6%) developed local recurrence. In neither patients of the group with axillary nor without axillary dissection could a regional recurrence be observed within this period. Also, a generalisation of this condition was not recorded in any patient. On the basis of our own results and those from the literature we postulate that, under the auspices of a risk adapted tumor surgery, axillary lymphadenectomy is no longer necessary under certain conditions in non-invasive breast carcinoma.

Between 1963 and 1993, 3720 women were treated both at the Universitäts-Frauenklinik Berlin-Charlottenburg and at the I. Frauenklinik der Universität München for a malignant condition of the breast. 187 of these (5%) exhibited stage p Tis, 102 (54.5%) of whom had an axillary lymphadenectomy. One patient had a micrometastasis (pN1a). During the observation period of up to 24 years, 11 patients (5.9%) developed local recurrence. In none of the patients a regional or generalised recurrence could be observed within this period. On the basis of our own results and those from the literature, we conclude that, under the aspect of a risk-adapted tumour surgery, axillary lymphadenectomy is no longer necessary under certain conditions: an invasive carcinoma should be excluded with high certainty in the tumourectomy specimen as well as in the remaining breast. Therefore, a histological work-up in serial sections must be provided to exclude multifocality (multicentricity) and a tumour diameter larger than 25 mm.

Primary hepatocellular carcinoma is a very rare disease, especially in association with a pregnancy. We report on a 22-year-old primigravida, who underwent Caesarean section in the 29th week of pregnancy in conjunction with tumour-reductive surgery for hepatocellular carcinoma. The further course of the disease was characterised by an early recurrence and lung metastases. Under palliative chemotherapy with 5-fluorouracil, the patient has been in a state of stable disease for several months. Typical risk factors for the hepatocellular carcinoma do not exist in the patient. Alternative explanations for the aetiology of the disease are discussed.

From January 1988 to December 1991, 343 women were operated for genital carcinoma at the 1st Gynaecological Department of the University Munich. Additionally to the corresponding cancer operations, pelvic or pelvic and paraaortic lymphadenectomy was performed. In a postoperative systematic and prospective study with ultrasound, we detected a high incidence of 48% of postoperative lymphocysts. Only a few were symptomatic and even less required therapy. In this study we were especially interested in the influence of closure of the pelvic peritoneum on the incidence of lymphocysts. Thus, we inaugurated a prospective study in 1991 with 49 patients with an open peritoneum and compared these results to 294 women who had standard closure of the peritoneum. There was a significantly higher rate of lymphocysts in patients with peritoneal closure (45.2%) in comparison to 20.4% lymphocysts in patients without peritoneal closure. In the study group (open peritoneum) 6.1% of the patients with lymphocysts showed symptoms, only 4.1% needed therapy. In the control group (closed peritoneum), 14.6% of the patients with lymphocysts were symptomatic and 8.2% needed therapy. These differences are not statistically significant. Other complications such as haemorrhage, fever or ileus were comparable in both groups. Our results do not supply sufficient proof, that leaving the peritoneum open significantly reduces symptomatic lymphocysts.

Congenital heart diseases are starting to benefit from the major advances provided by the advent of molecular biology methods. It is now possible to identify genes which are responsible for congenital heart diseases. The gene responsible for supravalvular aortic stenosis--an autosomal dominant trait--was cloned last year. It is the elastin gene. DiGeorge and Shprintzen syndromes, conotruncal anomaly face and some cardiac malformations have a common cause: a deletion of the 22q11 region resulting in a monosomy. Although the region of deletion is large, it is possible that monosomy of only one gene results in these conditions. Studies are underway to evaluate the impact of this new genetic factor on the incidence of congenital heart malformations. Studies on familial bundle branch block, and lateralization defect with midline anomalies are soon going to show a chromosomal region with the gene defect. Discovering the genes and their protein products which are implied in the cardiac morphogenesis will definitively change our understanding of these cardiac malformations.

An astoundingly high frequency of micrometastatic cells have been found in bone marrow aspirates of patients with colon carcinomas (G. Schlimok et al., J. Clin. Oncol., 8:831-837, 1990), although these tumors very rarely metastasize to the skeleton. This observation has raised questions about the malignant potential of such cells. In a first attempt to characterize this potential, we have assessed the expression of major histocompatibility complex (MHC) class I antigens on bone marrow micrometastases, inasmuch as down-regulation of these molecules is a potential mechanism to escape from MHC class I-restricted lysis by cytotoxic T-cells. The two groups of cancer patients compared were those with tumors known to rarely (stomach and colon cancer) or frequently (breast cancer) manifest skeleton metastases. Bone marrow aspirates taken from these patients were probed for individual disseminated tumor cells using the immunoalkaline phosphatase technique with monoclonal antibody CK2 to the epithelial differentiation antigen cytokeratin 18 (CK-18), as described previously (G. Schlimok et al., Proc. Natl. Acad. Sci. USA, 84:8672-8676, 1987). Specimens containing CK18-positive cells were colabeled with monoclonal antibody W6/32 directed to a framework (or nonpolymorphic) antigenic determinant of MHC class I heavy chains associated with beta 2-microglobulin. W6/32-positive CK-18-positive cells could be detected in 25 of 54 patients (46.3%) with significantly higher incidences in 26 breast cancer patients (61.9%) as compared to 28 patients with carcinomas of the stomach and colon (27.3 and 29.4%). Independent from the origin of the primary carcinoma, the incidence of W6/32-negative CK18-positive cells was positively correlated to both the differentiation grade of the primary tumor (P less than 0.05) and appeared to be linked to the occurrence of regional lymph node metastases (statistically not significant) determined by conventional histological examination. The present results demonstrate for the first time that down-regulation of MHC expression on individual micrometastatic cells correlates to the differential pattern of metastasis obtained by comparing breast and gastrointestinal carcinomas. This finding together with the suggestive link to clinical risk factors supports the significance of reduced MHC class I expression for the survival of residual metastatic cells which is a major determinant of prognosis for patients with solid tumors.

Parental permission for cardiac catheterization assumes detailed information about the character and frequency of all potential and inevitable threatening complications despite of maximal care. However, data on this subject were derived mainly from older and/or retrospective studies. In order to evaluate the actual risk we performed a prospective study lasting 11 months. All complications occurring during the 24 h following this invasive procedure were recorded. During 462 consecutive cardiac catheterizations in 421 patients (including 24 balloon-atrio-septostomies and five myocardial biopsies) there were complications requiring treatment in 18.2% of all examinations. There was no lethal complication. The following complications were documented: arrhythmia 6.5%, acidosis 6.1%, problems due to catheterizing an arterial or venous vessel 3.9% and 0.4% respectively; acute blood loss 1.5%, and problems concerning the probe in general 1.1%. In a frequency of less than 1% we encountered hypoxic spells, myocardial ischemia, hypoventilation/respiratory failure, febrile reaction, and allergic reactions due to contrast media. Contrary to data of the literature we could show a significant reduction of the risks involved in this examination. The following factors have contributed to this improvement: 1) a more careful patient selection for this invasive procedure; 2) a more experienced examiner; 3) better monitoring during the procedure; 4) a more detailed diagnostic work-up prior to the examination; and 5) better premedication of the patient.

A digoxin-like immunoreactivity (DLIS) was measured by two routinely used clinical digoxin-immunoassays (radio- and enzymeimmunoassay) in cord blood of 255 newborns, in sera of their mothers at birth and in sera of 211 newborns during the first two postpartal weeks. The highest DLIS levels were found in serum of neonates at the first day of life (median: 0.23 ng/ml, 25% and 75% percentile: 0.19 and 0.28 ng/ml) and in cord blood (median: 0.21 ng/ml, 25% and 75% percentile: 0.19 and 0.24 ng/ml); maternal serum was shown to have three times less DLIS (median: 0.08 ng/ml, 25% and 75% percentile: 0.05 and 0.10 ng/ml). There was no significant correlation between DLIS concentrations in serum of newborns, cord blood or pregnants. The DLIS serum levels of preterms with birthweight less than 2500 g and gestational age less than 37 weeks were significantly lower than those of normal neonates at term (p less than 0.01); concomitantly the lowest DLIS levels were found in maternal serum of preterms (p less than 0.01). These observations strongly suggest rather a DLIS origin in the newborn than in the mother. During the first two postpartal weeks the DLIS concentration of a vast majority of the 211 newborns (91%) decreased continuously to one half of the starting value. Within the second postpartal week preterms were found to have a significantly delayed decrease in the DLIS serum levels (p less than 0.01). Small for date newborns showed no difference in their postpartal DLIS time course compared to normal neonates.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to find out whether digoxin therapy of nursing mothers might produce discomfort in suckling infants we have investigated the kinetics of the transfer of digoxin from plasma to milk in 11 nursing mothers. After intravenous or oral application of a single dose of 0.5 mg or 0.75 mg digoxin simultaneous serum, fore- and hindmilk samples were taken. Obviously, a rapid equilibrium occurred between the serum and the milk compartments and there was no difference between fore- and hindmilk. All three digoxin concentration profiles ran parallel with a milk to serum ratio of 0.6 to 0.7. The curves could best be fitted by the sum of two exponential functions. For predicting the digoxin intake into the suckling infant, simulations were carried out on the basis of two coupled compartment models. When the kinetic milk data as well as the kinetic data obtained in infants were fitted by this model it could be shown that even in the case of long half-lives only about 3% of the therapeutic drug levels were reached in the baby. Thus, one can conclude that digoxin accumulation to toxic concentrations should not occur in infants of women treated with appropriate doses of digoxin.

Between 1963 and 1981, 1139 patients had surgery for unilateral breast cancer at the Charlottenburg Gynaecological Clinic of the Free University Berlin. A total of 948 patients had a simple mastectomy and 191 patients had an extended tumorectomy (or lumpectomy) with subsequent radiotherapy (40 Gy). Retrospective analysis of "matched cases" treated by tumorectomy or mastectomy showed the rate of local recurrence after tumorectomy to be nearly double that after simple mastectomy (8.7% after tumorectomy, 4.7% after mastectomy). Life expectancy with a local recurrence after conservative surgery, was however, better than that after simple mastectomy.

Giant cell reactions in the short tubular bones comprise mainly enchondromas, aneurysmal bone cysts and giant cell tumours. In both cases a history of trauma can be related. We therefore agree with Aegerter and Lorenzo that an intra-osseous haematoma due to minor trauma is likely to be of pathogenic significance.

Estradiol, estrone, and progesterone levels in serum and tissue were determined radioimmunologically from 160 endometrium and serum samples taken at various phases of the menstrual cycle in female patients who had undergone either curettage or hysterectomy for medical reasons. In addition, the cytoplasmatic estradiol and progesterone receptor concentrations and the (17beta-HSD) 17-beta-hydroxysteroid dehydrogenase activities in the endometrium were measured. In 132 cases, it was possible to correlate the endometrial histological findings and serum hormone levels with a particular phase of the cycle. The serum concentrations of sexual steroids displayed the usual biphasal pattern for estradiol and estrone with the postovulatory increase in progesterone. The tissue levels of these hormones followed a course partly paralled to and partly opposed to the serum levels. The progesterone profile in tissues essentially matches that in the serum except that the endometrium concentrations showed a marked prevulatory increase, with no appreciable postovulatory rise. The midcycle estradiol peak was also observed in the endometrium. After ovulation, the estradiol concentration in the tissue declined significantly. The changes in estrone levels in the secretory endometrium were at variance with those in the serum, increasing sharply after ovulation. The cytoplasmic estradiol receptor concentration exhibited a maximum in the middle of the proliferative phase and declined steadily over the rest of the cycle. The number of progesterone-binding receptors is only enhanced at midcycle. The concentration changes in the progesterone receptors could be clearly correlated with the estradiol peak in serum and tissue at midcycle. A 10-fold increase in 17beta-HSD activity is observed after ovulation, affecting changes in the tissue/serum estradiol and estrone ratios. The estradiol shifts ratio in favor of the serum during postovulatory phase, whereas the estrone ratio is displaced in favor of the tissue. A regulatory model for the endometrial cells during the menstrual cycle is suggested on the basis of the results obtained.

Hemodynamic effects of captopril were prospectively studied in 12 children suffering from dilative cardiomyopathy. Before the administration of the drug all patients were put on a stable medication of diuretics and/or glycosides. A median daily dose of 1.83 mg captopril/kg body weight was given in 3 or 4 single doses depending on age. Median body weight of the children was 18.6 kg (range 2.7-42.2) and the median age was 5.8 years (range 0.2-15). Left ventricular volume was determined in systole and diastole using 2-D echo, and the stroke volume als well as the ejection fraction were calculated. Cardiac index (CI) and systemic resistance (Rs) were measured by Doppler echo. Blood pressure and heart rate were recorded at each echo registration. ESVI (-32%), EDVI (-21%) and SVI (-7%) were significantly (p less than 0.05) reduced by short-term captopril treatment. This effect was maintained under long-term therapy. EF, CI, Rs, blood pressure and heart rate showed only minor changes under captopril. Adverse effects were recorded only in one child. They disappeared after dose reduction.

Between 1963 and 1982, 1,139 patients underwent surgery for unilateral mammary malignoma at the Charlottenburg Gynaecological Clinic of the Free University Berlin. Primary therapy consisted of simple mastectomy in 948 cases and tumourectomy/quadrantectomy with subsequent radiotherapy (40 Gy) in 191 cases. We performed a retrospective analysis of "matched samples" of tumourectomy/quadrantectomy and mastectomy. The observation period of both groups spans a minimum of one year to a maximum of 20 years after primary operation. In pT1- and pT2-tumours the overall survival after tumourectomy/quadrantectomy at 5, 10 and 15 years was no worse than after total breast removal. The results of our long-term follow-up study lead us to conclude that tumourectomy/quadrantectomy and breast irradiation are suitable for primary treatment of mammary cancer.

In 55 high-risk neonates of different birth-weight and gestational age, transcutaneous pO2 (tcpO2) was continuously monitored during transports from the Obstetric Units to the Neonatal Intensive Care Units. We were able to demonstrate that the need for oxygen was overestimated in most of the children and thus FiO2 could be reduced in nearly all cases. In this way, FiO2 can be adapted to the real need of the children and hypoxemias can be avoided as far as possible frequency and duration of hyperoxemias can be reduced. Moreover, valuable knowledge about further management of mechanical ventilation may be obtained. Complications, as e.g. obstruction of endotracheal tube, are more rapidly recognized than by ECG-monitoring alone.

Infants require higher therapeutic doses (per unit body weight and surface area) and also tolerate higher doses of digoxin than adults. In contrast premature and even mature newborns are more susceptible to digoxin intoxications. Serum protein binding contributes to the apparent volume of distribution. Since the volume of distribution for digoxin shows an age-dependency, the present study was designed to determine the plasma protein binding of digoxin in premature and mature newborns as well as in infants and adults. Using the equilibrium dialysis method the fraction of digoxin bound to serum protein averages 30% in all groups studied. Thus protein binding could not account for the differences in dosage and susceptibility of digoxin in newborns and infants as compared to adults.

The article gives a brief historical review of the now obsolete method of atmocausis and reports on two cases of very deep internal burns after direct intrauterine application of superheated steam; one of the patients died as a result of this procedure. In the thirties this method was used especially to arrest intrauterine perimenopausal bleeding, but has since been abandoned.

The results of 552 amniocenteses during the second trimester of pregnancy are reported. The amniocentesis were carried out under direct ultra-sonographic control. Six abnormal karyotypes were found and the pregnancies were terminated. Three spontaneous abortions due to intra-uterine infection following amniocentesis occurred. There were no maternal complications and no fetal injuries. 430 amniotic fluids were tested bacteriologically. Two samples showed E-coli and two samples grew staph epidermidis. The IGM values of 148 newborns with previous amniocentesis showed the same values as the IGM in newborns without amniocentesis during the pregnancy. Fetal monitoring prior and following the amniocentesis showed a temporary increase in uterine motility in 25% of the cases. Our observations and the review of the literature convinced us that complications of amniocentesis in the second trimester are rare. However, when complications occur the fetus and the pregnant woman are a serious risk. The fetal wastage caused by second trimester amniocentesis is approximately 0.5 to 1%. Therefore the patients must be informed about the risks very carefully prior to a second trimester amniocentesis.

A study has been made on the influence of estradiol, estrone, and progesterone on cytoplasmic estradiol and progesterone receptors and the 17β-hydroxysteroid dehydrogenase (17β-HSD) activity in normal myometrium and in fibromyomata during various phases of the menstrual cycle.

A study has been carried out to compare the influence of estradiol, estrone, and progesterone on the cytoplasmic estradiol and progesterone receptor levels and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity in human myometrium. The steroid hormone concentrations were measured simultaneously in both serum and cytosol of myometrial tissue. The estradiol receptor levels were highest during the midproliferative phase. The highest progesterone-binding capacity was found in myometrial cytosol around ovulation. The midcycle peak of the cytoplasmic progesterone receptor level correlated well with the first peak of tissue concentrations of estradiol and the increase of progesterone tissue concentrations. During the luteal phase, in contrast to the follicular phase, the progesterone receptor level decreased, whereas serum progesterone concentrations were high. The midcycle peak of cytoplasmic progester one-binding capacity and the increase of progesterone tissue levels at the same time were followed by an acti...

Computed tomographic findings in leiomyoma, leiomyosarcoma and benign leiomyoblastoma of the stomach are discussed. Gastroscopic biopsy was unsuccessful in every case, but CT was able to show the extragastric extension in all tumors. In one case, gastric leiomyoma and renal hypernephroma occurred simultaneously. Both tumors showed similar contrast medium enhancement, leading to a misdiagnosis.

Twenty-six women, most of them with advanced endometriosis (Stage III according to Acosta), were treated for six months with the LH-RH agonist Buserelin. After initially increased liberation both of the gonadotropins as well as of the sexual steroids there was consecutive inhibition of gonadal function, especially after inhibition of FSH secretion. Within two to four weeks estradiol production was completely and lastingly suppressed in 21 of the 26 women. In three women it lasted for three months and in two women estradiol again rose up to three times during the period of observation. Correspondingly, 22 of the women suffered from hot flushes as early as within the first two months. Twenty of the 26 women became completely free of symptoms within four to six weeks, and a clear regression of the pain was recorded in another four. In two women the complaints persisted without change. Withdrawal bleeding of short duration occurred simultaneously with the intermittent increases in estradiol levels; however, this bleeding usually caused little or no pain. Eleven of the 19 endometrium biopsies performed during therapy revealed a dormant endometrium, and only in one case was proliferated endomedium found, in the third month of treatment, in a stage of transition to hyperplasia. The remaining seven biopsies were insufficient for assessment. In seven women with advanced endometriosis, laparotomies were performed after drug treatment. Histologic study of the endometriosis tissue thus obtained revealed, except in the two nonresponders, cicatrized tissue with atrophic glands and severely reduced stroma.(ABSTRACT TRUNCATED AT 250 WORDS)

In an infant's acute theophylline intoxication following a medication error, plasma levels above 80 micrograms/ml were not associated with repetitive seizures, but also with heart rates above 200 bpm. The serum elimination kinetics were characterized by a first-order elimination process with a half-life of 15 h. Despite the exponential decay of plasma levels the heart rate remained at a high level during the first 20 h. This behavior is explained by a saturation phenomenon familiar in receptor and enzyme kinetics.