Biomedical subjects
Publications and source records attributed to B Lundberg.
An infant girl with congenital heart disease was fed glucose polymers as dietary supplements. During an attack of gastroenteritis with severe diarrhoea she developed hypernatraemic dehydration, probably due to the high osmotic load of the glucose polymers. This case illustrates the importance of giving adequate amounts of free water to a child on glucose polymers, especially during excessive fluid loss.
Proteus is an uncommon pathogen in neonatal meningitis and has, to our knowledge, not previously been described from Scandinavia. Our case illustrates the typical course of the disease when onset is within the first two weeks of life. The typical patient is a previously healthy, sometimes slightly preterm infant, who develops multiple brain abscesses and has a very poor prognosis. In cases with a later onset, factors predisposing for infection are common and the outcome is less severe. Our patient was a girl born at a gestational age of 36 full weeks, who was a little less alert than normal during the first three days and then became dramatically sick with convulsions and apnoeas. She died at the age of six days with severe brain damage.
The pharmacokinetics of free and total valproic acid (VPA) in plasma and whole blood after oral administration during steady state was investigated in seven infants (mean age 10.7 months) receiving monotherapy. The VPA concentrations in whole blood closely followed those in plasma but at a reduced level. A positive correlation was found between dose and mean plasma concentration (r = 0.71). Mean terminal half-lives were similar in plasma and whole blood (12.5 and 15.5 h, respectively), but were considerably longer than for free VPA (6.4 and 6.5 h, respectively; P less than 0.01). There was a significant decrease in half-lives with increasing age (P less than 0.05). Plasma and whole blood clearance for total VPA was higher than reported in older infants and adults (17.8 and 28.9 ml/kg per hour) and was considerably higher for free VPA (127.6 and 188.8 ml/kg per hour, respectively). The increase in clearance compared with that in older subjects is well in concordance with a lower protein binding of VPA (mean 85.3%). Of special importance is that the percentage of unbound VPA increased with increasing concentrations of total VPA. The fraction of unbound VPA in plasma increased even more in subjects with low albumin concentrations (P less than 0.01).
Herpes simplex virus (HSV) infections are common and, if afflicting the central nervous system, may cause death or severe sequelae. Since specific therapy is now available there is an increasing demand for the recognition of the various ways in which cerebral HSV-infections may be manifested. This report describes a 15-year-old boy who presented acutely with mental symptoms of confusion, hallucinations and sleep disturbance. Simultaneously, but without any increase in cerebrospinal fluid cell or protein content, an intrathecal production of HSV-antibodies of transient nature was detected. These findings suggest that the patient may have suffered from an unusual form of herpes infection in the central nervous system. We suggest that similar cases should be thoroughly explored for possible herpes etiology as early as possible during the acute phase of the disease.
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A model for performing fiberoptic bronchoscopy as a supplement to noninvasive diagnostic methods, in patients with community-acquired pneumonia, was prospectively studied. Twenty-four patients underwent bronchoscopy, seven pilot patients and 17 of 277 (6 percent) consecutive patients with CAP. Indications for FOB were early therapy failure (less than or equal to 72h)(n = 7), late therapy failure (greater than 72h)(n = 11), or before start of antibiotic therapy in severely ill or immunocompromised patients (n = 6). Samples were obtained by aspiration of bronchial secretion and with a protected brush catheter from which quantitative cultures with a detection level of 10(4) colony forming units per ml were performed. Results concluded that FOB, with the use of quantitative PB-cultures, offered a safe and specific diagnostic tool, which on special indications, can be of great value in the management of patients with CAP.
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Lipid microemulsions were prepared by sonication of mixtures of cholesteryl ester, triacylglycerol, phosphatidylcholine and cholesterol in aqueous dispersions and were purified by gel filtration. The resulting emulsion particles were characterized by differential scanning calorimetry, electron microscopy and analytical gel filtration and were shown to have the size and general organization of low-density lipoprotein. The lipid microemulsions were used as protein-free plasma lipoprotein models for studies of the receptor-independent transfer of lipids to human fibroblasts in culture. The transfer rate of [3H]cholesterol increased with the donor concentration and with the molar ratio between cholesterol and phosphatidylcholine in the donor particles. A maximal transfer value of 1 nmol per mg protein per h was obtained for cholesterol/phosphatidylcholine 1:1 particles. There was a profound temperature effect on the cholesterol transfer. The effect of altering the core lipid of the emulsion particles on the [3H]cholesterol transfer rate was small giving a somewhat higher rate with cholesteryl oleate and cholesteryl stearate than with cholesteryl linoleate. Addition of trioleoylglycerol to the cholesteryl ester core had no effect on the transfer rate. The transfer rate of palmitoyl[14C]oleoylphosphatidylcholine was found to be about 1/5 of that obtained for [3H]cholesterol. About 50% of the cell-associated [14C]cholesteryl oleate was found in the trypsin-releasable pool, while 25% was internalized by the cells at a rate of 0.06 nmol X mg-1 X h-1. Trioleoylglycerol was internalized at the same rate as the cholesteryl ester. Our data suggest that the lipoprotein lipid composition may play a role in the receptor-independent cellular uptake of cholesterol.
The receptor-mediated assimilation of low density lipoprotein (LDL) by many cancer cells is much higher than that of normal cells. This fact suggests that lipoproteins with incorporated cytotoxic drugs may be used as a carrier for chemotherapeutic agents to neoplastic cells. In this study a lipophilic cytotoxic compound is incorporated into reconstituted LDL by two different methods. Both the structure and cellular uptake were found to be similar to those of native LDL. Tests of the cytotoxic activity on cultured cells demonstrated that the drug delivered to the cells via the LDL pathway was able to kill 100% of the cells. Heparin and a low temperature, which are known to inhibit uptake of LDL by the receptor mechanism, abolished the cytotoxic activity of the drug-lipoprotein conjugates. The results suggest that it may be possible to use reconstituted LDL as a vehicle for lipophilic antineoplastic drugs in order to increase the drug accumulation and selectivity in tumor cell populations with high LDL receptor activity.
A 40-year-old white woman presented with fever, otalgia, and odynophagia and was found to have a peripheral white blood cell count of 90,000/mm3. A diagnosis of acute myelogenous leukemia was made. Further evaluation of symptoms and source for fever led to the diagnosis of Candida albicans epiglottitis. This is the first reported case of fungal epiglottitis in an immunocompromised adult.
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The effect of various physicochemical forms of substrate on the activity of acid cholesteryl ester hydrolase isolated from rat liver lysosomes was studied. The amount of sodium taurocholate was varied in the substrate mixture which contained constant amounts of egg phosphatidylcholine (PC) and cholesteryl oleate. The resulting substrate forms produced were PC vesicles, PC vesicles with incorporated sodium taurocholate, mixed micelles, and mixed micelles together with free bile salt micelles. Gradually increasing amounts of sodium taurocholate activated cholesteryl oleate hydrolysis until the molar sodium taurocholate/PC ratio of ca. 0.6; thereafter hydrolytic activity decreased rapidly. The presence of sodium taurocholate micelles clearly inhibits cholesteryl oleate hydrolysis. We therefore propose that the activation observed at low bile salt concentrations depends on bile salt interaction with the substrate vehicle, whereas the inhibition observed at high bile salt concentrations depends on sodium taurocholate interacting with the enzyme. When comparing different phospholipid components in the supersubstrate, the enzyme activity was highest in the presence of dioleoyl PC and decreased when present with dipalmitoyl PC and egg PC. Egg lysoPC completely inhibited the enzyme activity. A net negative charge on the surface of the vesicle substrate increased cholesteryl ester hydrolase activity while a net positive charge on the surface inhibited the enzyme activity. Only part of the product inhibition of cholesteryl oleate hydrolase caused by Na-oleate was reversible when tested with bovine serum albumin present in the incubation mixture.
Twelve epileptic adolescents on valproate (VPA) treatment were studied by means of clinical observation and gonadotropin-releasing hormone stimulation (GnRH) tests. Five patients were investigated before and during VPA treatment. Before treatment the basal and peak levels of gonadotropins were appropriate for age; during treatment both levels were depressed and the areas under the curves were significantly decreased. The long-term effect of VPA was studied in an additional seven patients. The basal levels of gonadotropins were as low and their response to GnRH as poor as in the second test of the first five patients--i.e., during VPA treatment. No recovery was noted in two patients after dose reduction or in a further two patients 10 months after the discontinuation of VPA treatment. In all the patients, however, the usual clinical signs of pubertal development and maturity were unaffected by VPA treatment. The significance of the results for sexual development and fertility is therefore uncertain.