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Biomedical subjects

R Lindberg

Publications and source records attributed to R Lindberg.

At least 55 records · Page 3Linked to original sources

Prevalence of debrisoquine oxidation phenotypes in glaucoma patients.

The oxidation of debrisoquine, a sympatholytic antihypertensive agent, exhibits genetic polymorphism. The debrisoquine/4-OH-debrisoquine metabolic ratio (MR) separates the population to poor (PM, MR greater than 12.6) and extensive (EM, MR less than 12.6) metabolizers. 5-10% of the caucasians belong to the PM phenotype. The oxidation of many other drugs, like timolol, correlates with the debrisoquine phenotype. We determined the debrisoquine phenotype in 102 glaucoma patients. The majority of the patients was treated with ophthalmic timolol. Five patients were classified as PMs. However, two of them were on quinidine, a well known inhibitor of debrisoquine oxidation. The prevalence of debrisoquine PM phenotype in glaucoma patients was 2.9% (excluding patients on quinidine) or 4.9% (with patients on quinidine). The figures are slightly lower than the mean value reported for the normal Finnish population. However, both figures lay within the 95% confidence limits of the prevalence of PM phenotype in the normal Finnish population. The beta-blocking activity of oral timolol is increased in PMs. The significance of timolol oxidation phenotype during ocular timolol therapy warrants further investigation.

Cross-Sectional Studies↗

Budd-Chiari syndrome secondary to hepatic vein thrombus from Wilm's tumor. Case report and literature review.

We describe a case of Budd-Chiari Syndrome in a 6-year-old boy secondary to Wilm's tumor. The patient had a right nephrectomy and mediastinotomy with removal of the tumor from the right atrium, inferior vena cava, and hepatic vein. Postoperatively, the patient had chemotherapy consisting of Actinomycin-D to be followed by radiation to the tumor bed to a total dose of 2000 rads in 10 fractions by using AP/PA field on 6 MeV Linear Accelerator. Currently, the child is receiving combination chemotherapy.

Budd-Chiari Syndrome↗

Treatment of soft tissue sarcomas by preoperative irradiation and conservative surgical resection.

From 1970-1984, 114 patients with soft-tissue sarcomas received preoperative irradiation at U.T.M.D. Anderson Hospital. Two patients refused surgery and two had progressing disease and therefore did not proceed to surgery; in the remaining 110 patients, conservative surgical resections were performed 3-6 weeks following irradiation. Analysis of survival by histologic type, age, primary size, and histologic grade revealed a significant negative correlation with grade 3 and to a lesser extent to primary size greater than 15 cm. Eleven patients failed within the radiation portal for the primary, four in conjunction with distant metastases. Of the remaining seven, four were salvaged by further surgery for an ultimate primary-only failure rate of three. Distant metastasis occurred in 35 patients and was the major mechanism of treatment failure in this experience. Adjunctive chemotherapy was not used for the majority of patients and it remains to be seen if its routine employment in large, high-grade, lesions will diminish the deaths caused by distant metastases.

Adult↗

Debrisoquine oxidation in a Finnish population: the effect of oral contraceptives on the metabolic ratio.

1. The debrisoquine hydroxylation phenotype was assessed in 211 healthy subjects of Finnish Caucasian origin. 2. A bimodal distribution was observed in the urinary debrisoquine/4-hydroxydebrisoquin ratio. Eleven subjects (about 5%) were poor metabolizers of debrisoquine, when a ratio of 12.6 was used as the cut-off point. 3. The mean metabolic ratio of 35 extensive metabolizers taking oral contraceptives was slightly lower than that of extensive metabolizers not taking contraceptives. This indicates that oral contraceptives may change the phenotyping near the metabolic ratio of 12.6. 4. The metabolic ratios were determined in eight subjects using both 4 h and 6 h urine collection times. The metabolic ratios corresponded well with each other indicating the usefulness of the shorter 4 h collection time.

Adult↗

Noradrenergic and dopaminergic effects of nomifensine in healthy volunteers.

Intravenous doses (100 mg in 20 minutes) of the antidepressant drug nomifensine, administered to male volunteers, increased heart rate and blood pressure, elevated the plasma levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and powerfully stimulated growth hormone release and inhibited the secretion of prolactin. Oral nomifensine, either as a single 100 mg dose or as a similar dose after 2 weeks' treatment with the drug (150 mg/day), caused none of the above effects. This was in line with the limited (less than 30%) oral bioavailability of the active, unconjugated form of the drug, estimated in the same subjects. MHPG in plasma was slightly but consistently reduced by the 2 weeks' treatment, suggesting reduced turnover of norepinephrine. The observed clinical effects of nomifensine are compatible with uptake inhibition and augmented release of norepinephrine and dopamine and possibly direct agonistic effects on dopamine receptors. Although nomifensine was withdrawn from the market because of immunologic complications, it serves as a model compound of a new pharmacologic class of antidepressants, devoid of many of the disturbing side effects of the tricyclic drugs.

Adult↗

Reduction of pain at venous cannulation in children with a eutectic mixture of lidocaine and prilocaine (EMLA cream): comparison with placebo cream and no local premedication.

The local analgesic efficacy of a cream formulation of lidocaine and prilocaine (EMLA) in reducing pain at venous cannulation was investigated in children scheduled for elective surgery. Forty children participated in a double-blind, randomized comparison between EMLA and inactive placebo cream. Another group of 18 children without any local treatment was studied as an additional control material. Subjective pain scores, expressed with a visual analogue scale, were significantly lower in the EMLA group compared with both the group treated with placebo cream (P less than 0.001) and the open control group (no cream; P less than 0.01). Local pallor and slight oedema were the only side-effects, registered in both cream-treated groups. A preliminary study was also carried out with 10 children (five with EMLA and five without) in order to determine whether catecholamine and vasopressin levels in venous blood are affected by the stress and anxiety associated with venepuncture in children premedicated with oral flunitrazepam. No significant hormone responses were, however, detected. The lidocaine concentrations measured in venous blood taken from the application site of EMLA cream were low, and there were no measurable levels of lidocaine in simultaneous blood samples from the opposite extremity. In our opinion EMLA cream is safe and alleviates effectively the pain associated with venepuncture, and thus deserves a place in the routine premedication of children.

Administration, Cutaneous↗

Sympatho-adrenal and pituitary hormone responses during and immediately after thoracic surgery--modulation by four different pain treatments.

Four different pain treatments (single intercostal block with bupivacaine, repeated intercostal block, epidural morphine and epidural bupivacaine infusions) were compared in 39 patients subjected to lung surgery under general anaesthesia. The patients' own estimate of the postoperative pain was not significantly different between the groups, but the epidurally treated patients required fewer doses of supplementary analgesic than those given just a single dose of intercostal bupivacaine. Bupivacaine levels in blood were below the toxic range in all groups. The concentration of antidiuretic hormone in blood was increased early during the operation, and had only partly returned to normal on the first postoperative morning. Growth hormone in plasma was increased only at the end of the operation. Catecholamine levels in blood increased gradually, reaching their peak postoperatively. There were only slight differences between the groups in these posterior and anterior pituitary and sympatho-adrenal responses to surgical stress. Thus, neither repeated intercostal blockade nor epidural administration of morphine or bupivacaine could prevent the endocrine responses to thoracic surgery, in spite of significant, albeit incomplete, pain relief. This was probably caused in part by residual pain, and also by poor access of the extradural medications to the autonomic afferent pathways mediating nociceptive signals from thoracic organs and tissues.

Aged↗

Placental and blood-CSF transfer of intramuscularly administered atropine in the same person.

Both placental and blood-CSF transfer of atropine (0.01 mg/kg intramuscularly) was measured (by RIA) in 11 parturients undergoing Caesarean section under spinal analgesia. In the foeto-placental unit a significant penetration into amniotic fluid was found, whereas in CSF there was a measurable level of the drug (greater than 1.5 ng/ml) in only one mother. Our results show that there is a fundamental difference in the penetrability of tertiary ammonium alkaloids like atropine through these two biological membranes. However, our results concern penetration into human lumbar CSF and do not necessarily reflect potential penetration into the ventricular CSF, choroid plexus or brain ventricular ependyma.

Amniotic Fluid↗

Inhibitory effects of neuroleptics on debrisoquine oxidation in man.

Liver oxidative metabolism, assessed by debrisoquine hydroxylation test, was studied in 107 healthy volunteers and in 71 patients with or without neuroleptic drug treatment. The mean metabolic ratio (MR = debrisoquine/4-hydroxydebrisoquine excretion in the urine) was 2.8 +/- 0.1 (s.e. mean) in the control group, six persons being poor metabolizers of debrisoquine (MR greater than or equal to 12.6). The mean MR (12.1 +/- 1.5) was significantly higher in those 42 patients taking neuroleptics than in patients without neuroleptics (0.8 +/- 0.1). In the former group, seventeen patients had a MR exceeding 12.6. Oral contraceptives, antiepileptics, benzodiazepines and progestin derivates did not increase MR values, the highest individual ratio being 2.72 in those subjects not receiving neuroleptics. These results suggest a probable competitive inhibition of oxidative metabolism by neuroleptics. This is a phenomenon of potential clinical importance both in patients with an inherited poor metabolic capacity and in patients receiving other drugs like beta-adrenoceptor blocking agents and tricyclic antidepressants oxidized by the same enzyme system.

Adolescent↗

Epidural and paracervical blockades in obstetrics. Catecholamines, arginine vasopressin and analgesic effect.

A comparative study of analgesic and endocrinologic effects of obstetrical epidural anesthesia (EA, n = 23) and paracervical block (PCB, n = 39) was performed. Pain intensity was assessed on a horizontal linear scale. Simultaneously, blood samples for the determination of concentrations of norepinephrine (NE), epinephrine (E) and arginine vasopressin (AVP) were obtained. NE and AVP levels did not bear any relationship to pain scores. Instead, the average plasma E profile during labor was practically identical with the profile of pain scores. Plasma levels of E decreased significantly after EA. A similar but short-lived effect was observed also after PCB. When comparable doses of bupivacaine were used (30 mg in the EA group and 25 mg in the PCB group); initial pain relief after EA and PCB was similar, though after 30 min the pain score increased for patients who received the PCB, while patients who received EA had continued pain relief. Faster absorption of bupivacaine was observed after paracervical than epidural injection. Decreased variability was seen in the fetal cardiograms in 25% after EA and in 33% after PCB. Transient bradycardia was observed in 2 cases after paracervical injection.

Adult↗

Topography and enterocyte morphology of the small bowel mucosal surface in equine granulomatous enteritis.

The jejunal mucosa of 4 cases of equine granulomatous enteritis and 2 control horses was investigated by light microscopy and by scanning and transmission electron microscopy. Attention was focused upon changes in mucosal topography and enterocyte morphology in the inflamed mucosa. Structural changes ranged in severity from only a slight thickening and shortening of villi to the appearance of a virtually flat mucosa, upon which crypts opened directly or through shallow cavities encircled by collars of epithelial cells. Between these extremes, the mucosa showed a variety of patterns, all characterized by distinctly abnormal villus projections. These were often united by epithelial bridges and were commonly markedly short, broad and irregular. Enterocytes of mildly changed mucosae showed a normal histology and fine structure, whereas more severely changed specimens displayed a flattened surface epithelium with ultrastructural abnormalities, the most consistent being a pronounced shortening of microvilli. In particular, greatly flattened cells showed evidence of cellular injury, such as prominence of cytolysosomes and degenerative changes of the rough endoplasmic reticulum, while other cells were chiefly characterized by an abundance of non-membrane-bound ribosomes and other features signifying an immature state. Cell-membrane-tight junctions of the surface epithelium appeared to be intact. No intracellular micro-organisms were detected. It is suggested that several factors are involved in the creation of the abnormal mucosal topography in this disease, including excessive enterocyte loss, crypt cell destruction, inflammatory distension of villi and villus fusions.

Animals↗

The monitoring of serum chloramphenicol levels in children with severe infections.

Serum chloramphenicol levels were evaluated in 52 children with severe infection treated intravenously with chloramphenicol succinate and orally with chloramphenicol palmitate, chloramphenicol monostearoylglycolate or chloramphenicol in capsules. Effective serum levels were recorded with all chloramphenicol preparations. The variability was largest with chloramphenicol monostearoylglycolate. In a case of neonatal Escherichia coli meningitis good serum levels of chloramphenicol were achieved with chloramphenicol palmitate orally, supporting the view that oral chloramphenicol palmitate can be used to treat serious infections in this age group. Our data and those in the literature show that monitoring of serum chloramphenicol levels in neonates is necessary. After the neonatal period monitoring of serum chloramphenicol levels is useful in avoiding too high concentrations. On the other hand, toxic effects of high concentrations can be recognized from reticulocyte and haemoglobin, neutrophil and platelet counts, which should be performed every three to four days.

Adolescent↗

Serum concentrations and urinary excretion of lidocaine and its two desethylated metabolites after spinal anaesthesia using lidocaine or lidocaine with phenylephrine.

In 13 patients undergoing transurethral prostatic resection under spinal anaesthesia with heavy lidocaine or with heavy lidocaine plus phenylephrine hydrochloride, the serum concentrations of lidocaine, monoethylglycinexylidide and glycinexylidide and their renal excretion were measured with a HPLC method. Seven patients were given lidocaine alone 1.25 mg/kg and six lidocaine 1.25 mg/kg mixed with phenylephrine hydrochloride 3 mg. There was no significant difference between the two groups either in the serum levels of lidocaine or in the renal excretion rate of lidocaine and its metabolites. This finding gives support to the opinion that phenylephrine in low doses has no prolonging effect on spinal anaesthesia performed with heavy lidocaine.

Aged↗

Determination of theophylline in serum with the Seralyzer Aris reagent strip test evaluated.

We evaluated a new Seralyzer Aris reagent strip test (Ames Div., Miles Labs.) for the determination of theophylline in human serum. The method is based on the monoclonal enzyme immunoassay with dry reagent chemistry. The analysis is rapid and simple to perform: results are available only 5-10 min after receipt of the sample. Intra-assay precision (CV) was 2.2-3.3% (n = 15) for theophylline concentrations of 5-25 mg/L; interassay CV was 5.9% (n = 19) at 15 mg/L. The results (y) agreed well with those by liquid chromatography (x): r = 0.949 (p less than 0.001), and y = 0.967x + 0.214. We conclude the method is useful for rapid evaluation of theophylline concentrations in asthmatic patients.

Antibodies, Monoclonal↗