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S Bakke

Publications and source records attributed to S Bakke.

8 recordsLinked to original sources

Efflux of rhodamine from CD56+ cells as a surrogate marker for reversal of P-glycoprotein-mediated drug efflux by PSC 833.

The expression of high levels of P-glycoprotein (Pgp) in circulating mononuclear cells allowed us to use an ex vivo assay as a surrogate measure of Pgp antagonism. Efflux of rhodamine from CD56(+) cells was measured before the start of PSC 833 and at varying times thereafter. Patients receiving PSC 833 had decreased rhodamine efflux from their circulating CD56(+) cells. Time course studies showed that following a single oral dose of PSC 833, decreased rhodamine efflux was found in some patients within 15 minutes of treatment. Maximal inhibition was observed at times ranging from 45 minutes to 60 minutes. A dose-response relationship was shown between the concentration of PSC 833 in the blood and the inhibition of rhodamine efflux, with an apparent plateau of the inhibition of rhodamine efflux at approximately 1,000 ng/mL. The Ki, defined as the concentration required for half-maximal inhibition of Pgp-mediated rhodamine efflux, was determined to be in the range of 29 to 181 ng/mL; although results in two patients were distinctly different, with Ki values of 914 and 916 ng/mL. MRK-16 staining was similar among all patients. We conclude that measurement of rhodamine efflux from CD56(+) cells provides a surrogate assay with the potential for monitoring Pgp antagonism in clinical trials.

ATP Binding Cassette Transporter, Subfamily B, Mem

Childhood autism: the need for physical investigations.

In this paper the results of an extensive medical investigation of 25 children with childhood autism are presented and compared with those found in a group of non-autistic individuals matched for sex, age and intellectual level, all referred for developmental deviancy of unknown etiology. The examination included a psychiatric assessment and a neurological examination in addition to neurophysiological, chromosomal, metabolic and neuroimaging evaluation. In the clinical examination macrocephaly was found only among the autistic individuals, while the frequency of pathological cerebral CT and clinical parameters such as tendon reflexes and mobility problems was significantly greater in the control group. All the other pathological findings were found to occur with the same frequency in the two groups. Except for research purposes this study did not lend support to those who argue for extensive medical examinations for all children with autism. Based on the present findings, ordinary procedures for assessment of developmentally delayed children should be followed. This should include a systematic clinical neuropaediatric examination, an assessment of vision and hearing and a chromosome study, including that for fragile X.

Adolescent

Sandostatin LAR in acromegalic patients: long-term treatment.

We have evaluated the long term effects and safety of Sandostatin LAR, a long acting formulation of octreotide, during 18 subsequent injections given every fourth week to 14 octreotide-sensitive acromegalic patients. The dosages (20, 30, or 40 mg) were adjusted according to GH response, side-effects, or symptom relief and assessed on day 28 after each injection. We found a stable and consistent suppression of GH and insulin-like growth factor (IGF-I) during the entire study period. Daily mean GH levels were suppressed below 2 micrograms/L in 9, to between 2-5 micrograms/L in 3, and to between 5-10 micrograms/L in 2 patients. The corresponding IGF-I values were suppressed to below 500 micrograms/L in 9 patients and to between 500-1000 micrograms/L in the remaining 5 patients. Increasing the dosage of Sandostatin LAR from 20 to 30 mg had no obvious additional effect on GH suppression, but provided a further decrease in IGF-I levels. Forty milligrams of the drug had no additional effect on GH or IGF-I compared to 30 mg. Acromegalic signs and symptoms improved during treatment. Although the fluctuations of daily mean octreotide levels were high, dosage increments caused an increase in the average serum concentration in the individual patient. Pituitary tumor size reduction was seen in all previously untreated patients (n = 4). We found only minor changes in glucose metabolism (oral glucose tolerance test and hemoglobin A1C) during treatment, but no biologically relevant changes in thyroid function (TSH, T3, and free T4). One patient developed asymptomatic gallstones, and another acquired vitamin B12 deficiency during treatment. The drug is well tolerated during long term treatment. Sandostatin LAR may well be the future medical treatment of choice for acromegalic patients.

Acromegaly

Fractionated stereotactic radiation therapy for intracranial arteriovenous malformations.

Fractionation of radiotherapy is a radiobiological advantage because the radiation effects on healthy brain tissue are reduced. We used fractionated stereotactic radiotherapy for cerebral arteriovenous malformations employing a modified linear accelerator and a noninvasive stereoadaptor. The treatment was given in two sessions (1,400 cGy x 2). Control angiography at least 2 years after treatment was performed on 20 patients. The malformation was completely eliminated in 14 of 15 patients with small arteriovenous malformations. None of the 5 patients with large malformations had their lesion eliminated, but in 4 the malformation was significantly reduced. Fractionated stereotactic radiation therapy using a conventional accelerator is an effective and safe technique in the treatment of intracranial arteriovenous malformations and compares favorably to radiosurgery.

Adolescent

Primary malignant melanoma of the lacrimal sac.

A case report of a primary malignant melanoma of the lacrimal sac is presented. After excision a local recurrence appeared one year later. Wide, but incomplete excision and postoperative irradiation resulted in local tumour control for 4 years. The patient succumbed to a uremic death caused by a rectal cancer removed 3 years before the occurrence of the malignant melanoma.

Adult

Long-term treatment of macroprolactinomas with CV 205-502.

The long-term efficacy and tolerability of CV 205-502, a non-ergot dopamine agonist with D-2 receptor affinity, were studied for up to 36 months in 16 patients with macroprolactinomas. Prolactin values were reduced in all cases, becoming either normalized or suppressed in 12. The pituitary tumor size was reduced in the 13 patients with an obvious tumor and visual function normalized in all six patients with initial defects. Concomitantly we observed improvement in gonadal function, galactorrhea, headache, libido and general well-being. Adverse reactions were experienced by 15 patients during dosage increment and caused one patient to discontinue the medication. Seven patients had persistent adverse effects which prohibited a dosage increase of CV 205-502, sufficient to normalize PRL levels in three. Two patients experienced serious adverse events, causing the discontinuation of treatment in one case. In eight patients treatment with CV 205-502 and bromocriptine could be compared. Three patients responded better to CV 205-502 than to bromocriptine treatment. Only one patient preferred bromocriptine to CV 205-502 for long-term treatment. We conclude that CV 205-502 is an effective and in most cases well-tolerated treatment for patients with macroprolactinomas. CV 205-502 is preferable to bromocriptine as an initial treatment and should also be tried in patients where treatment with bromocriptine has failed.

Adult