Disposition of sandostatin, a new synthetic somatostatin analogue, in rats

The distribution, excretion, and metabolism of Sandostatin, a long-acting octapeptide analogue of somatostatin, have been studied in the rat after iv administration. Similar plasma levels and excretion values were observed by using radioimmunoassay and HPLC-liquid scintillation techniques. For the latter technique Sandostatin was radiolabeled with either 14C or 3H. The plasma pharmacokinetics of Sandostatin were as follows: Vdss = 0.4 liter/kg, C/t = 4.2 ml/min, and t1/2 2.0 hr; this half-life was by far longer than that of somatostatin. The in vitro protein binding amounted to 59% in rat plasma; no Sandostatin was taken up by blood cells. The tissue concentrations of Sandostatin were similar when determined either by radioimmunoassay or by quantitative whole-body autoradiography; this suggests that the distribution of 3H or 14C radioactivity observed 0.5 hr after iv administration mostly represented unchanged Sandostatin. Kidney and liver were the only tissues in which Sandostatin levels were higher than in blood; high radioactivity levels were observed in the blood vessel walls, whereas levels in brain were insignificant. Unchanged drug accounted for most of the radioactivity found in plasma, urine, and bile, whereas only traces of unchanged drug were detected in feces. These results demonstrated the metabolic stability of Sandostatin in the tissues, primarily in the liver, and suggested an extensive degradation in the intestinal tract. The degradation products consisted of smaller peptides and free amino acids. About 50% and 20% of the applied dose were excreted as unchanged Sandostatin in bile and urine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Transcranial Doppler ultrasonography in head and neck tumors

Transcranial Doppler ultrasound (TCD) recording is a non-invasive diagnostic procedure for the evaluation of the cerebral collateral flow in patients, in whom therapeutic ligation or resection of the common and/or internal carotid artery is planned. Patients are first examined under resting conditions, and then under manual compression of the ipsilateral carotid artery. Since January 1989, 31 ENT and neurosurgical patients have been examined. In all patients an immediate decrease in flow velocity in the middle cerebral artery (mca) of about 25% to 90% was recorded. In 42.8% of the patients the mca flow velocity reached 90% or more of its value under normal conditions within a short period. In 29% of the patients the mca flow velocity under manual compression of the carotid artery remained under 50% of its original value. In 68% of the cases TCD with manual compression of the carotid artery showed reliable results for the function of cerebral collateralisation as a prognostic factor of the risk of ischaemia due to haemodynamic changes after carotid ligation. In these cases no further examination of the cerebral collateral flow conditions was needed. The method is inexpensive, reproducible, and in comparison with cerebral angiography, convenient and non-hazardous for the patient.     

Identification of antiarrhythmic drugs and their metabolites in urine

Identification of the antiarrhythmic drugs ajmaline, aprindine, diltiazem, disopyramide, flecainide, gallopamil, lidocaine, lorcainide, mexiletine, phenytoin, prajmaline, propafenone, quinidine, sparteine, tocainide and verapamil and their metabolites in urine is described. After acid hydrolysis of the conjugates, extraction and acetylation, the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 72, 84, 86, 136, 224, 266, and 426, the possible presence of antiarrhythmic drugs and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The method presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.     

Emergency aortic valve replacement for critical aortic stenosis

Objective: To demonstrate that emergency aortic valve replacement can be successfully performed in patients with critical aortic stenosis and reduced left ventricular function even in cardiogenic shock with associated severe multiple organ failure. Design: Retrospective, consecutive case series. Setting: Multidisciplinary intensive care unit of a tertiary care university hospital. Patients: Five patients admitted to the intensive care unit with critical aortic stenosis (aortic valve area 0.56 ± 0.13 cm²) and greatly reduced left ventricular ejection fraction (20 ± 3 %) in prolonged cardiogenic shock and associated multiple organ failure (Multiple organ failure score 6.8 ± 0.5; Acute Physiology, Age, and Chronic Health Evaluation III score 91 ± 27). Intervention: Emergency aortic valve replacement. Results: All patients survived with full recovery of organ function. At follow-up (18 ± 10 months) all patients were in New York Heart Association functional class I or II with improvement of left ventricular ejection fraction to 48 ± 25 %. Conclusions: This excellent outcome suggests that emergency aortic valve replacement should be strongly considered in patients with critical aortic stenosis even in cardiogenic shock and multiple organ failure.     

One-year results: palatal implants for the treatment of obstructive sleep apnea.

OBJECTIVE: To evaluate long-term effectiveness of palatal implants for treatment of mild to moderate obstructive sleep apnea (OSA). STUDY DESIGN: A prospective study of 26 referred patients with a pretreatment apnea-hypopnea index (AHI) of 10 to 30 and a body mass index of < or =30, representing an extended follow-up of a subset of 41 patients enrolled in previous short-term trials. RESULTS: Twenty-one of 26 patients (80.8%) experienced a decrease in AHI. Fifteen of 26 patients (57.7%) had a follow-up AHI <10 at 1 year, whereas 13 patients (50%) had a 50% or greater reduction to an AHI <10 at 1 year. Mean AHI was reduced from 16.5 +/- 4.5 at baseline to 12.5 +/- 10.5 at 3 months (P < 0.014) and to 12.3 +/- 12.7 at 1 year (P < 0.019). CONCLUSIONS: Patients initially responding to palatal implants with improved AHI maintained improvement through long-term follow-up at 1 year.     

Recombinant human interferonsα,β andγ reduce the antiproliferative action of cytarabine in K562 human myeloid leukaemia clonogenic cells

Summary The effects of recombinant human interferons , and (IFN) on the antiproliferative activity of cytarabine in K562 human myeloid leukaemia clonogenic cells were studied in an agar capillary microassay. The addition of IFN- did not affect the antiproliferative activity of cytarabine in K562 cultures treated with low concentrations of cytarabine (10–50 nM), whereas in those treated with high concentrations (100–150 nM) IFN increased the IC₅₀ of cytarabine on day 5 from 102 nM to 214 nM, i.e., cytarabine combined with IFN was about two-fold less potent than cytarabine alone. Similarly, low concentrations of IFN and IFN did not affect the antiproliferative activity of cytarabine on K562 colonies, but high concentrations of these two interferons: 4×10³ U/ml and 10⁴ U/ml respectively, increased the IC₅₀ of cytarabine on day 5 to 304 nM and to 316 nM respectively, i.e. cytarabine combined with IFN or IFN was about threefold less potent than cytarabine alone. The evaluation of the present negative interactions of interferons with cytarabine is warranted in fresh cells from myeloid leukaemia patients in primary culture.Abbreviation IFN interferon     

Temporomandibular joint: morphology and signal intensity characteristics of the disk at MR imaging

Magnetic resonance (MR) imaging has been used in the temporomandibular joint (TMJ) primarily to define the disk position. This report examines altered morphology and signal intensity characteristics of the TMJ disk as they relate to the severity of internal derangement. Two hundred sixteen joints in 133 patients with a history of such derangement. were imaged with MR. Disk position, signal intensity, morphology, and the presence of osteoarthritis were determined for each joint. The normal disk was not anteriorly displaced and had a normal "bow-tie" shape. A grade 1 disk was anteriorly displaced and had a normal shape; a grade 2 disk was anteriorly displaced and had an abnormal shape. Forty (19%) joints were considered normal; none of these exhibited osteoarthritis. One hundred thirty-nine (64%) joints were grade 1; osteoarthritis was found in 17%. Thirty-seven (17%) were grade 2; osteoarthritis was found in 95%. All forty normal joints had high or intermediate signal intensity in the disk. Osteoarthritic joints had a higher percentage of disks with diminished intensity (P less than .0001). Severe or untreated osteoarthritis is known to be a complication of TMJ internal derangements; hence this grading system seems to correlate with the severity of internal derangement.