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Biomedical subjects

P Ott

Publications and source records attributed to P Ott.

At least 109 records · Page 6Linked to original sources

Consumption, overdose and death from analgesics during a period of over-the-counter availability of paracetamol in Denmark.

During the period 1978-1986, annual sales of paracetamol in Denmark increased from 1 million defined daily doses (DDD) (3 g) to 47 million DDD, while the number of admissions and deaths from overdose increased from 26 to 202 and from 1 to 3-4, respectively. The corresponding figures for salicylates are a decrease in sales from 113 to 94 million DDD, an increase in admissions from 282 to 595, and an increase in deaths from 5 to 22. From 1 January 1984 paracetamol became available on an over-the-counter basis. The figures for 1983 and 1984 were an increase in sales from 14 to 28 million DDD, an increase in admissions from 114 to 198, and an increase in deaths from 0 to 4. The number of deaths from opioid overdose remained constant at a value of about fifty during this period, the mortality per dose being about 20-fold higher than for paracetamol and salicylates. Dextropropoxyphene-related deaths increased twofold to 121 in 1986, with unchanged sales figures. A campaign launched by the National Board of Health resulted in a reduction in the number of deaths from dextropropoxyphene to 66 in 1987. The main effect of over-the-counter release of paracetamol was a dramatic increase in sales, without the epidemic of deaths observed a decade ago in the UK. It is suggested that the higher mortality of paracetamol poisonings in the UK compared to Denmark is related to the dextropropoxyphene content of the combination product, which is not available in Denmark. From an epidemiological toxicological viewpoint such combinations are not justified.

Acetaminophen↗

The influence of extracorporeal circulation on erythrocytes and flow properties of blood.

The influence of extracorporeal circulation on red blood cells and flow properties of blood was studied in 10 patients undergoing aorta-coronary bypass grafting. Blood samples were drawn on admission, under general anesthesia before the operation, during extracorporeal circulation, immediately after extracorporeal circulation, and 24 hours after extracorporeal circulation. Echinocytes were found during and shortly after extracorporeal circulation, but disappeared within 24 hours. Washing the cells in buffer restored the normal discocytic shape, which indicated that a plasma factor was responsible. Red cell membrane lipids were not affected. Analysis of the membrane proteins revealed a decrease of ankyrin after extracorporeal circulation, which was prevented by protease inhibitors during preparation. This suggests an increased proteolytic activity of the plasma after extracorporeal circulation. Red cell deformability was not altered. Plasma viscosity and hematocrit were markedly reduced by hemodilution with the priming solution. Their low levels resulted in a low blood viscosity during extracorporeal circulation, which was even lower at 26 degrees C than before or after the operation at 37 degrees C. We conclude that the red cell is affected by extracorporeal circulation. The flow properties of blood, however, are not impaired, but are improved by hemodilution.

Aged↗

Predicting failure of low-dose prophylactic heparin in general surgical procedures.

Despite prophylaxis with low-dose heparin (LDH), postoperative thromboembolism (TE) still occurs in 10 per cent of patients undergoing abdominal operations. To identify predictors of TE in spite of LDH, 171 patients undergoing abdominal operations and receiving LDH were screened with the fibrinogen uptake test. Diagnosis of TE was confirmed in 24 (14 per cent; 95 per cent confidence limits of 9 to 20 per cent) by either venography or pulmonary scintigraphy, or both, or autopsy. As analyzed by multiple logistic regression, only age, body mass index, preoperative hemoglobin concentration and colorectal operations (yes or no) contributed to the prediction of failure of LDH, whereas sex, malignant lesion, previous TE, hypertension, diabetes mellitus and varicose veins did not. Based on the first 81 patients, an index was constructed that was able to identify 11 of 13 patients with TE and exclude 34 of 68 without TE. This index was then applied on a second series of 90 patients in whom it correctly identified ten of 11 patients with TE and excluded 40 of 79 patients without TE. It is concluded that, with the use of the index, it is possible to identify a group of patients undergoing elective abdominal operations in whom LDH is not sufficient prophylaxis. A practical approach to bedside prediction of failure of LDH prophylaxis by use of a simple score table is suggested.

Abdomen↗

A simple technique for predicting maintenance dosage of warfarin--is it better than empirical dosing?

In a prospective, randomised trial the clinical utility of a predictive warfarin maintenance dosing technique was compared with the more commonly employed empirical dosing method. A preliminary study in 35 patients established the applied technique for predicting the maintenance dosage of warfarin from the prothrombin activity on Day 4 of initial standardised warfarin administration. Forty-three patients admitted with venous thrombotic disease were investigated. All received the same loading dose of warfarin (10 mg daily) until the prothrombin percentage activity (Normotest) was less than 25%. Significantly more patients were correctly stabilised when warfarin doses were based on prediction than when they were empirically adjusted (86% vs 50%). Also, the median number of days to achieve stable anticoagulation was lower (8 vs 11 days). It is concluded that this simple predictive technique to determine the maintenance dosage of warfarin is superior to empirical dosing.

Adolescent↗

Haemolytic anaemia in analpha-lipoproteinaemia (Tangier disease): morphological, biochemical, and biophysical properties of the red blood cell.

A patient with familial analpha-lipoproteinaemia (Tangier disease) was found to have stomatocytosis and haemolytic anaemia. The analysis of the red cell membrane constituents revealed a low cholesterol content (90 nmol/ml red cells, control 130 nmol/ml red cells), a decreased cholesterol/phospholipid ratio (0.54, control 0.78), high phosphatidylcholine (41.5%, control 30.6%) and low sphingomyelin (18.8%, control 27.6%). The electrophoretic membrane protein pattern was normal. Osmotic gradient ektacytometry and osmotic resistance showed a decreased surface/volume ratio, which caused an increased filtration resistance in 3 microns pores. The elasticity of the membrane was unchanged. Functional membrane properties were altered: the anion exchange rate was increased, whereas alkali cation fluxes were normal. The capacity to release vesicles was reduced. This case represented a new type of stomatocytosis. It contributes to the understanding of the role of cholesterol and phospholipids in the red cell membrane and biomembranes in general.

Anemia, Hemolytic, Congenital↗

Erythrocyte phospholipid organization and vesiculation in hereditary high red cell membrane phosphatidylcholine hemolytic anemia.

We have studied the erythrocyte membrane phospholipid organization in hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) and the response of these red cells during incubation with sonicated suspensions of dimyristoylphosphatidylcholine (DMPC). Although both the absolute and relative amounts of phosphatidylcholine were elevated in these red cells, the relative distribution of phosphatidylcholine on both sides of the membrane bilayer and the transbilayer mobility of phosphatidylcholine were normal. HPCHA erythrocytes showed elevated absolute amounts per cell of both protein and lipid and an increased cellular ratio of protein to phospholipid. Incubation of normal red cells with DMPC led to the formation of echinocytes, followed by the release of acetylcholinesterase-containing vesicles. Both echinocyte formation and vesiculation were markedly reduced in red cells from patients with HPCHA. Studies with red cells from patients with liver disease, cells that also have elevated relative amounts of membrane phosphatidylcholine and increased amounts of lipid per cell, revealed normal echinocyte formation and normal DMPC-induced vesiculation. We conclude that the altered lipid composition of HPCHA erythrocytes per se is not responsible for the observed reduction in DMPC-induced vesiculation, but that it is more likely the result of a modification in the protein moiety of these cells. This putative protein abnormality could enhance binding of phosphatidylcholine to red cell membranes and could explain the elevated phosphatidylcholine content of HPCHA erythrocytes and their inability to vesiculate.

Anemia, Hemolytic, Congenital↗

[Doxazocin].

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Animals↗

Assessment of D-dimer in plasma: diagnostic value in suspected deep venous thrombosis of the leg.

D-dimer, a fibrin degradation product containing the gamma-gamma crosslink of fibrin, can now be assayed by the use of highly specific monoclonal antibodies. Such assays are not influenced by fibrinogenolysis and measurements can be performed on citrated plasma. The diagnostic values of four such assays--two based on ELISA technique and two on latex agglutination--were evaluated in 108 out of 118 consecutive patients admitted with suspected deep venous thrombosis of the leg. With cut-off limits defined by a pilot study and with venography as reference, a negative D-dimer test was confirmed in 45 of 46 patients (98%; 95% confidence limits: 88-99.9%) after ELISA-M, in 43 of 44 (98%; 88-99.9%) after ELISA-S, in 54 of 67 (81%; 69-89%) after Latex-M and in 40 of 44 (91%; 78-97%) after Latex-S. A positive D-dimer test was confirmed in 61% (48-73%), 59% (46-71%), 63% (47-78%), and 55% (42-67%) respectively. These data suggest the use of one of the ELISA assays for screening. A negative D-dimer test excludes deep venous thrombosis, whereas a positive D-dimer should be followed by venography. By this procedure a 40% reduction of venographic examinations can be expected.

Acute Disease↗

Effects of daytime noise load on the sleep-wake cycle and endocrine patterns in man: II. 24 hours secretion of anterior and posterior pituitary hormones and of cortisol.

The present study examines the effects of auditory stress on the plasma levels of pituitary hormones and cortisol. Each of twelve healthy male subjects participated in two experimental series; during one of them they were exposed to 85 dB(A) industrial noise from 9:00 to 21:00 h. Blood samples were taken by an indwelling venous catheter for 24 h at intervals of 20 min from 8:00 to 8:00 h. The plasma levels of ACTH, growth hormone, prolactin, oxytocin, vasopressin and cortisol were determined. In all subjects except one noise stress affected the profiles of the pituitary hormones but the responses were interindividually different. The oxytocin level was significantly elevated (p less than .01), ACTH also responded but less clearly, whereas the other hormones reacted only in individual cases. During the subsequent night sleep only PRL concentrations were elevated above the baseline plateau in several subjects. It was concluded that in humans the pituitary responses to noise stress are highly individual.

Adult↗

Modulation of red cell vesiculation by protease inhibitors.

Release of vesicles from human red cell membranes was induced either by ATP-depletion or by incubation of the cells in presence of sonicated dimyristoylphosphatidylcholine (DMPC) vesicles. Vesicles released from ATP-depleted red cells but not the DMPC-induced vesicles contained degradation products of band 3 protein. Furthermore, in ATP-depleted erythrocytes proteolytic breakdown products could be demonstrated that were not detected in cells incubated with DMPC. Proteolysis was neither significantly affected by the protease inhibitor N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) nor by other protease inhibitors tested in this study (diisopropylfluorophosphate, N-ethylmaleimide and phenylmethylsulfonyl fluoride). Both vesiculation processes were inhibited in a concentration dependent way by TLCK while other protease inhibitors did not significantly influence membrane vesiculation. Phase contrast microscopy showed that TLCK diminished the DMPC-induced formation of echinocytes which is known to precede vesicle release. These results suggest that the influence of TLCK on membrane vesiculation is not primarily due to inhibition of proteolysis but to a direct interaction of the inhibitor with the intrinsic domain of the erythrocyte membrane.

Adult↗

Modulation of erythrocyte vesiculation by amphiphilic drugs.

Release of acetylcholinesterase-containing vesicles from human erythrocyte membranes induced by dimyristoylphosphatidylcholine (DMPC) was inhibited by exposure of red cells to cationic amphiphilic drugs like tetracaine, chlorpromazine and primaquine which all are known to induce stomatocyte formation. On the other hand, the process was facilitated when red cells were exposed to crenators like the anionic drugs indomethacin and phenylbutazone or when DMPC was added to calcium-loaded red cells. The results suggest that agents which are known to modulate red cell shape do also influence the vesiculation behavior of the cells.

Acetylcholinesterase↗

Multicenter, double-blind comparison of doxazosin and atenolol in patients with mild to moderate hypertension.

In a double-blind multicenter study, the new alpha 1-adrenoceptor inhibitor doxazosin was compared with atenolol for efficacy, safety and effect on serum lipids. One hundred and twenty-six patients with mild to moderate hypertension were randomly assigned to receive either doxazosin (n = 63) or atenolol (n = 63). The mean final dosages, administered once daily, to obtain 24-hour blood pressure (BP) control were doxazosin 12 mg (range 1 to 16) and atenolol 91.8 mg (range 50 to 100). Of 12 doxazosin and 7 atenolol patient withdrawals from the study, 7 doxazosin and 4 atenolol patients withdrew for treatment-related reasons. No statistically significant differences between treatment groups were found after 20 weeks in changes from baseline in standing and sitting BPs measured 24 hours after administration. Sitting BP (systolic/diastolic) was reduced by 10.5/9.8 mm Hg after doxazosin treatment and by 10.9/10.7 mm Hg after atenolol therapy. Standing BP was reduced by 8.8/7.7 mm Hg after doxazosin administration and 9.7/9.3 mm Hg after treatment with atenolol. Supine BP was measured in a small cohort of the study population, and doxazosin had a smaller effect than atenolol. After 20 weeks of treatment, both drugs reduced heart rate with atenolol producing a statistically significantly greater decrease than doxazosin (standing, doxazosin 5 beats/min, atenolol 16.2 beats/min, p less than 0.001; sitting, doxazosin 5 beats/min, atenolol 13.1 beats/min, p less than 0.001). Side effects were reported by 37 patients receiving doxazosin therapy and 34 patients receiving atenolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗