Wear of the Christiansen hip prosthesis

The wear was examined in 39 Christiansen total hip prostheses, which were removed because of mechanical loosening after being used 5 (3-11) years. In the polyacetal acetabular cups, the head had made an eccentric defect, the mean volume of which was 680 (180-3310) mm³. The mean penetration of the head into the wall of the cup was 0.8 (0.1-3.2) mm. In two additional cups the head had penetrated right through the wall of the cup. In three prostheses the polyacetal sleeve of the trunnion was so worn that the head bore directly on the stem. There was a positive correlation between wear and the time the prostheses had been used before symptoms of loosening presented.     

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.     

Bronchial response to breathing dry gas at 3.7 MPa ambient pressure

In diving, pulmonary mechanical function is limited by the increased density of the gas breathed. Breathing cold and dry gas may cause an additional increase in airways resistance. We have measured forced vital capacity, forced expired volume in 1 s (FEV₁) and forced midexpiratory flow rate (FEF_25%–75%) before and after breathing dry or humid gas at 29–32°C during a standardized exercise intensity on a cycle ergometer at an ambient pressure of 3.7 MPa. The atmosphere was a helium and oxygen mixture with a density of 6.8 kg · m^–3. Six professional saturation divers aged 26–37 years participated in the study. There were no significant differences in convective respiratory heat loss between the exposures. The mean evaporative heat loss was 67 W (range 59–89) breathing dry gas and 37 W (range 32–43) breathing humid gas, corresponding to water losses of 1.7 g · min^–1 (range 1.5–2.2) and 0.9 g · min^–1 (range 0.8–1.1), respectively. There was a significant reduction in FEV₁ of 4.6 (SD 3.6)% (P<0.05), and in FEF_25%–75% of 5.8 (SD 4.7)% (P<0.05) after breathing dry gas. There were no changes after breathing humid gas. By warming and humidifying the gas breathed in deep saturation diving bronchoconstriction may be prevented.     

Attachment,spreading and growthin vitro of highly malignant and low malignant murine fibrosarcoma cells

Highly malignant cell lines and low-malignant cell lines isolated from three different methylcholanthrene-induced murine fibrosarcomas were examined for their ability to attach to plastic dishes and collagen-coated dishes under serumfree conditions and in the presence of serum. Most of the cells from the three highly malignant lines attached and spread under all conditions. By 72h, there was a significant increase in the number of cells indicating that at least some of the cells had undergone division (even in the absence of serum). In contrast, fewer of the cells from the three low-malignant lines attached and spread on the plastic or collagen substrates in the absence of serum or in the presence of 0.1 per cent serum. However, when 15g laminin per dish was added along with the lowmalignant cells, they then attached and spread on the plastic and collagen-coated dishes. Previous studies have indicated that the highly malignant lines express cell surface antigens that cross-react with laminin while the low-malignant cell lines do not. We speculate that the differences between the high- and low-malignant cells in the expression of cell surface laminin-like antigens contribute to the dissimilarities in attachment and spreading capacity. These differences may also contribute to the dissimilarity between these cells in malignant potential.     

A new assay for leukocyte chemotaxis using cell retrieval,electronic particle counting and flow cytometry

A new micropore membrane assay for leukocyte migration has been devised. It permits the complete retrieval in monodisperse suspension of functionally intact cells that have traversed the membrane, thus allowing the application of precise, automated techniques, including flow cytometry and electronic particle counting. Hemocytometers may also be used. Direct comparison with 2 different conventional membrane methods showed that the new method performed superiorly. It was also much more economical with regard to time and labor. This technique permitted detection of functional differences between leukocytes isolated from blood in different ways. Data on the duration of concentration gradients in chemotaxis chambers are also presented.     

Implications of pharmacogenetics for individualizing drug treatment and for study design

Adverse drug reactions and ineffective drug treatment are responsible for a large health care burden. Considerable variability in drug response makes the prediction of the individual reaction difficult. Pharmacogenetics can help to individualize drug treatment in accordance with the genetic make-up of the patient. Drug response is best understood as a complex interplay between pharmacokinetics, pharmacodynamics, and other disease-associated factors. There are a large number of genetic variants in the enzymes of phase I and phase II drug metabolism, in drug transporters, and drug targets, all of which account for differences in drug response. The polymorphisms in the cytochrome P450 enzyme system have been investigated most extensively. Genotype-based dose adjustment which should ensure "bioequivalent" drug concentrations in all patients has been derived from pharmacokinetic parameters, but this approach will have to be verified in prospective studies. Drug transport has recently been recognized as a further crucial determinant in pharmacokinetics. The effect of genetics on disease susceptibility and drug treatment has been studied quite extensively; however, hardly any of this progress is at present reflected in routine health care. The integration of pharmacogenetic factors in clinical trials requires novel considerations for study design and data interpretation. It is to be hoped that the new science bioinformatics will (a) help us identify the contribution of genetics to disease and treatment response and will (b) create data-processing devices which help the physician in the face of the enormously expanding scientific knowledge in selecting the best individually adapted treatment for the patient.     

Growth and metastasis of hypermotile,hyperinvasive cancer cells selectedin vitro by rapid locomotion under various conditions

Cancer cells selected from a cultured murine fibrosarcoma by rapid migration through micropore membranes moved considerably faster through such membranes and invaded biological tissues much more efficiently than did the unselected parent cells [5, 8]. The present data show that populations of cells selected by unstimulated migration or by haptotaxis to laminin moved not only faster, but also in larger numbers than the parent cells. However, the selected cells were far less efficient than the parent cells in forming spontaneous lung metastases in syngeneic mice, although all cell lines were 100 per cent tumorigenic. Analysis of paired data within each group showed no relationship between the primary tumor size at any observation time and the number of lung metastases finally formed. Therefore, although the parent cell line produced primary tumors growing slightly more rapidly than did the various lines of hypermotile cells, this was probably not the main cause of the difference in spontaneous metastasis formation between the groups. Lung colonization experiments performed by intravenous injection of cells could not explain the spontaneous metastasis results.In vitro, the cells selected by rapid haptotaxis to laminin grew considerably better than the other cells in 0.1 per cent fetal bovine serum, but there were no, or only minor, differences in higher serum concentrations. Combined, these results indicate that small subpopulations of cells selected by extreme efficiency in one step of the metastasis process may be so specialized that they perform poorly in other steps. Therefore, the results do not disprove the concept that tumor cell migration plays an important part in metastasis.     

Effects of age on volumes of cortex, white matter and subcortical structures

The effect of age was investigated in and compared across 16 automatically segmented brain measures: cortical gray matter, cerebral white matter, hippocampus, amygdala, thalamus, the accumbens area, caudate, putamen, pallidum, brainstem, cerebellar cortex, cerebellar white matter, the lateral ventricle, the inferior lateral ventricle, and the 3rd and 4th ventricle. Significant age effects were found for all volumes except pallidum and the 4th ventricle. Heterogeneous age responses were seen in that age relationships for cortex, amygdala, thalamus, the accumbens area, and caudate were linear, while cerebral white matter, hippocampus, brainstem, cerebellar white, and gray matter, as well as volume of the lateral, inferior lateral, and 3rd ventricles showed curvilinear relationships with age. In general, the findings point to global and large effects of age across brain volumes.     

Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated with cancer progression

We tested the hypothesis that PTEN inactivation may stratify cancer progression risk among putative endometrial hyperplasias, classified prognostically by means of the morphometric D score (DS). The DS, calculated from 3 morphometric variables measured in routine hematoxylin-eosin-stained endometrial biopsy slides, is the most sensitive and specific method of endometrial cancer risk prediction currently available. Clinical outcomes of 103 women with endometrial hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%) patients with carcinoma during follow-up were all distributed within the high-risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN]) (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed. All cases that progressed were PTEN null, indicating that this genotype is capable of further stratifying cancer progression risk in hyperplasias irrespective of histological categorization. However, only 16% of the PTEN-null cases progressed. When PTEN expression pattern was combined with EIN, the prognostic power was greatly increased (specificity from 63% for PTEN and 85% for EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We conclude that loss of PTEN expression is the first biomarker in EIN that increases the accuracy of the prognostic DS to predict cancer progression risk. Unless endometrial hyperplasias are stratified by histological morphometric D-Score, PTEN has a low positive predictive value.     

Hydrochlorothiazide and potassium chloride in comparison with hydrochlorothiazide and amiloride in the treatment of mild hypertension

A randomized, double-blind, cross-over study comparing 50 mg hydrochlorothiazide plus 5 mg amiloride (HCTZ/A) with 50 mg hydrochlorothiazide plus 26 mmol potassium chloride (HCTZ/K) was conducted in 18 patients with mild essential hypertension (diastolic pressure 90-105 mmHg). The sequence of treatment was: placebo for 2 weeks, one active drug for 3 weeks, placebo for 2 weeks, the other active drug for 3 weeks. The two agents were significantly and equally efficacious in lowering the systolic and diastolic blood pressure. Baseline vs. treatment mean serum potassium levels were 3.82 vs. 3.78 mmol/l for HCTZ/A and 3.82 vs. 3.70 mmol/l for HCTZ/K. The decrease in serum potassium level from baseline was significant for both agents but not significantly different when the two treatment forms were compared. Both treatment forms elevated fasting serum cholesterol and glucose. Serum triglycerides and uric acid rose significantly with HCTZ/K. Amiloride may affect the tubular handling of uric acid causing increased uric acid excretion, thus counteracting thiazide-induced hyperuricemia. During 3 weeks' extension of the main study, 5 patients received HCTZ/A in double the original dose (100 mg/10 mg) and 6 patients received HCTZ/K in double the original dose (100 mg/52 mmol). No further blood pressure reduction was observed on treatment with these doses. The mean serum potassium levels did not decrease further on doubling the HCTZ/A dose, while a significant fall was observed for HCTZ/K (3.60 vs. 3.42 mmol/l) (p less than 0.05, single tailed t-test). Both drug combinations were well tolerated and side-effects were not significantly different from those during placebo administration. This study demonstrates that 50 mg hydrochlorothiazide plus 26 mmol potassium chloride are as effective as 50 mg hydrochlorothiazide plus 5 mg amiloride, both in reducing blood pressure and preventing hypokalaemia in the treatment of essential hypertension. A small extension study indicates that amiloride might be more effective than potassium chloride in preventing hypokalaemia when high doses (100 mg/day) of hydrochlorothiazide are administered.