Reduction of Mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by Combined Treatment with Clofibrate and Nicotinic Acid

Consecutive survivors of a myocardial infarction from the Southern Hospital, below 70 years of age, were randomized into a Control group (n=276) and a Treatment group (n=279). The latter was openly prescribed the combination of clofibrate and nicotinic acid for serum lipid lowering. Each patient should remain in the study for 5 years and be seen regularly every 4 months at a special IHD outpatient clinic within the hospital. The concentration of serum cholesterol and triglyceride was lowered by 13% and 19%, respectively, in the Treatment group compared to the Control group. Total mortality was 82 cases in the Control group and 61 in the Treatment group, a 26% reduction (p<0.05). For patients above 60 years of age in the Treatment group the reduction in mortality was 28% (p<0.05). IHD mortality was reduced by 36% (p<0.01)in the Treatment group compared to the Control group. The beneficial effect of the serum lipid lowering treatment was related to the serum triglyceride concentration in two ways. First, it only occurred in patients with a triglyceride level >1.5 mmol/l (n=216). Secondly, it was most pronounced in the 44% of the treated patients who had a lowering of the serum triglyceride concentration by 30% or more, and in this subgroup the reduction of IHD mortality was 60% (p<0.01). For serum cholesterol there were no such relations. The difference between serum triglycerides and cholesterol concerning these relations to the treatment outcome may be due to the fact that hypertriglyceridaemia was the most common hyperlipidaemia among our patients, occurring in 50%, while hypercholesterolaemia only occurred in 13 %. Caution should be exercised in the interpretation of the results as the trial was not blind. However, the fact that the decrease in IHD deaths was directly related to the degree of serum triglyceride lowering indicates that it was the drug effect on serum lipids that was reponsible for the beneficial effect of the treatment.     

Effects of polymerization heat and monomers from acrylic cement on canine bone

We investigated the effects of polymerization heat and toxicity of polymethyimetacrylate bone cement in the canine tibial diaphysis. Heat was studied by filling the tibias with either bone cement or bone wax contained in a monomer tight membrane pouch. Toxicity was studied by filling both tibias with cement, with the control side contained in the membrane pouch. Bone blood perfusion was measured by microsphere technic, and bone remodeling by ^99mTc-methylene diphosphonate uptake and by histologic technique. In bone exposed to the combination of polymerization heat and monomer, both perfusion and remodeling were impaired. We did not find any effects of polymerization heat alone.

We conclude that hot toxic chemicals from bone cement during polymerization may inhibit bone blood perfusion and remodeling, whereas heat alone seems to be of minor importance for the regenerative processes in cemented diaphyseal bone.     

Limb lengthening by callus distraction: Complications in 53 cases operated 1980-1991

We reviewed our first 53 lengthenings performed in 45 patients with an average age of 19 years at the time of lengthening. The shortening was congenital in 16 patients, post-traumatic in 15 and had various causes in the 14 remaining. 31 femurs and 22 tibias with an average shortening of 6 and 5 cm, respectively, were lengthened 6 (2-14) cm. The aim was achieved in all but 4 patients, where lengthening had to be discontinued due to complications.

Potential complications of lengthening can be numerous but, if recognized, can in most cases be dealt with during the extended lengthening procedure. 38 cases of pin-tract infections healed with antibiotics. Restricted motion in one or more joints was registered in 49 cases during lengthening; minor restriction of joint motion persisted in 14 patients. 28 cases had angular deviations during lengthening. After additional surgery all but 10 could be corrected. 4 fractures occurred after removal of the external fixator. The total number of complications was 146, and of these 76 were minor, 42 moderate and 28 severe. 36 of the 42 patients available to follow-up were satisfied with the results of the lengthening procedure.     

Saturation analysis of specific 11C Ro 15-1788 binding to the human neocortex using positron emission tomography

The ¹¹C-labelled benzodiazepine antagonist Ro 15–1788 (flumazenil) and positron emission tomography (PET) were used to determine quantitative characteristics of benzodiazepine receptor binding in the neocortex of healthy young men. Saturating doses of unlabelled flumazenil administered i.v., before or together with the ligand-reduced ¹¹C-flumazenil accumulation in the neocortex by about 90 per cent. Saturating doses of unlabelled flumazenil had little effect on the accumulation of radioactivity in the benzodiazepine receptor-poor regions such as pons or white matter. By giving graded doses of unlabelled flumazenil together with the tracer, saturation isotherms were obtained allowing the calculation of receptor density (B_max) and equilibrium dissociation constant (K_d) values on the basis of certain assumptions B_max values were in the order of 90 pmol/g and K_d values in the order of 10 nM in the neocortex. Scatchard and Hill plots of the radioactivity data indicated that ¹¹C-flumazenil binds to saturable sites of a homogeneous population. The data indicate that intravenous doses of 1 or 2 mg flumazenil result in a benzodiazepine receptor occupancy of about 50 per cent. The method described should be useful for studying regional differences in benzodiazepine receptor characteristics in the living human brain in healthy subjects and neuropsychiatric disorders, and also in relation to treatment with drugs interacting with benzodiazepine receptors.     

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.

Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.     

Positron emission tomography of the thorax. The current clinical status]

The non-invasive diagnostic assessment of thoracic lesions has been greatly enhanced by the use of positron emission tomography with metabolic active radio-compounds such as fluor-18 labeled deoxyglucose. Four clinical fields of use were established: differential diagnostic evaluation of lesions (T-staging); classification of adenopathy (N-staging); therapy response monitoring; diagnostic evaluation of recurrence. The upcoming challenges for clinical use are limited availability and necessary technical and qualitative standardizations.     

Diagnosis of scaphoid fractures:A prospective multicenter study of 1,052 patients with 160 fractures

In a prospective multicenter study of 1,052 patients with clinical signs of a scaphoid fracture, mammo-graphic films and fine intensifying screens were used at the radiographic examination. 5 standardized projections including 3 special projections focused on the scaphoid were taken. 150 fractures were diagnosed at the first examination but in 10 cases the fracture was first diagnosed at a second radiographic examination after 10-14 days.

The second examination still seems mandatory despite the use of high quality radiographs with optimal spatial resolution and contrast, and the value of supplementary special projections.     

Cyclosporin A-induced remission of primary membranous glomerulonephritis in a child

Sir, A 4-year-old boy presented with oedema and weight gain of 5kg. There had been no preceding infections, vaccinations ormedication. The family history includes the mothers mesangioproliferativeglomerulonephritis. Laboratory results showed decreased albumin (13 g/l) concentration.Calculated glomerular filtration rate was 125 ml/min/1.73 m²and the     

Hydrodynamic aspects of pyelocalyceal peristalsis

This study was undertaken to determine the nature of pressure changes in manometric studies of renal pelvis and calyces. In previous studies in pigs it has been assumed that pressure increases occur in the contracting segments of the renal pelvis and calyces, but our observations suggested that these increases were actually due to distension of noncontracted segments. Pressures were recorded with two catheters introduced percutaneously into the pyelocalyceal system with simultaneous video recording of the fluoroscopic image. There was no pressure rise in the calyces or the renal pelvis when these segments contracted; however, pressure rose when the noncontracted calyces were distended by a remote contraction ring. These findings confirmed the observations at kinetic urography. They agreed with the hydrodynamic experience that the pressure in a ring-shaped contracted segment is lower than upstream and downstream of that segment. It was concluded that if the porcine pyelocalyceal system is a valid model of the human, the pressure increases, assumed to be contractions, were actually caused by the injection and distension of the noncontracted segments.     

Children with deficits in attention,motor control and perception (DAMP) almost grown up: The contribution of various background factors to outcome at age 16 years

Fifty-six children with and forty-five children without deficits in attention, motor control and perception (DAMP) had been recruited from the general population at age 7 years. They were followed up neuropsychiatrically at age 16 years after intermediate term follow up at age 10 and 13 years. Cases were subdivided into those with good and not good outcome on the basis of absence or presence of psychiatric and personality disorders, multiple traumatic accidents and speech and language problems at age 16 years. The presence of DAMP in itself was the strongest predictor of poor outcome. High scores for minor neurological dysfunction, low performance IQ, autistic features at age 7 years and poor reading skills at age 10 and/or 13 years were important background factors in cases with poor outcome. In the small subgroup with poor outcome among those without DAMP at age 7 years, major life events was the most important background factor.

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Zusammenfassung 56 Kinder mit und 45 Kinder ohne Störungen der Aufmerksamkeit, der motorischen Kontrolle und der Wahrnehmung (DAMP) waren aus einer Gesamtpopulation 7jÄhriger rekrutiert worden. Sie wurden neuropsychiatrisch im Alter von 16 jahren nachuntersucht, nachdem zwischenzeitliche Untersuchungen im Alter von 10 und 13 Jahren erfolgt waren. Die Probanden wurden in solche mit gutem und nicht gutem Ausgang unterteilt, in AbhÄngigkeit vom Vorliegen psychiatrischer AuffÄlligkeiten, Persönlichkeitsstörungen, multiplen Traumata und Sprech- und Sprachproblemen im Alter von 16 Jahren. Das Vorhandensein von DAMP war der stÄrkste PrÄdiktor für einen schlechten Ausgang. Hohe Werte für leichte neurologische AuffÄlligkeiten, ein niedriger Handlungs-IQ, autistische Züge im Alter von 7 Jahren und schlechte LesefÄhigkeiten im Alter von 10 und/oder 13 Jahren waren wichtige Hintergrundfaktoren bei den Probanden mit einem schlechten Ausgang. In der kleinen Untergruppe mit einem schlechten Ausgang bei den Kindern, die im Alter von 7 Jahren kein DAMP ausgewiesen hatten, bildeten schwerwiegende Lebensereignisse den wichtigsten Hintergrundfaktor.

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Résumé Cinquante-six enfants atteints et quarante-cinq enfants non atteints de déficits de l'attention, du contrÔle moteur et de la perception (DAMP), ont été recrutés en population générale à l'âge de 7 ans. Ils ont été évalués sur la plan neuropsychiatrique à l'âge de 16 ans, après des évaluations intermédiaires à l'âge de 10 et 13 ans. Les cas ont été subdivisés entre bons et mauvais devenir sur la base de la présence ou de l'absence de troubles de la personnalité, l'importance du nombre d'accidents traumatiques, les difficultés d'élocution et de langage à 16 ans. La présence de DAMP était en soi, le facteur prédictif le plus important de mauvais devenir. Des scores élevés à des dysfonctionnements neurologiques mineurs, un QI bas, des traits autistiques à l'âge de 7 ans, et de mauvaises capacités en lecture à l'âge de 10 ou 13 ans ont été des facteurs importants dans les cas de mauvais devenir. Dans le petit sous-groupe à mauvais devenir caractérisé par une absence de DAMP à l'âge de 7 ans, des événements de vie marquants ont semblé Être des antécédents importants.