Treatment Strategies for In-Stent Restenosis

In-stent restenosis has become a significant clinical problem. It is estimated that in 1997, up to 100,000 patients with in-stent restenosis were treated worldwide. Serial intravascular ultrasound analysis has shown that neointimal hyperplasia represents the most important cause for in-stent restenosis, while late recoil and remodeling are neglectabe. With the recent explosion in the use of coronary stents, clinical investigation on stent restenosis has lagged behind. For example, the true prevalence of in-stent restenosis varies with the lesion and patient subset. It is much higher in the "real world" than in selected patients who are typically controlled in most studies. Diffuse restenosis can be expected in about two-thirds of stented patients, and it is difficult to treat because of unfavorable long-term results. Conventional catheter-based treatment modalities include plain balloon angioplasty (PTCA), rotational atherectomy (RA), excimer laser coronary angioplasty (ELCA), directional coronary atherectomy (DCA), and additional stent implantation. Exact individual recurrence rates for these approaches are not known and show a considerable degree of variability. Recently, brachytherapy has emerged as the most promising way to treat in-stent restenosis.     

Binding of 14C-spermidine to melanin in vivo and in vitro

It has been shown that melanin has the properties of a polyanion and may in vivo and in vitro bind inorganic cations and drugs which are positively charged at physiological pH by a cation-exchange mechanism. In the present study, we explored if the organic aliphatic polycation spermidine would bind to melanin in vivo after administration of ¹⁴C-spermidine to pigmented mice and in vitro at incubations with pigment from beef-eyes. The results showed a high labelling of the pigmented tissues in the mice after the administration of ¹⁴C-spermidine. At long survival intervals, the radioactivity in the melanin was higher than in any other tissue. A strong melanin affinity of ¹⁴C-spermidine was found in vitro. An analysis of the binding by the method of Scale hard showed that the data could be best fitted by the assumption of two classes of binding sites. The in vivo bound material could be displaced by in vitro incubation in solutions containing inorganic cation-chloride salts or HCI and HC1 was also very effective in inhibiting the melanin-binding of ¹⁴C-spermidine in vitro. The results indicate that an electrostatic interaction between spermidine and melanin will occur both in vivo and in vitro.     

Conformational analysis of dopamine by the INDO molecular orbital method

The results of INDO calculations on dopamine are reported. A conformational energy map and an isodistance map for the key distances N—OH₁, N—OH₂ in dopamine as functions of the two main torsion angles τ₁ and τ₂ were constructed. In addition to the three known minima of dopamine corresponding to the trans and gauche forms, two new minima were found. The key distances of the rigid analogues of dopamine, apomorphine, isoapomorphine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene and isoquinoline were plotted on the isodistance map of dopamine. By taking the corresponding τ values as coordinates on the energy map, conformations of dopamine, resembling the rigid analogues, could be found. When a conformation is close to a local minimum it is assumed that this conformation is energetically favourable. The possible relation between the energy minima and the biological action of dopamine is discussed. An explanation is suggested for the lack of dopaminergic activity of isoapomorphine.     

PSEUDOHYPOALDOSTERONISM Clinical, Biochemical and Morphological Studies in a Long-term Follow-up

ABSTRACT. A boy with pseudohypoaldosteronism was followed from birth to the age of 7 years. Failure to thrive, vomiting, dehydration, hyponatraemia and urinary sodium loss were prominent findings. Urinary excretion of corticosteroid metabolites was normal. Before treatment, excessively high plasma renin concentration was found, associated with a marked activation of aldosterone secretion. A renal biopsy showed pronounced hypertrophy of the juxtaglomerular apparatus. Persisting metabolic acidosis and an insufficient urinary acidifying capacity suggested the presence of distal renal tubular acidosis. Treatment with sodium bicarbonate and sodium chloride from 19 to 31 months of age resulted in normal growth and normal physical and mental development. The plasma electrolytes were normalized but a pronounced activation of the renin–aldosterone system persisted after therapy, and on sodium restriction this system responded with a considerable further activation.     

DIAGNOSIS AND MAIN CLINICAL FEATURES OF CYSTIC FIBROSIS WITH SPECIAL ATTENTION TO SCREENING PROCEDURES

Kollberg, H. (Department of Paediatrics, University of Umeå, Umeå, Sweden). Diagnosis and main clinical features of cystic fibrosis with special attention to screening procedures. Acta Paediatr Scand 1982; suppl 301:15-25. – The diagnosis of cystic fibrosis (CF) must be based on a combination of clinical observations of all symptoms and the results of laboratory tests. The numerous symptoms from the respiratory and gastrointestinal tracts and from the sweat glands are briefly described and the specific diagnostic tests referring to these systems are enumerated. CF is a common disease which constitutes a substantial problem both for the individuals concerned and for the community. Screening most probably would result in an improvement for the early diagnosed patients with respect both to survival and to physical function. The society has the means to provide resources both for confirming the diagnosis and for providing complete long-term therapy for CF patients, but the diagnostic and therapeutic possibilities need to be organized more firmly. Alternative ways of diagnosis other than screenning are unsatisfactory and lead to a diagnostic delay which most probably is detrimental for the patient. Promising screening tests are on the way; the test for trypsin in serum, in particular, seems to be specific, non-injurious to the patient and applicable to all newborns in countries with Caucasian populations, but it remains to be seen whether it is sufficiently sensitive and inexpensive. It is concluded that CF is a top ranked candidate for general screening in the neonatal period and further intensive studies in this field must get every support. The multicentre study for screening, proposed and supported by ICF(M)A is heartily welcomed.     

PREVALENCE AND TEN-YEAR (1970-1979) INCIDENCE OF INSULIN-DEPENDENT DIABETES MELLITUS IN CHILDREN AND ADOLESCENTS IN FINLAND

ABSTRACT. The prevalence and incidence of insulin-dependent diabetes mellitus in Finnish children and adolescents were studied by means of a national register of drug-treated diabetics and hospital records. At the end of 1979 the prevalence of diabetes in children aged 0-14 was 191/100000, and in those aged 0-19, 262/100000 respectively. During the 10-year period from 1970 to 1979, 3916 new diabetics aged 0-19 years were registered. The annual incidence of diabetes was 27.3/100000 in the age group 0-19 years and 28.6/100000 in those 0-14 years. The peak incidence of diabetes in girls occurred at 12 years of age and in boys at 14 years. There was a seasonal variation in the symptom debut, with peaks in April and in September and low rates in the summer. A regional variation in the prevalence and incidence rates was evident the rates being highest in eastern and lowest in northern Finland. The prevalence of diabetes mellitus increased clearly during the observation period, and the incidence tended to increase especially during the last years. Both prevalence and incidence rates of diabetes mellitus in Finnish children are high by international standards, possibly the highest in the world.