New pansomatostatin ligands and their chelated versions: affinity profile, agonist activity, internalization, and tumor targeting.

PURPOSE: Somatostatin receptor (sst) targeting is an established method to image and treat sst-positive tumors. Particularly, neuroendocrine tumors express the receptor subtype 2 in high density, but sst1, sst3, sst4, and sst5 are also expressed to some extent in different human tumors. Currently used targeting peptides mainly have sst2 affinity. We aimed at developing (radio)peptides that bind with high affinity to all receptor subtypes. EXPERIMENTAL DESIGN: Carbocyclic octapeptides were coupled with macrocyclic chelators for radiometal labeling. Affinity, internalization, and agonist potencies were determined on sst1- to sst5-expressing cell lines. Biodistribution was determined on nude mice bearing HEK-sst2 or AR4-2J and HEK-sst3 tumors. RESULTS: High affinity to all receptor subtypes was found. Y(III)-KE88 showed agonistic properties at all five sst receptor subtypes as it inhibits forskolin-stimulated cyclic AMP production. Surprisingly, very low or even absent sst2 receptor internalization was found compared with currently clinically established octapeptides, whereas the sst3 internalization was very efficient. Biodistribution studies of [(111)In]KE88 and [(67)Ga]KE88/[(68)Ga]KE88 reflected the in vitro data. In nude mice with s.c. implanted sst2 (HEK-sst2, AR4-2J)-expressing and sst3 (HEK-sst3)-expressing tumors, high and persistent uptake was found in sst3-expressing tumors, whereas the uptake in the sst2-expressing tumors was lower and showed fast washout. The kidney uptake was high but blockable by coinjection of lysine. CONCLUSION: This peptide family shows pansomatostatin potency. As radiopeptides, they are the first to show a full pansomatostatin profile. Despite some drawback, they should be useful for imaging sst2-expressing tumors with short-lived radiometals, such as (68)Ga, at early time points and for sst3-expressing tumors at later time points with longer-lived radiometals, such as (64)Cu or (86)Y.     

A controlled trial of methionyl growth hormone therapy in prepubertal children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group

Thirty short and slowly growing children with normal plasma growth hormone (GH) responses to standard provocation tests were randomly assigned to either a group (n = 20) undergoing treatment with methionyl GH (somatrem), 2 IU per m2 body surface s.c. daily, or a control group (n = 10). Twelve out of 18 children who completed the first year of treatment showed a height velocity increment of more than 2 cm/year. The mean (SD) growth velocity of the treatment group increased by 3.0 (1.9) cm/year over the first year, compared with -0.2 (0.7) cm/year in the control group. Neither parameters of endogenous GH secretion nor plasma IGF-I levels showed a significant correlation with the growth response. Of the auxological variables studied, pre-treatment growth velocity (r = -0.8) and the short-term height velocity increment (r = 0.7-0.9) showed significant correlations with the growth response in the first year of treatment. Somatrem therapy was without side effects, except in one child who developed anti-GH antibodies in combination with a poor growth response.     

Two-year results of treatment with methionyl human growth hormone in children with Turner syndrome. Dutch Growth Hormone Working Group

Methionyl growth hormone (somatrem) in a daily dosage of 4 IU/m2 body surface area was administered to 16 girls with Turner syndrome. Low dose ethinyl estradiol (0.1 microgram/kg body weight) was added in girls aged 13 years or more. Mean (SD) height velocity increased from 3.4 (0.9) to 7.2 (1.7) and 5.3 (1.3) cm/year in the first and second year, respectively. Bone age advanced 1.8 years over 2 years and predicted adult height was increased. Apart from the occurrence of anti-GH antibodies there were no side effects. In conclusion, somatrem is an efficacious and safe therapy for short stature in Turner syndrome over a period of 2 years. Longer follow-up is needed before conclusions about its effect on final height can be drawn.     

Secondary transplantation following a period of isografting: experimental study in rats

The authors describe a study in which groin flaps from 20 Wistar rats were transplanted to another group of 20 Wistar rats and, after various time intervals, the groin flaps were re-transplanted back to the original animals. The goal of the first transfers was to preserve the flap in the second group of animals (isopreservation). During the isopreservation period, the second rat (the preserver) was treated with steroids or FK506 for immunosuppression. Thirty-three free groin flap transfers were performed between 40 rats. If possible, the same flap was transferred twice between two animals, one as an isograft, and other as an autograft following an isopreservation period in 13 pairs of animals. (A second transfer was not possible in seven pairs of animals.) The period for isopreservation varied between 2 days and 1 week. The survival of the flap was observed by visual inspection, laser Doppler flowmeter measurements, and was correlated with serial histopathologic examinations of skin and vessel biopsy specimens, including the anastomosis site. The severity of histopathologic signs that might be related to developing rejection was increased by the preservation time, and was more noticeable after the second transfer. The authors showed that successful secondary transplantation of the rat groin flap with a 1-week follow-up could be achieved, following isopreservation of at least up to 5 days.     

Acquired disorders of color vision

This article is a general view of acquired disorders of color vision. The revision of the best known methods and of the etiopathogenic classification is not very important in ophthalmology but on the other hand, the detection of the blue defect advertise and associated ocular pathology. There is a major interest in serious diseases as multiple sclerosis, AIDS, diabetes melitus, when the first ocular sign can be a defect in the color vision.     

Secondary cataract treatment with laser YAG-ND

The purpose of the study is to present the favorable results of YAG: Nd laser capsulotomy for the treatment of secondary opacification of the posterior capsule, in our department. A 3 years retrospective study was performed. For 1440 cataract operations, most of them extracapsular extractions with PMMA IOL placed in the posterior chamber (ciliary sulcus or capsular bag), 285 laser capsulotomies were done. The results are presented statistically, including sex and age distribution, type of cataract surgery and implant, treatment protocol (number of sessions, number of impulses per session, energy per impulse) and complications. The frequency of secondary capsular opacification in our study is 19.78%. It is most important in the age group 60-70 years, where the surgery for cataract is performed more often. Capsulotomy was done after extracapsular extraction with IOL placed in the posterior chamber, but especially after extracapsular extraction without implant placement or with complications that have permitted only the use of an anterior chamber implant. Capsulotomy is performed in only one session in 88% of the cases. The energy per impulse is usually 3-5 mJ and the mean number of impulses per session is 10-30. There are few complications: transient elevation of intraocular pressure in 14.73%, discrete laser marks on the implant in 8.77% and moderate iritis in 1% of the cases. YAG: Nd laser capsulotomy appears to be a safe and efficient method of treating secondary cataract; it improved visual acuity in all cases, if different ocular pathology had not influenced it.     

The role and importance of antidrug educational program in preventing toxicomania in adolescents

If before 1989 the use of drugs in Romania was an exceptional situation, in the last few years our country evolved from a transit area to a potential market. The drug users in Romania a coming from all the social classes (workers, unemployed, students and even medical staff), but more vulnerable are the adolescents and the young unemployed people. There is a certain risk that the drug use in Romania to become a wide spread phenomenon, with a tendency of getting out of control. Thus we need an operational program in the fight against the drug use.     

Aspects of iatrogeny through communication in complex oral rehabilitation

Human intercommunication means transfer of information through many channels, with codes that have biological and socio-cultural determinism. The biological determinism is identifiable through the development of the phonetics and ergomotricity functions, through the possibility of perception of the sensorial organs. The channels of human intercommunication can be verbal, linguistic (the most specialised channel), and nonverbal, extralinguistic channels (mimics, written model, drawing, walking), that are effectively implicated in defining a direct dialogue between the dentist and the patient, completing and emphasising the communication. When the communication through the standard channels is disturbed, the dentist can't understand the patient's expectations, so the patient will not perceive the opportunity, the necessity and the efficiency of the complex oral rehabilitation. All these factors are contributing to the initiation of the iatrogeny through communication.