Keratoconus staging: a computer-assisted ultrabiomicroscopic method compared with videokeratographic analysis

PURPOSE: The aim of this study was to introduce a new paradigm for keratoconus assessment, the keratoconus index (KI), generated from the ratio of peripheral corneal thickness (PCT) to the thinnest corneal thickness (TCT), and calculated by a computer-assisted procedure after ultrabiomicroscope (UBM) examination. Then we compared KI and the keratoconus severity index (KSI), obtained by videokeratography in patients with different stages of keratoconus. METHODS: We studied 60 eyes with different forms of keratoconus using the TMS-3 autotopographer, provided with a keratoconus screening program (using Smolek-Klyce methods) and the commercial version of the ultrasound biomicroscope (Paradigm UBM Plus Model P45) equipped with a 50-MHz probe, which was provided with our computer-assisted program. The proportion test Z and the correlation coefficient R were applied to the outcomes. RESULTS: The keratoconus severity index, KSI, obtained by color-coded videokeratographic maps, was in the range 95% to 32% (mean 52.22%). By means of UBM examination, we obtained 60 images and found values of TCT 0.278-0.592 mm and PCT 0.475-0.704 mm. Applying the computer-assisted method, we obtained values for KI of 1.112-2.159 (mean 1.428). CONCLUSIONS: KI is correlated as well as KSI with the severity of the keratoconus (R = 0.76, P < 0.0001). It can be used as a similar parameter to measure the evolution of the disease, on the basis of corneal thickness rather than the curvature.     

Blinding decreased recruitment in a prevention trial of postmenopausal hormone therapy

PURPOSE: To compare the effect of blind design (active drug and placebo) and nonblind design (active drug and no treatment) on recruitment. SETTING: A primary prevention trial with postmenopausal hormone therapy in Estonia. METHODS: Women who were eligible and willing to participate on the basis of the questionnaire survey were randomized into blind and nonblind groups. Recruitment rates are based on record keeping, and reasons for participating were requested in the first-year follow-up. RESULTS: The recruitment was 30% higher in the nonblind group: of the 4,295 women invited, 37% (95% confidence interval CI=35-39%) in the blind group and 48% (95% CI=46-49%) in the nonblind group were recruited. In both groups, once randomized, most of the losses were women who did not attend the first clinical examination: 49% (blind; 95% CI=47-51%) and 40% (nonblind; 95% CI=38-42%). The rest were found ineligible or lost their interest during clinical examinations. The reasons for joining the trial were relatively similar in the two groups. CONCLUSIONS: Blinding decreased women's interest in joining a long-term preventive trial. Women's reasons for joining the trial were not influenced by blinding.     

Transglutaminase-mediated cross-linking of a peptic fraction of omega-5 gliadin enhances IgE reactivity in wheat-dependent,exercise-induced anaphylaxis

BACKGROUND: Patients with wheat-dependent, exercise-induced anaphylaxis (WDEIA) experience recurrent anaphylactic reactions when exercising after ingestion of wheat products. We have identified omega-5 gliadin (Tri a 19) as a major allergen in WDEIA, but the role of exercise in eliciting the symptoms remains obscure. OBJECTIVE: The aim was to examine whether tissue transglutaminase (tTG)-mediated cross-linking could be involved in modulating the IgE-binding ability and in vivo reactivity of digested omega-5 gliadin peptides in WDEIA. METHODS: Purified omega-5 gliadin was digested with pepsin or with pepsin and trypsin and treated with tTG. The binding of IgE antibodies in pooled sera from 10 patients with WDEIA was studied by means of immunoblotting before and after tTG treatment of the digested peptides. The peptides derived from pepsin digestion were separated by means of gel-filtration chromatography, and IgE reactivity of 4 different peptide fractions was studied by immunoblotting before and after tTG treatment. The fraction showing the greatest degree of cross-linking by tTG was further studied by means of IgE ELISA, ELISA inhibition, and skin prick testing. RESULTS: The IgE-binding ability of omega-5 gliadin was retained after pepsin and pepsin-trypsin digestion. tTG treatment of the whole peptic digest formed large peptide complexes, with molecular weights ranging from 40 to greater than 200 kd. These cross-linked aggregates bound IgE antibodies in immunoblotting more intensely than untreated, pepsin-digested, or pepsin-trypsin-digested omega-5 gliadin. A gel-filtration fraction of the whole peptic digest corresponding to the highest peak of the chromatogram and showing the greatest degree of tTG-mediated cross-linking showed an increase in serum IgE reactivity in ELISA after tTG treatment, as well as a shift of reactivity to cross-linked complexes. In the 20 patients with WDEIA, the mean skin prick test wheal elicited by this tTG-treated peptic fraction was 77% larger (P <.001) than that elicited by the untreated peptic fraction and 56% larger (P <.01) than that elicited by intact omega-5 gliadin. CONCLUSIONS: Omega-5 gliadin-derived peptides are cross-linked by tTG, which causes a marked increase in IgE binding both in vitro and in vivo. Activation of tTG during exercise in the intestinal mucosa of patients with WDEIA could lead to the formation of large allergen complexes capable of eliciting anaphylactic reactions.     

Heterotopic nociceptive EMG-reactions in M. masseter

Peculiarities of EMG-reactions of m. masseter to noxious homo- and heterotopic stimulation were studied on healthy volunteers. Homotopic noxious electrical stimulation of n. mentalis elicited several successive responses in m. masseter consisting of R-component, early exteroceptive suppression period, early excitation period, late exteroceptive suppression period, and late excitation period. Heterotopic noxious stimulation (forehead, ear lobe, index finger) induced only the late exteroceptive suppression period and late excitation period. It is concluded that the excitatory components have a reflex nature, and that the late exteroceptive suppression period is formed under the effect of central cerebral structures, which mediate their influence via the spinal-corticospinal return loop.     

Update on female pubertal development

PURPOSE OF REVIEW: To elucidate recent findings regarding female puberty. The successful completion of puberty is a prerequisite for reproduction. Many later disorders of fertility and metabolism may develop during puberty. New more sensitive and specific assays provided us with possibilities for a better understanding of the process of puberty, and the discovery of new factors such as leptin evoked the hope of finding key regulators of the onset of puberty. RECENT FINDINGS: The secular trend towards earlier menarche appears now to have come to an end, but discussions about changes in the age of pubertal onset still continue. In a few detected cases of leptin mutations puberty has not occurred spontaneously. The intact secretion of leptin seems to be a necessary prerequisite for the onset of puberty. Apart from that, recent research has indicated that leptin levels mainly reflect body composition. Leptin as well as gonadotropins, steroids and growth hormone shows specific circadian patterns. The 24 h pattern of leptin is similar before and after puberty, but the 24 h pattern of the other hormones changes. The serum concentration of inhibin B increases in the years preceding puberty and in early puberty, whereas inhibin A increases in mid to late puberty. SUMMARY: The biological significance of the changing circadian patterns remains to be determined. Inhibin B serum concentrations together with follicle-stimulating hormone may indicate remaining potential ovarian activity during childhood in, for example, patients with Turner syndrome, but more information and other possible markers are needed.     

Reactions of N,N-bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil) with 2'-deoxyadenosine

N,N-bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1; 0.6 mM) was allowed to react with 2'-deoxyadenosine (16.1 mM) at physiological pH (cacodylic acid, 50% base), and the reactions were followed by HPLC-MS and HPLC-MS/MS techniques. Although the predominant reaction observed was chlorambucil hydrolysis, ca. 7% of 1 reacted with various heteroatoms of the nucleoside. The principal site of alkylation was N1. Several other adducts were also detected. The N1, N6, N3, and N7 derivatives were characterized by means of MS/MS, UV, and (1)H NMR. The N6 adduct is derived directly from alkylation of N6 of 2'-dAdo. Dimroth rearrangement of the N1 adduct to the N6 adduct was very slow under the reaction conditions employed. Minor adducts such as a carbohydrate derivative were tentatively characterized by MS/MS. No cross-links were detected. The role of chlorambucil-2'-deoxyadenosine adducts in the cytotoxicity and mutagenicity of 1 is also discussed.     

Choice of a surgical correction method in hypermetropic anisotropia in children

The results of surgical techniques applicable to hypermetropia correction, i.e. lamellar keratotomy (LK), lamellar keratotomy with thermal keratocoagulation (LKTKC) and sub-flap photokeratectomy (LASIK), in 80 children, aged 6 to 14, with hypermetropia ranging from 3.5 to 9.5 diopters and with astigmatism ranging from 0.75 to 2.75 diopters are analyzed. The follow-up varied from 1 to 3 years. LASIK (reduction of astigmatism by 1.61 +/- 0.43 diopters or 78%) was proven to be an optimal method in the correction of astigmatic hypermetropic anisometropia. LASIK (reduction of anisometropia by 3.44 +/- 0.44 diopters or 80%) is preferable in the correction of a spherical hypermetropic anisometropia of up to 3.0 diopters inclusively; the LK method (an improvement of clinical refraction by 4.37 +/- 0.87 diopters) is effective in anisometropia of 3.0 to 5.5 diopters; and LKTKC is effective in anisometropia of 5.5 to 7.5 diopters. The latter ensures an improvement of the corneal refraction by more than 2 diopters (2.15 +/- 0.44 diopters) versus LK. TKC is possible as a single-stage procedure made in the remote time period. LASIK is more preferable in astigmatism of more than 1.5 diopters.     

Effectiveness of dose-intensive polychemotherapy with autologous hemopoietic cell transplantation for high-grade non-Hodgkin lymphoma

The study included 29 patients with high-grade non-Hodgkin's lymphoma. Nine patients (group 1) received 6-8 cycles of CHOP, another 20-6 cycles of CHOP and Dexa-BEAM followed by autologous hemopoietic cell transplantation with CBV or BEAM conditioning regimen (bone marrow or peripheral stem cells) (group 2). The groups were comparable as far as gender and age are concerned. Overall 5-year survival was in 24.1 and 71.4%, respectively. Double CHOP-Dexa-BEAM plus autologous hemopoietic cell transplantation proved superior to standard CHOP-therapy.     

New prolyl oligopeptidase inhibitors developed from dicarboxylic acid bis(l-prolyl-pyrrolidine) amides

Isophthalic acid bis(l-prolyl-pyrrolidine) amide is a very potent prolyl oligopeptidase inhibitor, but it has a log P value of -0.2, which is very low for a compound targeted to the brain. Therefore, these types of compounds were further modified to improve the structure-activity relationships, with the focus on increasing the log P value. The inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. The most promising compounds resulted from replacing the pyrrolidinyl group at the P5 site by cycloalkyl groups, such as cyclopentyl and cyclohexyl groups, and by a phenyl group. These compounds are slightly more potent, and they have a significantly higher log P value. The potency of these compounds was further increased by replacing the pyrrolidinyl group at the P1 site by 2(S)-cyanopyrrolidinyl and 2(S)-(hydroxyacetyl)pyrrolidinyl groups.