Variability of contour line alignment on sequential images with the Heidelberg Retina Tomograph

Background: The influence of the contour line alignment software algorithm on the variability of the Heidelberg Retina Tomograph (HRT) parameters remains unclear. Methods: Nine discrete topographic images were acquired with the HRT from the right eye in six healthy, emmetropic subjects. The variability of topometric data obtained from the same topographic image, analyzed within different samples of images, was evaluated. A total of four mean topographic images was computed for each subject from: all nine discrete images (A), the first six of those images (B), the last six of those nine images (C), and the first three combined with the last three images (D). A contour line was computed on the mean topographic image generated from the nine discrete topographic images (A). This contour line was then applied to the three other mean topographic images (B, C, and D), using the contour line alignment in the HRT software. Subsequently, the contour line on the mean topographic images was applied to each of the discrete members of the particular images subsets used to compute the mean topographic image, and the topometric data for these discrete topographic images was computed successively for each subset. Prior to processing each subset, the contour line on the discrete topographic images was deleted. This strategy provided a total of three analyses on each discrete topographic image: as a member of the nine images (mean topographic image A), and as a member of two subsets of images (mean topographic image B, C, and/or D). The coefficient of variation (100×SD/mean) of the topographic parameters within those three analyses was calculated for each discrete topographic image in each subject (intraimage coefficient of variation). In addition, a coefficient of variation between the nine discrete topographic images (interimage coefficient of variation) was calculated. Results: The intraimage and interimage variability for the various topographic parameters ranged between 0.03% and 3.10% and between 0.03% and 24.07% respectively. The intraimage coefficients of variation and interimage coefficients of variation correlated significant (r ²=0.77;P<0.0001). Conclusion: A high intraimage variability, i.e. a high variability in contour line alignment between sequential images, might be an important source of test re-test variability between sequential images.     

Hypoglycaemic effects of the novel antidiabetic agent repaglinide in rats and dogs

1. Repaglinide, a novel compound with a nonsulphonylurea structure, is currently being clinically tested as a therapeutic agent. In the present study, the hypoglycaemic effects of repaglinide in rats and dogs were investigated.
2. Whereas the R-enantiomer, AG-EE 624 ZW, showed only weak hypoglycaemic activity, the S-enantiomer, repaglinide, turned out to be a potent hypoglycaemic compound in rats after oral as well as after intravenous administration. Only 50% of the dose of repaglinide was needed to be equieffective with the racemic mixture AG-EE 388 ZW. The corresponding ED₅₀ values calculated for the effects after 120 min p.a. (intravenous administration) were 3.4 μg kg⁻¹ (repaglinide) and 6 μg kg⁻¹ (AG-EE 388 ZW).
3. When compared to glimepiride or glibenclamide, repaglinide displayed a 18 to 25 times higher potency in fasted rats. The ED₅₀ values calculated for the effects after 120 min p.a. (oral administration) were 10 μg kg⁻¹ (repaglinide), 182 μg kg⁻¹ (glimepiride) and 255 μg kg⁻¹ (glibenclamide).
4. In glucose loaded rats (0.5, 1.0, 2.0 and 3.0 g kg⁻¹ glucose, p.o.) repaglinide exerted a very strong antihyperglycaemic activity which was even more pronounced than under normoglycaemic conditions. So for a reduction in blood glucose of 1 mmol l⁻¹, 10.3, 9.3, 7.0 8.4 and 7.2 μg kg⁻¹ repaglinide were needed after glucose loads of 0.0, 0.5, 1.0, 2.0 and 3.0 g kg⁻¹, respectively.
5. In beagle dogs repaglinide again showed a pronounced hypoglycaemic effect (ED₅₀ 28.3 μg kg⁻¹) which lasted for up to 24 h. However, insulin levels were only transiently increased.
6. The in vivo data presented are well supported by recently published in vitro findings. From its activity profile, repaglinide appears to be a promising new therapeutic agent.

     

Effects of [3H]-BIDN,a novel bicyclic dinitrile radioligand for GABA-gated chloride channels of insects and vertebrates

1. The radiolabelled bicyclic dinitrile, [³H]-3,3-bis-trifluoromethyl-bicyclo[2.2.1]heptane-2,2-dicarbonitrile ([³H]-BIDN), exhibited, specific binding of high affinity to membranes of the southern corn rootworm (Diabrotica undecimpunctata howardi) and other insects. A variety of γ-aminobutyric acid (GABA) receptor convulsants, including the insecticides heptachlor (IC₅₀, 35±3 nM) and dieldrin (IC₅₀, 93±7 nM), displaced [³H]-BIDN from rootworm membranes. When tested at 100 μM, 1-(4-ethynylphenyl)-4-n-propyl-2,6,7-trioxabicyclo[2.2.2]octane(EBOB), 4-t-butyl-2,6,7-trioxa-1-phosphabicyclo[2.2.2]octane-1-thione (TBPS), 1-phenyl-4-t-butyl-2,6,7-trioxabicyclo[2.2.2]octane (TBOB) and picrotoxin failed to displace 50% of [³H]-BIDN binding to rootworm membranes indicating that the bicyclic dinitrile radioligand probes a site distinct from those identified by other convulsant radioligands.
2. Dissociation studies showed that dieldrin, ketoendrin, toxaphene, heptachlor epoxide and α and β endosulphan displace bound [³H]-BIDN from rootworm membranes by a competitive mechanism.
3. Rat brain membranes were also shown to possess a population of saturable, specific [³H]-BIDN binding sites, though of lower affinity than in rootworm and with a different pharmacological profile. Of the insecticidal GABAergic convulsants that displaced [³H]-BIDN from rootworm, cockroach (Periplaneta americana) and rat brain membranes, many were more effective in rootworm.
4. Functional GABA-gated chloride channels of rootworm nervous system and of cockroach nerve and muscle were blocked by BIDN, whereas cockroach neuronal GABA_B receptors were unaffected.
5. Expression in Xenopus oocytes of either rat brain mRNA, or cDNA-derived RNA encoding a GABA receptor subunit (Rdl) that is expressed widely in the nervous system of Drosophila melanogaster resulted in functional, homo-oligomeric GABA receptors that were blocked by BIDN. Thus, BIDN probes a novel site on GABA-gated Cl⁻ channels to which a number of insecticidally-active molecules bind.

     

Activation of benzylic alcohols to mutagens by human hepatic sulphotransferases

Four primary and five secondary benzylic alcohols derived frompolycyclic aromatic hydrocarbons were tested for mutagenicityin Salmonella typhimurium TA98 in the presence of 3'-phosphoadenosine-5'-phosphosulphate,the cofactor for sulphotransferases, and varying amounts ofhepatic cytosol from three or four different human subjects,a 3-year-old child, an adult female, an adult male and one unknown.All compounds except one, 4H-cyclopenta[def] phenanthren-4-ol,were activated to mutagens. The interindividual variation inthe activities was at most 3-fold and the individual activitiestowards the different substrates were correlated with each other.The same compounds had previously been tested in the presenceof hepatic cytosol from rats and all compounds activated inone species were also activated in the other species. However,there were marked quantitative differences, which were furthercomplicated by the observation of a substantial sex differencein the rat. Male and female rat liver cytosol showed highersulphotransferase activities towards 1-hydroxymethylpyrene,9-hydroxymethylanthracene, 7-hydroxymethyl-12-methylbenz[a]anthraceneand 4H-cyclopenta[def]chrysen-4-ol than human liver cytosol.The largest difference in activity was seen with 7-hydroxymethyl-12-methylbenz[a]anthracene,reaching a factor of     

Spinal anaesthesia but not general anaesthesia enhances neutrophil biocidal activity in hip arthroplasty patients

The purpose of this study was to compare neutrophil cidal activity during general or spinal anaesthesia. Assays were performed on neutrophils extracted from the blood of patients after surgery had been under way for one hour. First, the ability of the neutrophils to kill a standard laboratory strain of S. aureus was examined. Neutrophils extracted from the blood during surgery in the spinal anaesthetic group and incubated with the staphylococci for one hour killed twice as many bacteria than those from two groups of patients that received halothane or isoflurane general anaesthesia (P < 0.05). This effect persisted, to a lesser extent, in the spinal group neutrophils after two hours of incubation with the bacteria. Second, neutrophils from patients under the same conditions of surgery and anaesthesia were tested to examine the effect of the different anaesthetic techniques on neutrophil biocidal mechanisms. Neutrophils extracted during surgery in the spinal group released more superoxide in response to phorbol-12-myristate-13-acetate (PMA) than those from both groups of patients that received general anaesthesia (P < 0.05). It is concluded that there is an increased state of reactivity of the neutrophil cell membrane NADPH oxidase system in patients receiving spinal anaesthesia than in patients receiving general anaesthesia.     

P53 and rb alterations in operable breast-cancer

We analyzed association between p53 and/or Rb expression and clinicopathologic variables or Ag-NOR counts, and then ascertained whether p53 and/or Rb expression would be useful for estimating prognosis in 81 breast cancer patients. Positive p53 expression was significantly associated with post-menopausal status, axillary lymph node metastases and Ag-NOR counts, whereas low level Rb expression was significantly associated with tumor size. Moreover, the combination of p53 and Rb expression was significantly associated with Ag-NOR counts, although there was no significant association between p53 and Rb expression. In the univariate study, p53 expression as well as age and axillary lymph node metastases were significantly associated with survival, whereas Rb expression was not. In the multivariate study, p53 and/or Rb expression did not provide independent prognostic information, although axillary lymph node metastases was an important factor affecting survival. Our findings suggest that p53 and/or Rb expression may reflect tumor proliferation of breast cancer, but the prognostic value of such assays is limited.     

Twenty-year review of the surgical management of perianal Crohn's disease

PURPOSE: A retrospective analysis of 48 patients treated over a 20-year period (March 1973–April 1993) was undertaken to assess the results of our practice of early surgical intervention in suppurative complications of perianal Crohn's disease. METHODS: All patients were either seen in the office within the last six months or contacted by phone. RESULTS: The average age of our patients was 30 years at initial diagnosis. Thirty-four patients (71 percent) initially presented with intestinal disease and four (8 percent) with only perianal disease. Thirteen patients (27 percent) initially presented with simultaneous intestinal and perianal disease. The various fistulas at initial presentation included 8 intersphincteric (17 percent), 14 transphincteric (29 percent), 11 complex or multiple (23 percent), 5 rectovaginal (10 percent), and 2 unclassified, for a total of 40 patients. Eight patients (17 percent) presented with only an abscess. Eighty five percent of our patients healed after their first procedure, with an average time to heal of 2.8 months. Thirteen (27 percent) patients had recurrences after initial healing of their wounds. The mean time to recurrence after healing was 5.25 years. Fifty-four percent of our recurrences (7 patients) were treated by incision and drainage of an abscess only. Seven of 13 recurrences healed after the second procedure (54 percent), and 5 of 6 healed after a third procedure (83 percent). Only seven (14 percent) of our patients underwent a proctocolectomy during the study period, through September, 1993. Our overall probability of avoiding proctectomy and healing perineal wounds of 86 percent is consistent with published literature. CONCLUSIONS: Early aggressive surgical management of suppurative complications of perianal Crohn's disease before complex management problems ensue results in a high incidence of healing and a low risk of subsequent proctectomy.     

Evaluation of low dose prostaglandin E1 treatment for ductus dependent congenital heart disease

This study reports our experience with low-dose prostaglandin E₁ (PGE₁) treatment of 91 newborns with ductus dependent congenital heart disease (CHD). PGE₁ efficacy, side-effects as well as the cardiovascular and respiratory profile of the patients were analysed. PGE₁ doses > 0.02 g/kg per minute were used for only 5.3% of the total 23 656 h of treatment. The mean systolic blood pressures did not differ from the normal mean for patients with cyanotic CHD, while the diastolic values were lowered. Respiratory support was required only during 13.7% of the total treatment time. Apnoeas occurred in 21 (38%) of the 55 spontaneously breathing infants, who all had a cyanotic CHD. The incidence of apnoeas was lower during treatment with doses < 0.01 g/kg per minute.     

Epidural anesthesia in anin vitro fertilization and embryo transfer program

Objectives To investigate the potential advantages of epidural anesthesia in an in vitro fertilization and embryo transfer program.Study Design Between January 1991 and December 1992, 148 infertile patients underwent transvaginal ultrasound guided oocyte retrieval. A total of 44 patients (group A) had 50 retrievals under epidural anesthesia, and 104 patients (group B, control group) 112 retrievals under intravenous sedation (propofol) with mask-assisted ventilation (nitrous oxide).Results In group A satisfactory anesthesia was achieved in 49 of the 50 cases (98%); one patient required additional intravenous administration of propofol owing to extreme anxiety. No complications were observed. Adversely, in group B nausea was observed in 16 cases (14%) and nausea and vomiting in 7 cases (6%). In group A the fertilization, cleavage and pregnancy rates were 67.2%, 92% and 20% respectively, while in group B the rates were 69.3%, 93% and 19.6% respectively; the differences are not statistically significant.Conclusions Epidural anesthesia is an effective method for transvaginal oocyte retrieval but does not improve the treatment outcome as compared to an intravenous sedation with mask-assisted ventilation using propofol and nitrous oxide.