Structure activity studies of tryptophan30 modified analogs of Ac-CCK-7.

Cholecystokinin represents a family of gut hormones which among other activities, have been proposed to participate in satiety signaling. Ac-CCK-7[Ac-Tyr(SO3H)-Met-Gly-Trp30-Met-Asp-Phe-NH2 (2)] possesses the full spectrum of activity and potency of the intact hormone; thus analogs of 2 may be useful as anorectic agents. A series of derivatives has been prepared in which the tryptophan indole moiety of 2 has been modified. The new compounds were assayed in CCK binding assays using homogenated rat pancreatic membranes and bovine striatum as a source of CCK-A and CCK-B receptors respectively and in vivo in rats for anorectic activity. Although previous studies have concluded that the indole ring of Trp30 is a critical pharmacophore for the interaction of CCK with both its A and B type receptors, we find 2-Nal30-Ac-CCK-7 (20) to be nearly equipotent to 2 in both CCK binding and as an anorectic agent sensitive to blockade by the Merck CCK-A receptor antagonist MK-329. The extreme structural sensitivity of this anorectic activity is illustrated by the 1-naphthylalanine30 (19) and (benzo[b]thien-2-yl)alanine30 (21) analogs which are 30 and 100 times less potent than 2 respectively. Other mono- and bicyclic Trp30 replacements, including substituted phenylalanines, 3-quinolinylalanine, and 2-(5,6,7,8-tetrahydro)naphthylalanine, gave inactive compounds.


Alkylation of histidine with maleimido-compounds.

Introduction of the maleimide function via a spacer into histidine-containing peptides was found to produce ring closure by nucleophilic addition of the Nim-imino function of the histidine side-chain to the activated double bond of the maleimide. As an intramolecular cyclization reaction it proceeds at remarkably higher rates than the bimolecular alkylation of histidine derivatives with N-ethyl-maleimide. Correspondingly, in the case of the histidine-peptides examined only mixtures of the cyclic isomeric compounds were isolated and structurally characterized by 1H-NMR analysis. As expected, prevention of this reaction in histidine-containing maleoyl-peptides can be achieved by Nim-protection of the imidazole group. However, upon removal of this protection, the reaction takes place again, thus remarkably hampering the usefulness of the maleimide/thiol addition principle in conjugate chemistry for peptides. On the other hand this reaction could represent an interesting new approach for the design of cyclic peptidomimetic analogs.


Geometry of proline-containing alpha-helices in proteins.

Crystal structure analysis of proline-containing alpha-helices in proteins has been carried out. High resolution crystal structures were selected from the Protein Data Bank. Apart from the standard internal parameters, some parameters which are specifically related to the bend in the helix due to proline have been developed and analyzed. Finally the position and nature of these helices and their interactions with the rest of the protein have been analyzed.


Degradation of aspartic acid and asparagine residues in human growth hormone-releasing factor.

Products of the degradation of human growth hormone-releasing factor (GRF) in aqueous solutions (15-200 microM) have been isolated and fully characterized. The cleavage product, GRF(4-44)-NH2, and the isomerization product, [beta-Asp3]GRF(1-44)-NH2, from the degradation of GRF(1-44)-NH2 in acidic solution and the corresponding products, GRF(4-29)-NH2 and [beta-Asp3]GRF(1-29)-NH2, from the degradation of GRF(1-29)-NH2 have been isolated and characterized. The products, [beta-Asp8]GRF(1-44)-NH2 and [Asp8]GRF(1-44)-NH2, from the deamidation of GRF(1-44)-NH2 at pH 8.0 and the corresponding products, [beta-Asp8]GRF(1-29)-NH2 and [Asp8]GRF(1-29)-NH2, from the deamidation of GRF(1-29)-NH2 have been isolated and characterized. All the degradation products of GRF(1-44)-NH2 and GRF(1-29)-NH2 were evaluated for biological activity and found to have much lower in vitro potencies than the parent peptides. Degradation occurs at Asp3 and Asn8 and the kinetics of these various transformations versus pH and temperature have been studied. GRF is most stable at pH 4-5. At pH below the pKa of the Asp3 side-chain (pH less than 4), cleavage at Asp3-Ala4 is the major route of degradation. For pH greater than 4, isomerization of Asp3 to beta-Asp3 (iso-Asp3) predominates. The rates of cleavage and isomerization are simple first order and vary with pH, independent of buffer concentration, such that the protonated (COOH) form of Asp3 undergoes cleavage while the ionized (COO-) form isomerizes. The more rapid deamidation of Asn8 to generate beta-Asp8 and Asp8 in about a 4:1 ratio, presumably via a cyclic imide intermediate, occurs at pH greater than or equal to 5 and is general base-catalyzed. Evidence was also obtained for direct hydrolysis of protonated Asn8 in GRF(1-29)-NH2 at pH less than or equal to 2 to give exclusively [Asp8]GRF(1-29)-NH2. The deamidation of Asn8 in GRF(1-29)-NH2 at pH 8.0, 22-55 degrees C, is relatively insensitive to temperature for T less than 37 degrees C, possibly due to conformational constraints. Asp25 and Asn35 are sterically, conformationally, or otherwise hindered with respect to these changes as no degradation at these sites was observed under the conditions employed.


Phosphoryl group participation leads to peptide formation from N-phosphorylamino acids.

N-phosphorylated amino acids without a side chain functional group can transfer themselves into peptides after prolonged standing in solvents at warm temperatures. Seven N-phosphorylpeptides and free peptides were isolated and their structures determined. The phosphoryl group participation is the key to the peptide formation. An intramolecular mixed carboxylic-phosphoric anhydride intermediate was proposed for this type of reaction which might provide a clue to the function of the phosphoryl group in the phosphorylated enzymes and in the prebiotic synthesis of protein.


New convenient synthesis of immunostimulating peptides containing meso-diaminopimelic acid. Syntheses of FK-565 and FK-156.

A new improved synthesis of two immunostimulating peptides: FK-156 (D-lactyl-alanyl-gamma-D-glutamyl-(L)-meso-2,6-diaminopimelyl-(L)- glycine) and FK-565 (heptanoyl-gamma-D-glutamyl-(L)-meso-2,6-diaminopimelyl-(L)- D-alanine) is described. A proper differentiation between the two chiral amino acid moieties of diaminopimelic acid was accomplished by selective enzymatic hydrolysis of one methyl ester group of the L-centre of Z2-meso-A2pm(OMe)2 (2). Utilization of a commercially available protease and diester 2 as an enzyme substrate made possible the relatively simple synthesis of a key intermediate 4 and considerably simplified the final deprotection steps. Aminolysis of the N-carboxyanhydride (4) with D-AlaONBzl or GlyONBzl was chosen to obtain the appropriate dipeptides with one free amino group as convenient intermediates for further peptide synthesis. The BOP reagent, used for peptide bond formation, secured good yields and high chemical and chiral purity of the peptides. A modification of alanine deamination procedure leading to a significant increase of D-Lac(OAc) yield is presented.


Binding and spectroscopic properties of ostrich neurophysins. Probing the role of residue 35 at the monomer-monomer interface.

Binding and spectroscopic properties of ostrich neurophysins were examined with emphasis on the behavior of Tyr-35, a residue that provides a potential probe of the monomer-monomer interface and of allosteric interrelationships between this region and the binding site. Mesotocin-associated ostrich neurophysin was found to bind oxytocin and related peptides with affinities comparable to the mammalian proteins, but induced a significantly different optical activity in bound peptides than the mammalian proteins. Gel-filtration studies indicated higher dimerization constants for the ostrich neurophysins than for the bovine neurophysins. Consistent with this, Tyr-35 was found to be largely buried, as monitored by tyrosine titration and lack of reactivity towards tetranitromethane under non-denaturing conditions. Reaction of Tyr-35 of the mesotocin-associated protein with tetranitromethane under denaturing conditions, followed by refolding, allowed isolation of an active product with an altered interface region as partially evidenced by its titration properties and consistent with its markedly altered CD spectrum. Comparison of the CD spectra of the modified and native proteins and analysis of pH effects indicated the contribution of Tyr-35 to an unusual 237 nm band in the mesotocin-associated protein. Small shifts in the 350 nm CD band of nitrated Tyr-35 on binding peptide and apparent effects of nitration on the induced optical activity in bound peptide provided evidence of at least weak structural communication between Tyr-35 and the binding site. However, no significant effect of nitration on binding affinity was observed, suggesting that, in the mesotocin-associated protein, the region around residue 35 is not a stringent modulator of the thermodynamic behavior of the binding site.


An equine growth hormone molecular species lacking the 76-92 peptidic fragment.

A new eGH molecular species was isolated and purified by reverse phase HPLC. SDS-polyacrylamide gel electrophoresis, amino acid composition, and C- and N-terminal determinations support a primary structure identical to that described by Zakin et al. (1976), except for the lack of the 76-92 peptidic fragment and the maintaining of 30% of its biological activity.


Apparent specific volumes of some dipeptides (containing L-valine and L-leucine in aqueous alkylurea solutions).

The apparent molal volumes of nine dipeptides containing glycine, L-valine, and L-leucine have been determined in methyl, N,N'-dimethyl and ethylurea solutions from precise density measurements. Limiting partial molal volumes. V2(0), at various solute concentrations have also been calculated. The experimental values of V2(0) in water agree reasonably well with those calculated as the sum of V2(0) of both acids after accounting for the electrostrictive effect and loss of water. There is no correlation between the values of V2(0) of individual dipeptides in alkylureas which means that the intrinsic volume and the electrostrictive effect make the largest contribution to V2(0). The contribution from other effects is within the limit of experimental error. The volumes of transfer from water to alkylurea solutions are all positive and reflect by and large the electrostrictive effect.


Continuous flow solid (gel) phase peptide synthesis using unsupported ultra-high load polymers.

A simple, manually operated, continuous flow apparatus is described for solid (gel) phase peptide synthesis. The approach uses an unsupported phenolic bead form core network at an initial matrix loading of 5 mmol g-1, the theoretical maximum. The synthesis is performed in a flow reactor under low pressure conditions. "Layered displacement" of reagent solutions and washing solvents is an essential feature that has been developed to facilitate efficient peptide synthesis. The usefulness of the present system in conjunction with N alpha Boc protected amino acids is illustrated by the syntheses of [Leu5]-enkephalin and dermorphin. The potential for scale up synthesis has also been investigated.


Pepsin as a catalyst of peptide synthesis. Enzyme co-precipitation with emerging peptide products.

Pepsin successfully catalyzed the synthesis of several peptide derivatives from N-protected di- or tripeptides and amino acid or peptide esters or p-nitroanilides in dimethylformamide-water solutions at pH 4.6. An optimal substrates:pepsin ratio depended on the structure of starting peptides, especially their fit to the substrate binding sites of the enzyme. For hexapeptide Z-Ala-Ala-Phe-Leu-Ala-Ala-OCH3 formation, an equilibrium yield was attained at 1:3.10(5) enzyme-substrates ratio that indicated high efficiency of pepsin in synthesis reactions. In the course of the equilibrium peptide synthesis, pepsin gradually disappeared from the liquid phase due to its entrapment within a gel, formed by the hexapeptide product, while retaining its activity. The inclusion into the precipitate was not specific for pepsin, so far as inert proteins, lysozyme, ribonuclease A and carbonic anhydrase, when added to the reaction mixture, became also co-precipitated with the hexapeptide formed. It appears that co-precipitation of pepsin, an important factor limiting the enzyme efficiency, might be operative as well for other proteinases used to catalyze peptide synthesis.


Crystal structure of tert.-butyloxycarbonyl-L-prolyl-D-alanyl-D-alanyl-N-methylamide. Dimeric beta-sheet formation.

The crystal structure of the tripeptide t-Boc-L-Pro-D-Ala-D-Ala-NHCH3, monohydrate, (C17H30N4O5.H2O, molecular weight = 404.44) has been determined by single crystal X-ray diffraction. The crystals are monoclinic, space group P2(1), a = 9.2585(4), b = 9.3541(5), c = 12.4529(4)A, beta = 96.449(3) degrees, Z = 2. The peptide units are in the trans and the tBoc-Pro bond in the cis orientation. The first and third peptide units show significant deviations from planarity (delta omega = 5.2 degrees and delta omega = 3.7 degrees, respectively). The backbone torsion angles are: phi 1 = -60 degrees, psi 1 = 143.3 degrees, omega 1 = -174.8 degrees, phi 2 = 148.4 degrees, psi 2 = -143.1 degrees, omega 2 = -179.7 degrees, phi 3 = 151.4 degrees, psi 3 = -151.9 degrees, omega 3 = -176.3 degrees. The pyrrolidine ring of the proline residue adopts the C2-C gamma conformation. The molecular packing gives rise to an antiparallel beta-sheet structure formed of dimeric repeating units of the peptide. The surface of the dimeric beta-sheet is hydrophobic. Water molecules are found systematically at the edges of the sheets interacting with the urethane oxygen and terminal amino groups. Surface catalysis of an L-Ala to D-Ala epimerization process by water molecules adsorbed on to an incipient beta-sheet is suggested as a mechanism whereby crystals of the title peptide were obtained from a solution of tBoc-Pro-D-Ala-Ala-NHCH3.


Efficient approach to synthesis of two-chain asymmetric cysteine analogs of receptor-binding region of transforming growth factor-alpha.

The putative receptor-binding region of human transforming growth factor-alpha (TGF alpha) has been shown to be contributed by two fragments: an A-chain (residue 12-18) and a 17-residue carboxyl fragment (residue 34-50) that includes a disulfide-containing C-loop (residue 34-43). An approach to the synthesis of two-chain analogs containing an intermolecular disulfide linked A-chain and the 17-residue carboxyl fragment (C-fragment) possessing receptor-binding activity is described. The synthesis was achieved by the solid-phase method using the Boc-benzyl protecting group strategy. The single Cys of the A-chain was activated as a mixed disulfide with 2-thiopyridine to form the intermolecular disulfide bond with Cys41 or Cys46 of the C-fragment on the resin support. Prior to this reaction, the acetamido (Acm) protecting group of Cys41 or Cys46 was removed by Hg(OAc)2 on the resin support. The peptide and side chain protecting groups including the S-methylbenzyl moiety of the Cys34 and Cys43 were concomitantly cleaved by high HF. The intramolecular disulfide with two unprotected Cys was formed in the presence of an intermolecular disulfide. This intramolecular disulfide bond formation was usually not feasible under the traditionally-held scheme at basic pH since disulfide interchange would occur faster than intramolecular oxidation. To prevent the disulfide interchange, a new method was devised. The intramolecular disulfide bond oxidation was mediated by dimethylsulfoxide at an acidic pH, at which the disulfide interchange reaction was suppressed. The desired product was obtained with a 60-70% yield.(ABSTRACT TRUNCATED AT 250 WORDS)


Peptide crystal growth via vapor diffusion. Crystal structure of glycyl-L-tyrosyl-L-alanine dihydrate.

The structure of a dihydrated form of glycyl-L-tyrosyl-L-alanine (GYA) has been determined as part of a series of peptide structural investigations and development of microscale vapor diffusion experiments for peptide crystal growth. Crystals were grown by the hanging-drop method against sodium acetate. The tripeptide is a zwitterion in the crystal, adopting an extended conformation through glycine, a nearly perpendicular bend at tyrosine and a reverse turn for the C-terminal carboxylate. Principal backbone torsion angles are psi 1 175(1) degrees, omega 2 173(1) degrees, phi 2 -119(1) degrees, psi 2 120(1) degrees, omega 3 172(1) degrees, phi 3 -73(1) degrees, psi 31 -9(1) degrees, psi 32 171(1) degrees. The tyrosyl side chain adopts an unusual orientation (chi 1/2 = -86(1) degrees). The relationship of the GYA.2H2O structure to GYA sequences in proteins is examined, particularly as regards its helix-forming potential. Crystal data: C14H19N3O4.2H2O, M(r) = 345.36, orthorhombic, P2(1)2(1)2(1), a = 4.810 (4), b = 11.400(7), c = 30.162(23)A, V = 1653.8(24)A-3, Z = 4, Dx = 1.387 Mgm-3, lambda(CuK- alpha) = 1.540 A, mu = 9.053 mm-1, F(000) = 736, T = 199 K, R = 0.041 for 1458 observations with I greater than or equal to 3 sigma(I).


Application of arylsulphonyl side-chain protected arginines in solid-phase peptide synthesis based on 9-fluorenylmethoxycarbonyl amino protecting strategy.

One of the main problems still hampering solid-phase peptide synthesis using orthogonal protection strategies based on the 9-fluorenylmethoxycarbonyl amino protecting group is the difficult removal of currently used arginine arylsulphonyl guanidino protecting groups. Poor acid liability of 4-methoxy-2,3,6-trimethylbenzenesulphonyl-protected arginine has led to the popularity of the newer 2,2,5,7,8- pentamethylchroman-6-sulphonyl guanidino protecting group. This group was initially believed to have liability to trifluoroacetic acid, the reagent commonly used to simultaneously deprotect peptides and detach them from the synthesis resin, comparable to tert.-butyl and trityl type protecting groups used for the protection of other peptide side-chain functionalities. In a comparison of three established cleavage/deprotection mixtures we have shown that this is not always the case, particularly in multiple arginine peptides. We have found that only hard-acid deprotection with trimethylsilyl bromide reliably removed both arylsulphonyl guanidino protecting groups from a variety of arginine-containing peptides.


Unusual thionation of a cyclic hexapeptide. Conformational changes and dynamics.

One carbonyl oxygen of the cyclic hexapeptide cyclo(-Gly1-Pro2-Phe3-Val4-Phe5-Phe6-) (A) can be selectively exchanged with sulphur using Yokoyama's reagent. Surprisingly it was not the C=] of Gly1 but that of Phe5 which was substituted and cyclo(-Gly1-Pro2-Phe3-Val4-Phe5 psi [CS-NH]Phe6-) (B) was obtained. Thionation results in a conformational change of the peptide backbone although the C=O of Phe5 and the corresponding C=S are not involved in internal hydrogen bonds. Two isomers in slow exchange, containing a cis Gly1-Pro2 bond in a beta VIa-turn (minor) and a trans Gly-Pro bond in a beta II'-turn (major), were analyzed by restrained molecular dynamics in vacuo and in DMSO as well as using time dependent distance constraints. It is impossible to fit all experimental data to a static structure of each isomer. Interpreting the conflicting NOEs, local segment flexibility is found. MD simulations lead to a dynamic model for each structure with evidence of an equilibrium between a beta I- and beta II-turn about the Val4-Phe5 amide bond in both the cis and trans isomers. Additionally proton relaxation rates in the rotating frame (R1 rho) were measured to verify the assumption of this fast beta I/beta II equilibrium within each isomer. Significant contributions to R1 rho-rates from intramolecular motions were found for both isomers. Therefore it is possible to distinguish between at least four conformers interconverting on different time scales based on NMR data and MD refinement. This work shows that thionation is a useful modification of peptides for conformation-activity investigations.


Effect of copper(II) chloride on suppression of racemization in peptide synthesis by the mixed anhydride and related methods.

In segment couplings by the mixed anhydride method using isobutyloxycarbonyl chloride, the use of copper(II) chloride as an additive suppressed racemization completely in the same manner as in the carbodiimide method reported previously. This was confirmed by employing a number of couplings between Z-dipeptides and amino acid esters. The racemization-suppressing effect of other compounds were also evaluated by employing one of these model couplings to be at best only limitedly effective. Copper(II) chloride was effective also in the related method using EEDQ. Thus, in the couplings where a low level of racemization was observed without an additive, the addition of copper(II) chloride eliminated racemization even at ambient temperature where EEDQ is usually used. The effectiveness of copper(II) chloride was confirmed also in the BOP-Cl method. In the presence of HOBt racemization was reduced to a low but still detectable level, while it was suppressed completely by the addition of copper(II) chloride.


Synthesis and biological activity of the mono- and di-galactosyl-vespulakinin 1 analogues.

Syntheses are described of some mono- and di-glycosylated analogues of vespulakinin 1. The solid phase procedure, based on the Fmoc chemistry, was used to prepare (Gal alpha)Thr3-vespulakinin 1, (Gal beta)Thr3-vespulakinin 1 and the di-glycosylated analogue ((Gal alpha)Thr3, (Gal alpha)Thr4-vespulakinin 1. The beta-glycosylated derivative was also prepared by the continuous flow variant of the Fmoc polyamide method. The synthesized glycopeptides were purified and characterized by amino acid analysis, optical rotation, analytical HPLC, 1H- and 13C-NMR and FAB-MS. Preliminary pharmacological experiments showed that the carbohydrate-free vespulakinin 1 is less active than bradykinin (about 0.3 times on a molar basis) when tested by guinea pig rectum contraction, and the two monoglycosylated analogues are equiactive (about 0.9 times the bradykinin activity). The most active derivative, the (Gal alpha)Thr3, (Gal alpha)Thr4-vespulakinin 1 analogue, was about 2.5 times as active as bradykinin.


Ethylcarbamoyl protection for cysteine in the preparation of peptide-conjugate immunogens.

During the solid-phase synthesis of over 100 peptides, we have observed that the ethylcarbamoyl group is useful for the side chain protection of cysteine in peptides containing a single cysteine residue. The ethylcarbamoyl group is stable to the conditions of acidolytic cleavage, purification and long term storage. Brief treatment of peptides containing an S-ethylcarbamoyl-cysteine residue with aqueous sodium hydroxide gives the deprotected cysteine peptide that can be coupled to carrier molecules such as proteins to give immunogen conjugates.


FMOC solid phase synthesis of an endothelin converting enzyme substrate. Use of allyl ester as the third orthogonal protecting group.

The synthesis of a substrate for the endothelin converting enzyme using the continuous flow FMOC solid phase method has been accomplished. The allyl group, employed to protect Glu side chain, was cleanly removed during the synthesis in the presence of tert.-butyl based protecting groups to enable the introduction of the Edans moiety. The substrate was obtained in 31% yield after reverse phase hplc purification.


Synthesis and conformation of the trimeric coiled-coil segment of laminin.

A disulfide linked 95-mer parallel hetero-trimeric active site segment of laminin was designed and synthesised. The three subunits, A (32-mer), B1 (30-mer) and B2 (33-mer), were prepared by Boc-based solid-phase peptide synthesis involving a two-step trimethylsilyl bromide-thioanisole and HF deprotection procedure. The interlinking of the three subunits was accomplished by the stepwise selective formation of two disulfide bridges using air-oxidation and thallium (III) trifluoroacetate oxidation. The conformations of the synthetic peptides were studied by circular dichroism (CD) spectroscopy, showing that the hetero-dimer, B1-B2, one of the homo-dimers, B1-B1, and the trimer are 30 to 40% in the alpha-helical conformation in aqueous buffer. Variable temperature CD studies demonstrated that the trimer is considerably more stable (melting temperature (Tm) = 61 degrees) than the hetero-dimer, B1-B2 (Tm = 36 degrees).


Central function and visual field damage in glaucoma.

82 eyes of 82 patients with different types of glaucoma were examined with various psychophysical tests assessing central and paracentral function, including foveal temporal contrast sensitivity function, FM 100-Hue test, and foveal and parafoveal blue-on-yellow-sensitivity. For all eyes visual field tests were performed with the Humphrey-Field-Analyzer, program 30-2. Global visual field indices were calculated as follows: Mean Sensitivity MS, Mean Deviation MD, and Corrected Pattern Standard Deviation CPSD. Linear regression analysis and multiple regression analysis correcting for a possible influence of age between the central and paracentral criteria and the global indices was performed. For the entire study population highly significant correlations are present between foveal and parafoveal blue-on-yellow-sensitivity and MS, MD and CPSD. Whereas in the Normal Tension Glaucoma subgroup (19/82 eyes) no significant correlations are found, the subgroup of 35/82 eyes with markedly elevated intraocular pressure (> or = 30 mmHg) shows highly statistically significant correlations between the low- and high-frequency end of the foveal temporal contrast sensitivity function and foveal and parafoveal blue-on-yellow-sensitivity and the global field indices. The results of the present study support the idea that there are two different mechanisms of glaucomatous damage, one which is pressure-dependent and one which may be pressure-independent. The pressure-dependent mechanism is responsible for deficits of central or paracentral function which are correlated to overall visual field damage.


The pattern ERG in glaucoma: effect of pattern reversal time.

Pattern reversals with a ramp-like temporal course evoke transient pattern electroretinograms (PERG) that are delayed and attenuated in comparison with responses evoked by a step-like course (abrupt pattern reversals). This delay depends on the reversal time and probably represents a measure for temporal characteristics of the activated retinal structures. A pattern reversal stimulator with adjustable reversal periods (matrix of 8 x 14 rectangular red light emitting diodes, element size 2 degrees x 1 degree, stimulus area 16 degrees x 14 degrees) was used to record transient PERGs from 20 glaucomatous eyes with early or moderate visual field damages (measured with computer perimetry). The q-wave (P1) amplitude difference between the glaucoma group and normal subjects with step-like reversal stimulation was not significant (P = 0.23). On the other hand, a highly significant separation (P < 0.0001) between both groups was possible using the P1 latency at ramp-like stimulation or the response latency shift between step and ramp-like stimulation (Pattern reversal time, 30 ms).


Is oculokinetic perimetry useful?

An evaluation was carried out comparing Oculokinetic Perimetry (O.K.P.) with Automatic Perimetry of Thresholds (Hipocampus Perimeter) for ocular hypertension and glaucoma studying 145 eyes. The O.K.P. shows a sensitivity between 35.65 and 38.54%, a specificity of 76.67-79.59%, a + predictive value of 78.72-85.42%, and a-predictive value of 23.71-39.80%.


Oculokinetic perimetry compared with standard perimetric threshold testing.

To calibrate oculokinetic perimetry (OKP) as developed by Damato in terms of conventional perimetric threshold values, 33 eyes with either glaucoma or ocular hypertension were tested with a standard Humphrey Field Analyzer using the Central 30-2 test and twice with a 26-point OKP chart. The frequency of seeing of the OKP test spot was plotted against 30-2 thresholds. This showed a weak relation between the two tests. Subsequently eyes that were considered to have had poor fixation were omitted, but false positive and false negative results still occurred in 19 remaining eyes. To check whether Troxler's effect (local adaptation) might have caused false positives, 6 subjects were tested with OKP, controlling the fixation times. Increasing the fixation time from 'very short' to 2 and 5 seconds yielded more 'not seen' responses in OKP. False negative data were found to occur preferentially in border areas of visual defects. The average frequency of seeing curve over all data showed a 50% frequency of seeing for the OKP stimulus at a 14.6 dB equivalent conventional threshold value. The spreading of the curve was 7 dB (95% confidence interval 28 dB).


Intra- and inter-observer variation of optic nerve head measurements in glaucoma suspects using disc-data.

The aim of this study was to determine the intra- and inter-observer variation in the use of a system designed for exact measurements from standard optic nerve head photographs. The commercially available system consisted of a colour CCD Videocamera, a dedicated frame grabber and customized software run on a IBM AT compatible computer. Masked measurements were made 3 times by 2 observers, from stereophotographs of the optic nerve head of 56 eyes from 30 glaucoma suspects. The cup was defined on the basis of contour, not pallor and the disc area was defined as the area inside Elschnig's ring. Intra-observer variances were 0.001 +/- 0.001 mm2 for cup area (mean +/- SD), 0.002 +/- 0.002 mm2 for disc area and 0.002 +/- 0.003 mm2 for rim area. These values for intra-observer variance were comparable with the results obtained using manual planimetric techniques. Intra-observer variance for disc area was significantly larger for the less trained of the two experienced observers. Inter-observer variances were 0.004 +/- 0.009 mm2 for cup area, 0.008 +/- 0.013 mm2 for disc area and 0.009 +/- 0.014 mm2 for rim area. These inter-observer variances were significantly larger than those previously reported for manual planimetry. The absolute differences between the two observers ranged from -0.35 to +0.20 mm2 (-0.08 +/- 0.11 mm2) for cup area, from -0.38 to +0.15 mm2 (-0.08 +/- 0.11 mm2) for disc area and from -0.29 to +0.34 mm2 (-0.06 +/- 0.12 mm2) for rim area.(ABSTRACT TRUNCATED AT 250 WORDS)


Similarities between disc haemorrhages and thromboses of the retinal veins.

999 patients with glaucoma (G) visited the office from the beginning of 1980 until the end of 1991. 381 patients with disc haemorrhages and 164 with thrombosis (T) were found and followed when possible. At the detection 17 cases with thrombosis and 41 cases with disc haemorrhage (H) had glaucoma. During follow-up 52 cases with glaucoma got a thrombosis and 26 cases with thrombosis developed glaucoma, 105 cases with glaucoma got a disc haemorrhage and 33 cases with disc haemorrhage developed glaucoma. At the end of the follow-up 179 cases with glaucoma have had a disc haemorrhage, and 95 have had a thrombosis. In this material disc haemorrhages and thromboses, both thromboses of a branch (TB) and thromboses of the central vein (TC), behaved in the same way with respect to the occurrence of glaucoma, and the hypothesis that the materials H, TB or TC are of similar origin and symptoms of glaucoma seems reasonable.


Retinal nerve fiber layer defects and automated perimetry evaluation in ocular hypertensives.

Preliminary results of a larger investigation on correlation between Retinal Nerve Fiber Layer Defects (RNFL) and Automated Perimetry (AP) are presented. A group of ocular hypertensive patients was recruited and a cross-section, randomized study was carried out. The group was composed of 54 eyes from 28 patients; 15 men and 13 women, mean age 42.76 year, mean visual acuity 0.95 (Snellen cart) and mean visual defect expressed in diopters was +0.514 (from -2.5 to +5). A total of 17 (31.48%) refractive fields were pathologic according to our criteria, one from a normal RNFL and the others from nerve fiber defects. We observed 6 no reliable RNFL photographs, 18 normal, 11 slits, 6 wedge, 11 diffuse and 2 mixed defects. Comparing RNFL and AP, 53.33% of eyes with fiber defects had abnormal perimetries. The more evolutioned the defect, the larger percentage of abnormal visual fields were observed: 36.36% in slit defects, 66.66% in wedge, 54.55% in diffuse and 100% in mixed ones. Comparing location of defects with location of cluster of decreased sensibility points in visual field, a higher correlation in inferior than superior defects was found.


Correlations between densitometry of red-free photographs and reflectometry with the scanning laser ophthalmoscope in normal subjects and glaucoma patients.

To compare image measurements of the retina produced by scanning laser ophthalmoscopy with those from red-free photographs (RFP) of the nerve fibre layer. The left eyes of 23 subjects (10 normal, 7 glaucoma suspect and 6 glaucomatous) were included in this study. All the eyes were photographed using standard red-free photography, and images of the retina were digitised directly from the SLO. The correlation coefficient for all except three subjects was > 0.45, and the probability (p) that R = 0 was < 0.05 in all but 5 eyes. The data indicate that variations in retinal surface reflectivity as measured by the SLO are similar to those recorded on negative film during RFP. This further suggests that the SLO can be useful for making objective measurements of the RNFL, without the intermediate and variable steps of photography.


Diffuse nerve fiber layer loss in normal tension glaucoma.

14 eyes of 14 normal tension glaucoma (NTG) patients with the maximum intraocular pressure (IOP) > or = 19 mmHg and 16 eyes of 16 NTG patients with the maximum IOP < 19 mmHg were examined. All patients had a scotoma confined to the upper or lower hemifield. Eyes with the maximum IOP > or = 19 mmHg showed significantly diffuse retinal nerve fiber layer (RNFL) loss in the RNFL area corresponded to the spared visual hemifield as compared to those with the maximum IOP < 19 mmHg. The results suggests that, even in NTG, IOP may be an important factor causing optic nerve damage.


Spectrometric investigations in ocular hypertension and early stages of primary open angle glaucoma and of low tension glaucoma--multisubstance analysis.

The approximation of logarithmic difference spectra between the reflectance of the normal fundus and the fundus reflectance in different stages of glaucoma is demonstrated by a model. The influences of fundus pigments like oxihemoglobin, melanin, xanthophyll and rhodopsin as well as the intensity and the exponent of the scattered light are optimized. Glaucomatous alterations in the extinction of these pigments and of the scattering parameters are different in the macula, in the papillo-macular bundle and in the parapapillary region temporal to the optic disc. A lack of oxihemoglobin only in the papillo-macular bundle in first relative losses in the visual field function points to a damaged microcirculation in early POAG. In progressive glaucoma the extinction spectrum of xanthophyll is detectable in the papillo-macular bundle. A decreased intensity of the scattered light and an altered scattering exponent are suggestive of a damage in the nerve fiber layer at early stages of glaucoma.


Optic nerve fiber loss in relation to atrial fibrillation and blood pressure.

This study investigates the relationship of atrial fibrillation, systemic blood pressure and nerve fiber loss. 213 institutionalized glaucoma patients (mean age 83.9 years) and 100 control patients (mean age 81.8 years) were examined ophthalmologically and analyzed for blood pressure. A 12-lead electrocardiogram, analyzed according to the Minnesota code, was taken for 212 glaucoma patients and 100 control patients. 17% of the glaucoma patients had atrial fibrillation (AF), which was significantly more than in the control group (8%). Patients with AF had lower systolic blood pressures (mean 146.5 mmHg) than the other patients (mean 153.7 mmHg). Visual acuity (VA) of the patients having AF was lower than that of the other patients. Severe visual field defects occurred more frequently in patients having AF (in 70% v.s. 42%). Patients with severe visual field defects and lower VA had lower systolic blood pressures than the patients with better visual fields and VA. 75% of geriatric glaucoma patients with AF and 64% of geriatric glaucoma patients without AF had intraocular pressures < 18 mmHg. Atrial fibrillation and low systolic blood pressure are connected with impairment of ocular functions of geriatric glaucoma patients.


Anatomical risk factors in primary angle-closure glaucoma. A ten year follow up survey based on limbal and axial anterior chamber depths in a high risk population.

A population of 539 persons was examined in 1979, using LCD and ACD estimations acc. to van Herick et al. and by Haag Streit pachymetry, respectively. ACD had been measured already in 1969, due to a remarkable occurrence of primary angle-closure glaucoma (PACG) in the survey population of Greenland Eskimos (District of Uummannaq). The present follow up study in 1989 aimed at persons presently above age 40, who had shown either an LCD value graded as 0 (contact) or 1 (< 0.25 of corneal thickness = CT), or a value of 2 (= 0.25 CT) if an ACD value of < = 2.70 mm (CT included) had also been found. PACG patients or suspects known in 1979 already were excluded from the present analyses. A total of 75 persons was now examined. Five had developed acute (n = 2) or intermittent PACG (n = 3) during the ten year period. At the survey 3 intermittent and 4 latent PACG cases were detected, yielding in ten years a PACG prevalence of 12/75 = 16% (sex ratio: M/F = 2/10). One male case of severe secondary (partly inflammatory) ACG was also found. Past and present LCD and ACD values are given as well as gonioscopical status. Creeping, synechial angle-closure was frequent. Among probands who could not be examined, mostly due to death before 1989, 5/54 had developed PACG during the ten year period. Non-probands according to above criteria were mostly not examined. Yet their records were scrutinized for any event suspect of PACG. Thus among 258 persons above age 40 no PACG case was found.(ABSTRACT TRUNCATED AT 250 WORDS)


Color Doppler imaging in evaluation of optic nerve blood supply in normal and glaucomatous subjects.

The authors evaluate by means of Color Doppler Imaging (CDI) the blood flow in ophthalmic artery, posterior ciliary arteries and central retinal artery in a group of glaucomatous patients. The data obtained in this study show a statistically significant reduction of the mean systolic peak flow velocity in ophthalmic artery in glaucomas in comparison with controls. In Glaucomatous patients with uncontrolled IOP there was a reduction of end-diastolic flow velocities and a rise of resistivity index in ciliary arteries and central retinal artery.


Pr VECPs related to ciliary perfusion pressure in primary open angle glaucoma. A study using contact lenses to compensate for refraction changes during artificially raised IOP.

Pr VECP studies in glaucoma patients with the IOP raised artificially by the suction cup method have recently been performed by several authors, who arrived at different results. The reason for those differences may be the changes employed. The refraction changes depend on the shape of the suction cup and the height of the artificial IOP raise. By using contact lenses and a suitably shaped suction cup refraction changes could be compensated for. Studies of the pr VECP with suction cup IOP elevation and simultaneous compensation for refraction changes by applying contact lenses were made on 17 patients with primary open angle glaucoma and 21 healthy volunteers. In healthy subjects pr VECP amplitudes were found unaltered or even slightly increased until 120 mmHg of negative pressure were reached in the cup. Beyond that range they dropped. Latencies remained unaltered over that range of negative pressures. Plotting the pr VECP amplitudes and latencies against ciliary perfusion pressure we obtained unaltered potentials over a range of ca. 20 mmHg, which we interpreted as autoregulative capacity. In the 17 glaucoma patients various degrees of impaired autoregulation were found corresponding to the progression of glaucoma damage.


Axial and para-axial fluorophotometry in glaucoma simplex.

In this fluorophotometric study, in 25 eyes with middle advanced stages of glaucoma simplex (visual field defects ranged from 500 dB to 800 dB) and treated with topical antiglaucomatous agents, the posterior vitreous penetration ratio (PVPR) was compared with that from normal subjects. Vitreous fluorophotometry (Fluorotron Master, Coherent) was used to measure posterior vitreous fluorescein concentration. Due to additional fixation light in horizontal plane, three scans were taken along the following directions: temporal (t), foveal (f), nasal (n). The angle of deviation from the foveal scan was 15 degrees in each direction. The average values of posterior vitreous penetration ratio in group of patients with glaucoma were higher in comparison with those in healthy subjects. In both groups the PVPR was significantly lower in nasal (n) scan (optic disc area) in comparison with temporal (t) or foveal (f) scans (p < 0.05).


X-PERT NCT advanced logic tonometer valuation.

The air pulsed automatic tonometer X-PERT NCT has been tested in hospitals on glaucomatous patients. This new technique avoids direct contact with the patient's eyes and therefore avoids any risk of contamination. The population studied consisted of 118 eyes of 60 patients whose intraocular pressure (I.O.P.) is measured by applanation with the Goldmann tonometer and then by the air pulsed tonometer. The average I.O.P. obtained by Goldmann tonometer is 17.5 +/- 5 mmHg while by X-PERT tonometer, the average I.O.P. is 17.4 +/- 1.5 mmHg. Statistical analysis of these data showed a very good correlation (r = 0.969) in the two methods of measurement.


A clinical evaluation of XPERT NCT (Reichert) for glaucoma screening by optometrists.

XPERT NCT advanced logic pneumotonometer (Reichert) was studied for its reliability and use in glaucoma screening. The evaluated 2400 NCT measurements on 300 eyes were compared to the results of Goldmann applanation tonometry (GAT) from the same eyes. Repeated NCT tonometry had no significant effect on IOP. Local anesthesia reduced mean NCT-GAT difference and standard deviation significantly (p < 0.05), i.e. feeling due to the diminished air pulse force provided by the instrument had still considerable influence on IOP. NCT-GAT regression was significant (p < 0.01). Mean IOP readings provided by NCT were four mmHg higher than GAT values. Although accuracy was not satisfactory for exact measuring, it was satisfactory for screening. The results suggested that four mmHg less than the mean IOP value seen on the display is acceptable for screening when the difference between the minimal and maximal individual readings on the display is less than 2SD i.e. six mmHg. In the case of a greater difference, the maximal value is to be replaced, as NCT tends to read higher values than GAT.


The Pulsair-Keeler non-contact tonometer in self-tonometry: preliminary results.

The authors considered the possibility of using the Pulsair-Keeler non-contact tonometer in self-tonometry. For this reason, 45 patients have been trained to use the instrument and, after a reasonable trial period, were able to self-measure their IOP. The results have been compared to the tonometric values measured with Goldmann tonometer to evaluate statistically the limits and the dependability of this method of measurement. The results shows that self-tonometry with the Pulsair-Keeler tonometer can be used in monitoring glaucomatous patients at home.


Self-tonometry: technical aspects of calibration and clinical application.

Self-tonometry could be established as an important diagnostic tool in the early diagnosis and follow-up of glaucoma provided that a self-tonometer is precise, safe and easy to use. Furthermore, it has to comply with the legal standards for tonometer calibration. A new software-controlled detection system for the self-tonometer permits the evaluation of external factors during the measurement which influence the precision of the tonometric readings. The updated version of the self-tonometer (ST) was compared to the Draeger hand-held applanation tonometer (HAT) in a clinical study with 82 patients (151 eyes). The results show a regression line characterized by a slope of 0.99, an y interception of 1.41, a correlation coefficient of 0.96 and a standard deviation for the ST readings of +/- 1.78 mmHg. Self-tonometry improves the IOP monitoring as well as patient compliance and therefore is a potential diagnostic tool in the management of glaucoma.


Does aqueous humor secretion decrease with age?

Aqueous humor flow was calculated during day-time in 148 healthy volunteers and 75 older patients using the Fluorotron Master II anterior chamber protocol (Coherent, Palo Alto, USA). Healthy volunteers as well as patients had no history of ocular pathology, surgery or laser treatment. Slitlamp examination revealed no ocular pathology. Hypertension, diabetes, local and systemic drug therapy, neoplasia, kidney or liver disease, contact lens and ocular trauma were excluded. Mean age of volunteers was 26.5 +/- 3.8 years; age of patients: 65.5 +/- 10.5 years. Aqueous humor flow during day-time in healthy volunteers in the OD: (mean +/- s.d.) 2.26 +/- 1.0 microliters/min, in the OS: 2.17 +/- 1.0 microliters/min, OS: 1.86 +/- 1.1 Ml/min. Correlation coefficient: r = 0.8. The mean aqueous humor flow in the older patients during day-time: OD: 1.91 +/- 1.1 microliters/min. Correlation coefficient: r = 0.54. The Mann-Whitney-U-test revealed a significant difference when comparing the right eyes of healthy volunteers with the right eyes of patients (p < 0.01). When comparing all left eyes the difference is also significant (p = 0.01). The results of the study underline, that the mean aqueous humor secretion does significantly decrease with age. However, the data show that there is only a slight decrease of flow of approximately 2.5% per decade. From the clinical point of view it should be concluded, that although the aqueous humor secretion does decrease with age, this is not of clinical importance, even in cases of glaucoma surgery.(ABSTRACT TRUNCATED AT 250 WORDS)


A fluorophotometric study on the aqueous humor dynamics in primary open angle glaucoma.

One hundred and ten eyes in 40 normal persons with no ocular pathology, 20 with ocular hypertension and 50 with primary open angle glaucoma were studied. The value of the aqueous humor flow was obtained and then compared with the different samples and with general (age, sex) and ocular factors (intraocular pressure, tonographic outflow facility, campimeter and disk/cup ratio, among others).


Study on the aqueous humor flow measured by fluorophotometry after argon laser trabeculoplasty.

We have investigated the variations in the aqueous humor flow (F) after argon laser photocoagulation (ALT) in the trabecular meshwork. The research has been done on 60 eyes with primary open angle glaucoma within initial stages. The argon laser trabeculoplasty was made around 360 degrees in anterior trabecular meshwork with 100 burns. The flow (F) has been studied by fluorophotometry using Yablonsky's protocol. Aqueous humor flow has been measured after 24 hours and after 7 days, to determine the immediate effects of laser trabeculoplasty; and also after 6 months for the long term effects. The initial aqueous humor flow was 1.35 microliters/min. By means of ANOVA we found statistically significant differences on aqueous humor flow after the 7th day (F = 1.67 microliters/min, p < 0.01), which remain six months later (F = 1.71 microliters/min, p < 0.01). This findings suggest that the effects of argon laser trabeculoplasty, either by mechanical or biological changes in the trabecular meshwork do not appear until the 7th day and remain throughout the follow up study.


Long-term drift and timolol therapy: possible role for pulsed therapy.

Eyes treated with a topical betablocker may exhibit the phenomenon of longterm drift, leading to loss of intraocular pressure control. It has been suggested that discontinuation of the betablocker may restore sensitivity to betablocker therapy, and that this phenomenon might be enhanced by the administration of an adrenergic agonist during this holiday period. This study was set up to examine further this hypothesis. Nine patients with ocular hypertension receiving treatment with timolol were entered into the study. Timolol was discontinued then re-started after four weeks of treatment with dipivefrin. This treatment cycle was repeated after a further four weeks. IOP was measured every two weeks. Re-introduction of timolol was associated with a significant lowering of IOP at two weeks (3.2 mmHg in the first cycle, p < 0.01, 3.4 mmHg in the second cycle, p < 0.01). Discontinuation of timolol and treatment with dipivefrin was not associated with a significant change in IOP.


Effects of timolol on visual-field mean retinal sensitivity in normal subjects.

This single-blind, randomized study investigated the effects of unilateral instillation of 0.5% maleate timolol twice a day for 7 days on visual-field parameters of both eyes. Twelve normal, young subjects (30.6 +/- 4.2 years) participated in this study. Using program G1 of the Octopus 500 automated perimeter, the visual fields were measured one week and one day before therapy and a third time one week after beginning therapy. The paired T-test was used for statistical analysis, where a P-value < or = 0.05 indicated significance. Whereas nothing statistically significant was found in the treated eyes, the contralateral, untreated eyes showed a statistically significant decrease of mean sensitivity between the first visual fields and the third ones (P < 0.01) This diminution of mean sensitivity in the untreated contralateral eyes may be due to statistically significant lowering of blood pressure (P < 0.01) and slowing of cardiac frequency, which were not compensated by a local decrease of intraocular pressure. If confirmed, these findings could be of clinical importance in the management of glaucoma patients, since some authors have, in some cases, recommended a unilateral therapy.


Changes in depressive status associated with topical beta-blockers.

Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.


The effects of dopamine, haloperidol and bromocriptine on intraocular pressure.

In a double-blind randomised, prospective single dose study, we measured intraocular pressure (IOP), pupil diameter, systemic blood pressure and heart rate in 43 ocular normotensive subjects before (baseline) and 2, 4, and 6 hours after topical instillation of the following drugs: dopamine 2% (n = 11), a dopamine receptor blocking drug, haloperidol 0.5% (n = 11), a dopamine receptor stimulating drug, bromocriptine 0.05% (n = 11) and 0.1% (n = 10). In the groups receiving dopamine or haloperidol, there were no significant differences in IOP compared with baseline values (p > 0.01). But, a significant decrease in IOP compared with the baseline values was found in both bromocriptine groups (p < 0.001). With the 0.05% and 0.1% concentrations, maximum reductions in intraocular pressure were 22.0% +/- 5.8% and 28.4% +/- 9.8%, respectively. No significant differences in mean pupil diameter, systemic blood pressure and heart rate were detected in all of these groups. In addition, in the group receiving bromocriptine 0.1%, there was no change in serum prolactin levels. These results suggest that topically administered bromocriptine has satisfactory intraocular pressure lowering capacity without serious ocular or systemic side effects. Consequently we conclude that, an ophthalmic formulation of bromocriptine may have substantial clinical potential for the treatment of glaucoma.


Changes in the ocular dimensions after trabeculectomy.

Ocular wall dimensions (axial eye length, anterior chamber depth, lens thickness, vitreous length, thickness and volume of the ocular wall) were determined by echobiometry on 10 eyes of 10 patients with glaucoma one day before and four days after trabeculectomy. The results showed significant differences: decreased axial eye length, and increased thickness and volume of the ocular wall were found after trabeculectomy. The observed changes in the ocular dimensions might be due to ocular hypotony and postoperative inflammation. Echographic follow-up of the changes in the ocular wall is a useful monitor to study alteration in eye dimensions after glaucoma surgery.


Therapeutical and genetical aspects of congenital glaucomas.

Therapy for congenital glaucoma is primarily surgical. We have investigated 249 cases who have undergone trabeculectomy. There was a 79% success rate as regards to control of the IOP. Vision could be saved among the patients who had applied relatively early. At the end of the follow up which was 5 years IOP remained normal in the successful group. All the patients and their families were analysed genetically by their pedigrees and caryotypes. An autosomal recessive pattern with variable penetrance was found. The majority of the patients came from families with consanguineous marriages giving a rate of 66.6%. It was suggested that the course of the disease is highly affected by and related to parental consanguinity. An early age of onset and an accelerated clinical course could be well correlated.


Photoablative filtration surgery with the excimer laser for primary open-angle glaucoma: a pilot study.

We have performed ab-externo photoablative filtration surgery on 19 patients affected by uncontrolled primary open-angle glaucoma. All cases had wide open angles, were previously treated with argon laser trabeculoplasty and were considered good candidates for trabeculectomy. After topical and peribulbar anesthesia, a limbus-based conjunctival flap was dissected. Photoablation of a rectangular area at the limbus was performed with an argon fluoride excimer laser (193 nm), at 180 mJ x sq cm fluence. The beam was shaped in the appropriate fashion using a custom-made metal mask. Photoablation was continued until aqueous appeared percolating through the juxtacanalicular tissue at the bottom of the crater; a water-tight closure of conjunctiva was then performed. Postoperatively, the anterior chamber reaction was minimal; in no case a flat chamber or choroidal detachment was observed. In 18 of the 19 cases the IOP was significantly lowered, and a filtering bleb developed. Mean preoperative IOP was 26.4 (+/- 7) mmHg. At a median follow-up of 9 months (range 4-15) the IOP is < or = 18 mmHg on no medications in 16 (84%) of the eyes, with a mean value of 13.3 (+/- 6) mmHg. Our short-term results support excimer laser photoablative filtration as a relatively safe and effective procedure for primary open-angle glaucoma.


Daunorubicin versus 5-fluoro-uracil in surgical treatment of primary open angle glaucoma: a prospective study.

In a prospective randomized study, we compare the results at 20 months of 5 Fluoro-Uracil and Daunorubicin filtering surgery in two groups of 25 patients with primary open-angle glaucoma. For the first group of 14 eyes, 10 injections of 5FU are done and only one subconjunctival preoperative injection of Daunorubicin in the second group of 13 eyes. 5FU group consists of 13 patients: 9 males, 4 females. The mean age is 52.3 +/- 18.4 years. The mean follow-up is 6.9 +/- 7 months. Daunorubicin group consists of 12 patients: 9 males, 3 females. The mean age is 50.2 +/- 21.4 years. The mean follow-up is 7.3 +/- 7 months. By Kaplan-Meier method, the probability success rate is 79 per 100 with 5FU and 68 per 100 with Daunorubicin. After 5FU procedure, the most disturbing complication is related to the decrease in IOP during the first postoperative days: flat anterior chamber (9 eyes) (7 eyes after Daunorubicin), choroïdal detachment (6 eyes) (2 eyes after Daunorubicin), cataract (3 eyes in the two groups). After Daunorubicin, corneal complications are less frequent: corneal ulcer (2 eyes) (3 eyes after 5FU), corneal dystrophy (1 eye in the two groups). Transient chemosis and local palpebral oedema are constant after Daunorubicin. We compared the IOP reduction rate and visual function loss in the two groups.


Mitomycine, suterelysis and hypotony.

In 35 patients 37 trabeculectomies (TE) were performed using mitomycin as a fibrosisinhibitor. Mitomycin (0.5 mg/ml) was applied to the sclera (under the scleral flap) and conjunctiva in the area of the projected TE during 5 minutes using a small sponge. The indications for operation were: visual field progression in 15 eyes, too high IOP in 13 eyes and severe visual field defects (central island and/or centro coecal visual field defects) in 9 eyes. Six patients had Normal Pressure Glaucoma, 17 Primary Open Angle Glaucoma and 12 had other forms of glaucoma. There were 22 first TE's and 15 re-operations. The scleral flap was sutured with 5 to 8 10/0 nylon sutures. The system of a large number of sutures and subsequent suturelysis was our routine management for reducing complications after TE. This report deals with the postoperative period of the first three months. Suturelysis in combination with mitomycine caused an unexpected high number of postoperative hypotonies (IOP < = 6 mmHg with reduced visual acuity and/or retinal folds or large persistent choroidal detachment and shallow anterior chamber) In the 27 eyes who had suturelysis performed, 7 developed a hypotony. The hypotony may develop as late as three weeks postoperative after suturelysis!. Two eyes developed a hypotony without suturelysis. Seven patients needed resuturing of the scleral flap. The use of mitomycine to enhance filtration after TE may cause serious hypotonies if the scleral flap is not securely closed and if suturelysis is used too early or too extensively.


Long term follow-up of the argon laser trabeculoplasty in eyes treated 180 degrees and 360 degrees of the trabeculum.

The results obtained with the Argon Laser Trabeculoplasty (ALT) on 196 eyes with an average follow-up period of 5.24 years (maximum 9 years) have been reviewed. Of the 123 eyes treated with 75-115 burns in the 360 degrees of the trabecular meshwork, 71 eyes were successful with a follow-up of 64.3 +/- 28.3 months (mean +/- SD). This treatment reduced the previous anti-glaucomatous medical treatment in 35 eyes (28.5%). The remaining 73 eyes were treated with 40-60 burns in 180 degrees of the trabeculum, 38.4% (28 eyes) were successful therapeutically with a follow-up of 56.5 +/- 23.1 months. The treatment reduced the additional medical treatment in 9 eyes (12.3%). The comparison of these results and the survival curves of both groups showed statistically significant differences in favour of the treatment on 360 degrees of the trabeculum.


Intraoperative and post operative treatment with 5-fluorouracil and mitomycin-c: long term effects in vivo on subconjunctival and scleral fibroblasts.

Rabbits undergoing full thickness glaucoma filtering surgery were exposed to one of 4 treatments. Group 1 received intraoperative distilled water, group 2 received intraoperative mitomycin-c 0.2 mg/ml for 5 minutes, group 3 received 5 post operative injections of 5-Fluorouracil (5-FU) 5 mg in 0.1 ml, and group 4 received intraoperative 5-FU 50 mg/ml followed by 5 post operative injections of 5-FU. 30 days after the operation tissue biopsies were taken from the subconjunctival and scleral tissue at the treated area and 90 and 180 degrees from the treated area. The biopsies were then placed in tissue culture media and the outgrowths quantitated. The fibroblast outgrowths from all areas did not differ significantly from each other except for the outgrowths from the areas directly treated with mitomycin 0.2 mg/ml which were significantly smaller. In addition then cells were morphologically abnormal although there were foci of normal cells which appeared to be growing from localised areas in the tissue biopsies. The outgrowths from the areas 90 and 180 degrees from the treated area were normal. Intraoperative treatments with mitomycin-c result in long term inhibition of fibroblast proliferation limited to the treated area, when compared with intraoperative and postoperative treatment with 5-FU. Failure of filtration surgery in eyes treated with intraoperative mitomycin may in part be due to unaffected cells reproliferating.


Promotion of glaucoma filter bleb with tissue plasminogen activator after sclerectomy under a clot.

Since 1987 we have performed, with good results, glaucoma filtering surgery in which the limbo-scleral fistula was closed by an autogenic full blood clot (sclerectomy under a clot). In 8 patients with advanced stages of glaucoma simplex, 1-3 days after sclerectomy under a clot with rise IOP, 25 micrograms of tissue plasminogen activator (tPA) was injected subconjunctivally. Two weeks after surgery normalization of IOP below 15 mmHg and normal outflow facility in all tPA treated eyes were obtained. No increase in early post-operative complications, such as hemorrhage or corneal haze, was attributable to tPA use. In early period after sclerectomy under a clot, when blockage of outflow appears, the use of tPA can cause the re-creation of filtering tract.


Improved suture for fornix-based conjunctival flap in filtering surgery.

Major problems in the early postoperative phase in filtering surgery are hypotony, flattening of the anterior chamber and choroidal detachment. We describe a new suture technique for the closure of the conjunctiva in goniotrephination with a fornix-based conjunctival flap which is helpful in reducing these complications. After dissecting the conjunctiva from the limbus, a shallow groove is cut directly behind the former conjunctival insertion. At the end of the operation the conjunctiva is sutured into this groove using a running 10.0 nylon suture in a meander-like fashion. A very tight wound closure results. We used this technique in 104 consecutive goniotrephinations. We found a low incidence of only mild external fistulation, hypotony, flattening of the anterior chamber and choroidal detachment. Astigmatism induced by the operation was -1.2 +/- 1.2 D, usually with the rule.


Treatment of glaucoma following penetrating keratoplasty with transscleral YAG cyclophotocoagulation.

Thirteen patients with refractory glaucoma following penetrating keratoplasty were treated with 180 degree transscleral Neodymium: YAG cyclophotocoagulation. Intraocular pressures below 21 mmHg were achieved in nine patients (69%) with a mean follow up of 19.8 months. Multiple treatments were required in six patients and graft decompensation occurred in five. No patient developed hypotony. Transscleral YAG cyclophotocoagulation is a useful alternative to further surgery in some patients with glaucoma following penetrating keratoplasty.


The effect of high-intensity focused ultrasound on intraocular pressure in therapy-resistant glaucoma 3-4 months and 1 year after treatment.

The effect of therapeutic ultrasound for the treatment of refractory glaucoma was evaluated in 44 patients by comparing average IOP curves measured before and 3-4 months after treatment. The insonification regime was standardized and the glaucoma medication in each individual patient was unchanged during IOP curve measurements. The average IOP decrease 3-4 months after insonification was 42.2% +/- SD 31.9. In 23 patients who were followed for at least one year the average IOP 3-4 months after treatment was compared with the average IOP 1 year after treatment. In this group average IOP 3-4 months after treatment was 25.3 mmHg +/- SD 16.4 and average IOP 1 year after treatment was 24.1 mmHg +/- SD 15.9. The correlation coefficient between IOP 3-4 months after treatment and IOP 1 year after treatment was 0.79 (P < 0.0001).


Surgical management of closed angle glaucoma: our experience.

In this paper we present our experience of the last three years in the surgical treatment of eyes with closed angle glaucoma. We have performed an extracapsular lens extraction and posterior chamber intraocular lens implantation on 34 eyes of 34 patients. All of them were affected by closed angle glaucoma with variable control after a Yag laser iridotomy: 6 eyes had high I.O.P. notwithstanding maximal therapy, 11 eyes had I.O.P. under control (less than 21 mmHg) without therapy, 9 with I.O.P. controlled with topical therapy, 8 with I.O.P. controlled with maximal therapy (C.A.I. included). The cases with well controlled glaucoma were operated on because of the presence of a more or less significant lens opacities. After a follow-up of up to 40 months (mean = 20.3, range = 1-40), all eyes show satisfactory intraocular pressure and no eye needed a filtering procedure. The results of our studies are as follows (values are mean +/- SD). In the group of 6 eyes with high I.O.P., the mean pre-operative intraocular pressure was 29.7 +/- 5.6 mmHg and the mean post-operative I.O.P. was 15.1 +/- 1.4 mmHg. The mean reduction was 14.5 +/- 6.6 mmHg (p < 0.005). In the 28 eyes with pre-operative I.O.P. under control (17.5 +/- 1.6), the mean post-operative I.O.P. was 14.4 +/- 2.3 mmHg, with a mean reduction of 3.1 +/- 3.1 mmHg (p < 0.005). Before the E.C.C.E., 11 eyes had I.O.P. less than 21 mmHg without anti-glaucoma medication, whereas after the E.C.C.E. 28 eyes did not need such a medication.(ABSTRACT TRUNCATED AT 250 WORDS)


Combined small-incision cataract surgery and trabeculectomy--technique and results.

In a prospective study 35 eyes of 25 patients with coexisting cataract and glaucoma underwent trabeculectomy, phacoemulsification and implantation of a folded polyHema intraocular lens through the trabeculectomy opening. Follow-up ranged from 6 to 27 months (mean 13.3). The mean age was 76.4 (68 to 88 years). 22 eyes suffered from primary open angle glaucoma, 10 eyes from a pseudoexfoliation glaucoma and 3 eyes had a chronic angle closure glaucoma. Preoperatively intraocular pressure was controlled in 10 eyes with a mean medication of 2.1 but uncontrolled in 25 eyes (mean medication: 2.5). The preoperative visual acuity ranged from 20/40 to hand motions. Postoperatively intraocular pressure was controlled (< 18 mmHg) in all (100%) eyes and without therapy in 32 (91%) eyes. Three (9%) eyes had to be treated with topical timolol twice a day after surgery. Mean intraocular pressure dropped from 21.2 +/- 6.0 mmHg preoperatively to 13.5 +/- 2.1 mmHg postoperatively. Vision improved in all but 4 eyes, 25 (74%) achieving a visual acuity of 20/40 or better. The causes for failed improvement or deterioration of vision were senile macular degeneration in 2 eyes and central retinal vein occlusion and vascular optic nerve atrophy in one eye respectively. Post-operative complications included hyphema in 9 (26%) eyes, fibrin effusion to a various extent into the anterior chamber in 19 (54%) eyes and delayed hypotony (< 5 mmHg) with chorioidal effusion in 1 (3%) eye. Fibrin effusion was frequently observed in eyes with intraocular pressure below 10 mmHg, iris surgery and hyphema. Finally the complications did not effect the results regarding visual acuity or glaucoma control.(ABSTRACT TRUNCATED AT 250 WORDS)


[The validity of infant mortality statistics in Navarra].

In order to explore the validity of official infant mortality statistics, the number of infant deaths registered in the cohort of live births and resident in Navarra (Spain) from 1985 to 1989, according to data supplied by the Department of Statistics of Navarra, has been compared with that obtained in a retrospective search into the information of the hospitals. Among 24,383 live births of the cohort, 291 were certified as infant deaths. An over-register of 13 cases (4.5%) and an under-register of 26 cases (8.9%) was detected. By excluding those live births with less than six months of gestation, as done by the National Institute of Statistics, the validity is altered, because apart from the errors mentioned, one must add those resulting from the incorrect filling-in of the "number of weeks pregnant"= variable. When correcting these deficiencies, the final statistics (Infant Mortality Risk = 11.17 per 1000 live births) did not differ much from the official figures (IMR = 11.48 per 1000 live births).


Tympanometry and otoscopy prior to myringotomy: issues in diagnosis of otitis media.

Tympanometry and pneumatic otoscopy were compared to findings at myringotomy in 86 children (163 ears). Seventy percent of the ears (115) had effusion, as revealed by myringotomy. Sensitivity and specificity for tympanometry were 90% and 86%, respectively. Sensitivity and specificity for pneumatic otoscopy were 93% and 58%, respectively. A chi-square was performed to compare the sensitivity and specificity to tympanometry to otoscopy, revealing tympanometry significantly better at determining non-effusion states. Additionally, a combined otoscopy and tympanometry sensitivity and specificity were calculated for those otoscopy and tympanometry determinations in agreement, revealing both sensitivity and specificity above 90%. A Fisher's exact probability test revealed no significant differences for the accuracy of tympanometry over otoscopy when the determinations of each were not in agreement. Implications of these results are discussed.


[Adolescence at risk: a health survey among pre-university students].

The present study investigates the level of health education in a representative sample of 804 pre-university Asturian students, randomly selected from the official list of the Ministry of Education and Science. We used a questionnaire (designed by us) in order to measure the knowledge, attitudes and behaviour related to some of the most important health determining factors. The survey was carried out by interviewing small groups of students in the classroom situation. Although it was found that the majority perceived themselves as healthy or very healthy, these young people are widely exposed to risk factors: 12% have suffered from more than 25 episodes of drunkenness during the previous year; 43.53% smoked to some extent and only 3.86% identified the days of maximum risk of pregnancy in a supposed menstrual cycle, although 31% maintained sexual relationships. Theoretically, 92% selected health as the most important factor among the three most fundamental values for life. They also think that illegal drugs are the most important health problem at present for young people. There is a contradiction between the high theoretical importance given to health, the good self-qualification of it, and the observed presence of important risk factors. A certain failure of the educational system with respect to primary prevention can be claimed.


[Traffic accident mortality in Catalonia and other autonomous communities (1983-1990)].

With the aim to understand road accident mortality in Catalonia, death certificates were studied, and a comparison between several autonomic communities was undertaken to highlight any differences. The road accident death rate increased from 9.8 in 1983 to 19.4 per 100,000 inhabitants in 1990. By 1990, the death rate for Catalan males was 31.3 per 100,000 inhabitants, and 7.9 for women, figures which showed increases of 90% and 50%, respectively, since 1983. Standardised mortality rates for Galicia, Asturias and Valencia have, on average, been higher those for Catalonia and Madrid (p = 0.014). Catalonia is the community which has experienced the greatest increase, with an evolution showing a good linear fit (p = 0.005).


Atopy and environmental factors in upper respiratory infections: an epidemiological survey on 2304 school children.

Upper respiratory infections (URI) during the first years of life are mostly viral in origin. However, a number of observations suggest the influence of both predisposing and triggering factors. Atopy in particular seems to play an important role as do environmental factors. Many children with early symptoms such as blocked or runny nose are likely to become skin-positive later in life to antigens such as, e.g., D. pteronissinus. A standardized questionnaire was administered to 2304 schoolchildren in order to ascertain the URI frequency and to correlate it with family and environmental factors and with results of prick tests for main allergens in our climate (D. pteronissinus and Grasses). Results showed a wide overlapping of URI and lower respiratory illnesses (in particular, asthma), which are widely distributed in the families of patients. Passive smoking and the quality of housing are the main triggering environmental factors. In our sample, skin positivity for D. pteronissinus and Grasses largely exceeds the symptomatic portion of the whole population. It is therefore suggested that many asymptomatic children are "at risk" for allergic respiratory illness. The highest incidence of winter rhinitis in skin-negative subjects (71.7%) and the skin positivity for D. pteronissinus in patients with perennial symptoms, suggest the importance of both atopy and viral infections in the occurrence of URI. Nasal troubles are most frequent in asthmatic subjects and may be considered the actual additional symptom in asthma.


Serum immunoglobulin E levels in children with chronic tonsillitis.

Serum immunoglobulin E (IgE) levels were estimated by ELISA in 50 children with chronic tonsillitis before and after tonsillectomy. When compared with the control group, mean serum IgE concentration was found to be significantly higher in children with chronic tonsillitis (P less than 0.001). After tonsillectomy the levels returned to normal.


Distribution characteristics of immunoglobulin-secreting cells in adenoids. Relationship to age and disease.

Forty-four adenoids and 52 palatine tonsils from 71 children and adolescents (age 3-21 years) undergoing surgery because of adenoidal hypertrophy or recurrent tonsillitis were examined for the presence of immunoglobulin-secreting cells (ISC) employing an enzyme-linked immunospot assay (ELISPOT). ISC constituted less than 2% of the mononuclear cell population. Adenoids contained IgG, IgA, and IgM ISC in significantly lower numbers than palatine tonsils. The predominant isotype of the ISC was IgG, in adenoids accounting for 62% of the ISC and in palatine tonsils for 73%. The relative numbers for IgA and IgM ISC were similar. A significant correlation existed between autologous adenoids and palatine tonsils for the numbers of IgA and IgM ISC, but not for the numbers of IgG cells. These observations suggest that, adenoid and palatine tonsils display similar immunoglobulin distribution patterns within a single individual. However, individuals with hypertrophied adenoids exhibited a numeric decrease in IgG ISC with increasing age (P less than 0.01). Both lymphoid tissues may be involved in mucosal immune defense.


[The measurement of satisfaction in health services].

The satisfaction analysis in health services has been object of rising interest recently. The different instruments of measurement known show the diversity of conceptualism, range of applications and methodologies. The article revises selectively and not exhaustively different instruments as well as the approximations to the concept of satisfaction from the marketing disciplines and the investigations in health services. Special emphasis is dedicated to the analysis of satisfaction in hospital services and the use of questionnaires for its measurement.


Why and how should we study infant cry?

The study of the acoustics of infants' vocalizations has important implications for the study of infant development and for clinical prediction. We suggest procedures that enhance the probability of discriminating among sub-glottal, periglottal, and supraglottal sites of pathology, With these procedures, then, it should become possible to contribute to diagnosis and therefore to treatment.


Congenital abnormalities of the submandibular duct.

Five newborns presented with cystic lesions of the floor of mouth. Four of these patients proved to have congenitally imperforate submandibular salivary gland ducts and the other newborn proved to have a duplication anomaly of the submandibular gland duct and gland. The patients with imperforate Wharton's ducts underwent marsupialization with or without ductoplasty and have been without evidence of recurrence for up to three years. The duplication anomaly of the submandibular gland duct responded to simple excision. The diagnosis of congenital anomalies of the submandibular gland and duct can be made on physical examination. Magnetic resonance imaging can be helpful in differentiating congenital imperforate submandibular duct and duplication anomalies of the ductal system. Treatment of the former consists of duct marsupialization in the floor of mouth with or without ductoplasty. Treatment of the duplicated ductal system may best be treated with excision. A failure in diagnosis and treatment may result in ranula formation or sialoadenitis requiring more extensive therapy.


[Blood pressure, physical activity and anthropometry in adolescents].

The relationship of blood pressure with physical activity and anthropometry was studied in 295 adolescents (mean age, 15.3 years) who entered 1. "formación profesional" (a technological training) in 1990 in Puerto Real, a village of Cádiz, Spain. Systolic and diastolic (fifth-phase Korotkoff) blood pressure, and anthropometrics measurements (weight, height and triceps and subscapular skinfolds thickness) were measured with standardized techniques. Habitual and sports physical activity were assessed by a self-reported questionnaire. The results reported in this study suggest that systolic blood pressure is associated with habitual physical activity in girls, and that the systolic blood pressure is associated weakly with sports activity in girls and in boys. The stronger predictor of blood pressure was Quetelet Index (kg/m2).


Epipharyngeal teratoma in infancy.

Epipharyngeal teratomas are rare congenital lesions that often cause respiratory distress, stridor at birth. The management of such anomalies should include establishment of secure upper airways, radiographic exclusion of midline CNS malformations and early surgical excision to prevent malignant transformation, asphyxia or permanent facial distortion. The diagnosis of congenital stridor, dyspnea and rhinitis should be performed very carefully.


Contribution of MR in the diagnosis of 'occult' posterior laryngeal cleft.

This paper reports three cases of 'occult' submucous posterior laryngeal cleft in which MR examination has visualized the deficiency of the posterior cricoid lamina. Laryngeal cleft is an uncommon anomaly, and its clinical and endoscopic diagnosis is always difficult. To our knowledge, the role of MR in this diagnosis has not yet been emphasized.


Apnea and the elongated uvula.

Four cases of respiratory distress and apnea associated with an elongated uvula are presented. In all cases, the uvula was found to intermittently fall onto the epiglottis and vocal cords. In all four patients, resection of the uvula led to resolution of all airway symptoms. It is hypothesized that the uvula, touching the vocal cords, caused intermittent laryngospasm and subsequent symptoms of cough, airway obstruction, and cyanosis. The anatomic reasons for such phenomenon are discussed.


Faculty/student perception of organizational climates in the schools of nursing, Oyo State, Nigeria.

This study examined the influence of educational status and gender on the faculty and students' perceptions of their school climates. A self-designed questionnaire was used to elicit information from the 385 subjects (320 students and 65 tutors). Analysis using the t-test technique revealed that there were no significant differences at the 0.05 level of probability in the perceptions of: (a) faculty and students on climate variables "thrust" (t = 0.31) and "control" (t = 1.19); and (b) both sexes on climate variables "thrust" (t = 1.69), "control" (t = 1.13) and "disengagement" (t = -0.53). The conclusion therefore, is that educational status and gender have little or no influence on the peoples' perception of their school climates.


Students' and lecturers' preferred teaching strategies.

A survey of lecturers (n = 47) and students (n = 110) was undertaken to explore their preferred teaching strategies, using a questionnaire based on Heron's (1977) Dimensions of Facilitator Styles (Human potential research project, University of Surrey, Guildford). Overall it was found that the students tended to prefer a teacher-centred approach to teaching, whilst the lecturers preferred a student-centred approach. These findings are discussed in the light of current educational trends in the nursing profession.


Positioning of the stroke patient: a review of the literature.

Stroke is a common and disabling illness, adversely affecting the quality of life of hundreds of people each year. While there are many therapeutic approaches to stroke patient rehabilitation, encouraging patients to adopt "reflex-inhibiting" patterns of posture is a widely advocated strategy for helping patients to avoid complications of hemiplegia such as spasticity and contractures. However, while the central role of nurses in thus helping patients is recognized, the influence of posture on recovery from stroke has never been evaluated. Prior to undertaking such an evaluative study, texts on stroke patient care were reviewed to clarify the received view about the recommended positioning for patients with hemiplegia. Consensus on some issues was evident (such as positioning the patient with the affected shoulder protracted, spine straight, fingers extended and avoiding external rotation of the affected hip). However, opinion was divided on others and a number of potentially important aspects were ill-covered. This paper integrates a summary of the findings of this review with the physiological rationale for the recommendations. The main areas of agreement are highlighted and issues as yet unanswered are raised for further consideration.


Resistance to documentation--a nursing research issue.

In this case study, the views of a sample of four hospital nurses were elicited to determine underlying causes of persistent antipathy towards documentation in patients' charts. The results of this review supported a common belief that resistance to charting is influenced by extrinsic, or environmental factors, such as inflexibility of charting systems and insufficient allocation of time. In addition, intrinsic factors or cognitive and psychosocial factors, not emphasized in earlier studies, such as lack of confidence about written expression, a tendency to succumb to group norms governing charting and difficulty in articulating the nature of nursing practice, surfaced as impediments to documentation. This review suggests that a broader study approach is required; one that addresses intrinsic, as well as extrinsic, factors.


Patients' night-time pain, analgesic provision and sleep after surgery.

One hundred patients were interviewed about their experiences of pain and sleep following abdominal surgery. This information was supplemented by data on analgesic provision which were gathered from medication charts. Pain was the most commonly reported cause of night-time sleep disturbance and analgesics helped more patients to get back to sleep than any other intervention. About half of the patients felt that pain was worse at night than during the day. An examination of patterns of analgesic provision revealed that the number of doses given peaked at two points during the 24-hour cycle. The highest numbers of doses were given between 8 a.m. and 12 noon and 8 p.m. and 12 midnight. Fewer doses were given at night, between midnight and 4 a.m. Analgesic provision at night, therefore, did not appear to be explicitly related to need. The assessment and control of post-operative pain at night requires further attention in order to optimize pain control and promote sleep.


The need for graduate nursing education and nursing research in The Netherlands: an exploratory study.

In 1989 research was performed aimed at discovering the views of Dutch administrators of intramural health care institutions on the need for graduate nursing education and nursing research in The Netherlands. The study was completed in 1990. Because the research aim was to learn the informants' point of view, a grounded theory method was applied. The sample size was 13. The subjects were selected by using two separate sampling procedures, so as to minimize bias. Data were collected by means of semi-structured interviews of 1 hour, which were tape recorded and transcribed verbatim. Analysis of the data was done by using the constant comparative method, involving concurrent collection, collation and analysis. The three major themes that finally emerged from the data analysis were named Change, Problems and Solutions. In order to keep as open a mind as possible the systematic review of the literature was done after the field work and analysis of the data. This article presents the findings and the implications of the study.


Empirical evidence shows that measuring users' opinions is not a satisfactory way of evaluating computer-assisted learning in nurse education.

Users' opinions have been one of the cornerstones of the evaluation of both CAL, in general, and CAL packages, in particular, in nurse education. This paper reports on two experiments that reliably show student nurses' opinions of their current computer-use are formed more by the change from a previously-used computing facility rather than the actual features that the current one possesses. The use of such opinions as a valid evaluation measure within nursing CAL is, consequently, weakened. The evaluation context in which these experiments are conducted derives from the highly-researched multidisciplinary area of Human-Computer Interaction (HCI), and the experiments are introduced and discussed with respect to the HCI concepts of computer-use and usability which examine the interactions taking place at the human-computer interface. Graphical hypertext and the doctrine of functionality are also introduced and discussed, for these aspects have considerable implications for computer-use and the process of planning and choosing computer-use facilities within nurse education.


The use of guided tissue regeneration to facilitate ideal prosthetic placement of implants.

Placement of implant fixtures in an ideal position for restoration is not often possible using standard protocol, because most patients lack sufficient bone in the alveolar process. To facilitate ideal restorative placement of implant fixtures, principles of guided tissue regeneration can be used to provide adequate bone and prevent dehiscence and fenestration of the implant. Four cases of such treatment are presented.


Guided tissue regeneration in interproximal defects in the monkey.

The potential for guided tissue regeneration was evaluated in one-walled interproximal sites in Macaca fascicularis. Histologic differences were evaluated at 1 and 3 months. Within the experimental (barrier) group, 100% of the root surfaces with potential for regeneration were covered with new cementum, whereas the control specimens had 20% or less new cementum. The amount of regeneration was determined by the position of the barrier membrane; the more coronal the barrier, the greater the regeneration. Observations indicated that the optimal time for barrier removal is between 1 and 3 months.


Initiating restorative procedures at the first-stage implant surgery with a positional index: a case report.

With the use of a positional index, the restorative dentist and laboratory technician can be provided with an accurate record of implant fixture location after first-stage surgery. Thus it is possible to fabricate a master cast with implant analogs and initiate laboratory procedures immediately after first-stage surgery, and a provisional restoration can be processed and delivered at the time of second-stage surgery. A case report is presented to illustrate the technique.


Clinical response to the use of the HTR polymer implant in human intrabony lesions.

Fifteen patients, men and women aged 18 to 65 years, were treated for periodontitis. Each patient had at least two bilateral intrabony defects; one was designated the experimental site and the other the control site. Both sites were surgically debrided, but one osseous defect received an HTR polymer implant. Patients were followed for 12 months postoperatively. Maximum pocket reduction occurred within 2 months of initial therapy in both experimental and control sites. Initially, pocket reduction was significantly greater in implanted sites than in control sites, but this difference did not occur subsequently. At the end of the 12 months, pocket reduction responses were similar at control and implanted sites.


Gelb depth gauge: a diagnostic aid in implant placement.

Case reports describe the use of a radiographic depth gauge in conjunction with computerized axial tomography. This gauge identifies for the surgeon the precise site of implant preparation that will not only be in accord with anatomic vital structures, but also achieve parallelism with adjacent teeth and other implant sites. Discrepancies in angulation can be corrected, and maximum suitable fixture length can be determined.


A clinical evaluation of hand and ultrasonic instruments on subgingival debridement. 1. With unmodified and modified ultrasonic inserts.

This clinical investigation evaluated the effect on subgingival surfaces of three instruments: hand instruments and ultrasonic instruments with modified and unmodified inserts. Ten operators (five dentists and five dental hygienists) performed randomly assigned operative procedures. Pocket depth, instrument limit, and instrument efficiency were evaluated for each type of instrument. The results indicated that there are advantages to using modified ultrasonic inserts for scaling and root planing.


Cement thickness and microleakage under metal-ceramic restorations with a facial butted margin: an in vivo investigation.

Ten metal-ceramic restorations with buccal porcelain butt margins and palatal metal beveled margins were fabricated for periodontally hopeless teeth. After cementation, the experimental crowns remained in the oral environment for 3 to 6 months; the teeth were then extracted and used for microscopic and microleakage evaluation. All ten crowns showed at least a small amount of microleakage, but adaptation of beveled margins proved to be superior to that of shoulder porcelain margins.


Spinal patterns as predictors of personality profiles: a pilot study.

The present pilot study is part of an ongoing effort to further the investigation of the relationship between spinal patterns and personality. The present pilot study seeks to identify likely spinal patterns of certain personality profiles and asks whether changing posture can affect personality, and/or can emotional states alter posture? Forty patients of a private chiropractic practice participated in the study. Four radiographs (x-rays) of each subject were taken and each subject completed the Minnesota Multiphasic Personality Inventory (MMPI). Measurements obtained from the radiographs and the MMPI data were used to derive general linear models of the predictability of the MMPI in terms of the spinal/postural measures. Several models were highly significant and preliminary support for the authors' hypothesis that spinal patterns are likely to be predictive of personality profiles is suggested. Support for previous research is offered and directions for future research are discussed.


Surface EMG topography and pain distribution in pre-chronic back pain patients.

The relationship between surface EMG recordings from paraspinalis recording sites and subjective pain ratings were examined in a group of pre-chronic back pain patients. thirty-eight back pain patients without major orthopedic diagnosis and a pain duration between 2 to 6 months participated in a three week long subjective pain rating. Following the completion of their pain diary, the paraspinal sites were assessed under the "static" postural conditions of sitting and standing using an EMG scanning procedure. Results of the correlational analysis revealed significant and positive relationships between pain and muscle activity in the upper back (Trapezius, T1 paraspinalis sites) and significant but negative relationships between erector spinae activity (L3 paraspinalis site) and pain. When considering etiological factors of pre-chronic back pain, the results support both the organicity model for upper back, as well as the biomechanical model for the lower back.


Self-regulation and assessment approaches for vaso-occlusive pain management for pediatric sickle cell anemia patients.

An interdisciplinary program with the goal of teaching self-regulation and minimizing excessive narcotic use in the management of vaso-occlusive pain (V-O) in pediatric sickle cell anemia patients is described. A small group of patients do not respond well to any of our outpatients or inpatients medical regimens, leading us to suspect that psychological factors are influencing pain reports. We outline our multi-faceted assessment approach to evaluating such psychological factors, which includes a pain flow sheet, symptom check list, and a psychophysiologic profile. Published reports of self-regulation training including biofeedback, relaxation/imagery, and hypnosis have been associated with decreased pain symptoms, reduced number of emergency room and hospital visits for pain, decreased narcotic use, and increased school attendance. A case study of a nine-year-old patient with sickle cell disease is described before and after self-regulation training. Finally, other alternative approaches that avoid excessive narcotic use are discussed with some case reports.


Anorexia nervosa as manifested in Russia.

The authors describe current theoretical and clinical conceptualizations and treatment of anorexia nervosa in Russia, based on their experience in the follow-up of 800 patients. Three-quarters of the patients exhibited anorexia nervosa linked with a border-line state, and one-quarter associated with schizophrenia. Different relationships to dysmorphophobic fears were observed in the different anorexic groups. In the border-line group, follow-up study indicated that the clinical symptoms of anorexia nervosa were significantly reduced. However, the disorder preserved its connection with dysmorphophobic fears even in the remote stages of the disease, and in later stages there was an occurrence of pathological personality changes. In the second group, from the very beginning, anorexia nervosa in schizophrenia was closely connected with affective disorders, pathological body sensations, hypochondriacal complaints, and a gradual personality deterioration. As the schizophrenic defect increased, anorexia nervosa was reduced to an exhausted form of vomiting behaviour, and lost its connection with dysmorphophobic experiences.


Relaxation as an altered state of consciousness: a rationale for a general theory of relaxation.

A general theory of relaxation is presented. It is based on an integrated model of the main states of consciousness, which enables one to differentiate "techniques for relaxing" leading to the "relaxing states" and "meditative techniques" leading to the differentiated waking states of consciousness. These latter include specific "only the relaxation response states" and the "ultraconsciousness states". Each state is described along the following dimensions: of biological rhythms, i.e., Sleep-Wakefulness and the Basic Rest-Activity Cycle; brain hemispheric activity; the threshold of the extero- and interoceptive stimuli reception; perceptual dominance of stimuli from external or internal sources; spontaneous versus goal-oriented imagination activity, i.e., passive or active state of mind; feed-back relation with the surroundings.


Clarification of the concept of psychological stress ("psystress").

The concept of "stress" in the current academic literature is unstandardized, and therefore confusing. The theoretical approach of regarding stress as an intervening variable seems most generally agreed on by researchers; the unambiguous term "Psystress" proposal to denote the mental state involved. Aspects of vocabulary concerning psystress production and response are also discussed.


Hassles, life events, and health status among Chinese college students in Hong Kong.

Major life events and daily hassles were examined in a sample of 102 university undergraduates. While the major clusters of events were related to personal loss, life-style changes, family conflict, and personal insecurity, those of hassles were related to drudgery and uncontrollable environmental irritants, personal concerns, time and work management, minor routine expenses, and the dilemma of emigration. Using life events and hassles, and hassle clusters added significantly to the sensitivity of the concurrent prediction of undifferentiated and differentiated physical and psychological symptom criteria, and consistently showed better performance as predictors. However, the independent contributions of events and event clusters could hardly be discounted. The combined effects of major discrete and minor chronic stress on health status and the limitations of the present retrospective study were discussed.