Biomedical subjects
Publications and source records attributed to A Vogel.
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AIMS/BACKGROUND: Compared with nanosecond (ns) pulses of conventional Nd-YAG lasers, picosecond (ps) laser pulses allow intraocular surgery at considerably lower pulse energy. The authors report initial clinical experiences using a Nd:YLF ps laser for the treatment of various indications for photodisruption. METHODS: A Nd:YLF laser system (ISL 2001, wavelength 1053 nm) was used to apply pulse series of 100-400 microJ single pulse energy at a repetition rate of 0.12-1.0 kHz. Computer controlled patterns were used to perform iridectomies (n = 53), capsulotomies (n = 9), synechiolysis (n = 3), and pupilloplasties (n = 2). Other procedures were vitreoretinal strand incision (n = 2) and peripheral retinotomy (n = 1). For comparison, 10 capsulotomies and 20 iridotomies were performed with a Nd:YAG ns laser. The ps laser cut of an anterior capsule was assessed by scanning electron microscopy (SEM). RESULTS: Open, well defined iridectomies (mean total energy 4028 mJ, mean diameter 724 microns), were achieved at first attempt in 92% of the cases. In 64% an iris bleeding and in 21% an IOP increase of > 10 mm Hg occurred. All capsulotomies were performed successfully (mean energy 690 mJ/mm cutting length) but with a high incidence of intraocular lens damage. The attempted vitreoretinal applications remained unsuccessful as a result of optical aberrations of the eye and contact lens. Although ps laser capsulotomies and iridectomies required much higher total energy than ns procedures, the resulting tissue effects of the ps pulses were more clearly defined. SEM examination of a ps incision of the anterior lens capsule demonstrated, nevertheless, that the cut was more irregular than the edge of a continuous curvilinear capsulorhexis. CONCLUSION: Series of ps pulses applied in computer controlled patterns can be used effectively for laser surgery in the anterior segment and are considerably less disruptive than ns pulses. The ps laser is well suited for laser iridectomies while the ns laser is preferable for posterior capsulotomies. As vitreoretinal applications remained unsuccessful, the range of indications for intraocular photodisruption could not be extended by the ps laser.
AIMS: To explore experiences with, and attitudes to, the use of dummies (pacifiers). METHODS: Seven focus group discussions were held with groups of mothers and of health professionals. RESULTS: Most mothers and health care workers had a generally negative view of dummy use. This related particularly to dislike of toddlers with them and practical issues such as getting lost or dirty. All would allow their use in a very unsettled baby. No mothers had personally experienced problems with breastfeeding due to the use of a dummy, but concern about this possibility was expressed by some health care workers. Recommendations varied about the length of time that dummies need to be avoided. CONCLUSIONS: Mothers in New Zealand use dummies selectively for their infants and were concerned with issues of weaning the baby from the dummy, keeping it clean and not losing it. In analysing the relationships between dummy use and breastfeeding it is important to take into consideration the context of dummy use.
BACKGROUND: Picosecond laser intrastromal photorefractive keratectomy (ISPRK) aims at achieving a flattening of the central cornea by plasma-mediated tissue evaporation without affecting the anterior or posterior corneal layers. We investigated the laser-induced tissue effects to establish a functional relationship between laser parameters and tissue removal and to assess their influence on the healing process and long-term refractive changes. MATERIALS AND METHODS: A modified ISL 2001 System with a cone angle of 30 degrees was used for in vitro investigations of the laser effects in water and porcine cornea. Photographic methods were used to determine the plasma volume and the thickness of the laser-generated intrastromal bubble layer as a function of the pulse energy and the number and separation in which the pulses were applied (216 eyes). Histological evaluation was done by polarization microscopy (9 eyes). RESULTS: Polarization microscopy revealed only minor signs of thermal tissue damage. The maximum amount of tissue that can be evaporated without damaging the outer corneal layers corresponds to a layer about 10 microns thick. With a 6-mm optical zone, this tissue removal yields an immediate refractive effect of only 0.85 dpt. Stronger long-term refractive changes observed in animal experiments and clinical studies must thus be due to the healing response of the cornea. The healing response may be induced by mechanical distortion due to intrastromal bubble formation affecting about one third of the corneal thickness. CONCLUSION: Since the refractive effects are apparently strongly influenced by corneal healing, they are poorly predictable and can probably not be used for clinical purposes.
BACKGROUND: Information on the extent and degree of the thermal effect produced is of great importance for control of the laser dosage in laser thermokeratoplasty (LTK) and for postoperative follow-up. We investigated on acute LTK effects which information images obtained by optical low coherence tomography (OCT) offer compared to those obtained by polarization microscopy. METHODS: Porcine eyes were irradiated through a 400 microns quartz fiber using light from a laser diode emitting up to 300 mW at a wavelength of 1.86 microns. Thermal lesions of varying strength were scanned using an experimental OCT device with about 25 microns lateral and 20 microns axial resolution. Histologic evaluation of the scanned areas was done by polarization microscopy after Sirlus-Red staining, and similar lesions were also analyzed by TEM. RESULTS: Both methods differentiated three damage zones a transition zone, a zone of moderate coagulation, and a central zone of strong coagulation. In the transition zone, increased birefringence was seen in polarization microscopy, which correlated with increased light scattering seen in the OCT images. In the moderately coagulated zone, a decrease in birefringence was associated with an even stronger increase of the OCT signal. In the central zone, a loss of the fibrillar tissue structure was observed, which led to a complete loss of birefringence and a strong reduction of the OCT signal. CONCLUSIONS: Although OCT does not provide the detailed information on thermal changes of tissue seen by the histologic method, it offers information on the extent and degree of tissue changes without preparation artifacts and provides a non-invasive method of immediate and follow-up control of LTK lesions. A quantitative analysis of changes in corneal thickness and curvature is much simpler than by a slit lamp. Time-resolved measurements of corneal light scattering may be used for on-line control of the laser-light dosage during LTK.
PURPOSE: The aim of this study was to understand the dynamics of ablation products during excimer laser photorefractive keratectomy, and their influence on the formation of central islands. METHOD: Laser flash photography was used to investigate the dynamics of ablation products during photorefractive keratectomy. The ablation plume over polymethyl methacrylate (PMMA) and porcine cornea targets ablated with different zone diameters was imaged at various times between 10 musec and 100 msec after the ablating laser pulse. On PMMA targets, the profiles of the resulting ablation craters were measured. RESULTS: In all cases, the ablation products formed a ring vortex. The plume velocities on cornea were found to be approximately twice as fast as on PMMA for all zone diameters. For both materials, the ablation plume evolves faster for smaller zone diameters. Central islands were observed for zone diameters between 1 and 7 mm on PMMA substrates. The islands became more pronounced with increasing zone diameter. CONCLUSIONS: A major cause for the formation of central islands was found to be particle redeposition at the center of the ablation zone. Because of the vortex dynamics, redeposition of particles favorably occurs at the center of the ablation zone. Additionally, the dynamics of the ablation plume lead to a concentration of airborne particles over the center of the ablation zone, which also may contribute to the creation of central islands by partial absorption of the next excimer laser pulse.
PURPOSE: To determine the relationship between laser parameters and tissue removal with picosecond laser intrastromal photorefractive keratectomy (ISPRK) and to assess the effect of the parameters on the healing process and the long-term refractive changes. SETTING: Medical Laser Center Lübeck, Germany. METHODS: A modified Intelligent Surgical Lasers (ISL) 2001 system with a cone angle of 30 degrees was used for in vitro investigations of the laser effects in water and on the porcine cornea. Photographic methods were used to determine the plasma volume and to investigate the thickness of the intrastromal bubble layer as a function of the laser pulse energy, the number of layers in which the pulses were applied, and the layer separation. The data were used to calculate the amount of tissue removal. Histologic evaluation was done by polarization microscopy after Sirius-red staining. RESULTS: The laser pulses produced a sponge-like appearance of the stroma in a layer extending through about one third the corneal thickness, accompanied by mechanical distortions of the stromal lamellae. Thermal changes were weak. Tissue removal was impaired by the cavitation bubbles from preceding laser pulses. The amount of evaporated tissue depended only weakly on laser pulse energy and number of layers in which the pulses were applied. The maximum amount of tissue that could be evaporated without damaging the outer corneal layers was a 10.0 microm thick layer. With a 6.0 mm optical zone, the tissue removal produced an immediate refractive effect of only 0.85 diopter. CONCLUSIONS: Intrastromal PRK does not work as originally envisioned because the amount of evaporated tissue is very small. The greater long-term refractive changes observed in animal experiments and clinical studies must therefore be due to the healing response of the cornea. Because the refractive effects are strongly influenced by the healing response of the cornea, they are poorly predictable.
PURPOSE: To evaluate how well several histologic techniques differentiate degrees of thermally induced changes in corneal tissue after laser thermokeratoplasty (LTK) or corneal ablation. SETTING: Medical Laser Center Lübeck, Germany. METHODS: Corneas of freshly enucleated porcine eyes were treated with a continuous wave laser diode (1.86 microns) and a pulsed chromium-thulium-holmium: YAG laser (2.1 microns) to produce LTK lesions or ablated with a Q-switched and a free-running chromium-erbium: YSGG laser (2.70 microns), a free-running erbium: YAG laser (2.94 microns), and an argon-fluoride excimer laser (193 nm). The lesions were evaluated by light microscopy (LM) (hematoxylin and eosin, Azan, van Gieson's, and Masson-Goldner's trichrome stains), transmission electron microscopy (TEM), and polarization microscopy after Sirius-red staining. Sirius-red, a strongly elongated, birefringent molecule binding parallel to collagen molecules, was used to enhance corneal birefringence. RESULTS: With routine LM, it was difficult to discriminate the degrees of thermal alterations in LTK lesions. Combined Sirius-red staining and polarization microscopy distinguished between a strongly coagulated central zone and the transition zone to normal tissue. Sirius-red uptake was increased in both zones, reflecting the availability of new binding sites. The central zone appeared darker under polarization than normal collagen because of a loss of birefringence. Intrinsic birefringence was greatly reduced; however, form birefringence partly remained as long as some collagen fibrils were intact. In the center of very strong lesions, where the collagen was hyalinized, birefringence was completely lost because of the complete disintegration of the fibrillar structure, which was visible under TEM. The transition zone toward normal cornea showed increased birefringence because the natural birefringence was largely preserved and enhanced by the increased Sirius-red uptake. Mechanical stretching between neighboring LTK lesions was manifested by increased birefringence. CONCLUSION: Sirius red offered an improved and simple histologic method for analyzing thermal collagen changes. It may contribute to a better understanding of the working mechanisms of LTK and improve analysis of thermal effects in corneal ablation.
The paper reviews the principles of nonlinear absorption with reference to the present major clinical applications of plasma-mediated effects: intraocular microsurgery and laser lithotripsy. Emphasis is laid on the analysis of the working mechanisms, sources of collateral damage, and on strategies for both the optimization of efficacy and the minimization of side effects.
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We examined systematically the ability of chick limb bud stumps to regenerate distal structures when fibroblast growth factor (FGF)-4 is applied. When amputations were made within 600 mu m of the tip and FGF-4 applied either posteriorly or both apically and posteriorly, outgrowth of stump tissues occurred and a virtually complete skeleton developed. 'Regeneration' of distal structures was correlated with reactivation of Msx-1 and Shh expression. At proximal amputation levels where FGF-4 did not lead to 'regeneration', neither Msx-1 nor Shh expression was induced. We also grafted cells from progressively more proximal levels of mouse limb buds to chick wing bud tips beneath the apical ridge and the pattern of reactivation of Msx-1 expression along the proximal distal axis of the limb buds was similar to that found in chick limb buds.
PURPOSE: In a vascular model the mechanisms of a pulsed dye laser working in a liquid and a gaseous environment was tested and documented by means of a high-speed camera. METHODS: The pulse application (630 nm wavelength) on a target of calcified arterial plaque material was detected at intervals of 20 microseconds up to 800 microseconds total time. RESULTS: In water the laser beam created a cavitation bubble which expanded from 0 to 450 microseconds from a radius 0 to 3 mm and collapsed afterwards. The average expansion velocity of the bubble was 80 m/s in the first 20 microseconds and the resulting velocity of the tube model wall was 10 m/s. Compared with gaseous atmosphere there was no bubble and consecutively no wall stress. CONCLUSION: It is obvious that laser angioplasty causes wall stress and destruction of different vascular layers. This might be the initial stimulation for restenosis. In gaseous atmosphere laser angioplasty should be more protective.
Patterning across the anteroposterior axis of the vertebrate limb bud involves a signal from the polarizing region, a small group of cells at the posterior margin of the bud. Retinoic acid (RA; Tickle, C., Alberts, B., Wolpert, L. and Lee, J. (1982) Nature 296, 554-566) and Sonic hedgehog (Shh; Riddle, R. D. Johnson, R. L., Laufer, E. and Tabin, C. J. (1993) Cell 25, 1401-1416; Chang, D. T., Lopez, A., von Kessler, D. P., Chiang, C., Simandl, B. K., Zhao, R., Seldin, M. F., Fallon, J. F. and Beachy, P. A. (1994 Development 120, 3339-3353) have been independently postulated as such signals because they can mimic the mirror image digit duplication obtained after grafting polarizing cells to the anterior of limb buds. Here we show that a embryonal carcinoma cell line, P19, transfected with a Shh expression vector shows low polarizing activity, but when cultured with retinoic acid, duplications like those induced by the polarizing region (ZPA) arise. Complete duplications are also obtained by cotransfecting P19 Shh cells with a constitutively active human retinoic acid receptor (VP16-hRARalpha). These data suggest that Shh and RA cooperate in generating ZPA activity and that Shh, while essential, may not act alone in this process.
Fibroblast Growth Factors (FGFs) are signaling molecules that are important in patterning and growth control during vertebrate limb development. Beads soaked in FGF-1, FGF-2 and FGF-4 are able to induce additional limbs when applied to the flank of young chick embryos (Cohn, M.J., Izpisua-Belmonte, J-C., Abud, H., Heath, J. K., Tickle, C. (1995) Cell 80, 739-746). However, biochemical and expression studies suggest that none of these FGFs is the endogenous signal that initiates limb development. During chick limb development, Fgf-8 transcripts are detected in the intermediate mesoderm and subsequently in the prelimb field ectoderm prior to the formation of the apical ectodermal ridge, structures required for limb initiation and outgrowth, respectively. Later on, Fgf-8 expression is restricted to the ridge cells and expression disappears when the ridge regresses. Application of FGF-8 protein to the flank induces the development of additional limbs. Moreover, we show that FGF-8 can replace the apical ectodermal ridge to maintain Shh expression and outgrowth and patterning of the developing chick limb. Furthermore, continuous and widespread misexpression of FGF-8 causes limb truncations and skeletal alterations with phocomelic or achondroplasia phenotype. Thus, FGF-8 appears to be a key signal involved in initiation, outgrowth and patterning of the developing vertebrate limb.
Laser thermal keratoplasty (LTK) is currently under clinical trial for the correction of hyperopia and hyperopic astigmatism by means of collagen coagulation in the peripheral cornea. The purpose of our study was to optimize the ratio between the volume of damaged corneal stroma and the refractive effect so as to minimize potential side effects such as endothelial damage or induction of glare phenomena. We therefore performed histological and morphometrical examinations of enucleated pig eyes to determine the relationship between the coagulated stromal volume and the refractive change after LTK using a pulsed Cr:Tm:Ho:YAG laser (wavelength 2.12 microns) on enucleated pig eyes. The refractive change was documented with a Littman ophthalmometer. Morphometrical analysis was performed using polarized light microscopy of sirius red-stained specimens. This special stain separated the thermally changed stroma into a dark nonbirefringent center and a birefringent peripheral zone. The volume of both zones was positively correlated with the refractive change induced. The volume was in turn influenced by the choice of laser parameters. From the ratio of the volume to the refractive change it was found that pulse energies above 30 mJ let to an enlargement of the coagulation volume without increasing the refractive change effectively. The use of high pulse energies did not improve the effect of LTK but only increased the risk of unwanted side effects. However, an increase in the laser repetition rate at a constant pulse number per spot led to refractive changes with minimal coagulation volume. The highest relative refractive change was achieved with a dark central zone and a birefringent zone, each having a volume of about 50-80 x 10(-3) mm3.
The positional cues that govern the fate of cells along the dorsoventral axis of the developing vertebrate limb are established in the mesoderm before outgrowth of limb buds. In Drosophila, a LIM/-homeodomain gene, apterous, expressed in the dorsal compartment of the wing disc, specifies dorsal cell fate. Here we report the isolation of a vertebrate LIM-homeodomain containing gene, Chick Lmx1 (C-Lmx1). Transcripts for C-Lmx1 are detected in the presumptive dorsal limb mesoderm and are restricted thereafter to the dorsal mesoderm of the developing chick bud. C-Lmx1 expression is regulated by the overlying ectoderm where Wnt7a messenger RNA is localized. Wnt7a, required for normal development of the dorsoventral axis in mouse limbs, can induce ectopic expression of C-Lmx1 in ventral mesoderm. Misexpression of C-Lmx1 during limb outgrowth causes ventral to dorsal transformations of limb mesoderm. We propose that C-Lmx1 specifies dorsal cell fate during chick limb development.
Fibroblast growth factors (FGFs) are central to signaling in the developing limb. FGF-2 and FGF-4 can substitute for the apical ectodermal ridge to maintain both limb bud outgrowth and polarizing region signaling. Here, we have repeated and extended previous studies and investigated local effects of the apical ectodermal ridge on gene expression of Msx-1, 5' members of the HoxD complex, and Bmp-2 in the limb bud mesenchyme and tested whether members of the FGF family can substitute for the ridge to maintain their expression patterns. We found that expression of Msx-1, Hoxd-13, and Bmp-2 in posterior limb bud mesenchyme is dependent on a local signal from the apical ectodermal ridge. When the apical ectodermal ridge of young chick wing buds is removed, or when posterior cells are taken from the bud and placed in culture, expression of Msx-1, Hoxd-13, and Bmp-2 is not detectable in posterior mesenchymal cells. Local application of FGF-soaked beads to posterior limb mesenchyme following ridge removal or addition of FGF to cultured cells maintains expression of Msx-1, Hoxd-13, and Bmp-2. In contrast, expression of Hoxd-11 in posterior mesenchyme appears to be stable in the absence of either the apical ectodermal ridge or FGF. Expression of Msx-1 in anterior and apical cells is also locally maintained by the apical ectodermal ridge and this effect can be reproduced by local application of FGF. Furthermore, the addition of FGF to cultured anterior limb bud cells maintains their ability to respond to positional cues when grafted back into limb buds.
Various experimental lens refilling procedures have been proposed. One of these methods uses endocapsular polymerization of the injected material by light exposure. In this study we wanted to characterize the potential risks of this procedure due to light and temperature hazards. We performed in vitro experiments on enucleated pig eyes and an in vivo study on 15 rabbits. During the polymerization process the highest temperature recorded (45.1 degrees C) was measured at the posterior lens capsule for a few seconds. The measured irradiance (0.065 W/cm2) and the risk of photochemical damage to the retina during 20 s of polymerization was comparable to that caused by 1.5 min of standard coaxial illumination with our operating microscope. In vivo we found no serious inflammatory reactions except for four cases where surgical problems had occurred. No direct retinal damage could be detected histopathologically. In conclusion, we think that lens refilling and endocapsular polymerization are promising techniques. However, refilling materials with better physical properties than those available so far need to be developed.