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Immune responses in hepatitis C virus infection.

Infection with the hepatitis C virus (HCV) commonly causes persistent disease, which may lead to cirrhosis and hepatocellular carcinoma. The pathogenesis of HCV infection is not well understood. It is most likely that both viral and host factors contribute to HCV persistence. This review focuses on the host's immune response to HCV in an attempt to present the current knowledge and concepts of the interactions between the virus and the host during HCV infection. Expansion of B lymphocytes and antibody production to virtually any HCV protein can be detected in most infected patients. However, observations in HCV-infected humans as well as experimental infections in chimpanzees suggest that natural HCV infection does not induce protective immunity, and reinfection can readily be demonstrated after inoculation with homologous or independent strains in HCV-seroconverted animals. Nevertheless, the immune system may gain partial control over HCV even in patients with chronic infection, as HCV infection in severely immunocompromised patients runs a particular cholestatic course which may rapidly lead to death from liver failure. Cytotoxic CD8+ T lymphocyte responses to HCV proteins have been characterized in peripheral blood and liver tissue and were found to be remarkably polyclonal and multispecific. Epitopes were identified on all of the putative HCV proteins, although only few major histocompatibility complex molecules were considered restriction elements. Immunoregulation may be particularly important in HCV infection. The HCV core and NS4 proteins appear to be most immunogenic for peripheral blood lymphocytes, and NS4 specific CD4+ lymphocytes are preferentially compartmentalized to the liver. However, there is an inverse relationship between CD4+ lymphocyte responses and antibody levels in infected patients. Furthermore, a strong cellular response to the HCV core protein apparently favors a benign course of infection. This unusual T-B cell relationship may be the consequence of an altered cytokine release during HCV infection. Alternatively, this virus may have found devices that can disturb immunoregulation in infected patients. A better understanding of these immunological mechanisms induced by HCV infection should make it possible to develop more effective strategies for the prevention and treatment of this insidious disease.

CD4-Positive T-Lymphocytes↗

New tubular bioabsorbable knitted airway stent: feasibility assessment for delivery and deployment in a dog model.

PURPOSE: The aim of this study was to determine whether it is possible to deliver and deploy a new device, a poly-L-lactic acid (PLLA) tubular knitted airway stent, under bronchoscopic guidance in a dog model. DESCRIPTION: The delivery system consisted of a flexible balloon catheter (controlled radial expansion balloon dilator, M00558440, Boston Scientific Corporation, MA, USA) preloaded with a stent. A delivery catheter preloaded with a stent was advanced to a target point in the trachea under bronchoscopic guidance. Once the stent was positioned, the balloon was inflated for sixty seconds. The stent was in full contact with the tracheal wall upon deflation of the balloon. EVALUATION: The stents were successfully delivered into the tracheal lumen and successfully deployed in all dogs. CONCLUSIONS: This is the first study to prove the feasibility of delivering and deploying the PLLA stents in a dog model, using a balloon expansion technique. Further investigation with large numbers of subjects and long-term follow-up will be necessary to assess the utility of the bioabsorbable knitted tubular stent before clinical applications begin.

Absorbable Implants↗

Capsular tissue: a new local flap.

Capsular tissue, the interface that forms between an implanted device and the body's own soft tissues, has recently been shown to develop its own unique blood supply. This capsular tissue with its extensive vascular plexus has not been described previously as an isolated flap. The purpose of our study was to determine whether an isolated flap of capsular tissue would survive as a local pedicle flap and provide enough inherent vascularity to support a skin graft. Isolated expanded and nonexpanded capsular flaps were compared by using 20 expanders (10 expanded and 10 nonexpanded) in two mixed-breed female pigs. Expanded and nonexpanded capsular flaps were elevated 8 weeks following expander placement. These flaps were raised on their capsular bases alone, and skin grafts were placed onto the capsular surfaces. All the expanded capsular flaps and their skin grafts had 100 percent survival. Skin grafts on the nonexpanded flaps survived an average of 28 percent, with graft survival corresponding to flap survival. This study confirms that flaps of isolated expanded capsular tissue survive and provide enough inherent vascularity to support a split-thickness skin graft.

Animals↗

[Experimental study of the architecture of skin following tension traction and wound closure].

The experiment performed on domestic pig, was designed to investigate the architecture of the stretching skin and the effect of tension traction on the wound closure. An 7 cm x 3.5 cm was drawn at a standard position. Drawing horizontal and vertical lines on the traction area, points of 1 cm apart were tattooed on the lines. A traction force measuring device was used to draw the wound edges together. Measurements of the distances between the points were made. An 7 cm x 10 cm wound was made on identical sites of each hind leg. In the experiment the traction tension was applied on the edges of wound immediately after the wound debridement. The results showed the stretched distance in the two areas was 5-7 times the width of the wound. The gain of skin from traction was 61-89 percent in the width of the wound. The wounds from traction five days could be closed 5 days after traction. It was concluded that the skin which could be used for traction was abundant. Wound closure with the skin traction technique had many advantages, such as rapid decreasing the size of wound and early closing of wound.

Animals↗

[Establishment of facial nerve elongation model by string-type loading].

OBJECTIVE: To study the repairing method of facial nerve defect using nerve elongation, and the biomechanical properties of peripheral nerves. METHODS: A novel device for peripheral nerve elongation was designed and manufactured. With the device, facial nerves of rabbits were expanded acutely and chronically by string-type loading. The facial nerves were studied with histological and electrophysiological examinations before and after elongation. RESULTS: There were no considerable necrosis, degeneration, and infection in the facial nerves after elongation. The experimental animals took food normally and their body temperature were stable. Histological examinations showed dispersing Sunderland degree III injury and occasionally broken capillary blood vessels in the acute group, thicker nerve and fibroblasts hyperplasia between nerve bundles in the chronic group. The electromyogram(EMG) of buccal muscle and nerve conductive velocity(NCV) showed the maximal range was (18.7 +/- 2.4)% in the acute group, and (30.8 +/- 2.4)% in the chronic group. CONCLUSION: It suggests that the novel nerve elongation method is feasible, and it can be used to study the nerve elongation basically and clinically.

Animals↗

Closure of the skin defect overlying infected non-union by skin traction.

Skin traction based on an Ilizarov frame has been used to achieve skin closure in five cases of infected non-union of the tibia including one case of infected knee arthrodesis. Five patients presented with infected non-union of the tibia (all Staph. aureus, two of them MRSA) with overlying sinuses discharging pus at an average 16 months from injury (range 3-36 months). The infections were treated by excision of the sinus and infected skin, excision of the infected non-union, stabilisation of bone with an Ilizarov circular frame and either acute shortening with compression followed by distraction (3 patients), or bone transport (2 patients). After excision of the sinus, the skin defect was gradually closed using a skin traction device placed on an Ilizarov circular frame. The size of the wounds ranged from 5 x 14 cm to 3 x 5 cm and skin traction was completed at 4 weeks (range 2-8 weeks). When the wound edges were approximated, the wires were left in place until healthy granulation tissue built up to seal the remaining gap (sutures were used in two patients). At follow-up assessment at 18 months (range 7-24 months), all non-union were solidly united with no signs of infection of either the bone or underlying skin. The quality of skin at the stretching site was found to be of normal sensation, colour, mobility but thinner than normal. The quality of the skin at the docking site (left to granulate) was found to be adherent to the underlying bone, red or pink in colour, hypersensitive in 2 patients and numb in 3 patients.

Adult↗

A stereotypic, transplantable liver tissue-culture system.

A method of coculturing adult rat hepatic parenchymal cells (PC) and stromal cells in a three-dimensional framework of nylon filtration screens or biodegradable polymer meshes was developed in our laboratory. Rat liver stroma, which includes vascular and bile duct endothelial cells, fat-storing cells, fibroblasts, and Kupffer cells, were isolated by gradient centrifugation after in situ liver perfusion and expanded in monolayer culture prior to seeding onto nylon screens or bioresorbable polyglycolic acid (PGA) polymers oriented into a felt-like construct. A second inoculum of freshly isolated PC was applied after the stromal cells became established. Histological analyses revealed that PC proliferation occurred until all available space for expansion within the template was exhausted. These cells retained their rounded morphology, and after 4-5 wk 7-9 "layers" of PC filled the 140-microns deep template. Dioxin-inducible cytochrome P450 activity was detected for up to 58 d in culture, and albumin, fibrinogen, transferrin, and soluble fibronectin were detected in the medium by enzyme-linked immunosorbent assay (ELISA) for 48 d in vitro. Immunohistochemical analysis of sections through the cultures confirmed the presence of these proteins as well as cytokeratin at the cellular level; the extracellular matrix stained for both collagen type III and laminin. Long-term PC proliferation and function were enhanced by the presence of stromal cells as well as by a meshwork template whose geometry allows the interaction of PC with stroma and matrix on several different planes. To permit transplantation, cocultures of hepatic PC and stromal cells were established on PGA felt constructs instead of nylon screens. After approximately 24 d in vitro, these constructs were grafted into sites in the mesentery, omentum, and subcutaneous tissues of adult Long-Evans rats. The growth of hepatocytes after 30 d in situ was evident by histological analysis; grafts of cocultures regenerated a liver-like architecture consisting of sinusoids and putative biliary structures. In addition, PC at these extrahepatic graft sites were positive for albumin, transferrin, and fibrinogen synthesis by immunohistochemistry. Graft survival was enhanced when recipients were subjected to approximately 40% hepatectomy. Hepatic PC:stromal cell cocultures may prove useful in the restoration of liver function either by direct transplantation using PGA or similar templates, or as extracorporeal devices, using nylon screens.

Albumins↗

The impact of HLA sensitization and donor cause of death in heart transplantation.

Current expansion of the recipient population and increased utilization of left ventricular assist devices as a bridge-to-transplantation have resulted in HLA sensitization becoming an increasingly important clinical problem in cardiac transplantation. We evaluated the impact of HLA sensitization and donor cause of death on survival in 500 cardiac transplant recipients. Donor cause of death was grouped into two categories, trauma and nontrauma. Panel reactive antibodies at the time of transplant were assayed and used as a marker for sensitization if more than 10%. Sensitized recipients had a poorer 1-year survival than those not sensitized (76 vs. 89%, respectively, P=0.2). Donor cause of death had an overall significant impact on survival with 1-year survival for recipients of trauma organs of 92 and 82% for recipients of nontrauma hearts (P=0.02). Trauma hearts transplanted into sensitized recipients yielded a survival of 93% at 1 year whereas if nontrauma donor hearts were transplanted into these recipients, survival was only 52% at 1 year, P<0.001. These intriguing results suggest that graft survival in HLA-sensitized recipients could be significantly improved through the use of hearts from trauma death donors.

Adolescent↗

[Spinal instrumentation, source of progress, but also revealing pitfalls].

The second half of the XXo century and especially the last 30 years have been the source of a great improvement for surgical treatment of spinal pathology essentially in 3 directions:--First, for the patient himself and his comfort by suppression for most of the cases of any post operative external support thanks to the rigidity, security and strength of segmental fixation given by the hooks, screws and rods systems, as well for posterior as anterior instrumentation. In addition, these new techniques allow the patient to return quickly to standing and walking activity and subsequently the surgery for adult people increased dramatically especially for all kind of degenerative diseases and more and more extended spinal deformities.--The second major improvement came from the real and new understanding of the 3 dimensions for all the physiology and pathology of the spine leading to practical applications for the design and surgical strategies for correction. The exploding expansion of the era of computer technology brought a lot of help in such understanding as well as for the development of spinal instrumentation.--Finally the impressive development of medical imaging with CT scan and less and less invasive techniques like MRI allow a much better vision of spinal cord and roots (a major concern for the spinal surgeon). All this occurs also because simultaneous revolution occurred in the field of anesthesia and intensive care especially post operatively, but also because the big progress for monitoring of vital function as well as neurological monitoring during surgery. The consequence of that was an improvement for the results concerning the patient for functional quality of life as well as for cosmesis. The subsequent failures resulting of these improvements came from various fields even if we exclude infection or neurological complications more and more controlled now.--At the level of the indications because of these lack of post operative external immobilization, indication for cosmesis extend widely including adults. But also because these adult peoples are asking more and more for an active way of life including often sports. The indications for function also extend requiring more and more pre operative checking to limit the increase of the risk.--At the level of the pre operative strategy, most surgeons were establishing the strategy looking only on more or less close similar cases already done. In fact no personalized strategy done on biomechanical static and dynamic data of the patient as well as its connective and bone tissue proper qualities were really performed. It is why it is still now difficult to know pre operatively the behavior of the not fused area above and mainly below the instrumented area. Because the power of correction was very much improved with the new instruments, we can get some 3D imbalance immediately after or secondary acquired after such surgery as well from anterior or posterior devices. It is why we need pre operative simulation of surgery thanks to the computer.--At the level of surgery itself: it is not entered in the practical field any per operative 3D reliable measurement to know exactly the surgeon is doing because the maximum of reduction is not the optimum for many cases and this has to be quantified. The last thing is of course the difficulty to translate the lying position of the patient during surgery to the standing functional one. Some answers or perspectives for the future may come from:--The real pre operative simulation of the surgery (including levels of instrumentation amount of correction in 3D) according to the personalized values, stiffness, quality of soft tissues, weight, size, of the patient, localization and type of the deformity, etc.... Computer software already exists or are on the way to be expanded.--Per operative 3D control of what is doing the surgeon are also emerging with real time information in order to adjust the correction according to the pre op. simulation. In addition the noticed improvements on the biological field for fusion with bone activators like BMP, Hydroxyapatite, or bone substitutes like bio-active ceramics will probably help for fusion and decrease necessity of bone grafting. It is the same about disc regeneration which is on the way. Finally it is evident that the first steps already done for spinal surgery avoiding fusion will extend.--For children and growing spine, the challenge is major, but with memory metal instruments, laser precise destruction of abnormal growing structures as well as posterior flexible instrumentation avoiding stripping of the periosteum and leaving integrity of the disc and facet joints function, improvements are also on the way.--For adult and degenerative spinal deformities and pain, the development of spinal arthroplasty already done for the disc replacement will improve as well as for the posterior joints units where artificial ligaments experience will be replaced by real artificial joints still on experiment. In conclusion, some general biological medical questions are still waiting for answers:--Neurology and erect posture--Growth and degeneration--Malignancy (comprehension and control)--Pain and suffering. And of course what is the fact of the genetics for all of these problems: plenty of work for the future.

Adolescent↗

Randomized trial of conventional balloon angioplasty versus cutting balloon for in-stent restenosis. Acute and 24-hour angiographic and intravascular ultrasound changes and long-term follow-up.

BACKGROUND: The aim of this study was to investigate the angiographic and intravascular ultrasound (IVUS) changes following cutting balloon (CB) and percutaneous transluminal coronary angioplasty (PTCA) treatment in in-stent restenosis. METHODS: Fifty consecutive patients with in-stent restenosis were randomized to treatment with CB (n = 25) or PTCA (n = 25). The size of the device was selected using IVUS according to a 1:1 device-to-stent ratio and balloons were inflated to a maximal pressure of 8 atm. Quantitative coronary angiography (QCA) and IVUS (both planar and volumetric) evaluations were carried out before and after treatment and 24 hours later. In case of suboptimal results at 24 hours (> or = 50% diameter stenosis at QCA and/or < or = 4.7 mm2 minimal lumen area [MLA] at IVUS), the patients were re-randomized to receive additional treatment (CB for PTCA and vice versa) or to follow-up. Measurements included the minimal lumen diameter and diameter stenosis for QCA and the external elastic membrane area (EEMA), stent area (SA), MLA, restenosis area (RA = SA - MLA) and plaque + media area (PMA = EEMA - SA) for IVUS. RESULTS: A similar minimal lumen diameter increase (1.19 +/- 0.44 vs 1.37 +/- 0.55 mm) and diameter stenosis decrease (-37 +/- 14 vs -45 +/- 13%) was found after PTCA and CB. No significant difference was found in MLA increase (4.81 +/- 1.9 vs 5.45 +/- 2.0 mm2) and RA decrease (-3.8 +/- 1.3 vs -4.2 +/- 1.7 mm2) in PTCA and CB. SA, EEMA and PMA did not significantly change after treatment in either group. Of the total mean lumen enlargement after PTCA and CB, 20% was due to additional stent expansion and 80% was due to RA decrease. At 24 hours, a greater minimal lumen diameter increase (-0.23 +/- 0.34 vs -0.06 +/- 0.23 mm, p = 0.03) and MLA loss (-1.9 +/- 1.4 vs 0.37 +/- 0.8 mm2, p = 0.000) and RA increase (1.74 +/- 1.3 vs 0.37 +/- 0.52 mm2, p = 0.000) were detected in PTCA vs CB. Volumetric changes paralleled planar IVUS variations. A suboptimal result was more frequently found in PTCA as compared to CB (36 vs 4%, p < 0.01). At follow-up, PTCA had a higher target lesion revascularization as compared to CB (40 vs 12.5%, p < 0.05). CONCLUSIONS: In in-stent restenosis, PTCA and CB share similar effects and mechanisms of lumen enlargement. In-stent tissue is mainly redistributed along a larger stent rather than being extruded out of the stent struts. At 24 hours, a significant lumen loss (instant restenosis) occurred more frequently in PTCA as compared to CB and may account for a higher target lesion revascularization in this group.

Aged↗

A reproducible model of an epidural mass lesion in rodents. Part II: Characterization by in vivo magnetic resonance imaging.

OBJECT: The goal of this study was to characterize a novel epidural space-occupying lesion caused by balloon expansion in rodents by using sequential in vivo magnetic resonance (MR) imaging. METHODS: Ten Sprague-Dawley rats were intraperitoneally sedated. A trephination was performed over the left parietal cortex to attach a balloon-expansion device, which was secured with dental cement. Measurements were performed using a 1.5-tesla MR imaging device to obtain sequential T2-weighted and diffusion-weighted (DW) sequences in the coronal plane. A three-dimensional, constructed interference in steady state sequence was used for calculation of the balloon volume. The animal's temperature, heartbeat, and the arterial percentage of oxygen saturation were monitored continuously. After a baseline examination had been performed, the balloon was inflated for a 30-minute period until it reached a maximum volume of 0.3 ml; this procedure was followed by a period of sustained inflation lasting 30 minutes, balloon deflation, and a period of reperfusion lasting 3 hours. After perfusion fixation of the animals, morphometric analysis of the lesion size and examination of the percentage of viable neurons in the hippocampus were performed. Magnetic resonance imaging allowed for the precise visualization of the extension and location of the epidural mass lesion, narrowing of the basal cisterns, and development of a midline shift. A white-matter focus of hyperintensity, consistent with brain edema, developed, predominantly in the contralateral temporal lobe. During sustained inflation the volume of the balloon did not change and comprised 5 to 7% of total intracranial volume. During the same period the white-matter edema progressed further but no increased signal was revealed on DW images. After balloon deflation the brain reexpanded to the calvaria and imaging signs of raised intracranial pressure subsided. A cortical area of hyperintensity on T2-weighted images developed in the parietal lobe in the region of the former balloon compression. This area appeared bright on DW images, a finding that corresponded to an early cytotoxic edema. After deflation white-matter vasogenic edema in the temporal lobes regressed within 3 hours after reperfusion. The cortical edema in the parietal lobe and the ipsilateral basal ganglia became sharply demarcated. The histopathological results (that is, the extent of tissue damage) corresponded with findings of the authors' companion investigation, which appears in this issue. CONCLUSIONS: Magnetic resonance imaging allows for a precise and sequential in vivo monitoring of a space-occupying epidural mass lesion and visualizes the time course of vasogenic and cytotoxic brain edema. This rodent model of an epidural mass lesion proved to be reproducible.

Animals↗

Sustainability of mechanically lengthened bowel in rats.

INTRODUCTION: It has been shown that the length of an intestinal segment may be doubled by applying gradual mechanical stretching. This study evaluated whether the lengthened intestinal segment retained the structure and function after the stretching device was removed. METHODS: A 1.5-cm jejunal segment was separated from intestinal continuity in 20 rats. After advancing a screw into the isolated jejunal segment by 5 mm 3 times a week until it was stretched by 3 cm, the screw was removed. Three weeks later, the jejunal segments were retrieved for analyses. Comparisons were made between the lengthened jejunal segments. RESULTS: The jejunal segment doubled its length after gradual stretching and retained this length 3 weeks after the screw removal (3.1 +/- 0.8 vs 3.2 +/- 0.4 cm, P > .05). The villous height, the muscular thickness, and the total alkaline phosphatase and lactase activities of the stretched jejunal segments were also unchanged 3 weeks after the screw removal. CONCLUSIONS: Mechanical force induced the sustained lengthening of isolated jejunal segments in rats. The histologic and enzymatic alterations also persisted 3 weeks after the mechanical force was removed. This phenomenon may provide a novel method for the treatment of short bowel syndrome.

Animals↗

Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome.

BACKGROUND AND PURPOSE: Hyperglycemia at the time of ischemic stroke is associated with increased mortality and morbidity. Animal studies suggest that infarct expansion may be responsible. The influence of persisting hyperglycemia after stroke has not previously been examined. We measured the blood glucose profile after acute ischemic stroke and correlated it with infarct volume changes using T2- and diffusion-weighted MRI. METHODS: We recruited 25 subjects within 24 hours of ischemic stroke symptoms. Continuous glucose monitoring was performed with a glucose monitoring device (CGMS), and 4-hour capillary glucose levels (BGL) were measured for 72 hours after admission. MRI and clinical assessments were performed at acute (median, 15 hours), subacute (median, 5 days), and outcome (median, 85 days) time points. RESULTS: Mean CGMS glucose and mean BGL glucose correlated with infarct volume change between acute and subacute diffusion-weighted MRI (r>or=0.60, P<0.01), acute and outcome MRI (r=0.56, P=0.01), outcome National Institutes of Health Stroke Scale (NIHSS; r>or=0.53, P<0.02), and outcome modified Rankin Scale (mRS; r>or=0.53, P=0.02). Acute and final infarct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CGMS or mean BGL glucose >or=7 mmol/L. Multiple regression analysis indicated that both mean CGMS and BGL glucose levels >or=7 mmol/L were independently associated with increased final infarct volume change. CONCLUSIONS: Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infarct expansion and is associated with worse functional outcome. There is an urgent need to study normalization of blood glucose after stroke.

Acute Disease↗

Review of image-guided radiation therapy.

Image-guided radiation therapy represents a new paradigm in the field of high-precision radiation medicine. A synthesis of recent technological advances in medical imaging and conformal radiation therapy, image-guided radiation therapy represents a further expansion in the recent push for maximizing targeting capabilities with high-intensity radiation dose deposition limited to the true target structures, while minimizing radiation dose deposited in collateral normal tissues. By improving this targeting discrimination, the therapeutic ratio may be enhanced significantly. The principle behind image-guided radiation therapy relies heavily on the acquisition of serial image datasets using a variety of medical imaging platforms, including computed tomography, ultrasound and magnetic resonance imaging. These anatomic and volumetric image datasets are now being augmented through the addition of functional imaging. The current interest in positron-emitted tomography represents a good example of this sort of functional information now being correlated with anatomic localization. As the sophistication of imaging datasets grows, the precise 3D and 4D positions of the target and normal structures become of great relevance, leading to a recent exploration of real- or near-real-time positional replanning of the radiation treatment localization coordinates. This 'adaptive' radiotherapy explicitly recognizes that both tumors and normal tissues change position in time and space during a multiweek course of treatment, and even within a single treatment fraction. As targets and normal tissues change, the attenuation of radiation beams passing through these structures will also change, thus adding an additional level of imprecision in targeting unless these changes are taken into account. All in all, image-guided radiation therapy can be seen as further progress in the development of minimally invasive highly targeted cytotoxic therapies with the goal of substituting remote technologies for direct contact on the part of an operator or surgeon. Although data demonstrating clear-cut superiority of this new high-tech paradigm compared with more conventional radiation treatment approaches are scant, the emergence of preliminary data from several early studies shows that interest in this field is broad based and robust. As outcomes data accumulate, it is very likely that this field will continue to expand greatly. Although at present most of the work is being performed at major academic centers, the enthusiastic adoption of many of the devices and approaches being developed for this field suggest a rapid penetration into the community and the use of the technology by teams of specialists in the fields of radiation medicine, radiation physics and various branches of surgery. A recent survey of practitioners predicted very widespread adoption within the next 10 years.

Humans↗

Fracture phenomena in an isotonic salt solution during freezing and their elimination using glycerol.

Thermal stress and consequent fracture in frozen organs or cell suspensions have been proposed to be two causes of cell cryoinjury. A specific device was developed to study the thermal stress and the fracture phenomena during a slow cooling process of isotonic NaCl solutions with different concentrations of glycerol (cryoprotectant) in a cylindrical tube. It was shown from the experimental results that glycerol significantly influenced the solidification process of the ternary solutions and reduced the thermal stress. The higher the initial glycerol concentration, the lower the thermal stress in the frozen solutions. Glycerol concentrations over 0.3 M were sufficient to eliminate the fracture of the frozen solutions under the present experimental conditions. To explain the action of glycerol in reducing the thermal stress and preventing the ice fracture, a further study on ice crystal formation and growth of ice in these solutions was undertaken using cryomicroscopy. It is known from previous studies that an increase of initial glycerol concentration reduced frozen fraction of water in the solution at any given low temperature due to colligative properties of solution, which reduced the total ice volume expansion during water solidification. The present cryomicroscopic investigation showed that under a fixed cooling condition the different initial glycerol concentrations induced the different microstructures of the frozen solutions at not only a given low temperature but also a given frozen fraction of water. It has been known that ice volume expansion during solidification is a major factor causing the thermal stress and the interior microstructure is critical for the mechanical strength of a solid. Therefore, functions of glycerol in reducing the total ice volume expansion during water solidification and in influencing interior microstructure of the ice may contribute to reduce the thermal stress and prevent the fracture in the frozen solutions.

Animals↗

Repair of peripheral nerve defect with direct gradual lengthening of the proximal nerve stump in rats.

We investigated the effect of direct gradual lengthening on the proximal nerve stump and subsequent nerve regeneration in rats. A 10-mm-long nerve segment was resected from the sciatic nerve of each rat. The proximal nerve stump was directly lengthened at a rate of 1 mm/day using an original external nerve distraction device. Experiment I: After distraction periods of 10, 15, and 20 days, the length of each nerve was evaluated, and the lengthened nerve stump was also examined by immunohistochemical analysis. Experiment II: After a distraction period of 20 days, both nerve stumps were refreshed and direct end-to-end neurorrhaphy was performed. For control, 10-mm nerve grafting was immediately performed after nerve resection. Nerve regeneration was evaluated electrophysiologically and histologically 7, 9, and 15 weeks after nerve resection in both groups. The whole proximal nerve stump, including the endoneurium and the axon, could be lengthened in proportion to the distraction period. There were no significant differences in motor nerve conduction velocity and tetanic muscle contraction force between both groups. Histologically, the total number of myelinated fibers was significantly greater in the nerve lengthening group than in the autografting group. This study demonstrated that the whole proximal nerve stump including the endoneurium and the axon could be lengthened by direct gradual distraction, and that this method might have potential application in the repair of peripheral nerve defects.

Animals↗

Capsulorhexis ovaling and capsular bag stretch after rigid and foldable intraocular lens implantation: experimental study in pediatric human eyes.

PURPOSE: To compare the amount of capsulorhexis ovaling and capsular bag stretch produced by various intraocular lenses (IOLs) implanted in pediatric human eyes obtained post-mortem. SETTING: David J. Apple, MD Laboratories for Ophthalmic Devices Research, John A. Moran Eye Center, Salt Lake City, Utah, USA. METHODS: In this nonrandomized comparative study, 16 pediatric human eyes obtained postmortem were divided into 2 groups: Eight eyes were obtained from children younger than 2 years (Group A), and 8 eyes were obtained from children older than 2 years (Group B). All eyes were prepared according to the Miyake-Apple posterior video technique. Six types of rigid and foldable posterior chamber IOLs manufactured from poly(methyl methacrylate) (single-piece), silicone (plate and loop haptics), and hydrophobic acrylic (single-piece and 3-piece AcrySof, Alcon Laboratories) biomaterials were implanted. The capsulorhexis opening and capsular bag diameters were measured before IOL implantation and after in-the-bag IOL fixation with the haptics (or the main axis) at the 3 to 9 o'clock meridian. The percentage of ovaling of the capsulorhexis opening was calculated by noting the difference in the opening's horizontal diameter before and after IOL implantation. The percentage of capsular bag stretch was also calculated by noting the difference in the horizontal capsular bag diameter before and after IOL implantation. RESULTS: All IOLs produced ovaling of the capsulorhexis opening and stretching of the capsular bag parallel to the IOL haptics. There were significant differences in capsulorhexis ovaling and capsular bag stretch (P<.001, analysis of variance) between the 6 IOL types in each group of eyes. The postimplantation difference was significant only between the single-piece hydrophobic acrylic IOL (AcrySof) and the other IOLs. The single-piece hydrophobic acrylic IOL was associated with significantly less capsulorhexis ovaling and capsular bag stretch in both groups (mean 12.06% +/- 0.59% [SD] and 7.6% +/- 1.47%, respectively). CONCLUSIONS: Modern rigid and foldable IOLs designed for the adult population implanted in the capsular bag of infants and children produced variable degrees of capsulorhexis ovaling and capsular bag stretch. The Miyake-Apple posterior video technique confirmed the well-maintained configuration of the capsular bag (with minimal ovaling) after implantation of a single-piece hydrophobic acrylic IOL because of its flexible haptic design.

Capsulorhexis↗

Restoration of accommodation.

PURPOSE OF REVIEW: This review examines the current status of accommodation restoration concepts with reference to the recent, published peer-reviewed literature with an emphasis on physiological aspects of accommodation and presbyopia. RECENT FINDINGS: The mechanisms of accommodation and the causes of presbyopia are described. The physiological amenability of the accommodative structures in the presbyopic eye to accommodation restoration is discussed. General theoretical concepts of accommodation restoration are introduced. The methods that have been used to assess accommodation restoration, including the use of animal models, drug stimulated accommodation, subjective near-vision tests and objective measurements, are reviewed. SUMMARY: While physiological and clinical evidence supports the notion that accommodation can be restored to the presbyopic eye, progress in this potentially exciting area is hindered by the scarcity of good, large-scale clinical studies using objective measurement techniques to evaluate the outcomes of accommodation restoration concepts.

Accommodation, Ocular↗