Corneal transplant for keratoconus: results in early and late disease

PURPOSE: To evaluate the results and complications rates associated with corneal transplantation for keratoconus and assess the prospects of using penetrating keratoplasty at a much earlier stage. SETTING: Buzard Eye Institute, Las Vegas, Nevada, USA. METHODS: In this prospective clinical study, 104 eyes of 76 patients had corneal transplantation for keratoconus identified by corneal topography, keratometry, pachymetry, and/or retinoscopy. Sutures were removed at a mean of 15 months; mean follow-up was 42 months. All surgeries were performed by one surgeon using a torque-antitorque suture method. Eyes were grouped according to severity of the disease: early (n = 24); moderate (n = 47); high (n = 33). Preoperative keratometry was 40.00 to 49.00, 50.00 to 59.00, and 60.00 to 90.00 diopters (D), respectively. The criteria for corneal transplant were a best spectacle-corrected visual acuity of 20/40 or worse and keratoconus clearly identified by one of the above methods. Secondary procedures included repair of wound dehiscence (33 eyes, 31%), relaxing incisions (33 eyes, 31%), wedge resections (5 eyes, 5%), and automated lamellar keratoplasty (4 eyes, 4%). RESULTS: Mean postoperative uncorrected visual acuity at last follow-up was 0.43 +/- 0.3 (20/50), with 46 eyes (44%) achieving 20/40 or better. Mean best corrected visual acuity (BCVA) at last follow-up was 0.83 +/- 0.2 (20/25). Sixty eyes (58%) achieved 20/40 or better BCVA at 1 month and 92 eyes (88%), at 3 months. At last follow-up, mean average keratometric astigmatism was 3.10 +/- 1.70 D, mean keratometry was 43.30 +/- 2.20 D, and mean spherical equivalent was -1.70 +/- 3.00 D. Complications included 21 graft rejections (20%); 19 were successfully treated with topical and oral steroids. No expulsive hemorrhage or endophthalmitis occurred. CONCLUSIONS: The risk-benefit for corneal transplantation has been significantly altered by improved surgical and postoperative techniques. The improved results, low complication rate, and postoperative enhancement management indicate that corneal transplantation is a viable option early in the clinical course of keratoconus.     

Early complications in the operative treatment of patella fractures

In this study two aspects of hybrid functional electrical stimulation (FES) orthoses were investigated: joint motion constraints and FES control strategies. First, the effects of joint motion constraints on the gait of normal subjects were investigated using modern motion analysis systems, including electromyogram (EMG) and heart rate measurements. An orthosis was developed to impose joint motion constraints; the knee and ankle could be fixed or free, and the hip joint could rotate independently or coupled, according to a preset flexion-extension coupling ratio (FECR). Compared with a 1:1 hip FECR, a 2:1 hip FECR was associated with a reduced energy cost and increased speed and step length. The knee flexion during swing significantly reduced energy cost and increased walking speed. Ankle plantar flexion reduced the knee flexing moment during the early stance phase. Second, trials on 3 paraplegic subjects were conducted to implement some of these findings. It appeared that the 2:1 FECR encouraged hip flexion and made leg swing easier. A simple FES strategy increased walking speed and step length and reduced crutch force impulse using fixed orthotic joints.     

Assembly of proteins to postsynaptic densities after transient cerebral ischemia

Transient ischemia leads to changes in synaptic efficacy and results in selective neuronal damage during the postischemic phase, although the mechanisms are not fully understood. The protein composition and ultrastructure of postsynaptic densities (PSDs) were studied by using a rat transient ischemic model. We found that a brief ischemic episode induced a marked accumulation in PSDs of the protein assembly ATPases, N-ethylmaleimide-sensitive fusion protein, and heat-shock cognate protein-70 as well as the BDNF receptor (trkB) and protein kinases, as determined by protein microsequencing. The changes in PSD composition were accompanied by a 2.5-fold increase in the yield of PSD protein relative to controls. Biochemical modification of PSDs correlated well with an increase in PSD thickness observed in vivo by electron microscopy. We conclude that a brief ischemic episode modifies the molecular composition and ultrastructure of synapses by assembly of proteins to the postsynaptic density, which may underlie observed changes in synaptic function and selective neuronal damage.     

Monoclonal antibodies against human collagenase and stromelysin

Mouse monoclonal antibodies against recombinant human fibroblast procollagenase and prostromelysin have been generated and characterized. The epitope-containing domains for the antibodies have been assigned based on their immunoreactivities against recombinant proenzymes, mature enzymes, truncated collagenases, proteolytic fragments of stromelysin, and chimeric molecules constructed from different domains of the two enzymes. These antibodies can be divided into four groups: (1) antibodies that recognize the truncated 19-kDa NH2-terminal collagenase, (2) antibodies that recognize the C-terminal domain of collagenase and stromelysin, (3) antibodies that recognize a 31-kDa NH2-terminal collagenase fragment, and (4) antibodies that recognize the 19-kDa NH2-fragment of stromelysin. The prostromelysin-specific antibody 11N13 is of particular interest; it neutralizes stromelysin activity in a stromelysin peptide substrate assay, with an IC50 value of 75 nM. MAb 11N13 may be useful for in vivo and in vitro studies to validate the roles of stromelysin in tumor cell invasion, metastasis, and connective tissue disorders.     

Inhibition of collagen-induced platelet activation by arachidonyl trifluoromethyl ketone

Collagen-induced platelet activation is associated with, and markedly potentiated by, the release of arachidonic acid and its subsequent conversion to thromboxane A2. The precise mechanism of arachidonic acid release is unknown. An inhibitor of isolated cytosolic phospholipase A2 (cPLA2), arachidonyl trifluoromethyl ketone (AACOCF3), was used to examine the role that cPLA2 plays in this process. AACOCF3 inhibited platelet aggregation in response to collagen and arachidonic acid but not to thrombin, calcium ionophore, phorbol ester, or a thromboxane mimetic. Thromboxane formation stimulated by thrombin or collagen was inhibited by AACOCF3. However, AACOCF3 did not inhibit collagen-induced [14C]arachidonic acid release. These data are consistent with the inhibitory effects of AACOCF3 on collagen-induced aggregation involving an action on the conversion of arachidonic acid to thromboxane.