Comparative assessment of CT and sonographic techniques for appendiceal imaging.

OBJECTIVE: We performed a comparative assessment of CT and sonographic techniques used to assess appendicitis. MATERIALS AND METHODS: One hundred patients with clinically suspected acute appendicitis were examined with sonography, unenhanced focused appendiceal CT, complete abdominopelvic CT using IV contrast material, focused appendiceal CT with colonic contrast material, and repeated sonography with colonic contrast material. Each sonogram was videotaped for subsequent interpretation by three radiologists and two sonographers. The mean sensitivity, specificity, positive and negative predictive values, inter- and intraobserver variability, and diagnostic confidence scores of all observers were used for comparative performance assessments. The three CT examinations were filmed and interpreted separately by four radiologists. Patient discomfort was assessed on a 10-point scale for each radiologic study. Diagnoses were confirmed by pathologic evaluation of resected appendixes or clinical follow-up for a minimum of 3 months after presentation. RESULTS: Twenty-four of the 100 patients had positive findings for acute appendicitis. Both sonographic techniques had high specificity (85-89%) and comparable accuracy (73-75%) but low sensitivity (33-35%) and inter- and intraobserver variability (kappa = 0.15-0.20 and 0.39-0.42, respectively). Unenhanced focused appendiceal CT, abdominopelvic CT, and focused appendiceal CT with colonic contrast material all significantly outperformed sonography (p <0.0001), with sensitivities of 78%, 72%, and 80%; specificities of 86%, 91%, and 87%; and accuracies of 84%, 87%, and 85%, respectively. Abdominopelvic CT gave the greatest confidence in cases with negative findings (p = 0.001), and focused appendiceal CT with colonic contrast material gave the greatest confidence for cases with positive findings (p = 0.02). In terms of inter- and intraobserver variability, focused appendiceal CT with colonic contrast material yielded the highest, and unenhanced focused appendiceal CT the lowest, agreement (interobserver kappa = 0.45 vs. 0.36 and intraobserver kappa = 0.85 vs. 0.76, respectively) (p <0.05). Colonic contrast material was unsuccessfully advanced into the cecum in 18% of patients and leaked in another 24%. Patient discomfort was greatest with focused appendiceal CT using colonic contrast material and least with unenhanced focused appendiceal CT (p <0.05). CONCLUSION: A standard abdominopelvic CT scan is recommended as the initial examination for appendicitis in adult patients. However, focused appendiceal CT with colonic contrast material material should be used as a problem-solving technique in difficult cases.

An epidemic of corneal destruction caused by plasma gas sterilization. The Toxic Cell Destruction Syndrome Investigative Team.

BACKGROUND: Toxic endothelial cell destruction (TECD) syndrome after intraocular ophthalmic surgery is rare and can result from exposure to a variety of toxins. During January 8 to 14, 1998, 6 patients developed TECD with corneal edema associated with unreactive or dilated pupils at Hospital A. METHODS: A case patient was any Hospital A patient with TECD within 24 hours after surgery during January 5 to 14, 1998 (epidemic period). A control was any hospital A ophthalmic surgery patient without TECD during the epidemic period. The medical records of hospital A ophthalmology surgery patients during the pre-epidemic (ie, September 1, 1997-January 4, 1998) and epidemic periods were reviewed. Inductively coupled plasma atomic emission spectrometry was used to detect trace inorganic elements on sterilized surgical instruments. Cannulated surgical instruments and laboratory rinsates were perfused directly to the corneal endothelium of isolated rabbit and human corneas. Corneal endothelial ultrastructure and swelling were assessed. RESULTS: The rate of TECD at hospital A was higher during the epidemic than pre-epidemic period (6/12 vs 0/118, P<.001). The only change during the periods was the introduction, on November 5, 1997, of a new sterilization method, AbTox Plazlyte, for sterilization of ophthalmic surgery instruments. Findings from spectrometry revealed that copper and zinc residues were higher in instruments sterilized with Plazlyte than in those sterilized with ethylene oxide (median copper value, 7.64 mg/L vs 0.14 mg/L, respectively, P =.02; median zinc value, 5.90 mg/L vs 1.35 mg/L, respectively, P =.2). Corneal endothelial perfusion of Plazlyte sterilized-instrument rinsates or laboratory solution with copper and zinc produced irreversible damage, similar to toxic corneal endothelial destruction, to rabbit and human corneas. CONCLUSION: A new sterilization method degraded brass to copper and zinc on cannulated surgical instruments resulting in TECD of the cornea. Arch Ophthalmol. 2000;118:1167-1176

The effects of intraocular lidocaine on the corneal endothelium.

OBJECTIVE: The study aimed to evaluate the direct effect of intraocular lidocaine hydrochloride (HCl) 1% on corneal endothelial cell function, ultrastructure, and viability using an in vitro perfusion specular microscope system. DESIGN: Paired rabbit and human corneas were isolated and mounted in an in vitro specular microscope for endothelial perfusion evaluation. Corneas were perfused with a control solution (BSS Plus for humans, glutathione bicarbonate Ringer's [GBR] for rabbits) for a 1-hour stabilization period. After the stabilization period, one cornea of each matched pair was perfused with preservative-free lidocaine HCl 1% for 15 minutes followed by control solution for an additional 2 to 3 hours. The control cornea continued to receive either GBR or BSS Plus. Corneal thickness measurements were taken every 15 minutes throughout the perfusion period. Corneal swelling and deswelling rates were calculated by linear regression analysis. At the end of the experiment, corneas were fixed for scanning and transmission electron microscopy. In another group of corneas, the endothelial viability was assayed after direct perfusion with lidocaine HCl 1%. RESULTS: Lidocaine HCl 1% caused endothelial cell edema, which reversed on removal of lidocaine from perfusion media. Corneal swelling and deswelling rates did not differ significantly between the lidocaine and control groups. Electron microscopy showed the effects of transient endothelial cell edema with an otherwise normal mosaic pattern and ultrastructure for both treatment groups. Endothelial cell viability was maintained after the direct lidocaine exposure and a 2-hour washout. CONCLUSIONS: Lidocaine HCl 1% causes a transient endothelial cell edema to the in vitro perfused endothelium of human and rabbit corneas. Proper attention should be given to the type of lidocaine injected intraocularly (i.e., concentration, vehicle, preservatives, pH, osmolarity). Although lidocaine HCl 1% appears to be safe to both human and rabbit endothelium during short-term in vitro exposure, further in vivo and in vitro studies are needed to determine long-term effects of intraocular lidocaine on the corneal endothelium.

Diagnosis and differentiation of congenital diaphragmatic hernia from other noncardiac thoracic fetal masses.

This retrospective study was designed to evaluate individual sonographic parameters that might help differentiate congenital diaphragmatic hernia (CDH) from other noncardiac thoracic masses such as cystic adenomatoid malformation of the lung (CAML) and congenital lobar emphysema (CLE) prenatally. Twenty-four cases of CDH, CAML, and CLE detected during prenatal ultrasound and documented postnatally (with surgical, autopsy, or radiological proof) were identified through extensive chart and record review. The hard copy gray-scale images were retrospectively reviewed for imaging characteristics that may differentiate the three entities. Additionally, the prospective diagnosis during prenatal ultrasound was also compared with the postnatal diagnosis. The most reliable indicators in our retrospective review included confident visualization of a diaphragmatic defect (92.3/100.0 PPV/NPV, p< or =0.002) and/or localization of the stomach within the chest as well as the presence of severe cardiac deviation (both 92.3/62.5 PPV/NPV, p< or =0.01). Other sonographic indicators (including the presence of cystic areas, side and size of the lesion and the presence of polyhydramnios) offered lower levels of sensitivity and specificity. Prospective diagnosis during real-time assessment was also integral, offering >80% sensitivity and specificity (p< or =0.001). Accurate prenatal diagnosis of CDH is difficult despite the relative frequency of this lesion. The classic triad of a thoracic mass accompanying a displaced heart, absence of a normally positioned fluid-filled stomach and polyhydramnios, although seen with CDH, may not adequately differentiate this entity from other noncardiac fetal thoracic masses. Realtime assessment remains integral to the appropriate diagnosis.

Endothelial cell loss after 4 mm cataract surgery.

To assess whether a 4 mm scleral tunnel incision with a 1.5 mm internal corneal lip (three-step procedure) causes increased endothelial cell loss and damage to the cornea, we retrospectively evaluated the outcomes of 20 patients (40 eyes) who had a standard 4 mm scleral tunnel incision (two-step procedure) in one eye followed by a three-step incision in the second eye, with in situ phacoemulsification and insertion of a foldable silicone lens in each eye. Mean phacoemulsification time was 2.4 +/- 1.1 minutes for the two-step incisions and 3.4 +/- 1.4 minutes for the three-step incisions. Preoperative and postoperative endothelial cell counts were obtained to determine the effects of surgery on the corneal endothelium. Although the three-step procedure had a trend toward increased endothelial cell loss from the central corneal region compared with the two-step incision, the result was neither clinically nor statistically significant. The difference between the three-step and two-step incisions in postoperative endothelial cell counts from the superior corneal region was statistically significant. The difference in postoperative counts from the inferior region was not statistically significant. Although the three-step 4 mm incision does seem to affect the corneal endothelium, its clinical significance is unknown.

Corneal endothelial permeability of human tissue after storage in Optisol.

The purpose of this study was to compare Optisol to moist chamber storage for maintaining human corneal endothelial barrier function. Human corneas preserved in Optisol were stored for up to 35 days at 4 C. Endothelial carboxyfluorescein permeability (P(ac)) was measured and endothelial ultrastructure was evaluated by electron microscopy. Endothelial P(ac) (x 10(-4) cm/min) of Optisol-stored corneas was 1.7, 2.0, and 3.1 at five, seven, and 14 days, respectively. The P(ac) increased to 6.5 at 35 days of storage. Endothelial P(ac) in moist chamber stored-eyes was 2.6 at two days, and increased to 13.5 14 days of storage. Multiple regressional analysis showed that storage time and donor age affected P(ac); but time from death to enucleation, time from enucleation to storage, or endothelial cell number did not. Electron microscopy showed that endothelial junctions were maintained through two weeks by Optisol. Large areas of cellular destruction were seen after five days of moist chamber storage. These results show that Optisol can preserve endothelial barrier function through 14 days; barrier function is lost by three days of moist chamber storage.

Swelling in the isolated perfused cornea induced by 12(R)hydroxyeicosatetraenoic acid.

PURPOSE: To evaluate the effect of 12(R)hydroxyeicosatetraenoic acid (12(R)HETE) on corneal swelling when directly perfused to human and rabbit corneal endothelium. METHOD: Excised rabbit and human corneas were mounted in the in vitro specular microscope and the endothelium was perfused with 12(R)HETE at 10(-5), 10(-6), and 10(-7) mol/l. Both 12(R)HETE and 12(S)HETE were compared at equal molar (10(-6) mol/l) concentrations. The reversal of 12(R)HETE and ouabain corneal swelling was also compared. Endothelial permeability to carboxyfluorescein was measured after 12(R)HETE perfusion. High-performance liquid chromatographic analysis confirmed that 12(R)HETE remained in the perfusion media. RESULTS: 12(R)HETE caused a dose-dependent corneal swelling of 25 +/- 2, 24 +/- 1, and 14 +/- 0.5 microns/hr at 10(-5), 10(-6), and 10(-7) mol/l, respectively. Equal molar concentrations (10(-6) mol/l) of 12(S)HETE did not cause corneal swelling. Removal of the 12(R)HETE from the perfusion media resulted in reversal of corneal swelling whereas corneal swelling induced by ouabain did not reverse after ouabain removal. 12(R)HETE (10(-6) mol/l) perfused to the human corneal endothelium inhibited temperature reversal corneal thinning when compared to the paired corneal endothelium perfused with BSS Plus (Alcon Laboratories, Inc., Fort Worth, TX). Na/K adenosine triphosphatase activity was inhibited by 10(-6) mol/l ouabain by 35%, 10(-6) mol/l 12(R)HETE by 54%, and 10(-6) mol/l 12(S)HETE by 0.5%. Endothelial permeability to carboxyfluorescein was unaffected by 12(R)HETE. CONCLUSION: 12(R)HETE causes corneal swelling by inhibiting endothelial pump function. This inhibition of transport appears to be at least partly mediated by inhibition of endothelial Na/K adenosine triphosphatase.

Corneal endothelial cytoskeletal changes in F-actin with aging, diabetes, and after cytochalasin exposure.

We investigated the changes in endothelial cytoskeletal F-actin that occur with aging, diabetes, and exposure to cytochalasin D. Rabbit corneas, human donor corneas (with or without polymegethism), and corneas of diabetic individuals were studied. Endothelial F-actin was stained using nitrobenzoxadiazole-phallacidin. Results of these experiments demonstrated that F-actin of the rabbit and human corneal endothelium was arranged in linear circumferential strands that formed a hexagonal array. After in vitro perfusion of cytochalasin D to the corneal endothelium, the F-actin became randomly distributed throughout the cytoplasm, the hexagonal shape of the endothelial cell was disrupted, and endothelial permeability to carboxyfluorescein increased. Changes in F-actin were also observed in the endothelium of the human corneas with polymegethism, and in donor tissue having had previous posterior chamber intraocular lens implantation. The corneas of diabetic individuals also showed marked irregular F-actin fibers crossing the endothelial cell cytoplasm. These abnormal patterns of F-actin may contribute in part to the polymegethism observed in the corneal endothelial cells and may be the result of constant stress in cell volume regulation, particularly in the corneas of diabetic individuals.

Effects of intraocular irrigants on the preserved human corneal endothelium.

Either a simple balanced salt solution (BSS) or a bicarbonate-buffered, glutathione-containing commercial irrigant (BSS Plus, Alcon Laboratories, Fort Worth, Texas, U.S.A.) may be used during the vitrectomy portion of a corneal transplant procedure. To simulate the conditions present in the anterior chamber during the first few hours after vitrectomy and grafting, we performed in vitro perfusions of stored human corneas using each irrigant and measured corneal thickness over a 3-hour period. Irrespective of the preservation medium used (McCarey Kaufman, Chondroin Sulfate or Dexsol, all from Chiron Ophthalmics, Irvine, California) or duration of storage (2 or 4 days), corneas irrigated with BSS Plus exhibited significantly (p less than .05) decreased thickness compared with their paired mates irrigated with BSS. In ultrastructural studies performed on postperfusion corneas, there was a tendency toward improved surface morphology in the in vitro BSS Plus-perfused tissue. This study shows that in vitro corneal thickness after preservation is significantly irrigant dependent, with BSS Plus providing the essential ingredients to promote the corneal endothelial pump function.

Selective depletion of CD8+ T lymphocytes for prevention of graft-versus-host disease after allogeneic bone marrow transplantation.

The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA-identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-transplant for 6 months. Thirty-three patients had initial engraftment. Three failed to have hematologic recovery, and one patient with initial engraftment had late graft failure. The actuarial incidence of grade greater than or equal to 2 acute graft-versus-host disease was 28% +/- 18% and was usually confined to the skin. Of 33 patients with engraftment, 32 were complete chimeras and one had mixed chimerism. The tempo of hematologic and immunologic recovery was comparable with that reported with transplantation of unmodified bone marrow, although CD4+ and CD8+ T cells recovered at comparable rates. The actuarial rate of leukemia relapse was 11% +/- 10%, occurring in three patients with acute leukemia but in none of 13 patients transplanted for chronic myelogenous leukemia. Actuarial survival was 57% +/- 17% at 2 years. These data indicate that after transplantation of marrow depleted of CD8+ cells, engraftment with prompt hematologic and immunologic recovery generally occurs, with a relatively low rate of acute graft-versus-host disease. Graft failure remains a problem despite retention of CD4+ cells within the donor marrow. The lack of leukemia relapse in patients with chronic myelogenous leukemia suggests retention of a graft-versus-leukemia effect, at least for this malignancy.

Bone marrow transplantation for severe aplastic anemia. Effect of a preparative regimen of cyclophosphamide-low-dose total-lymphoid irradiation and posttransplant cyclosporine-methotrexate therapy.

Twenty-nine patients with severe aplastic anemia were entered into a study of pre- and posttransplant immunosuppressive therapy for bone marrow transplantation. Four of twenty-five previously transfused recipients prepared with cyclophosphamide 200 mg/kg and total-lymphoid irradiation 3 Gy experienced graft failure, indicating that this regimen was inadequate to ensure sustained engraftment. Posttransplant treatment with cyclosporine and methotrexate resulted in an actuarial incidence for grade greater than or equal to 2 graft-versus-host disease of 22 +/- 16%. Actuarial survival was 78 +/- 15%. These data indicate that more effective treatment is necessary to prevent graft failure, but since many patients can be successfully retransplanted, overall survival is comparable to other recent studies.