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D F Martin

Publications and source records attributed to D F Martin.

At least 19 recordsLinked to original sources

Evaluation of a delivery system providing long-term release of cyclosporine.

OBJECTIVES: To examine the clearance of cyclosporine after intravitreal injection and to assess the kinetics and toxic effects of an intravitreal device that provides sustained delivery of cyclosporine. METHODS: Rabbits were divided into two groups to evaluate (1) the elimination kinetics after 1-microgram and 10-microgram intravitreal injections of cyclosporine and (2) the levels produced after implantation of a device that contained cyclosporine over 6 months. The toxic effects of the intravitreal device over 6 months were assessed in rabbits and cynomolgus monkeys. RESULTS: After the 10-microgram injection, the half-life was longer (10.8 hours vs. 4.2 hours) and the distribution volume was smaller (1.7 mL vs 3.2 mL) than after the 1-microgram injection. This difference can be attributed to saturable partitioning of the drug. The device resulted in a vitreous concentration of approximately 500 ng/mL throughout the study period. In the rabbit it resulted in reversible lens opacification and decreased b-wave amplitude. This toxic effect was not detected in the monkey. CONCLUSIONS: The device produces sustained intravitreal levels of cyclosporine. Although it was associated with reversible toxic effects in the rabbit, it was well tolerated in primates. Sustained-release implants are a promising new treatment for chronic uveitis.

Animals

Postoperative hypopyon after intravitreal bovine thrombin for macular hole surgery.

PURPOSE: We used intravitreal autologous fibrinogen with bovine thrombin for the surgical closure of macular holes in 60 cases. METHODS: Pars plana vitrectomy with separation of the posterior cortical vitreous was performed after air/fluid exchange. One to two drops each of autologous fibrinogen and bovine thrombin (20 to 80 U) were instilled in each patient. RESULTS: Five (8%) of 60 patients developed a hypopyon without unusual pain on the first postoperative day. Inflammation responded to frequent topical corticosteroids within 48 to 72 hours. CONCLUSION: Postvitrectomy hypopyon after the use of bovine thrombin may represent an immune reaction that must be differentiated from endophthalmitis. We recommend careful observation and frequent topical corticosteroids.

Adult

Stenting for choledocholithiasis: temporizing or therapeutic?

Maxton and colleagues report their experience using biliary endoprostheses for treatment of failed common bile duct stone clearance after sphincterotomy. Of 283 patients with choledocholithiasis referred to their tertiary facility, 85 failed to have their ducts cleared with the first ERCP. There were 21 male and 64 female subjects; mean age was 77.5 yr. Clinical presentations were jaundice (39), cholangitis (23), and biliary colic and/or abnormal liver blood tests in the remainder. The patients were characterized as "elderly and ill with either jaundice or cholangitis present in almost 75%." Follow-up data were obtained for all patients. ERCP was first performed using a duodenoscope with a 3.2-mm instrument channel. A 7-French double pigtail stent was placed in each of the 85 patients with retained stones. Subsequent ERCP were performed at 2- to 3-month intervals using a therapeutic duodenoscope (4.2-mm instrument channel). A second stent was placed if stones remained in the bile duct after repeated extraction attempts. Patients deemed too frail and elderly for frequent ERCP had their first stent left in place, with stent exchanges and attempts at stone extraction every 6-12 months. Mechanical lithotripsy was used in 23 patients, extracorporeal shock wave lithotripsy (ESWL) in 11, and dissolution therapy via nasobiliary catheter in 10. Acute illnesses resolved in 84 of 85 patients, with significant decreases in bilirubin and alkaline phosphatase levels by the second ERCP. Six patients died with temporary stents in situ, one form a respiratory arrest the day of ERCP; the other deaths were unrelated to ERCP or choledocholithiasis. Fifty of the remaining 79 patients had successful stone clearance; 68% of these required two ERCP, 20% three ERCP, 6% four ERCP, and, in another 6%, a total of five ERCP were required before their ducts were free of stones. Seven cases of cholangitis among these 50 patients were treated successfully with i.v. antibiotics, fluids, and "early" stent replacement. Twenty-six patients had long term biliary drainage with the original stents in situ over 12 months. Four of these patients were among the six deaths, all unrelated to biliary stones or ERCP. Three patients were referred for surgical stone removal. The authors conclude that placement of a single 7-French stent after failure to clear common duct stones is safe, provides affective biliary drainage, can prevent the need for urgent surgical intervention, and allows for transfer of sick patients to centers of expertise. Further attempts at bile duct clearance were successful in most cases.

Aged

Synergistic effect of rapamycin and cyclosporin A in the treatment of experimental autoimmune uveoretinitis.

Immunosuppressive drugs currently available for the treatment of autoimmune diseases display a narrow therapeutic window between efficacy and toxic side effects. The use of combinations of drugs that have a synergistic effect may expand this window and reduce the risk of toxicity. We evaluated the combination effect of rapamycin (Rapa) and cyclosporin A (CsA) in an autoimmune disease model of the eye. The dose-effect relationship of Rapa with CsA was measured in vitro on the inhibition of proliferation of retinal S-Ag-primed lymphocytes. A median effect analysis was performed and a combination index (CI) calculated for 50% inhibition of proliferation. Rapa and CsA were markedly synergistic over a wide dose range (lowest CI = 0.31). Calculated dose reduction factors indicated that Rapa could be reduced nine-fold and CsA reduced five-fold when these drugs were used in combination. These reduced doses were tested in vivo for the treatment of experimental autoimmune uveoretinitis (EAU). Twelve of 15 rats treated with CsA, 2 mg/kg/day, developed EAU with a median severity of 2.5. Fourteen of 15 rats treated with Rapa, 0.01 mg/kg/day, developed EAU with a median severity of 3.25. Complete inhibition of EAU was achieved in all 15 animals treated with the combination of Rapa and CsA (combined vs CsA alone, p < 0.0002; combined vs Rapa alone, p < 0.00001). The demonstrated synergistic relationship between Rapa and CsA will allow the use of reduced doses of each drug to achieve a therapeutic effect. The use of lower doses may reduce the toxicity of these drugs for the treatment of autoimmune uveitis.

Animals

Parents' knowledge of the purposes and content of preparticipation physical examinations.

OBJECTIVES: To determine whether parents of student athletes plan to use the preparticipation physical examination (PPE) as their student athlete's only annual health evaluation, to identify factors associated with this decision, and to assess their knowledge about the objectives of PPEs and more comprehensive examinations. DESIGN: Survey. SETTING: General community, school-sponsored PPEs. PARTICIPANTS: A convenience sample of parents or guardians of high school student athletes who obtained a school-sponsored, multiple-station format PPE were surveyed by using an anonymous paper-and-pencil questionnaire. Questionnaires were completed by the parents of 381 of 763 student athletes who obtained PPEs (participation rate, 49.9%). RESULTS: Thirty percent of the parents in this sample planned to use the PPE as their student athlete's only contact with a health care provider. Parents whose adolescent's health insurance provided for comprehensive health assessments were more likely than those without this benefit to plan a comprehensive care evaluation (75% vs 60%, respectively) (P = .01 by chi 2 analysis). In addition to addressing problems that might affect sports participation, parents thought that the PPE visit should evaluate medical problems that are unrelated to athletics (34%), perform health screening procedures (22%), assess social or behavioral issues (16%), and provide immunizations (7%). CONCLUSIONS: Many parents plan to use the PPE as their student athlete's only scheduled contact with a health care provider; this decision may be influenced by factors that are related to access to health care and misperceptions with regard to the mission of these specialized examinations. For these adolescents, important medical, social, and behavioral needs may not be met. Consideration should be given to including elements of the PPE in health assessments that are performed by individual clinicians or expanding the scope of large-group, multiple-station format PPEs.

Adolescent

Three-dimensional MRI of the glenoid labrum.

The objective of this study was to assess the accuracy of three-dimensional (3D) magnetic resonance imaging (MRI) reformation in the evaluation of tears of the glenoid labrum complex (GLC). Fifty-five shoulders were evaluated by MRI using standard spin-echo sequences. Gradient-refocused-echo axial projections were used to assess the GLC on the two-dimensional (2D) studies. Three-dimensional Fourier transform multiplanar gradient-recalled imaging with a resolution of 0.7 mm was also performed in all patients. Independent analyses of the anterior and posterior labra were performed in a blinded manner for both the 2D and 3D studies by three experienced musculoskeletal radiologists. Observations of the imaging studies were compared with the videoarthroscopic findings. The appearance of the GLC was rated on a scale of 0 to 4 (0-2 = normal, 3, 4 = abnormal or torn). The diagnostic confidence was averaged from the three reader's scores. Anterior labral tears were effectively detected with sensitivities of 89% and 96% and specificities of 96% and 100% (P < 0.0001) for the 2D and 3D studies, respectively. For posterior labral tears, the sensitivity and specificity of the 2D method were 47% and 98%, respectively. The sensitivity and specificity of the 3D volume sequence were 53% and 98%, respectively. The lower sensitivity of both imaging methods for detecting posterior labral tears may be influenced by the smaller number (n = 5) of arthroscopically confirmed cases in our study and reflects the difficulty of visualizing the posteroinferior borders of the GLC with present MRI techniques.

Adult

Long-term visual results of children after initially successful vitrectomy for stage V retinopathy of prematurity.

PURPOSE: To assess the effectiveness of vitrectomy for stage V retinopathy of prematurity (ROP) at the authors' institution, 33 patients with ROP who had initially successful total or partial anatomic retinal attachments (51 eyes) were evaluated for visual function and long-term anatomic stability. In addition, this study was an attempt to differentiate levels of visual function in children with very low vision and attendant developmental delays. METHODS: Visual function was assessed before retinal examination by an experienced pediatric vision specialist. The behavioral visual assessment was divided into seven segments with two to five tasks in each segment designed to establish a level of functional vision, ranging from light perception to form identification (and ambulation). The status of the retina was classified by the patient's retinal surgeon. RESULTS: The median follow-up was 61 months, and median age at the time of examination was 68 months. Of 51 eyes treated, form identification was achieved in 5, and all five patients had ambulatory vision. Of 51 eyes, 15 had no light perception, 11 had light perception, 6 could localize light, 10 could follow lights, and 4 were able to detect form. Only one eye in ten children with comparable ROP in each eye underwent surgery, and vision improved in six of ten of the surgical eyes. Redetachment was high, with 35 retinas totally or partially detached and only 13 retinas fully attached 61 months after surgery. CONCLUSION: The visual results are very low and disappointing. Initially successfully attached retinas can detach. There is some evidence that vitrectomized eyes function better than nonvitrectomized eyes. There is also evidence that visual function lower than form identification is useful to these children and that they are able to use their limited vision better than previously though.

Child

Side effects of rapamycin in the rat.

The side effects of Rapamycin was evaluated by histopathological examination of the heart, kidneys, and eyes of treated Lewis rats. Rapamycin was administered during 14 days by continuous intravenous infusions at doses of 0.5, 1.0, and 1.5 mg/kg/day. Focal myocardial infarction was observed in three of five rats with Rapamycin given at 1.5 mg/kg/day and two of 22 rats with 1.0 mg/kg/day. There were no sign of myocardial toxicity at a Rapamycin dose of 0.5 mg/kg/day. The retina of one eye of a rat treated at a dose of 1.5 mg/kg/day had a small area of focal ischemic necrosis. The kidneys were normal at all doses.

Animals

Muscle thickness, measured with ultrasound, may be an indicator of lean tissue wasting in multiple organ failure in the presence of edema.

Multiple organ failure (MOF) is accompanied by muscle wasting, but changes in body composition are frequently obscured by fluid retention (edema), mainly in superficial and visceral tissue. There is a need to assess body composition and changes in body composition in these circumstances independently of edema. A relation was sought between fat-free (lean tissue) mass [calculated from body weight and skinfold thicknesses and measured by using dual-energy X-ray absorptiometry (DXA)] and muscle thickness (measured using ultrasound at a variety of sites accessible in an unconscious supine subject) to determine which sites correlated best with lean body mass. The three best sites were midbiceps, midforearm anteriorly, and midthigh anteriorly: R2 for the simple sum of the three sites correlated with fat-free mass from skinfold thicknesses was 71.1%, and with lean tissue mass from DXA was 76.1%. Serial measurements of both muscle thickness and midupper-arm circumference in nine patients with MOF showed a complete dissociation; in all nine there was a significant negative correlation of muscle thickness with time (P < 0.05) but changes in arm circumference were random. Only one patient showed a significant negative correlation with time, seven showed no change, and one other showed a significant increase. The muscle thicknesses that correlate best with lean body mass are measured over the biceps, anterior forearm, and anterior thigh. Monitoring muscle thicknesses at these three sites identifies wasting in edematous patients as it is happening.

Absorptiometry, Photon

Removal of optic disc stalks during diabetic vitrectomy.

BACKGROUND: The morphologic features and clinical consequences of removing residual optic disc stalks during vitrectomy for complications of diabetic retinopathy have not been described. METHODS: Twenty-four residual optic disc stalks that were surgically removed from eyes with proliferative diabetic retinopathy and dense nonclearing vitreous hemorrhage and/or traction retinal detachment were studied histologically using conventional hematoxylin and eosin staining as well as a modified Glees staining technique. RESULTS: Histologic examination demonstrated that 79% of the specimens consisted of vascularized glial tissue with an infiltrate of mononuclear cells and 21% consisted of glial membranes devoid of vasculature. Axons were identified in 33% of all tissues studied. Intra-operative hemorrhage occurred in three eyes with strongly adherent optic disc stalks and was controlled with transient elevation of the intraocular pressure. The presence of axons in the removed optic disc stalks was not correlated with a decreased final postoperative visual acuity (median time to follow-up 21 months). CONCLUSIONS: Residual optic disc stalks removed during vitrectomy for proliferative diabetic retinopathy frequently contained axons. The presence of axons does not portend an unfavorable postoperative visual outcome.

Adult

Retained common bile duct stones after endoscopic sphincterotomy: temporary and longterm treatment with biliary stenting.

Basket extraction after endoscopic sphincterotomy failed to clear the bile ducts immediately in 85 (30%) of 283 consecutive patients with common bile duct stones. Temporary biliary drainage was established by the insertion of a single 7 Fr double pigtail stent before further planned endoscopic attempts at stone removal. In 84 patients (21 male: 63 female, mean age 77 years) this measure relieved biliary obstruction, mean serum bilirubin falling from 101 to 18 umol/l by the time of the second endoscopic retrograde cholangiopancreatography. Six patients died from non-biliary causes with temporary stents in situ. Common bile duct stone extraction was achieved endoscopically in 50 of the remaining 79 patients after a mean of 4.3 months (range 1-12), 34 (68%) requiring only one further procedure. Three patients were referred for biliary surgery. Single stents were also effective for longterm biliary drainage in the remaining 26 elderly patients with unextractable stones. The main biliary complication of stenting was 13 episodes of cholangitis but all except one responded to medical treatment and early stent exchange. If common bile duct stones remain after endoscopic sphincterotomy, a single 7 Fr double pigtail stent is effective and safe for temporary biliary drainage before further endoscopic attempts at duct clearance and for longterm biliary drainage especially in the old and frail.

Adult

Etiology of iliotibial band friction syndrome in distance runners.

The objectives of our study were: 1) to examine differences between a noninjured cohort of runners (N = 70) and runners afflicted with iliotibial band friction syndrome (ITBFS) (N = 56) according to selected anthropometric, biomechanical, muscular strength, and training measures; 2) to explore multivariate relationships among these measures in both the well and injured groups; and 3) to develop specific hypotheses concerning risk factors for injury that will later be tested in a prospective observational study. High speed videography (200 fps), a force platform (500 Hz), and a Cybex II+ isokinetic dynamometer were used to assess rearfoot motion, ground reaction forces, and knee muscular strength and endurance, respectively. A linear discriminant function analysis of the training data revealed weekly mileage, training pace, number of months using current training protocol, % time spent swimming, and % time spent running on a track to be significant (P < 0.10). Height was a significant anthropometric discriminator, while seven isokinetic strength and endurance measures were found to discriminate significantly between the groups. Calcaneal to vertical touchdown angle, and maximum supination velocity were significant rearfoot movement discriminators. Maximum braking force was the only significant kinetic discriminator. A combined discriminant analysis using those variables found to be significant in the previous analyses revealed weekly mileage, and maximum normalized braking force to be the best discriminators (model P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Diagnosis of reactive lymphoid hyperplasia by chorioretinal biopsy.

We treated a patient with reactive lymphoid hyperplasia in whom the diagnosis was made by chorioretinal biopsy. Histopathologic examination and culture of the biopsied specimen allowed us to rule out a neoplastic or infectious process. The biopsy result allowed us to treat him with systemic corticosteroid alone, thus avoiding the potential harmful side effects of other medications, including antituberculous drugs. There were no surgical or postoperative complications. This study confirms the usefulness of chorioretinal biopsy for establishing a diagnosis and formulating a rational treatment plan.

Antigens, CD

Treatment and pathogenesis of traumatic chorioretinal rupture (sclopetaria).

Eight eyes (seven patients) with traumatic chorioretinal rupture (sclopetaria) from severe ocular trauma were examined. All seven patients were referred with diagnoses of retinal detachment, giant retinal tear, or ruptured globe. Instead, all eyes had large, peripheral, full-thickness breaks of the choroid and retina without retinal detachment. Seven of eight eyes were initially managed by observation only; one eye was treated with a scleral buckling procedure. The retina remained attached in all eyes for at least six months. Late retinal detachment (more than one year after initial injury) occurred in two eyes because of retinal breaks at a site distant from the original chorioretinal rupture. Two eyes later developed vitreous hemorrhage associated with posterior vitreous detachment and one of these eyes required vitrectomy to clear the visual axis. The pathogenesis of sclopetaria appears to be mechanical disruption and retraction of tissue rather than acute tissue dissolution. The risk of acute retinal detachment is low. We recommend nonsurgical management for the initial treatment of these patients, with continued observation for complications that may later occur.

Adolescent

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant. A randomized controlled clinical trial.

BACKGROUND AND METHODS: We performed a randomized controlled clinical trial to assess the safety and efficacy of a 1 microgram/h ganciclovir implant for the treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients with previously untreated peripheral CMV retinitis were randomly assigned either to immediate treatment with the ganciclovir implant or to deferred treatment. Standardized fundus photographs were taken at 2-week intervals and analyzed in a masked fashion. The study end point was progression of retinitis based on the photographic assessment. RESULTS: Twenty-six patients (30 eyes) were enrolled. The median time to progression of retinitis was 15 days in the deferred treatment group (n = 16) vs 226 days in the immediate treatment group (n = 14) (P < .00001, log-rank test). During the study, 39 primary implants and 12 exchange implants were placed in immediate-treatment eyes, deferred-treatment eyes that progressed, or contralateral eyes that developed CMV retinitis. Postoperative complications in the total series included seven late retinal detachments and one retinal tear without detachment. Final visual acuity was 20/25 or better in 34 of 39 eyes. The estimated risk of developing CMV retinitis in the fellow eye was 50% at 6 months. Biopsy-proven visceral CMV disease developed in eight (31%) of 26 patients. The median survival was 295 days. CONCLUSION: The ganciclovir implant is effective for the treatment of CMV retinitis. Patients with unilateral CMV retinitis treated with the implant are likely to develop CMV retinitis in the fellow eye, and some patients will develop visceral CMV disease.

AIDS-Related Opportunistic Infections