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Biomedical subjects

J L Davis

Publications and source records attributed to J L Davis.

At least 55 records · Page 3Linked to original sources

Effect of potent antiretroviral therapy on recurrent cytomegalovirus retinitis treated with the ganciclovir implant.

PURPOSE: To determine the effect of highly active antiretroviral therapy on cytomegalovirus (CMV) retinitis treated with ganciclovir implants. METHODS: A retrospective cohort study was performed of 15 patients with recurrent CMV retinitis treated with the ganciclovir implant and highly active antiretroviral therapy (cases) and 38 patients with recurrent retinitis treated with ganciclovir implants before availability of improved antiretroviral therapy (controls). Progression was defined as occurrence of new lesions in the treated eye or advancement of the retinitis border by more than 750 microm. RESULTS: Cases and controls were statistically similar in age, ethnicity, and duration of acquired immunodeficiency syndrome (AIDS). Controls had received intravenous ganciclovir for 9.5 +/- 9.5 months vs 3.5 +/- 4.6 months in cases (P = .003). The mean (+/- SE) time to progression of retinitis after implantation of the device was 26.7 +/- 2.4 months (95% confidence interval, 22.1 to 31.3) in the cases receiving highly active antiretroviral therapy vs 6.2 +/- 0.9 months (95% confidence interval, 4.5 to 7.9) in the controls (P = .001). Multivariate analysis, adjusted for preoperative variables, confirmed a significantly prolonged time to progression in patients receiving highly active antiretroviral therapy (P = .0003). The odds ratio for progression in the cases vs controls was 0.034 (95% confidence interval, 0.003 to 0.350). Cases had higher CD4+ T-lymphocyte counts (P = .004) and longer survival (P < .001) than controls. CONCLUSION: Highly active antiretroviral therapy is associated with improved outcomes in patients with AIDS and recurrent CMV retinitis treated with the ganciclovir implant.

AIDS-Related Opportunistic Infections↗

Monitoring interposition graft venous pressures at higher blood-flow rates improves sensitivity in predicting graft failure.

Monitoring the patency of hemodialysis interposition grafts is recommended to improve graft survival. Which blood flows best predict graft survival is not known. We monitored venous pressures in 32 dialysis patients over a median of 252 days at variable flow rates of the blood pump (Qb). Venous pressure trends (VPTs), maximum venous pressure (MVP), and the variability of venous pressure (percent coefficient of variation) were calculated. Kaplan-Meier curves were constructed from the time of the end of VPT monitoring to time to failure, defined as angioplasty, clotting, or surgical revision. Risk for graft failure for each 10-mm Hg increase in venous pressure was calculated by the Cox proportional hazards model. There were 12 graft failures, but no failures in 12 fistulas over the course of the study. The variability in venous pressure was less at greater Qbs. For grafts, VPTs were predictive of event only when calculated for Qbs greater than 100 mL/min. At Qbs of 400 mL/min, there was a 70% risk for graft failure with each 10-mm Hg increase in VPT. The risk for graft failure increased between 28% and 44% for each 10-mm Hg increase in MVP at all Qbs. MVP of 230 mm Hg at a Qb of 400 mL/min provided the best efficiency of test performance. Dialysis venous chamber pressure monitoring is a useful test to predict graft stenosis or thrombosis. There is a substantial variability in venous pressures in the same patient that reduces with increasing Qbs. Venous pressure monitoring at greater Qbs provides a more sensitive method for predicting access failure.

Arteriovenous Shunt, Surgical↗

Normative data on computerized paced auditory serial addition task performance.

Computerized testing has increased in popularity over the past two decades. The present study examined properties of the computerized version of the Paced Auditory Serial Addition Task (PASAT). The PASAT was administered to 168 college students ages 17 to 48 years with no history of neurological or emotional problems. Analysis of variance showed no significant effects of gender or age. With increasing rate of presentation, participants gave fewer correct responses. The number of errors decreased rather than increased across PASAT trials, reflecting participants' tendency to "skip" items. Additional normative data are presented. Performance on the computerized PASAT appears similar to published norms on the PASAT version presented via audiocassette. It is suggested that the computerized and audiocassette versions of the PASAT may be used as alternate forms in well-educated adults.

Adolescent↗

Differential diagnosis of CMV retinitis.

Diagnosis of cytomegalovirus retinitis (CMVR) is usually made by retinal examination by an experienced ophthalmologist. The characteristic appearance of the infection is distinctive enough that recourse to ancillary tests or diagnostic procedures is rarely needed. However, atypical cases of CMVR or infections with other organisms in individuals at high risk for CMVR may require invasive diagnostic testing of ocular fluids or tissues using comparative antibody titers, amplification of organismal DNA or RNA, culture, or histology. A small number of other organisms are frequent enough as causes of intraocular infection that the typical appearances of these infections have become known. Familiarization of the clinician with the expected clinical presentation of various infections can facilitate diagnosis, selection of confirmatory diagnostic tests, and empiric therapy.

Animals↗

Management of CMV retinal detachments in the new era of antiretroviral therapy.

In the past, retinal detachment occurred at a rate of 38% after one year of cytomegalovirus retinitis (CMVR). The current rate of detachment may be reduced by improved therapies for CMVR. In addition, the number of new patients acquiring CMVR has fallen, resulting in a lower incidence of these detachments. Another important effect of the new era of antiviral therapy on CMVR-related detachments includes longer patient survival with a need to select surgical strategies that will provide the best long-term visual outcome while still recognizing the unique difficulties posed by detachments in necrotic retinas. Vitrectomy with planned removal of silicone oil, scleral buckle, vitrectomy with gas tamponade, and laser demarcation are strategies that may provide excellent visual and anatomic results for retinal detachments with various characteristics. The final selection of the surgical approach depends on the mechanical factors of the detachment and patient factors such as immune status, expected survival, control of retinitis, and visual needs.

Anti-HIV Agents↗

Similarities in the metabolism of alloxan and dehydroascorbate in human erythrocytes.

The beta-cell toxin alloxan is reduced within cells to dialuric acid, which may then decompose to release damaging reactive oxygen species. We tested whether such redox cycling of alloxan occurs in the human erythrocyte, a cell with stronger antioxidant defenses than beta-cells. Erythrocytes incubated with increasing concentrations of alloxan progressively accumulated dialuric acid, as measured directly by HPLC with electrochemical detection. At concentrations up to 2 mM, alloxan decreased cellular GSH slightly, but did not affect erythrocyte contents of ascorbate or alpha-tocopherol. Intracellular H2O2 generation, measured as inhibition of endogenous catalase activity in the presence of 3-amino-1,2,4-triazole (aminotriazole), was decreased by alloxan. Despite its failure to induce significant oxidant stress in erythrocytes, 2 mM of alloxan doubled the activity of the hexose monophosphate pathway (HMP). This likely reflected consumption of reducing equivalents during reduction of alloxan to dialuric acid. Alloxan pretreatment enhanced the ability of erythrocytes to reduce extracellular ferricyanide while protecting alpha-tocopherol in the cell membrane from oxidation by ferricyanide. Ninhydrin, a hydrophobic derivative of alloxan, showed similar effects, but caused progressive GSH depletion and cell lysis at concentrations above 50 microM. The ability of alloxan to enhance ferricyanide reduction and to spare alpha-tocopherol suggests that dialuric acid or other reducing species within the cells can protect or recycle alpha-tocopherol and donate electrons to a transmembrane transfer process. This behavior resembles that observed for the dehydroascorbate (DHA)/ascorbate pair, and leads to the unexpected conclusion that alloxan increases the reducing capacity of the erythrocyte.

Alloxan↗

Chronic multifocal retinal infiltrates in patients infected with human immunodeficiency virus.

PURPOSE: To describe the clinical features of a disorder characterized by chronic multifocal retinal infiltrates and uveitis in individuals with human immunodeficiency virus (HIV) disease. METHODS: We reviewed the medical records of HIV-infected patients with multifocal retinal infiltrates of unknown cause seen by investigators at four institutions. The following data were collected: demographic characteristics, presenting signs and symptoms, laboratory test results, and course of disease. RESULTS: We identified 26 HIV-infected patients (50 involved eyes) with this syndrome. Median CD4+ T-lymphocyte count at presentation was 272 per microl (range, 7 to 2,118 per microl). The most common presenting symptom was floaters. Median visual acuity of involved eyes at presentation was 20/20 (range, 20/15 to 20/100) and remained stable (median, 20/20; range, 20/15 to 20/70) after a median follow-up period of 9 months (range, 0 to 110 months). Typical retinal lesions were gray-white or yellow, irregular in shape, and less than 200 microm in greatest dimension. All were located in the midperiphery or anterior retina and enlarged slowly or remained static in size. Mild to moderate anterior chamber or vitreous humor inflammatory cells were present in 47 of 50 eyes (26 of 26 patients). Retinal lesions possibly responded to zidovudine but not to acyclovir or ganciclovir. Anterior chamber and vitreous humor inflammatory reactions responded to topical or periocular injections of corticosteroid. CONCLUSIONS: Uveitis with chronic multifocal retinal infiltrates is a distinct clinical entity of unknown cause that occurs in HIV-infected patients. Retinal lesions may respond to antiretroviral therapy. Visual prognosis is good.

Acyclovir↗

Cytomegalovirus retinitis after cardiac transplantation.

PURPOSE: To determine the prevalence of cytomegalovirus retinitis after cardiac transplantation. METHODS: Records of patients who had cardiac transplantation at Jackson Memorial Hospital between November 1986 and November 1994 were reviewed. Patients who had not previously had ophthalmic evaluation after transplantation were invited for retinal examination. RESULTS: Eighty-two patients had cardiac transplantation during the study period. One to 68 months (mean, 24.5 months) after transplantation, ophthalmoscopic examination was performed in 41 patients. Six (14.6%) of 41 patients had healed scars consistent with cytomegalovirus retinitis or active cytomegalovirus retinitis. CONCLUSIONS: Cytomegalovirus retinitis lesions were found in six (14.6%) of 41 patients. If remaining patients were unaffected and no patient developed cytomegalovirus retinitis after ophthalmoscopic examination, the prevalence would be 7.3% (6/82). We recommend ophthalmic screening of all patients 3 to 4 months after cardiac transplantation with repeat examinations yearly or as ocular symptoms occur.

Cytomegalovirus Retinitis↗

Endogenous Aspergillus endophthalmitis. Clinical features and treatment outcomes.

OBJECTIVE: This study evaluated the clinical features and treatment outcomes in patients with endogenous Aspergillus endophthalmitis. DESIGN: The study design was a multicenter retrospective chart review. PARTICIPANTS: Ten patients (12 eyes) with culture-proven endogenous Aspergillus endophthalmitis treated by 1 of the authors were studied. INTERVENTION: Intravitreous amphotericin B injection, pars plana vitrectomy, systemic amphotericin B therapy, and oral anti-fungal therapy were performed. MAIN OUTCOME MEASURES: Elimination of endogenous Aspergillus endophthalmitis and Snellen visual acuity, best corrected, were measured. RESULTS: All patients had a 1- to 3-day history of pain and marked loss of visual acuity in the involved eyes. Varying degrees of vitritis was present in all 12 eyes. In 8 of 12 eyes, a central macular chorioretinal inflammatory lesion was present. Four patients (six eyes) had associated pulmonary diseases and were receiving concurrent steroid therapy. One of these patients with chronic asthma also was abusing intravenous drugs. Overall, six patients (six eyes) had a history of intravenous drug abuse, whereas a seventh patient (one eye) was suspected of abusing intravenous drugs. Blood cultures and echocardiograms were negative for systemic aspergillosis. Management consisted of a pars plana vitrectomy in 10 of 12 eyes. Intravitreous amphotericin B was administered in 11 of 12 eyes. Systemic amphotericin B therapy was used in eight patients. One patient was treated with oral antifungal agents. In three eyes without central macular involvement, final visual acuities were 20/25 to 20/200. In eight eyes with initial central macular involvement, final visual acuities were 20/400 in three eyes and 5/200 or less in four eyes. Two painful eyes with marked inflammation, hypotony, and retinal detachment were enucleated. CONCLUSIONS: Endogenous Aspergillus endophthalmitis usually has an acute onset of intraocular inflammation and often has a characteristic chorioretinal lesion located in the macula. Although treatment with pars plana vitrectomy and intravitreous amphotericin B is capable of eliminating the ocular infection, the visual outcome generally is poor, especially when there is direct macular involvement.

Adult↗

Three-dimensional kinematics of the shoulder complex during wheelchair propulsion: a technical report.

Methods for the three-dimensional (3-D) kinematic analysis of the shoulder complex (humerus relative to trunk) are presented and their use demonstrated in this analysis of shoulder motion during wheelchair propulsion. Ten subjects propelled two different wheelchairs (adjustable and conventional chairs) while the motions of the left arm and trunk were measured using a video tracking system. Eulerian angles described the sequence-dependent rotations of the humerus relative to the trunk. Wheel angular velocity and acceleration, hand position on the handrim, and duration of cycle subphases were also measured. Selected temporal and kinematic parameters were derived from the time-normalized average cycle of each subject on each wheelchair. Within-subject variation of these parameters according to wheelchair type were compared using a two-tailed t-test for paired observations. The adjustable chair made available a larger propulsion are compared with the conventional chair. Only the minimum amount of elevation demonstrated a significant difference between chairs (the conventional chair had a smaller minimum than the adjustable chair) at the corrected significance level of p < 0.001. Other differences, though not statistically significant, were still informative. Less shoulder internal rotation but more overall shoulder motion was observed during recovery phase in the adjustable chair as compared with the conventional chair. The methods presented for measuring the 3-D kinematics of the shoulder complex during wheelchair propulsion proved feasible for future use in studies that will address shoulder kinetics, energy requirements, wheelchair design, and chronic use disorders.

Adult↗

Retroviral particles produced from a stable human-derived packaging cell line transduce target cells with very high efficiencies.

The goal of this work was to determine whether a stable 293 amphotropic packaging line, which we have designated 293-SPA, is useful for the production of high-titer stable virus by comparison to the murine psiCRIP line. Here, we report our unexpected findings that particles derived from the 293-SPA line transduce target cells (both NIH-3T3 cells and primary melanoma cells) with greatly enhanced efficiencies (at least 10-fold) compared to particles derived from the psiCRIP packaging line. We show that the presence of a transferable inhibitor in the psiCRIP line at least partially accounts for this dramatic difference in transduction efficiency. This work has important implications for improving the efficiency of retrovirus-mediated gene transfer in general as well as in the design of new packaging cell lines.

3T3 Cells↗

Iritis and hypotony after treatment with intravenous cidofovir for cytomegalovirus retinitis.

OBJECTIVE: To describe intraocular inflammation due to treatment with intravenous cidofovir dihydrate for cytomegalovirus retinitis. DESIGN: Retrospective cohort. SETTING: Three university outpatient ophthalmology clinics. PATIENTS: All patients treated with intravenous cidofovir therapy before October 31, 1996. INTERVENTION: Treatment with intravenous cidofovir was given according to standardized protocols. Intraocular inflammation was treated according to the best medical judgment. MAIN OUTCOME MEASURES: The presence of new intraocular inflammation, the severity of inflammation, visual acuity, and intraocular pressure. RESULTS: Eleven cases of iritis (26%) occurred among 43 patients. In 6 cases, the iritis was bilateral. Patients who experienced iritis were more likely to have been previously treated for cytomegalovirus retinitis (P = .03), to be diabetic (P = .05), or to be receiving protease inhibitors (P < .001). Four patients and 15 control subjects had also taken rifabutin (P = .70). The onset of iritis occurred at a mean (+/-SD) of 4.9 +/- 1.8 days after a cidofovir dose and after a mean (+/-SD) of 4.2 +/- 1.6 doses of cidofovir. Six eyes of 4 patients had hypotony. Five eyes of 5 patients had a persistent decrease in visual acuity of at least 2 Snellen lines. CONCLUSIONS: Acute intraocular inflammation may occur with or without hypotony after intravenous cidofovir therapy, similar to the reactions seen after intravitreous administration. Although the manifestations may be severe, they are manageable with topical corticosteroid therapy in most cases. Cidofovir therapy can be continued in some patients if medical necessity warrants, but recurrent inflammation or permanent hypotony may occur.

Adult↗

Diagnosis of intraocular lymphoma by flow cytometry.

PURPOSE: To evaluate flow cytometry of vitreous cellular specimens as a means of diagnosing intraocular lymphoma and ocular inflammatory disease. METHODS: We undertook a retrospective, observational study of hematopoietic cell-surface markers in 20 patients with vitreous cellular infiltration in whom lymphoma was considered in the differential diagnosis. Immunophenotyping of vitreous cells obtained by vitrectomy was performed by flow cytometry using antibodies directed against specific cell-surface antigens, including ones associated with B-lymphocyte and T-lymphocyte lymphomas and activated inflammatory cells. Smears were examined cytologically. Cytofluorography was compared with the cytopathologic diagnosis and with final diagnosis. RESULTS: With flow cytometry, a diagnosis of intraocular lymphoma was confirmed in two of four patients with known lymphoma, one of whom had recurrent disease after radiation, and not confirmed in two patients who had had prior treatment with radiation or corticosteroids. In six patients with no prior diagnosis of lymphoma, five were diagnosed with lymphoma on the basis of cytofluorography. Thus, seven (70%) of 10 patients with intraocular lymphoma were diagnosed by cytofluorography compared with three (30%) of 10 with lymphoma diagnosed by cytology. With flow cytometry, 10 patients with uveitis or intraocular infections were distinguishable from patients with lymphoma by lack of a monotypic population and, in some cases, by elevated CD4:CD8 ratios and a high percentage of activated cells. CONCLUSIONS: Cytofluorography of vitreous cells is an effective alternative or adjunct to cytology. Information can be gained from specimens that are uninterpretable by routine cytology. The optimal technique for diagnosis may vary among institutions.

Adult↗

Laser photocoagulation for retinal detachments and retinal tears in cytomegalovirus retinitis.

OBJECTIVE: Retinal detachment complicates the course of cytomegalovirus (CMV) retinitis in nearly 30% of human immunodeficiency virus-infected patients. The study goal was to evaluate laser photocoagulation in the treatment of CMV retinitis-related retinal detachments and retinal tears. DESIGN: Nonrandomized, observational cohort study. PARTICIPANTS: Sixty-three patients with CMV retinitis-related retinal detachments and nine patients with peripheral retinal tears in eyes with CMV retinitis were studied. INTERVENTION: Of the 63 eyes with retinal detachment, 23 patients were treated with demarcating laser photocoagulation, 24 patients underwent vitrectomy with silicone oil, and 16 patients were observed without treatment. All nine patients with peripheral retinal tears received laser photocoagulation. MAIN OUTCOME MEASURES: Time to progression of retinal detachment, final visual acuity, and need for vitrectomy surgery were studied. RESULTS: Median time to progression of the retinal detachment in the laser-treated patients was 175 days versus 39 days in observed patients (P = 0.012). Both initial (P < 0.001) and final (P = 0.005) visual acuities were better in the patients with laser-treated detachment than in the observed or vitrectomy patients. The retinal detachment groups were comparable in follow-up, zone and location of detachment, and size of holes, but the vitrectomy and observed groups had more cases with extensive CMV retinitis. Vitrectomy surgery was required in 9 of 16 (56%) in the observed group and 7 of 23 (30%) in the laser group. Two of nine patients (22%) who failed to respond to laser treatment for retinal breaks required vitrectomy surgery. CONCLUSIONS: Laser photocoagulation of selected retinal detachments and retinal tears delayed or avoided vitrectomy with silicone oil. It may be an important treatment modality for patients with nonmacular detachments and for those who are receiving local anti-CMV therapy with intravitreal injections or pellets, in whom silicone oil may affect the efficacy of the local treatment.

AIDS-Related Opportunistic Infections↗