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Biomedical subjects

J G Gross

Publications and source records attributed to J G Gross.

At least 19 recordsLinked to original sources

Patterns of repair of dystrophic mouse muscle: studies on isolated fibers.

Repair of damaged skeletal muscle fibers by muscle precursor cells (MPC) is central to the regeneration that occurs after injury or disease of muscle and is vital to the success of myoblast transplantation to treat inherited myopathies. However, we lack a detailed knowledge of the mechanisms of this muscle repair. Here, we have used a novel combination of techniques to study this process, marking MPC with nuclear-localizing LacZ and tracing their contribution to regeneration of muscle fibers after grafting into preirradiated muscle of the mdx nu/nu mouse. In this model system, there is muscle degeneration, but little or no regeneration from endogenous MPC. Incorporation of donor MPC into injected muscles was analyzed by preparing single viable muscle fibers at various times after cell implantation. Fibers were either stained immediately for beta-gal, or cultured to allow their associated satellite cells to migrate from the fiber and then stained for beta-gal. Marked myonuclei were located in discrete segments of host muscle fibers and were not incorporated preferentially at the ends of the fibers. All branches on host fibers were also found to be composed of myonuclei carrying the beta-gal marker. There was no significant movement of donor myonuclei within myofibers for up to 7 weeks after MPC implantation. Although donor-derived dystrophin was usually located coincidentally with donor myonuclei, in some fibers, the dystrophin protein had spread further along the mosaic myofibers than had the myonuclei of donor origin. In addition to repairing segments of the host fiber, the implanted MPC also gave rise to satellite cells, which may contribute to future muscle repair.

Animals↗

Muscle precursor cells injected into irradiated mdx mouse muscle persist after serial injury.

Muscle of donor origin was formed after implantation of H-2Kb-tsA58 muscle precursor cells (mpc) into irradiated mdx nu/nu mouse muscles. A series of injections of the myotoxin, notexin, which destroys mature muscle fibers but spares muscle precursor cells and other tissues, was made into the mpc-injected muscles, leaving time for regeneration to occur between each injection. New muscle fibers of donor origin were formed after up to four notexin treatments, providing evidence that some of the implanted mpc reentered an undifferentiated, quiescent, stem cell-like state and were capable of myogenesis after further injuries to the muscle. A similar model could be used to assay whether preparations of human mpc contain long-lasting precursor cells, prior to their implantation into patients. In control mdx muscles, which had been irradiated, injected with tissue culture medium, and given three notexin injections, regeneration also occurred, indicating that radiation-resistant mpc were present, presumably within the treated muscle.

Animals↗

Potentiation of myoblast transplantation by host muscle irradiation is dependent on the rate of radiation delivery.

Transplantation of muscle precursor cells (mpc) has been suggested as a treatment for myopathies, such as Duchenne muscular dystrophy. Irradiation of skeletal muscle with 16-20 Gy prevents muscle regeneration and also augments muscle formation from implanted muscle precursor cells (mpc). However, when mdx nu/nu mouse muscles are preirradiated at 0.73 Gy/min rather than at 1.29 Gy/min prior to their injection with normal mpc, significantly more muscle fibres of donor origin are formed. This suggests that the rate at which irradiation is delivered has a physiological effect on the muscle. Although it would not be feasible to irradiate a patient's muscles prior to mpc implantation, once the factor(s) which are altered in irradiated muscle have been identified, it might be possible to use these to increase the success of myoblast transplantation.

Animals↗

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↗

Subfoveal neovascular membrane removal in patients with traumatic choroidal rupture.

PURPOSE: To describe the clinical outcomes of patients undergoing pars plana vitrectomy to remove subretinal neovascular membranes caused by traumatic choroidal ruptures. METHODS: Three patients with traumatic choroidal rupture in whom subfoveal choroidal neovascularization developed underwent pars plana vitrectomy with surgical excision of the neovascular membrane. Surgical specimens were examined histopathologically in two patients. RESULTS: The choroidal neovascularization was removed completely in each patient. Visual results were excellent with visual acuities improving to 20/30 or better in each patient. Recurrence of choroidal neovascularization has not been observed. Fibrovascular membranes with reactive retinal pigment epithelium were observed in two specimens examined histopathologically. CONCLUSION: Surgical removal of subretinal neovascular membranes emanating from traumatic choroidal ruptures produced an excellent visual outcome in three patients studied. The neovascular membranes, which were removed with minor disturbance to the underlying pigment epithelium, have similar characteristics to those obtained from patients with ocular histoplasmosis syndrome.

Adult↗

Evaluation of outpatient experience with vitreoretinal surgery.

The experience of 55 consecutive individuals undergoing outpatient vitreoretinal surgery was evaluated. Objective variables, including preoperative and intraoperative information, subjective postoperative pain, and discomfort were measured with a previously validated 100 mm visual analogue scale. Patients also ranked the overall experience. Average pain and discomfort scores in the recovery room were 21.8 and 22.6 and overnight were 26.7 and 30.4 (scale 0 to 100), respectively. Eighty eight per cent of subjects were satisfied with the experience. Elevated pain and discomfort scores were statistically correlated with scleral buckling, prolonged surgical or recovery room time, requirement for parenteral pain medications, and high intraocular pressure on the first postoperative visit. None of the patients needed further hospital treatment. This study suggests that vitreoretinal surgery in an appropriately selected population does not require routine inpatient care.

Adult↗

Role of HIV and CMV in the pathogenesis of retinitis and retinal vasculopathy in AIDS patients.

Cotton-wool spots and cytomegalovirus (CMV) retinitis are seen frequently in AIDS patients. Human immunodeficiency virus (HIV) infection of the retina has been proposed as a mechanism for the high incidence of retinal pathology. An autopsy study of the eyes from 25 consecutive cases of AIDS was performed using gross examination, light microscopy, trypsin digestion of retinal vasculatures, and immunohistochemistry to evaluate the possible role of HIV, as well as CMV, in the pathogenesis of retinitis and retinal vasculopathy. Brain tissue was studied in the first 20 of these cases to evaluate any correlation between retinal and central nervous system pathology. CMV retinitis was observed in 15 cases (60%). Cotton-wool spots were seen in nine cases (36%). CMV encephalitis was detected in four cases, whereas HIV encephalitis was noted in five cases. We were unable to demonstrate a correlation between CMV retinitis and CMV encephalitis. However, the number of cases studied was small, and the frequency of CMV encephalitis was low. On the other hand, bilateral CMV retinitis demonstrated a correlation to HIV encephalitis (P less than 0.005, Fisher's exact test). HIV infection of the retina was not detected by typical morphologic changes or immunohistochemistry. Immunohistochemistry localized CMV infection solely to areas of active retinitis. These findings suggest that bilateral CMV may serve as a marker of HIV encephalitis, possibly indicating a severely immunodepressed state.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Endogenous Aspergillus-induced endophthalmitis. Successful treatment without systemic antifungal medication.

A 32-year-old man had unilateral visual loss, a gravitational layering of preretinal inflammatory cells in the macula (pseudohypopyon), subretinal infiltrates, and hemorrhagic vasculitis. The patient initially denied intravenous drug abuse. Apsergillus terreus was cultured from undiluted vitreous obtained from a diagnostic and therapeutic vitrectomy specimen. Intravitreal and subconjunctival injections of amphotericin B alone were successful treatment. To the author's knowledge, antemortem diagnosis and treatment of A. terreus-induced endophthalmitis has not been reported previously. This article describes the second case of aspergillar endophthalmitis successfully treated without adjunctive systemic antifungal therapy.

Adult↗

Experimental endoretinal biopsy.

We performed transvitreal endoretinal biopsy in rabbit eyes to develop a reliable and safe technique to obtain retinal specimens from attached retina. Pars plana vitrectomy without lensectomy was followed by injection of Ringer's solution into the subretinal space to produce a focal retinal detachment. The apex of the focal detachment was excised by intraocular scissors and removed from the eye by pneumohydraulic expulsion. A fluid-air exchange reattached the retina. The biopsy sites were evaluated clinically and by light and electron microscopy at regular intervals up to 20 weeks postoperatively. The initial five procedures were performed without heparin in the infusion fluid, and they were complicated by severe fibrin reaction and early retinal detachment. Of the remaining 17 eyes, 15 were without intraoperative complication and maintained attached retinas. The biopsy site developed an early ring of hyperpigmentation along the border, and the biopsy bed became increasingly hyperpigmented because of cytoplasmic hyperplasia and hypertrophy of the pigment epithelium. Epiretinal membranes and subretinal neovascularization were observed histologically. Retinal biopsy specimens were reproducible and suitable for diagnostic studies.

Animals↗

Magnetic resonance imaging in the evaluation of vitreoretinal disease in eyes with intraocular silicone oil.

Media opacification in eyes filled with silicone oil makes the evaluation of recurrent retinal detachment difficult. Ultrasonography through silicone oil is subject to significant imaging artifacts. We performed magnetic resonance imaging on six patients with unilateral intravitreal silicone oil to determine if the technique would detect detached retina and subretinal oil. All patients had undergone pars plana vitrectomy with silicone oil injection for proliferative vitreoretinopathy; five patients had encircling solid silicone scleral buckles. In five patients the media were clear, and ophthalmoscopic findings were correlated with magnetic resonance findings. Four patients had recurrence of inferior retinal detachment; magnetic resonance imaging demonstrated subretinal oil in three of these patients. One patient had a concentric, shallow, anterior retinal detachment; magnetic resonance scanning demonstrated a globular hyperintensity suggestive of subretinal oil. In the sixth patient, who had an opaque cornea, magnetic resonance imaging suggested that the retina was attached preoperatively; this was confirmed at subsequent surgery. A chemical shift artifact was helpful in defining the contour of retinal detachments and the presence of subretinal oil by outlining the silicone oil within the eye.

Eye↗

Longitudinal study of cytomegalovirus retinitis in acquired immune deficiency syndrome.

The authors prospectively evaluated 67 consecutive patients with the acquired immune deficiency syndrome (AIDS) and cytomegalovirus (CMV) retinitis during a 33-month period to assess the clinical patterns of retinal infection, efficacy of treatment, long-term survival, and relationship of retinitis to immune function. Immediately sight-threatening retinitis presented in six patients (9%) with peripapillary disease; primary foveal infection was not observed. Eighty-seven percent of patients were treated with ganciclovir. Thirty-nine patients (58%) presented with unilateral disease and contralateral infection developed in 15% of those while on ganciclovir. Smoldering (incompletely responsive) retinitis was seen in 33% of the 21 patients whose retinitis progressed while receiving ganciclovir. Progression of treated retinitis was associated with a lower lymphocyte count (P = 0.04). Median survival after diagnosis of CMV retinitis was 8 months. This represents the largest reported prospective study of CMV retinitis and indicates that (1) CMV infrequently poses an immediate threat to vision on presentation, (2) response to therapy may be related to immune function, and (3) smoldering retinitis should be recognized as an important clinical entity associated with treatment failure.

Acquired Immunodeficiency Syndrome↗

Pathologic observations made by retinal biopsy.

The authors report four cases in which retinal biopsy findings yielded unexpected or previously unreported diagnoses in patients with inflammatory retinitis. The tissue diagnoses included Wegener's retinal vasculitis in an immunosuppressed patient with a clinical diagnosis of cytomegalovirus retinitis, a novel viral form in the retina of a patient with cytomegalovirus retinitis, a case of acute retinal necrosis due to cytomegalovirus infection in an immunologically normal adult, and a case of ganciclovir-resistant herpes family viral retinitis. These cases illustrate the use of retinal biopsy in obtaining tissue for diagnosis and guiding treatment in selected cases of retinitis.

Acquired Immunodeficiency Syndrome↗

The 30-degree curved endolaser probe.

Straight, 30-, and 45-degree endolaser probes were compared to determine the optimal curve for peripheral endolaser photocoagulation during pars plana vitrectomy. The 30-degree probes allowed panretinal laser coverage in phakic eyes, thereby negating the need for peripheral cryopexy which may cause increased inflammation and contribute to the development of proliferative vitreoretinopathy. The 30-degree probe was less likely to strike the lens inadvertently, produced a more consistent burn, was more versatile in posterior treatments, and had a longer fiberoptic core life than the 45-degree probe. It was impossible to treat the peripheral retina using the straight probe without hitting the lens during phakic pars plana vitrectomy.

Equipment Design↗

Combined penetrating keratoplasty and vitreoretinal surgery with the Eckardt temporary keratoprosthesis.

The Eckardt style temporary keratoprosthesis was used in six cases of five eyes undergoing simultaneous penetrating keratoplasty and pars plana vitrectomy. This device provided excellent visualization of posterior and peripheral intraocular structures and maintained a closed system during surgery. Corneal grafts remained clear in 80% of the cases, and macular attachment was achieved with either silicone oil or perfluoropropane gas in 50% of cases followed for at least 6 months. Visual function remained the same or improved in three eyes. Suggested refinements to the placement of this device include enlarging the trephination to 6.75 mm and the use of 8-0 nylon sutures to prevent cheesewiring of the soft silicone rim. A plano contact lens required during surgery to visualize the retina did not minify the image. Since the optical cylinder of the Eckardt temporary keratoprosthesis is shorter than that of a Landers-Foulks keratoprosthesis of similar diameter, it provides greater peripheral visualization. It is, however, less durable.

Adult↗

Posttraumatic yellow maculopathy.

Blunt trauma to the eye may cause several types of macular abnormalities, including commotio retinae, macular hole, intraretinal and subretinal hemorrhage, and choroidal rupture. In most cases the diagnosis is readily apparent; however, the complex appearance of simultaneous hemorrhage, pigmentary change, and ruptured tissue planes may be confusing. The authors present two cases of blunt trauma in young males that resulted in a subretinal hemorrhage that became yellow and was initially misinterpreted as a vitelliform lesion. A history of trauma should be sought in any patient with the clinical appearance of a yellow subretinal lesion.

Adult↗

Severe visual loss related to isolated peripapillary retinal and optic nerve head cytomegalovirus infection.

We examined ten patients from a consecutive series of 73 patients with either isolated cytomegalovirus papillitis or limited cytomegalovirus retinitis contiguous with the optic disk. Patients with peripheral retinitis and other areas of retinitis were excluded. All patients were treated with ganciclovir. Two distinct types of cytomegalovirus infection of the peripapillary area were identified. Type I was characterized by spread of limited retinitis to the optic disk margin, good central visual acuity, and permanent arcuate and altitudinal visual field defects that enlarged and became more complete as the retinitis progressed toward the disk. Type II appeared to be a true cytomegalovirus infection of the optic nerve characterized by primary, isolated papillitis with peripapillary retinitis, an early afferent pupillary defect, and good initial visual acuity, which rapidly deteriorated despite prompt antiviral therapy. Peripapillary cytomegalovirus retinitis appears to be an important and underreported cause of visual morbidity in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

The agar-albumin sandwich technique for processing retinal biopsy specimens.

Retinal biopsy may be useful procedure in the diagnosis of certain cases of infectious retinitis complicated by retinal detachment. The small, delicate pieces of retina obtained by retinal biopsy are difficult to handle and prepare for histologic processing. The tissue is friable, may curl upon itself, and is often lost during normal processing. Routine methods for handling small biopsy specimens of other tissues are inadequate for preparing retinal specimens. We developed an agar-albumin tissue mount for the sterile recovery and transport of small pieces of retina from the operative field to the laboratory. The agar-albumin sandwich mount facilitates tissue processing without interfering with histologic sectioning or interpretation. The ability to recover small, friable pieces of retina in a manner that allows good histologic examination is essential if retinal biopsy specimens are to be used in the diagnosis and management of patients with infectious retinitis where the causative agent is unclear.

Agar↗