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Biomedical subjects

D S Rootman

Publications and source records attributed to D S Rootman.

70 records · Page 4Linked to original sources
PubMed1989

Recurrent HSV-1 corneal lesions in rabbits induced by cyclophosphamide and dexamethasone.

Herpes simplex virus type 1 (HSV-1) ocular shedding and recurrent corneal epithelial lesions were assessed following an intravenous injection of cyclophosphamide (75 mg/kg) and 24 hr later an intravenous injection of dexamethasone (4 mg/kg) in 24 eyes of 15 rabbits latently infected with HSV-1 strain McKrae. Sampling for HSV-1 ocular shedding and epithelial lesion began on the day after cyclophosphamide injection and continued for 8 consecutive days. Ocular tear film was collected on a Dacron swab with care taken to avoid swabbing the corneal epithelium. Slit-lamp biomicroscopic examination was used to observe and characterize induced HSV-1 corneal epithelial lesions as deep punctate keratitis, dendritic keratitis or geographic epithelial defects. The ratio of positive days of epithelial lesions per total days was 82/187 (44%). There were 32 deep punctate lesions, 17 dendritic lesions, and 33 geographic epithelial defects. The ratio of positive swabs per total swabs was 78/187 (42%). Of the 82 positive lesion days, 54 (66%) were associated with a positive swab. Of the 78 positive swabs, 54 (69%) were associated with an epithelial lesion. Of the 54 days of both positive lesion and swab, 16 (30%) were associated with a dendritic lesion. By chi-square analysis, there was a significant association between HSV-1 swabs and HSV-1 lesions (P less than 0.001). These results confirm that intravenous injections of cyclophosphamide and dexamethasone induce both HSV-1 ocular shedding and recurrent herpes simplex corneal lesions in rabbits latently infected with HSV-1 strain McKrae.

Animals↗
PubMed1988

Iontophoresis of tobramycin for the treatment of experimental Pseudomonas keratitis in the rabbit.

Iontophoresis of tobramycin sulfate was employed to treat bacterial keratitis induced in rabbits by an intrastromal injection of Pseudomonas aeruginosa. Quantitation of bacterial killing was achieved by culturing corneal homogenates and counting viable bacteria per cornea after treatment. When the rabbits received two iontophoretic treatments, iontophoresis significantly reduced the number of bacterial colony-forming units, compared with the use of an eyecup without current or two subconjunctival injections of 20 mg of tobramycin sulfate, and with untreated controls. The results of iontophoresis were not significantly different from those involving treatment with topical fortified drops (40 mg/mL). A single iontophoresis treatment was compared with the use of an eyecup without current or less fortified topical drops (13.6 mg/mL), as well as with untreated controls. Iontophoresis was significantly better than either the eyecup or the topical fortified tobramycin drops in reducing viable bacteria in the corneas. Iontophoresis may be a useful adjunct in the treatment of severe corneal bacterial infections.

Animals↗
PubMed1988

Treatment of experimental Pseudomonas keratitis using collagen shields containing tobramycin.

To study the effectiveness of collagen shields containing tobramycin sulfate in the treatment of Pseudomonas keratitis, rabbits were infected via an intrastromal injection of Pseudomonas aeruginosa and treated 22 hours later with either collagen corneal shields rehydrated in 4% tobramycin and applied to the cornea or 4% tobramycin drops. Bacterial killing was quantitated by culturing corneal homogenates and calculating the number of viable bacteria (colony-forming units) per cornea. Corneas receiving shields rehydrated in 4% tobramycin and applied for four hours demonstrated significantly reduced numbers of bacteria compared with untreated control corneas. The collagen shields were as effective in reducing the number of viable bacteria per cornea as 4% tobramycin drops applied every 30 minutes over a four-hour period. Over a nine-hour treatment period, the addition of four drops of 4% tobramycin to shields in situ was as effective as exchange with a new shield rehydrated in 4% tobramycin. These results suggest that collagen shields rehydrated in a water-soluble antibiotic such as tobramycin may be an effective and convenient mode of therapy for Pseudomonas keratitis.

Administration, Topical↗
PubMed1988

Accuracy and precision of the Tono-Pen in measuring intraocular pressure after keratoplasty and epikeratophakia and in scarred corneas.

Intraocular pressure measurements with the Goldmann and Schiotz tonometers are unreliable when the cornea is irregular due to disease or surgery. The Tono-Pen (Oculab, Glendale, Calif) is an electronic applanation tonometer based on the same principle as the MacKay-Marg tonometer. We measured intraocular pressure in 37 eyes with irregular corneas, in 50 eyes that had recently undergone penetrating keratoplasty, in 16 eyes that had undergone epikeratophakia, and in 12 eyes with normal corneas with both the MacKay-Marg and Tono-Pen tonometers. The same two instruments were used, and the sequence of measurement was randomized. Analysis of variance demonstrated no significant difference between measurements obtained with the two tonometers in any of the groups. The data suggest that the Tono-Pen is as accurate as the MacKay-Marg tonometer in those situations where the Goldmann tonometer is inaccurate.

Cicatrix↗
PubMed1988

Collagen shield drug delivery: therapeutic concentrations of tobramycin in the rabbit cornea and aqueous humor.

Collagen shields made of porcine collagen were placed in a solution containing tobramycin sulfate (40 or 200 mg/ml) for five minutes, then applied to rabbit eyes. One, four, or eight hours after application, the corneas, aqueous humor samples, and shields were assayed for antibiotic. At all intervals, the concentration of antibiotic in the corneas and aqueous humor samples exceeded the mean inhibitory concentration for tobramycin, as determined for most strains of Pseudomonas. Shields immersed in 200 mg/ml tobramycin produced significantly higher concentrations of antibiotic in the cornea at one hour than subconjunctival injections of tobramycin (20 mg) (P = .0001). Shields immersed in 40 mg/ml tobramycin produced higher, although not significantly higher, concentrations of antibiotic in the cornea at one hour than subconjunctival injections of tobramycin (20 mg) (P = .318). Shields immersed in commercially available tobramycin drops or injectable tobramycin solution (40 mg/ml) caused no epithelial damage visible by slitlamp examination. Collagen shields containing antibiotics can serve as a vehicle for drug delivery and may prove superior to current methods for preoperative and postoperative antibiotic prophylaxis and the initial treatment of bacterial keratitis.

Animals↗
PubMed1988

Iontophoretic application of tobramycin to uninfected and Pseudomonas aeruginosa-infected rabbit corneas.

Pseudomonas aeruginosa keratitis was induced in rabbits to study the effects of corneal infection on the delivery of tobramycin by iontophoresis. Some rabbits were treated by use of an eye cup with no current as a control for iontophoresis, and others were treated with fortified drops (1.36%) delivered topically for comparison with results of earlier studies. One hour after treatment with tobramycin, the concentration of drug in the infected corneas was compared with that achieved in mock-infected and uninfected eyes. Iontophoresis of 25 mg of tobramycin per ml at 0.8 mA for 10 min delivered significantly more drug (P = 0.0001) to corneal tissue than did drops or use of an eye cup without current in P. aeruginosa-infected eyes mock-infected eyes, or uninfected eyes. Tobramycin concentrations in the infected corneas (605.9 micrograms/g) were not significantly different (P = 0.815) from the concentrations in mock-infected eyes (641.4 micrograms/g), but were lower (P = 0.007) than those obtained by iontophoresis in uninfected corneas (853.6 micrograms/g). Use of an eye cup without current delivered tobramycin equally to infected, mock-infected, and normal eyes, i.e., 176.5, 171.0, and 163.1 micrograms/g, respectively (P greater than 0.709). Tobramycin delivered by use of fortified drops delivered topically was detectable in mock-infected corneas (20 micrograms/g) and P. aeruginosa-infected corneas (6.0 micrograms/g). These results suggest that iontophoresis has value as an ocular drug delivery system and that an eye cup could also be useful in a therapeutic regimen for ocular infections.

Animals↗
PubMed1988

A morphometric study of endothelial cells of human corneas stored in MK media and warmed at 37 degrees C.

No study has yet been done to investigate the changes in endothelial cell size, perimeter, and density that may result from the warming of corneas in MK (McCarey-Kaufman) medium for specular microscopy. In the present investigation eye bank eyes were stored in MK medium at 4 degrees C and rewarmed daily for six days at 37 degrees C before specular photography of the endothelium was performed. These photographs were compared with wet mount preparations stained with trypan blue and alizarin red made from the same corneas and those stored without rewarming for six days. In addition all corneas were qualitatively analysed with the scanning electron microscope (SEM). The data from serial specular photography were insufficient to allow significant conclusions to be drawn about day to day changes in cell morphology. However, analysis of wet mount preparations revealed that cell density and perimeter varied significantly between those corneas rewarmed daily and those held in cold storage for six days. SEM studies showed an intact cell monolayer with cell loss along the folds of corneal endothelium. We therefore concluded that repeated rewarming at 37 degrees C of corneas stored in MK medium at 4 degrees has a deleterious effect on cell morphology and that folds induced by swelling of corneal tissue result in endothelial cell damage with some loss.

Cell Count↗
PubMed1988

Neural activity from the acutely infected HSV-1 rabbit cornea.

Herpes simplex virus type 1 (HSV-1) infections of the human cornea are often accompanied by abnormal sensations. In this study, a combination of physiological and structural methods was used to examine the innervation of the corneas of rabbits with HSV-1 lesions of varying severity. Degeneration of the plexiform neural layer adjacent to dendritic lesions and surrounding normal neurology provided a basis for the limited physiological changes. Extensive degeneration of the corneal innervation at all levels occurred within the anesthetic area of the geographic lesion. Abnormal physiological activity characterized by hyperexcitability and loss of stimulus specificity were included in the physiological profile. Collateral sprouts seen in the geographic lesion were suggested as an anatomical substrate for the abnormal neural activity. Thus, the neural changes could be associated with the severity of HSV-1 lesions.

Action Potentials↗
PubMed1988

Rotational tarsal conjunctival flap in the treatment of scleral necrosis.

Scleral necrosis and perforation are difficult to manage. We describe a technique whereby a vascular strip of tarsal tissue with overlying conjunctiva can be rotated and sutured to a necrotic area of sclera that has been debrided, leading to rapid healing. The technique is performed easily, and can aid in the healing of areas of necrotic sclera that threaten perforation by providing a vascular pedicle.

Aged↗
PubMed1988

Corneal nerves are necessary for adrenergic reactivation of ocular herpes.

Herpes simplex virus type 1 (HSV-1) can infect the cornea and achieve ganglionic latency. HSV-1 can later be activated by a variety of effectors although the exact mechanism of reactivation is unknown. Rabbits harboring latent HSV-1 strain McKrae can be induced to shed virus by ocular iontophoresis of epinephrine to the cornea. No studies have been done to investigate if corneal nerves are necessary for epinephrine induction of HSV-1 ocular shedding. We did penetrating keratoplasty (PKP) in one eye each of 23 rabbits; the other eye served as an unoperated control. The surgery effectively denervates the area of the transplant for up to 90 days. Eighteen rabbits carrying latent HSV-1 strain McKrae received corneas from uninfected rabbits. Five uninfected rabbits with no latent virus received corneas from rabbits harboring latent HSV-1. On days 10-14 after penetrating keratoplasty, 24 eyes in the HSV-1 latent group and all ten uninfected eyes received iontophoresis of 0.01% epinephrine (0.8 mAmps for 8 min or 0.6 mAmps for 6 min) once daily for 3 days by means of an eye cup whose diameter was less than the diameter of the transplant. Six rabbits in the HSV-1 latent group received intravenous injections of cyclophosphamide (75 mg/kg) and dexamethasone (4 mg/kg). Following iontophoretic or immunosuppressive induction, the eyes were swabbed daily for 9 days. Of the 12 rabbits with latent virus which were treated by iontophoresis, one of the transplanted eyes and eight of the nontransplanted eyes were induced to shed virus. The mean duration of shedding in the nontransplanted eyes was 3.25 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Recurrent HSV-1 corneal epithelial lesions induced by timolol iontophoresis in latently infected rabbits.

Herpes simplex virus type 1 (HSV-1) ocular shedding and recurrent corneal epithelial lesions were assessed following ocular iontophoresis of 0.01% timolol at 0.8 mAmp for 8 min for 3 consecutive days in 17 rabbits latently infected with HSV-1 strain McKrae. The collection of ocular tear film for the detection of HSV-1 ocular shedding and the slit lamp biomicroscopic evaluation for HSV-1 epithelial lesions began on day 4 after the first iontophoresis and continued for 7 consecutive days. The tear film was collected on a Dacron swab with care being taken to avoid swabbing the corneal epithelium. The observed HSV-1 lesions were characterized as deep punctate lesions, dendritic lesions and geographic epithelial defects. The ratio of total days of eyes exhibiting HSV-1 epithelial lesions to the total number of observation days was 113/235 (48%). There were 46 punctate lesions, 27 dendritic lesions and 40 geographic epithelial defects. The ratio of positive swabs to total swabs was 77/235 (33%). Of the 113 positive lesion days, 65 (58%) were associated with a positive swab. Of the 77 positive swabs, 65 (84%) were associated with an epithelial lesion. Of the 122 negative lesion days, 110 (90%) were associated with a negative swab. Of the 158 negative swabs, 110 (70%) were associated with no epithelial lesions. By chi-square analysis, there was a significant association between HSV-1 swabs and HSV-1 lesions (P less than 0.001). These results demonstrate that ocular iontophoresis of timolol induces both HSV-1 ocular shedding and recurrent HSV-1 corneal epithelial lesions in rabbits latently infected with HSV-1 strain McKraw.

Animals↗
PubMed1988

Pharmacokinetics and safety of transcorneal iontophoresis of tobramycin in the rabbit.

Transcorneal iontophoresis of tobramycin in normal eyes of New Zealand white rabbits was compared to an eye cup control and application of fortified topical drops. Iontophoresis was performed with 25 mg/ml of tobramycin at 0.8 mAmps for 10 or 5 min. The eye cup with 25 mg/ml of tobramycin was placed on the eye for 10 min without current. Topical fortified drops (13.6 mg/ml) were applied every half hour for 4 hr. Epithelium, stroma, and aqueous humor were assayed separately at 1, 4, 8 and 16 hr after treatment. The eyes were examined using the slit-lamp biomicroscope before and immediately after the treatment, and prior to sacrifice. Two eyes were examined by light and scanning electron microscopy 5 and 10 min after iontophoresis. Iontophoresis yielded significantly higher tobramycin concentrations than the eye cup or fortified topical drops at 1 hr and 4 hr after treatment (P = 0.001). In all treated eyes, iontophoresis resulted in epithelial edema and mucous discharge, which resolved by 24 hr after the treatment. Histologically there was evidence of epithelial disruption in the superficial layer after 5 min of iontophoresis and in all layers of the epithelium after 10 min of iontophoresis. Iontophoresis is a relatively safe, effective method to deliver medications to ocular tissues and may be useful alone or as an adjunct to current modes of antimicrobial chemotherapy.

Animals↗
PubMed1987

Recurrent herpes simplex virus type 1 corneal epithelial lesions after radial keratotomy in the rabbit.

The effects of radial keratotomy (RK) on herpes simplex virus type 1 ocular shedding and recurrent corneal epithelial lesions were assessed for 14 days after RK in rabbits latently infected with strain McKrae. Ten latently infected rabbits had RK performed on the right eye. The left eye was used as the control. Viral shedding was monitored by ocular tear-film swabs. The recurrent lesions were monitored by slit-lamp examination. In the RK-treated eyes, 15 (11%) of 140 swabs were positive, compared with six (4%) of 140 swabs in control eyes. Slit-lamp examination disclosed recurrent lesions on 18 (33%) of 55 days on which it was performed in the RK group vs three (5%) of 55 days for the control group. The results suggest that patients who have a history of ocular herpes simplex virus type 1 disease are at risk for recurrences after RK.

Animals↗
PubMed1987

Adrenergically induced recurrent HSV-1 corneal epithelial lesions.

Herpes simplex virus type 1 (HSV-1) ocular shedding and recurrent HSV-1 corneal epithelial lesions were assessed after ocular iontophoresis of 0.1% 6-hydroxydopamine followed by topical ocular instillation of 0.1% Propine in ten rabbits latently infected with HSV-1 strain McKrae. Iontophoresis was performed once at 0.5 mAmp for five minutes and 0.1% Propine drops were instilled four times a day beginning three days after iontophoresis and continuing for five consecutive days. Over an eight day period beginning three days after iontophoresis, ocular tear film samples were collected on Dacron swabs with care taken to avoid contact with the corneal epithelium. The corneas were examined daily for the presence of epithelial lesions using a slit-lamp biomicroscope. Three types of lesions were observed: deep punctate lesions, dendritic lesions, and geographic epithelial defects. The ratio of positive HSV-1 eye swabs to total eye swabs was 36/157 (23%). The ratio of total positive days of corneal lesions to total days was 40/160 (25%). There were 23 deep punctate lesions, 13 dendritic lesions, and four geographic epithelial defects. There were 24/36 (67%) positive HSV-1 eye swabs associated with concurrent HSV-1 corneal epithelial lesions. There were 105/121 (87%) negative eye swabs with concurrent negative slit-lamp examinations. Chi square analysis showed significant (p less than 0.001) association of HSV-1 positive eye swabs and HSV-1 corneal lesions. These results suggest that adrenergic ocular treatment may induce both HSV-1 ocular shedding (reactivation) and HSV-1 corneal epithelial lesions (recurrence) in rabbits latently infected with HSV-1 strain McKrae.

Animals↗
PubMed1981

Postnatal histogenetic death of rat forelimb motoneurons.

Previous workers have reported a five fold decrease in motoneuron numbers occurring from birth to adulthood in the rat. It has also been reported that forelimb muscles receive connections from motoneurons in both ventral horns prior to day 14 of life in the rat and that the contralateral cells subsequently degenerate completely by day 21. In the present study, postnatal changes in motoneuron number and distribution within the ventral horn were studied in the rat using the technique of retrograde horseradish peroxidase (HRP) transport following intramuscular infusion of HRP into biceps brachii (BB). Peripheral nerves other than those to BB were sectioned and ligated to control for HRP diffusion. The spatial organization of BB motoneurons was compared in animals 9-14 days old and adult animals using computer 3-D reconstruction. This allowed observations of the BB motoneurons from a variety of perspectives in relationship to a number of spinal cord landmarks and avoided the necessity for transverse and horizontal sectioning of the cords in alternate animals. A decrease of 50-75% in the number of HRP filled motoneurons number was found from birth to adulthood (adults 98-150, neonates 172-243). The spatial arrangement of the BB motoneurons with regard to the root entry zones and other landmarks such as the dorsolateral convexity of the ventral horn, remains constant from birth to adulthood. No evidence was found to support the existence of inappropriate connections from motoneurons in either the ipsi or contralateral ventral horns of neonate rats. It is suggested that the comparatively small decreases in motoneurons postnatally could be a continuation of the histogenetic processes of cell death begun in utero and is related to the postnatal development of the central and peripheral connections of motoneurons.

Aging↗