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Biomedical subjects

D R Caldwell

Publications and source records attributed to D R Caldwell.

At least 19 recordsLinked to original sources
PubMed1999

Ketorolac tromethamine 0.5% ophthalmic solution in the treatment of moderate to severe ocular inflammation after cataract surgery: a randomized, vehicle-controlled clinical trial.

PURPOSE: To investigate the efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution (Acular; Allergan, Inc, Irvine, California) in the treatment of moderate to severe anterior segment inflammation developing after unilateral cataract surgery with intraocular lens implantation. METHODS: Only patients who exhibited moderate or greater levels of cells and flare 1 day after surgery were included in this multicenter, double-masked, randomly assigned, parallel-group study. Topical ketorolac or vehicle solution (Allergan, Inc) was administered to the treated eye four times daily, starting the day after surgery and continuing for 14 days. RESULTS: Ketorolac was significantly more effective than the vehicle solution in reducing anterior chamber cells (P < or = .030) and flare (P < or = .025), conjunctival erythema (P < or = .046), ciliary flush (P < or = .006), tearing (P < or = .012), photophobia (P < or = .014), and pain (P < or = .049). Half as many patients from the ketorolac group (14/51) were discontinued from the study for lack of efficacy, compared with the vehicle group (28/51; P = .005). There was no significant difference between ketorolac and the vehicle solution in changes in visual acuity, intraocular pressure, biomicroscopic or ophthalmoscopic variables, or adverse events. CONCLUSIONS: Ketorolac tromethamine 0.5% ophthalmic solution is safe and provides substantial anti-inflammatory activity in the treatment of moderate to severe anterior segment inflammation developing after cataract surgery and intraocular lens implantation.

Adult↗
PubMed1999

Pyruvate metabolism by Anaplasma marginale in cell-free culture.

Partially purified Anaplasma marginale initial bodies were cultivated in a cell-free system in the presence of [3-14C]pyruvate for 24 or 48 h. Experiments showed that a significant portion of the pyruvate supplied to the cultures was incorporated into initial body components. Label incorporation was reduced by 72% in the presence of oxytetracycline. Fractionation and chromatography of the organisms revealed radioactive incorporation as alanine. This is the first report of de novo amino acid synthesis by A. marginale demonstrating that the rickettsia is capable of using pyruvate, an erythrocyte glycolytic product, in its metabolism.

Alanine↗
PubMed1997

Matrix stimulates the proliferation of human corneal endothelial cells in culture.

PURPOSE: Extracellular matrices were tested for their ability to support the adhesion and proliferation of human corneal endothelial cells. METHODS: Human corneal endothelial cells were plated onto tissue culture dishes coated with purified fibronectin or a matrix elaborated by cultured bovine corneal endothelial cells. The presence of human cells in the cultures was confirmed by karyotyping. Cell size at increasing passage number was analyzed, and cellular response to growth factors was assessed using a 96-well microtiter plate assay. RESULTS: When tissue culture dishes were coated with fibronectin, the cells attached to the dish but grew slowly. Human corneal endothelial cells plated onto the matrices elaborated by bovine corneal endothelial cells attached to the culture dish and grew to fill the flask. At confluence, the cells had a hexagonal morphology similar to that seen in vivo. Karyotype analysis showed that the cells were of human and not bovine origin. The time required for senescence in culture was dependent on the age of the donor cornea. The bovine matrices enhanced the proliferative response of human corneal endothelial cell cultures to endothelial cell growth supplement and keratinocyte growth factor. Epidermal growth factor and hepatocyte growth factor stimulated human cell proliferation in a dose-dependent fashion, regardless of the substratum on which the cells were plated. CONCLUSIONS: The use of substratum elaborated by bovine corneal endothelial cells has proved useful in the preparation of human endothelial cell cultures from juvenile and adult donors. The method has been used to establish cultures from more than 50 donors from age 1 day to 76 years.

Adolescent↗
PubMed1997

The soft keratoprosthesis.

PURPOSE: The purpose of this work was to develop a keratoprosthesis which utilizes a biocolonizable skirt attached to a soft, elastomeric optic for world-wide application. METHODS: Over a period of 20 years, using in vivo animal implantation studies, a series of experiments was conducted testing materials for biocompatibility and durability which resulted in the development of an improved design. A new surgical technique was developed, using porous, biocolonizable haptics embedded within the sclera and combined with the established techniques of resection of Descemet's membrane and a conjunctival flap. RESULTS: Animal implantation studies indicated that 6 haptics, equidistantly placed, was the optimal shape. Two clinical trials resulted in the selection of an aliphatic polyether-based urethane for the optic and 60 mu pore polytetrafluoroethylene for the porous ingrowth material. Heated, pressurized injection moulding proved to be the optimal bonding method between the skirt and the optic. Sclerally embedded haptics achieved excellent integration with the tissue. CONCLUSIONS: This keratoprosthesis is a significant improvement over previous models with a rigid optic in that: 1. The porous ingrowth haptic is sclerally anchored, preventing extrusion. 2. It has a soft elastomeric optic which more successfully defuses the shearing forces of the keratoprosthesis/tissue interface secondary to blinking. 3. The optic is less massive and of greater circumference at the optic/tissue interface, thereby imparting less energy per area with a given movement. 4. The optic does not project posteriorly thereby decreasing anterior chamber irritation and reducing the possibility of glaucoma, uveitis, endophthalmitis, and retinal detachment. 5. This keratoprosthesis allows a normal field of view for the patient and an effective funduscopic view for the surgeon. 6. The large optical diameter eliminates problems with decentralization of the image. 7. It has a significantly better cosmetic appearance.

Aged↗
PubMed1996

Comparison of ciprofloxacin ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating bacterial corneal ulcers. Ciprofloxacin Bacterial Keratitis Study Group.

PURPOSE: The purpose of the study is to compare the clinical efficacy and safety of ciprofloxacin ophthalmic solution 0.3% (Ciloxan) with a standard therapy regimen (fortified tobramycin, 1.3%-cefazolin, 5.0%) for treating bacterial corneal ulcers. METHODS: This randomized, parallel group, double-masked, multicenter study was conducted in 324 patients at 28 centers in the United States, Europe, and India. Patients were randomized into 2 treatment groups: 160 to ciprofloxacin and 164 to fortified tobramycin-cefazolin. Positive microbiologic cultures were obtained in 188 (58%) of 324 patients. Of these, 176 patients met protocol criteria and were evaluated for treatment efficacy: 82 in the ciprofloxacin group and 94 in the standard therapy group. The dosing schedule for both treatment groups was 1 to 2 drops of the first study medication (ciprofloxacin or fortified tobramycin) every 30 minutes for 6 hours, then hourly for the remainder of day 1; 1 to 2 drops every hour on days 2 and 3; 1 to 2 drops every 2 hours on days 4 and 5, followed by 1 to 2 drops every 4 hours on days 6 to 14. The second medication (ciprofloxacin or cefazolin) was instilled 5 to 15 minutes after the first drug, following the same dosing frequency. Physician's judgment of clinical success, cure rate, changes in ocular sings, and symptoms and the rate of treatment failures were the primary efficacy criteria. RESULTS: Topical ciprofloxacin monotherapy is equivalent clinically and statistically to the standard therapy regimen of fortified antibiotics. No statistically significant treatment differences were found between ciprofloxacin (91.5%) and standard therapy (86.2%) in terms of overall clinical efficacy (P = 0.34). Similarly, no differences were noted in resolution of the clinical signs and symptoms (P > 0.08) or the time to cure (P = 0.55). The incidence of treatment failures was less in the ciprofloxacin group (8.5%) compared with the standard therapy group (13.8%). Significantly fewer patients treated with ciprofloxacin reported discomfort than did patients treated with the standard therapy regimen (P = 0.01). CONCLUSION: Ciprofloxacin ophthalmic solution 0.3% monotherapy is equivalent clinically and statistically to standard therapy (fortified tobramycin-cefazolin) for the treatment of bacterial corneal ulcers and produces significantly less discomfort.

Adolescent↗
PubMed1995

Identity and interactions of rumen microbes associated with dietary sulfate-induced polioencephalomalacia in cattle.

To study their role in sulfate reduction, anaerobic bacteria were cultured from rumen fluid samples of cattle fed high-carbohydrate, short-fiber diets with and without added sulfate. The steers fed the diet with added sulfate developed polioencephalomalacia. Microbiological methods included colony type profiles, molybdate sensitivity, presence of desulfoviridin, sulfate reduction rates of pure and mixed cultures, and incubation time effects on sulfate reduction. Colony-type profiles indicated decreased diversity, but no relative change in numbers of sulfate-reducing bacteria in rumen fluid from cattle fed diets with and without added sulfate. Thirteen bacteria] isolates were selected for further study on the basis of colony type, sulfate-reducing activity, and growth in lactate, sulfate, and yeast extract media. Seven of the isolates had Desulfovibrio-like characteristics (ie, they were gram-negative, motile rods that reduced sulfate, were inhibited by molybdate, and contained the pigment desulfoviridin). The remaining 6 isolates were gram-negative, nonmotile rods. Four of these released sulfide from cysteine, and 2 generated only limited amounts of sulfide from sulfate or cysteine. The 7 sulfate reducing isolates generated sulfide in rumen fluid broth medium at greater rates than those observed in fresh rumen fluid. Sulfate reduction Could be sustained in cultures for prolonged incubation times if the gas phase containing hydrogen sulfide was replaced at frequent intervals. Variations in the amount of sulfate reduced by the pure cultures were most pronounced at short incubation times. Sulfate reduction was not inhibited in mixed cultures of sulfate-reducing and nonsulfate-reducing bacteria.

Animals↗
PubMed1995

Ruminal microbial alterations associated with sulfide generation in steers with dietary sulfate-induced polioencephalomalacia.

Holstein steers were fed carbohydrate-rich, short-fiber basal diets with and without added sodium sulfate. Steers fed the high-sulfate diet developed the CNS disorder polioencephalomalacia (PEM). The onset of signs of PEM was associated with increased sulfide concentration in the rumen fluid. Over the course of the disease, anaerobic rumen bacteria were enumerated in roll tubes by use of the Hungate method Lo determine the effect of dietary sulfate on sulfate-reducing bacterial numbers. Media used included a general type for total counts and sulfate containing media with and without cysteine to assess sulfate-reducing bacteria. Changes in total and sulfate reducing bacterial numbers attributable to dietary sulfate content were not observed. The capacity to generate hydrogen sulfide from sulfate in fresh rumen fluid in vitro was substantially increased only after steers had been fed the high sulfate diet for 10 to 12 days, which coincided with the onset of signs of PEM. The low capacity for hydrogen sulfide production of rumen fluid taken at earlier times in the feeding period suggests that rumen microorganisms must adapt to higher dietary sulfate content before they are capable of generating potentially toxic concentrations of sulfide.

Animal Feed↗
PubMed1993

0.3% ciprofloxacin ophthalmic ointment in the treatment of bacterial keratitis. The Ciprofloxacin Ointment/Bacterial Keratitis Study Group.

OBJECTIVE: To determine the efficacy and safety of topical 0.3% ciprofloxacin hydrochloride ophthalmic ointment in the treatment of bacterial keratitis. DESIGN: Prospective case series with a nonrandomized comparison of culture-positive, evaluable cases (ciprofloxacin ointment group) with culture-positive, concurrent patients (nonenrolled group) treated with conventional therapy. SETTING: Multicenter clinical study. PATIENTS: After informed consent was obtained, 253 eligible patients underwent corneal scrapings and received topical ciprofloxacin ointment; 145 (57%) had positive cultures and completed the follow-up schedule. Forty (70%) of 57 apparently eligible patients had culture-positive bacterial keratitis but were not enrolled in the ciprofloxacin ointment study during the same period. INTERVENTION: Ciprofloxacin ophthalmic ointment instilled every 1 to 2 hours for 2 days, then every 4 hours for 12 days. MAIN OUTCOME MEASURES: Clinical evaluation of signs at 1, 3, 7, and 14 days of treatment and the overall condition classified as clinical success (cured or improved) or failure (unchanged or worse) during and after therapy. RESULTS: Clinical success with the initial treatment occurred in 135 patients (93%) in the ciprofloxacin ointment group and in 28 patients (70%) in the nonenrolled group. Of the 10 ciprofloxacin clinical failures, seven were staphylococcal; two, pneumococcal; and one, polybacterial. The 90% minimum inhibitory concentration of ciprofloxacin was 3 mg/L or less for corneal bacterial isolates. No serious adverse event attributable to ciprofloxacin ointment occurred, although 32 (13%) of 253 patients developed a transient white crystalline corneal precipitate shown with liquid chromatography in two cases to be ciprofloxacin. CONCLUSION: Ciprofloxacin ophthalmic ointment is an effective and safe topical antimicrobial agent for the treatment of bacterial keratitis caused by susceptible microorganisms.

Administration, Topical↗
PubMed1992

Efficacy and safety of lodoxamide 0.1% vs cromolyn sodium 4% in patients with vernal keratoconjunctivitis.

A multicenter, double-masked, parallel-group clinical study compared the efficacy and safety of lodoxamide 0.1% ophthalmic solution and cromolyn sodium 4% ophthalmic solution in 120 patients with vernal keratoconjunctivitis. On various follow-up visits, the clinical efficacy of lodoxamide 0.1% was statistically superior to cromolyn sodium 4% in alleviating four of the primary symptoms (itching, tearing, foreign-body sensation, and discomfort) and five of the primary signs (Trantas' dots, palpebral conjunctival changes, bulbar conjunctival hyperemia, erythema/swelling of the eyelids and periorbital tissues, and epithelial disease). At no time during the study was cromolyn sodium 4% statistically superior to lodoxamide 0.1% in demonstrating improvements in clinical signs and symptoms of vernal keratoconjunctivitis. The physician's clinical judgment of patients' response to treatment showed lodoxamide 0.1% effected a greater and earlier improvement than cromolyn sodium 4%. Both drugs were safe for topical ophthalmic use when used four times daily for up to 28 days.

Adolescent↗
PubMed1991

Goniotomy technique for removal of anterior chamber intraocular lenses.

Removal of an anterior chamber intraocular lens is often impeded by formation of peripheral anterior synechiae around one or more of the lens haptics. We describe a method of lysing adhesions under direct visualization through a contact gonioprism lens. This method is relatively atraumatic to vital anterior-chamber-angle structures.

Anterior Chamber↗
PubMed1990

A double-masked three-month comparison between 0.25% betaxolol suspension and 0.5% betaxolol ophthalmic solution.

In 352 patients with primary open-angle glaucoma or ocular hypertension, a multicenter double-masked, parallel-group clinical study compared the effects on intraocular pressure and ocular comfort of 0.5% betaxolol ophthalmic solution, a cardioselective beta-adrenergic blocking agent, with 0.25% betaxolol suspension. With twice-daily dosages, baseline intraocular pressure was significantly reduced (P = .0005), with no significant difference between the two groups, at Week 2 and at Months 1, 2, and 3. Further, the prevalence of ocular discomfort upon topical instillation was significantly lower for 0.25% betaxolol suspension than for 0.5% betaxolol solution (P = .0005).

Administration, Topical↗
PubMed1989

A limited comparison of apraclonidine's dose response in subjects with normal or increased intraocular pressure.

We performed a multicentered, placebo-controlled, randomized, crossover study comparing the efficacy of 0.5% and 1.0% apraclonidine hydrochloride in 15 normal volunteers and 17 subjects with increased intraocular pressure. Apraclonidine 1% produced a maximum 30.4% +/- 14.0% (4.7 +/- 2.4 mm Hg) decrease in mean intraocular pressure in normal eyes and a 31.3% +/- 16.5% (7.6 +/- 4.2 mm Hg) decrease in eyes with increased pressure. Apraclonidine 0.5% produced a maximum 25.8% +/- 9.7% (4.0 +/- 1.7 mm Hg) decrease in mean intraocular pressure in normal eyes and a 27.4% +/- 16.0% (6.8 +/- 4.5 mm Hg) decrease in eyes with increased pressure. There was no statistically significant difference in mean percent intraocular pressure lowering effect between the 0.5% and 1.0% apraclonidine concentrations. Most subjects treated with apraclonidine had a greater than or equal to 20% reduction in intraocular pressure from baseline. Twelve hours after instillation of apraclonidine, nine of the normal volunteers had an intraocular pressure of 10 mm Hg or less. Apraclonidine produced the same percent intraocular pressure decrease regardless of the initial level of intraocular pressure.

Adult↗
PubMed1989

Effects of methanol on the growth of gastrointestinal anaerobes.

The effects of methanol on the growth of representative, predominant, anaerobic gut bacteria were studied. Growth yields and rates were determined in a base medium to which methanol was added to produce media with methanol concentrations varying, in twofold steps, over a concentration range of 0.01 to 25%, by volume. The growth of many of the organisms was completely inhibited by a methanol concentration equal to, or less than, 6.2%. Isolates representing cellulolytic species were completely inhibited at a methanol concentration of 3.1%, and inhibitory effects on the yield of some cellulolytic isolates were found at a methanol concentration as small as 0.01%. Although most of the organisms studied were inhibited at relatively small methanol concentrations, isolates of Selenomonas ruminantium, Bacteroides ovatus, and Fusobacterium necrophorum were relatively methanol resistant. A methanol concentration of 12.5% was required to completely inhibit S. ruminantium. Substantial growth of B. ovatus was obtained in media containing 12.5% methanol, and for F. necrophorum, substantial growth occurred in media containing 25% methanol. The yields of F. necrophorum strain B85 and S. ruminantium strain PC18 were enhanced by relatively small methanol concentrations and reduced with further methanol concentration increase Anaerobic, nonsporing gut bacteria exhibit a diversity of responses to methanol.

Animals↗
PubMed1989

Herpes simplex virus-specific antibodies present in tears during herpes keratitis.

We examined the specificity and levels of antibodies present in rabbit tears after induced infection of the rabbit cornea. Two strains of herpes simplex virus-1 (HSV) with different patterns of ocular disease were used: RE which produces stromal disease, and F which produces epithelial disease. We found that (i) IgG, IgA, and IgM antibodies were produced, (ii) the number of specific HSV antigens recognized by these antibodies was no significantly different, and (iii) postinfection (PI) timing and concentration of antibodies varied according to the disease pattern of the virus strain. The animals infected with strain F produced high levels of IgG antibodies early PI which remained constant, while IgA and IgM antibodies also increased early PI but declined after Day 16 PI. Animals infected with strain RE showed low levels of IgA and IgM antibodies which remained low. IgG antibodies increased early PI but declined at Day 16 PI. These differences in times of appearance and in amounts of antibodies in tears may be related to the clinical course of the disease. It has been shown that stromal disease has an immunopathologic basis. Inflammation, cellular infiltration of lymphocytes, and plasma cells are seen in the stroma of RE-infected animals, but these are not present in the stroma of F-infected animals. Infectious virus was not isolated from corneal explants taken from animals during the quiescent stage of the disease. The difference in pathogenicity cannot be explained in terms of specificity of tear antibodies. Even though the disease patterns were different, the number and types of HSV polypeptides recognized by both sets of tears was similar. Consequently, we believe that the immunopathology seen in the stromal disease may be due to the anatomical site of HSV antigens, rather than to differences in specificity of tear antibodies.

Animals↗
PubMed1988

Morphologic studies of lymphocyte nuclei in follicular and diffuse mixed small- and large-cell (lymphocytic-histiocytic) lymphoma.

Twelve examples of mixed small- and large-cell lymphoma (eight follicular, one follicular and diffuse, and three diffuse) were investigated morphometrically using plastic-embedded tissue in order to study nuclear characteristics of lymphocyte populations in this form of non-Hodgkin's lymphoma (NHL) and to test morphologic bases for current NHL classification systems. This study illustrates that there are many inaccuracies, illusions, and misconceptions in the morphologic criteria currently used to classify mixed small- and large-cell lymphoma. A principal finding was that lymphocyte nuclear profiles in mixed-cell lymphomas tend to be smaller in size (P less than .005) and more irregular in shape (P = .0001) than the morphologically similar counterparts in germinal centers of lymph nodes with reactive hyperplasia. Intercase comparison of mixed small- and large-cell lymphomas revealed a considerable range of mean nuclear area values, some of which were within the size range of normal, small lymphocytes. At the magnifications used for morphometric assessment, a high proportion of lymphocyte nuclear profiles had shallow invaginations, but only a limited number of profiles (4% to 14%) had deep (cleaved) indentations. Contrary to current definitions for this subtype of NHL, lymphocytes with "small" nuclei had the same proportion of the nuclear diameter occupied by nuclear invaginations as lymphocytes with "large" nuclei and, in fact, mean nuclear invagination depth was shallower in "small" nuclei than in "large" nuclei. Furthermore, regardless of whether it is nuclear area or shape that is evaluated, lymphocytes in mixed-cell lymphoma do not separate into two populations of small-cleaved and large noncleaved cells. Morphometry reveals that only four of the 12 examples of mixed small- and large-cell lymphoma had a proportion of the lymphocytes in the size range of fully transformed germinal center lymphocytes that exceeded 25%, and none of the cases approached 50% even though the population of lymphocyte nuclei appearing "transformed," and therefore "large," ranged from 28% to 57%. Such results indicate that the large, noncleaved and cleaved component, as seen in histologic sections of mixed small- and large-cell lymphoma, do not have nuclei of uniform size and many, in fact, are not actually large. The morphometric findings indicate reasons for the poor observer reproducibility in classifying this subtype of NHL.

Cell Nucleus↗
PubMed1987

The effect of modulating the synthesis of arachidonic acid cascade products on HSV lesion recurrence.

Induction of HSV lesion recurrence may be achieved by a variety of stimuli. Trauma of almost any kind (physical, chemical, electromagnetic and thermal) to the healed primary lesion site has been successful for induction of recurrence. In common with each of these mechanisms is the release of inflammatory mediators (arachidonic acid (AA), complement, kinins, etc.) following trauma. Because blockade of the AA cascade with steroids has been noted to abort HSV skin lesions, and because steroids have numerous side effects making them a poor therapeutic choice in ocular lesions, we decided to test several relatively different types of AA cascade inhibitory drugs in mouse ear HSV recurrence models. In this series of experiments, it was found that topical steroids gave the greatest initial decrease in lesion number (80% fewer than control on day 3 post recurrence induction (PRI), while meclofenamate resulted in the greatest reduction of lesions by day 5 PRI (85% fewer lesions than control and 60% fewer than the steroid treated group). The NDGA treated group exhibited the least reduction in recurrence severity (27% fewer lesions than control on day 5 PRI and 200% more lesions than the steroid group. Chlorpromazine (thorazine) acted roughly equivalent to the steroid treated group by day 5 PRI (70% fewer lesions than the untreated control group). Relative efficacy in lesion reduction between groups by day 5 PRI is: meclofenamate greater than steroid = chlorpromazine greater than NDGA greater than control. Meclofenamate, steroid and chlorpromazine significantly reduced lesions (p less than .05) when compared with the saline treated control mice. NDGA did not significantly reduce lesions by day 5 PRI.

Animals↗
PubMed1987

Herpes simplex virus: recurrent and nonrecurrent strains.

A study of three Herpes Simplex strains with different frequencies of recurrent disease was done using the New Zealand white rabbit eye model. Each of the three strains, the McKrae strain (high frequency), the E-43 strain (low, frequency), and the CGA-3 (no recurrence) grew well in the rabbit corneal epithelium and produced overt recognizable disease for up to 5 days post-infection, thus minimizing differences in virus reactivation due to a lack of or insufficient ganglionic colonization. Asymptomatic shedding and spontaneous recurrences, as well as iontophoretically induced recurrences, were seen in the E-43 and McKrae strains, but not in the CGA-3-infected animals. The virus strain's optimum temperature was an important aspect of its reactivation process, as shown by the failure of the nonrecurrent CGA-3 to replicate at the host's core temperature (39 degrees C). The fact that these explants yielded infectious virus at 33 degrees C and not at 39 degrees C confirmed that the CGA-3 had colonized the ganglia, and its lack of recurrences or shedding suggests a temperature-dependency relationship. Our observations were further supported by the preferential growth at 39 degrees C of fresh clinical isolates obtained from HSV encephalitis and herpes labialis. Isolates from animals infected with the heterogeneous McKrae were classified as shedders (isolated in the absence of disease) and recurrent (isolated from a recurrent lesion). Both shedders and recurrent isolates were of a homologous nature and retained their phenotype when tested. From this study, we theorize that reactivation and disease may have different regulatory mechanisms. The type of recurrent disease (lesions, asymptomatic shedding, or none) is virus-dependent and frequency of disease may be regulated by host functions.

Animals↗