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Biomedical subjects

R F Meyer

Publications and source records attributed to R F Meyer.

At least 91 records · Page 5Linked to original sources

Intrastromal crystalline deposits following corneal graft rejection.

Five patients were noted to develop fine crystals in the corneal stroma following rejection of corneal grafts. Four had penetrating, and one lamellar, keratoplasty. All recovered from rejection after steroid therapy. The crystals were fine, gray to tan, refractile, not associated with visual loss, and stable over several months of follow-up. We speculate that these crystals may be related to immune globulin or immune complex deposition, although they may be lipid left after resolution of inflammatory infiltrate.

Administration, Topical↗

Demographic and predisposing factors in corneal ulceration.

We identified 224 patients hospitalized with corneal ulcerations at the University of Michigan Hospitals, Ann Arbor, between May 1975 and September 1981, and performed a chart review on a random sample of these cases. Bimodality in the patients' age distribution was attributed to nonsurgical ocular trauma in the younger group, and predisposing keratitis, surgical trauma, bullous keratopathy, and entropion in the older group. Bacterial and postherpetic causes accounted for 52 (52%) of the sampled cases. Pseudomonas aeruginosa and Staphylococcus aureus were the major isolates. Important predisposing factors included nonsurgical and surgical trauma, herpetic keratitis, contact lens wear, corticosteroid therapy, and bullous keratopathy. Both age and visual acuity on admission had prognostic implications for improvement in visual acuity after treatment.

Adult↗

A randomized trial of pressure patching for epithelial defects after keratoplasty.

A prospective randomly controlled trial of the effectiveness of pressure patching in the treatment of epithelial defects after keratoplasty in 41 patients (19 in the patched group and 22 in the unpatched group) showed no significant differences in healing between the two groups (P less than .25 to P less than .49 on postoperative days 1 to 6). The mean time needed for complete healing was 2.11 days in the patched group and 2.09 days in the unpatched group. Patients with bullous keratopathy preoperatively had larger initial defects (31.4 mm2) than those without (20.1 mm2) but the time needed for healing did not differ significantly (2.35 days vs 1.9 days; P less than .10).

Bandages↗

Evidence for corneal endothelial cell hypertrophy during postnatal growth of the cat cornea.

Endothelial cell counts made from specular micrographs of 1-month-old kitten and adult cat corneas demonstrate that a progressive increase in endothelial cell size and a reduced endothelial cell density occurs during the postnatal development of the cat cornea. In addition to confirming the difference in cell size, scanning electron micrographs show that kitten endothelial cells are much more pleomorphic than those of the adult. When the number of corneal endothelial cells/mm2 and the size of the whole cornea are calculated for the kitten and adult, hypertrophy rather than mitosis appears to be the principal mechanism responsible for maintaining a confluent endothelial cell monolayer during the postnatal development of the feline cornea. Hypertrophy also appears to play a role in establishing the adult corneal endothelial cell population of the rabbit when the previously published data of others are treated in a similar manner to those of the kitten and adult cat. Thus, endothelial cell hypertrophy plays a role in establishing an "adult" endothelial cell monolayer in species that have a widely divergent corneal endothelial cell mitotic capacity.

Animals↗

Penetrating keratoplasty in the cat. A clinically applicable model.

A series of 28 consecutive penetrating keratoplasties were performed on adult cats. Donor corneas (n = 14) were maintained in culture medium for 14--24 hours prior to transplantation. Rotational autografts (n = 7) were used to control for cell loss caused by culture maintenance as well as for the effects of surgery. Additional homografts (n = 7) were transplanted following removal of the corneal endothelium to study the extent of host corneal endothelial cell regeneration. Pre- and post-operative endothelial cell counts of the homografts made from specular micrographs demonstrated an average cell loss of 30% one month following surgery. A similar 30% average cell loss was present in the rotational autografts. Clinically, both homografts and autografts remained clear and were near normal in thickness. Homografts lacking endothelium exhibited persistent, severe edema that correlated with the inability of the host corneal endothelium to resurface the graft. Clinical and morphologic evidence of mild homograft rejection as observed in 15% of the animals that received normal homografts. Corneal endothelial cell loss following penetrating keratoplasty in the cat approximates that observed following the same procedure in the human. Additionally, regenerative capacity of the corneal endothelium in the cat, like that of the human, is limited. These features suggest that this cooperative, hardy animal is an excellent model in which to study many aspects of corneal transplantation that have direct application to the treatment of human corneal disease.

Animals↗

Angiotensin converting enzyme inhibitors: modifications of a tripeptide analogue.

Modified nonhydrolyzable tripeptide analogues of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline (1), designed to impart oral angiotensin converting enzyme (ACE) inhibitory activity, were made and evaluated in vivo and in vitro. The N-methyl and C5-methyl analogues of 1 were inactive. Insertion of heteroatoms (O, S, NH) into the C--C chain of 1 gave a series of compounds with high in vitro activity in the guinea pig serum ACE assay. The O-analogue was the most potent with an IC50 = 4.4 x 10(-9) M compared to 1 with an IC50 = 3.2 x 10(-9) M. The structure-activity relationships in this series of compounds lead one to speculate that the heteroatom provides an additional binding site to the surface of the enzyme; however, these compounds were inactive when tested for antihypertensive activity in the renal hypertensive rat at 30 mg/kg by the oral route (captopril is active at 1.0 mg/kg po).

Angiotensin-Converting Enzyme Inhibitors↗

Derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline: effect of changes at positions 2 and 5 of the hexanoic acid portion.

Several derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and tested for converting enzyme inhibition activity and blood pressure lowering effects in rats. One compound, 5(S)-benzamido-2(R)-methyl-4-oxo-6-phenylhexanoyl-L-proline (2a), had and I50 against angiotensin converting enzyme of 1.0 x 10(-9) M and is the most potent inhibitor prepared thus far in this class of compounds. Testing of 2a orally at 30 mg/kg for inhibition of the angiotensin I induced blood pressure increase in conscious normotensive rats gave 100% inhibition that required 143 min before the angiotensin I blood pressure response returned to 70% of the pretreatment control response. In the conscious renal hypertensive rat, 2a given orally at a dose of 3 mg/kg caused a lowering of blood pressure that reached its maximum of 40 mmHg 8 h following drug administration.

Angiotensin-Converting Enzyme Inhibitors↗

Complications associated with bovine corneal endothelial cell-lined homografts in the cat.

Cultured bovine corneal endothelial cells were subcultured onto feline corneas from which the native endothelium had been mechanically removed, and transplanted into cats via penetrating keratoplasty. Although the transplants remained thin and clear in the immediate postoperative period, correlative clinical and morphologic analysis disclosed evidence of a host response directed against the heterologous endothelium by the ninth postoperative day. Eyes with rotational autografts or transplanted homografts did not disclose evidence of a similar host response.

Animals↗

Giant papillary conjunctivitis after keratoplasty.

Giant papillae of the upper tarsal conjunctiva have been found in vernal conjunctivitis and, more recently, in giant papillary conjunctivitis in patients with contact lenses. A similar syndrome occurred in 11 patients who had undergone penetrating keratoplasty with interrupted nylon sutures. Minimal itching, mild mucous discharge, mild blepharoptosis, and giant papillae of the upper tarsal conjunctiva were associated with exposed suture ends. Removal of exposed sutures led to resolution of the condition. Conjunctival scrapings from three of five patients demonstrated eosinophils. Although the syndrome may have an immunologic basis, the findings are also consistent with a mechanical origin related to exposed nylon sutures.

Adolescent↗

Novel synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline and analogues: potent angiotensin converting enzyme inhibitors.

A new approach was developed for the synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline (1) and 23 analogues. The delta-(acylamino)-gamma-keto acid intermediates were obtained by a modified Dakin--West reaction using 3-carbomethoxypropionyl chloride. Acylation of L-proline and recrystallization of the mixture of diastereomers gave the optically pure title compound in three reaction steps. The in vitro angiotensin converting enzyme (ACE) inhibitory activity of 1 was confirmed. Some of the novel analogues (6, 11, 13, and 17) were also found to be potent inhibitors of ACE in vitro with an IC50 of 1.4-8.8 x 10(-9) M (IC50 for captopril = 0.9 x 10(-8) M). In vivo these compounds (6, 11, 17, and 18) were much less active than captopril, especially by the oral route. Against angiotensin I (AI) challenge in normotensive conscious rats, 1 and 6 produced less than 50% inhibition at 30 mg/kg po but 57 to 82% inhibition at 3 mg/kg iv. Inhibition by both routes lasted less than 1 h. In renal hypertensive rats, 1 and 15 of its analogues failed to produce significant blood pressure lowering effects, in contrast to the marked effects of captopril. Near maximum inhibition of AI was achieved by continuous intravenous infusions of 1 and 20, suggesting that limited oral activity may by due to degradation and/or clearance.

Angiotensin II↗

Granulomatous inflammatory reaction to degenerating Desçemet's membrane.

Granulomatous inflammatory reaction to degenerating Desçemet's membrane was found in histopathologic study of a keratoplasty specimen from a case of disciform keratitis following childhood varicella infection. The histologic findings suggest acquired autosensitivity to degenerating Desçemet's membrane as a likely cause for the chronic keratitis. Such a reaction may persist for many years in a corneal leukoma that, clinically, appears free of inflammation.

Adolescent↗

Amikacin treatment of Pseudomonas-caused corneal ulcer.

A Pseudomonas-caused corneal ulcer developed in a 44-year-old man with severe facial and upper torso thermal burns while in the hospital burn unit. The infecting strain was resistant to most antibiotics, including gentamicin sulfate and tobramycin sulfate. Treatment with topical and parenteral amikacin sulfate resulted in rapid healing. To our knowledge, there have been no reports of the use of amikacin for corneal ulcer. The successful healing in this case suggests that the use of amikacin should be considered in the treatment of corneal ulceration when it is suspected that the pathogen is a Pseudomonas strain resistant to gentamicin and other commonly used antibiotics.

Adolescent↗

Corneal epithelium in penetrating keratoplasty.

We studied corneal epithelium in 66 patients with bullous keratopathy treated with penetrating keratoplasty using McCarey-Kaufman stored donor corneas. Epithelium was evaluated at times of storage, surgery, and postoperative dressing changes. Epithelium was intact in 43 of the donor corneas at storage, and 23 had 5 to 100% (median, 50%) epithelium missing. At the end of the keratoplasty procedure, 16 grafts had epithelium intact, and 50 had 5 to 100% (median, 20%) epithelium missing. Postoperative epithelial healing time ranged from one to 12 days, with a median of two days. Postoperative healing was significantly prolonged when donor corneal epithelium was missing at keratoplasty. As the amount of epithelium intact at the end of surgery decreased, the number of days to heal postoperatively increased. We found that donor corneas could be stored as long as 79 hours, with 63 hours in McCarey-Kaufman medium, and still have epithelium intact at the end of the keratoplasty procedure.

Cornea↗

Penetrating keratoplasty in pseudophakic bullous keratopathy.

We studied 25 consecutive patients who underwent penetrating keratoplasty for pseudophakic bullous keratopathy. Follow-up time averaged 20 months. Ten patients required postimplantation surgical procedures because of complications after lens implantation. The time from lens implantation to onset of corneal edema averaged 18 months in patients without postimplantation surgical procedures and five months in patients with postimplantation procedures. The lens implants were removed in 11 patients at keratoplasty. Corneal clouding caused by graft rejection occurred in three patients, while 22 grafts remained clear. Final visual acuities were 6/6 (20/20) to 6/12 (20/40) in 13 patients, 6/15 (20/50) to 6/30 (20/100) in four patients, and 6/60 (20/200) or less in eight patients. We found no difference in final visual acuity between patients with lens implants removed at keratoplasty and those with lens implants left in place. Significant retinal pathology included cystoid macular edema, macular degeneration, and retinal detachment.

Aged↗

Single radial immunodiffusion method for screening Staphylococcal isolates for enterotoxin.

A direct system for screening large numbers of staphylococcal isolates for enterotoxin production has been developed. The system employs polyvalent (serotypes A, B, C, D, and E) immunodiffusion assay slides in conjunction with a multiple-culturing system for toxin production. With the combined system, as many as 50 cultures can be screened simultaneously on a single assay slide having a sensitivity of about 0.3 microgram/ml. The system should be useful for detecting potential enterotoxin in foods containing a predominance of non-enterotoxigenic strains.

Enterotoxins↗

Glutathione in the aqueous humor of human and other species.

Glutathione was measured in the aqueous humon of rabbit, dog, monkey, baboon, and man. The average concentrations were 17, 6, 6, 2, and 2 mumol/L of fluid, respectively. Except in the case of the monkey, where delay in aspiration of the aqueous apparently led to anomalous values, nearly all the glutathione was in the reduced state, the range being from 85% in the rabbit to over 99% in the human. Possible sources of the glutathione in the aqueous humor are discussed and also its significance for the physiology of the cornea.

Adult↗

Mackay-Marg tonometry over therapeutic soft contact lenses.

We evaluated the accuracy of Mackay-Marg electronic applanation tonometry over Bausch and Lomb Plano-T therapeutic soft contact lenses on eye bank, postoperative keratoplasty, and normal eyes. Intraocular pressure (IOP) measurements were compared in the same eye without and with the lens in place. The mean difference of IOP readings through the lens was not statistically different from that without the lens over an IOP range of 10 through 50 mm Hg. We constructed confidence intervals to predict the accuracy of future observations. Results revealed that with 95% confidence, the range of difference between IOP readings without and with the lens in place was from -4.7 to +3.6 mm Hg in eye bank eyes, from -4.3 to +7.4 mm Hg in postoperative penetrating keratoplasty patients, and from -3.5 to +7.4 mm Hg in postoperative lamellar keratoplasty patients, from -3.3 to +2.7 mm Hg in normal eyes. We concluded that IOP can be measured with the Mackay-Marg tonometer through a therapeutic soft contact lens over a corneal graft. Although the readings are not as accurate as without the lens, they are probably adequate as a guide to the necessity of treating increased IOP in postoperative keratoplasty patients.

Contact Lenses, Hydrophilic↗