The viscous sublayer at the sea floor.

A 0.6-centimeter-thick sublayer was found in horizontal flow profiles obtained by traversing a heated thermistor from 19 centimeters above to 2 centimeters below the water-sediment interface in 200-meter-deep water on the Oregon continental shelf. In this sublayer the speed of the current varies linearly with distance above the sediment. Estimates of viscous stress from this sublayer and turbulent stress from the profile agree within 5 percent. Stress calculated from a current-meter spectrum agrees within its 95 percent confidence limits.

Local influences on shear-flow turbulence in the equatorial ocean.

A 12-day series of 1749 profiles of turbulent kinetic energy dissipation above the equatorial undercurrent at 140 degrees west showed that, in the upper 110 meters of the ocean, the dissipation radically decreased during the solar heating period each day. Daily averages were linearly related to the local wind power. When integrated over the depth range of 10 to 110 meters, the dissipation was 10.6 ergs per square centimeter per second or 0.92 +/- 0.10 percent of the wind power, a proportion not substantially different from those found in mid-latitude surface mixed layers. These results suggest that much of the energy dissipated above the equatorial undercurrent may be extracted directly from the local wind.

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.

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.

Nuclear morphologic and morphometric analyses of large noncleaved cell and immunoblastic non-Hodgkin's lymphomas.

Both morphologically and immunologically, non-Hodgkin's lymphoma (NHL) of the large cell type has been shown to be a heterogeneous category. However, the homogeneity of the nuclear parameters, particularly size and condensed chromatin organization, used to classify this subtype of NHL has not been investigated. In fact, objective morphologic techniques have not been systematically applied to verify the segregation of NHL on the basis of nuclear parameters, a concept common to all current classification systems. In this study morphometric image analysis was used to compare the nuclei in 20 specimens from NHLs of the large cell type with those in mantle zone and germinal center lymphocytes from lymph nodes with reactive hyperplasia. Results of the assessment of mean nuclear area in large cell lymphomas revealed that this class is also heterogeneous, with some of the specimens having a nuclear size in the upper range of that for normal small lymphocytes. In addition, in only a few of these specimens was the mean nuclear area within the range of that for fully transformed germinal center lymphocytes. The majority of large cell lymphomas have a nuclear size more characteristic of partially transformed lymphocytes in germinal centers. In addition to indicating inconsistencies in the current diagnostic criteria used in NHL classifications, the results indicate reasons for interobserver variations in clinicopathologic trials; the validity of nuclear size as a prognostic indicator and the biologic basis for classifying NHL as a reflection of normal lymphocyte transformation are also questioned. In terms of patient management, the classifications of NHL currently used require objective reappraisal.

Nuclear morphologic and morphometric analyses of nodular poorly differentiated lymphocytic lymphoma: assessment of small cleaved nuclei.

Comparative analytic measurements of nuclear parameters in normal and neoplastic lymphocytes are limited. In the present morphometric study lymphocyte nuclear features in 21 cases of nodular poorly differentiated lymphocytic lymphoma (NPDLL) were assessed with respect to the theoretical aspects of some non-Hodgkin's lymphoma (NHL) classifications. The mean nuclear area of the lymphocytes in NPDLL is generally within the range of the areas of unstimulated (mature) lymphocytes of mantle and follicular regions of lymph nodes with reactive hyperplasia. On this basis, the neoplastic lymphocytes in NPDLL do not reflect, at least cytologically, the antigen-activated, transforming lymphocytes of normal follicular centers. All measured nuclear parameters of small, unstimulated lymphocytes of neoplastic follicles suggest that major proportions of this component are also part of the neoplastic cohort. Sectional nuclear profiles in NPDLL are much more irregular in shape and have a higher percentage of invaginations than normal lymphocytes. However, only 4 to 5 per cent of nuclear profiles in NPDLL are of sufficient depth to be termed clefted. Serial section reconstruction of both normal and neoplastic lymphocytes indicates the degree to which the numbers of invaginated or clefted nuclei are underestimated in the examination of histologic sections. For example, the 4 to 5 per cent of nuclear profiles with clefts in histologic sections of NPDLL actually represent about 25 to 30 per cent of the lymphocyte population. On the basis of computer modeling of stylized nuclei with simple invaginations of varying depths and serial section reconstruction of normal and neoplastic nuclei, it is likely that all lymphocyte nuclei have some form of nuclear membrane invagination and that in poorly differentiated lymphomas these invaginations may be single and multiple discrete indentations or linear, branching grooves. Assessment of the ratio of nuclear invagination depth to nuclear diameter in normal and neoplastic lymphocytes indicates that transforming normal lymphocytes in follicular centers do not undergo a phase of increased nuclear clefting and that this ratio is somewhat greater in lymphocytes in NPDLL than in follicular center lymphocytes. However, the latter effect is not due to increased depth of nuclear invaginations in NPDLL, but rather results from the fact that mean nuclear diameter in this subtype of NHL is considerably smaller than that of normal lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Non-Hodgkin's lymphoma classification: ultrastructural morphometric studies for the quantification of nuclear compartments in situ.

The condensed chromatin distribution in the nuclei of lymphocytes in non-Hodgkin's lymphoma (NHL) is a key element, along with nuclear size and shape, in the classification of this disease for therapeutic and prognostic purposes. This report describes the ultrastructural comparative quantification of the condensed chromatin and the interchromatinic (nuclear matrix or euchromatin) region in the nuclei of mitogen-stimulated human peripheral T lymphocytes and mouse spleen B lymphocytes, human germinal center lymphocytes, and lymphocytes in ten cases of NHL of a variety of subtypes. The sequential morphologic nuclear changes induced in lymphocytes by mitogens are reflected in human germinal center lymphocyte populations. The common features include the changes in the distribution and volume of condensed chromatin aggregates, as well as the fact that the major increments in nuclear volume during lymphocyte transformation result from increases in the volume of the interchromatinic region. In all subtypes of NHL analyzed morphometrically, subpopulations of lymphocytes were identified in which mean nuclear, condensed chromatin, and interchromatinic volumes were more or less equivalent to those of normal lymphocyte subsets in germinal centers in reactive hyperplasia. However, in NHL the abnormal cytologic characteristics of the nucleus result, at least in part, from a complex interplay of condensed chromatin distribution and amount, and the size of the interchromatinic region. Further complexity is introduced by the fact that in NHL these two nuclear compartments can independently be normal, increased, or reduced in size. Morphometric quantification of lymphocytes in NHL indicates that the interchromatinic (matrix) region of the nucleus is the key element in establishing the nuclear volume of neoplastic lymphocytes. The structural and functional, ribonucleoprotein interchromatinic region of the nucleus was visualized in normal and neoplastic lymphocytes by regressive uranyl-EDTA staining. Quantitative morphometric analysis indicates that the cytologic appearance of neoplastic lymphocytes, even within subtypes of NHL, is heterogeneous and that condensed chromatin quantity and distribution may be more critical than nuclear size in distinguishing between certain subtypes of NHL. Improvements in the classification of NHL will occur only with understanding of the alterations in the biologic mechanisms controlling gross nuclear organization and the morphologic events of the various differentiation pathways available to antigen-stimulated lymphocytes.

Analysis of corneal thickness and endothelial cell density in pseudophakic and aphakic patients undergoing penetrating keratoplasty.

We studied the effects of the presence or location of an intraocular lens on 54 eyes with a penetrating keratoplasty. Endothelial cell density and corneal thickness measurements were compared in the four subgroups (14 aphakic, 14 anterior chamber lenses, 11 iris-supported lenses, and 15 posterior chamber lenses), using analysis of covariance, with the covariable being months since transplant. There was no statistical difference in these parameters among the four groups. The correlation between endothelial cell density and postoperative time (P less than .0022) and between corneal thickness and elapsed time (P less than .05) was, however, significant in all categories. Based on our analysis, we believe the presence or location of an intraocular lens is not detrimental to the corneal endothelium in penetrating keratoplasty.

Effects of topical betaxolol in ocular hypertensive patients.

Betaxolol, a new beta 1-adrenergic blocker, was applied to 20 eyes of ten patients with ocular hypertension. Topical 0.25% betaxolol was found to significantly lower intraocular pressure compared with placebo. There were no subjective or objective ocular or systemic side effects detected. There were no changes in pulse rate, BP, or corneal sensitivity. Betaxolol may be useful in patients with asthma, chronic bronchitis, and certain cardiovascular diseases where timolol maleate therapy may be contraindicated.

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.

Frozen section diagnosis in ophthalmic surgery.

Frozen section diagnosis can afford the opportunity for histopathological examination of excised tissues in the operating room. Because frozen section techniques have traditionally been little used in ophthalmic surgery, many pathologists are not familiar with eye tissues. However, with cooperation and understanding between the ophthalmologist and the pathologist, frozen section diagnosis may be able to identify the tissue, the pathologic process and the extent of the lesion within 10-15 minutes. In this review, applications and problems of frozen section diagnosis in various types of ocular surgery are discussed.

Eye infections with herpes simplex viruses in neonates.

A newborn with severe ocular herpes simplex virus (HSV) type 2 infection acquired in utero is presented to exemplify problems in diagnosis and management. A review of 297 newborns with HSV type 1 or type 2 infection reveals that about one-fifth demonstrate ocular involvement including one or more of the following: microphatalmia, conjunctivitis, keratitis, chorioretinitis, optic neuritis and cataracts.

Postoperative recurrence of Reis-Bücklers' corneal dystrophy.

A 68-year-old white man with a documented family history of Reis-Bücklers' corneal dystrophy had a penetrating keratoplasty of the right eye in 1962. In 1977, vision decreased and foreign body sensation returned. Examination indicated a Reis-Bücklers' dystrophy that had appeared in the graft 15 years after the transplant.

Primary surgical repair of severe peripheral marginal ectasia in Terrien's marginal degeneration.

We have developed a safe, successful, and simple procedure for repairing the severe peripheral marginal ectasia in Terrien's marginal degeneration. The area of ectasia is incised along its thinnest paralimbal dimension down to Descemet's membrane. Ectatic stroma along both sides of the incision is then undermined until normal-thickness stroma is reached. After excision of excess ectatic stroma, if necessary, the normal-thickness stroma is then sutured together, primarily with 9-0 Prolene. The sutures are left in place permanently, and the remaining refractive error is corrected with spectacles or contact lenses. This technique substantially improved visual acuity in three of four patients and decreased corneal astigmatism in all four. Although one eye required resuturing, there were no complications in any case.

Penetrating keratoplasty with trabeculectomy.

Seven patients who had a mean preoperative intraocular pressure of 40 mm Hg (range, 34 to 52 mm Hg) underwent combined keratoplasty and trabeculectomy. This resulted in an average postoperative intraocular pressure of 23.7 mm Hg. Five of seven eyes had well controlled intraocular pressures throughout the postoperative period (mean follow-up, 16.1 months). This approach can achieve a satisfactory result while avoiding some of the complications of other forms of glaucoma therapy.

Azlocillin levels in human tears and aqueous humor.

We administered 4 g of azlocillin sodium intravenously to 24 patients scheduled to undergo elective intraocular surgery and collected specimens of serum, tears, and aqueous humor from zero to six hours after infusion for assay by high-pressure liquid chromatography. We found that azlocillin is distributed into tears and penetrates into the aqueous humor of human volunteers with noninflamed eyes after a single intravenous dose. Levels of 4.17 micrograms/ml and 4.44 micrograms/ml were achieved in tears and aqueous humor, respectively.

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.

Piperacillin levels in human tears and aqueous humor.

Thirty patients scheduled to undergo elective intraocular surgery were each given 4 g of piperacillin intravenously. Specimens of serum, tears, and aqueous humor were collected from zero to nine hours after infusion and assayed for piperacillin content by high pressure liquid chromatography. In noninflamed eyes piperacillin sodium distributed into tears and aqueous humor in concentrations exceeding the minimum inhibitory concentration required for many gram-positive and gram-negative organisms. Higher levels of piperacillin were anticipated in patients with inflamed eyes who possessed an altered blood-aqueous barrier, and in patients receiving serial doses of this agent.

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).

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.