Abstract  We recently reported the first case of accidental aspiration of polyacrylamide occurring in a 26-year-old man. The patient developed severe airway obstruction and parenchymal lung damage and died. Autopsy revealed numerous polyacrylamide particles in his lungs, as well as extensive bronchiolar and alveolar damage. Gas chromatographic and mass spectrometric assessment of the lung tissue failed to reveal polyacrylamide activity, although assessment of the suspending solvent of the polyacrylamide showed a pattern characteristic of an aliphatic hydrocarbon mixture with a prominent dodecane peak. This experimental study was performed to determine the nature and extent of damage to rat bronchial and alveolar epithelia following endotracheal instillation of polyacrylamide, hydrocarbon mixture (petroleum distillate), dodecane (C12H26), or normal saline. The rat lungs were examined grossly and microscopically 10 min and 24, 72, and 96 h after endotracheal instillation, following inflation and fixation with 10 percent buffered formaldehyde. Gross examination revealed congested, mottled visceral pleural surfaces in the rats treated with polyacrylamide and dodecane. There were no pleural exudates or effusions. Microscopically, vascular engorgement, bronchiolitis, and focal pneumonia were observed. Vascular engorgement was most pronounced at 72 to 96 h in rat lungs treated with polyacrylamide and dodecane and was moderate at 24 h in rats treated with petroleum distillate. Focal organizing pneumonia was marked at 96 h in rats treated with petroleum distillate, at 72 h in those treated with polyacrylamide, and at 24 h in those treated with dodecane. The saline-treated control animals showed no change. Our findings suggest that polyacrylamide, dodecane, and petroleum distillate are strong irritants to the airways. However, a direct obstructive/mechanical effect of the polyacrylamide upon the airway has not been excluded. Airway exposure to polyacrylamide may result in lung injury secondary to the polyacrylamide itself, its suspending agents, or both.

Abstract  OBJECTIVE: To investigate the effect of melatonin on the antioxidant enzyme activity and renal tubular necrosis induced by gentamicin.

MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were divided into three equal groups. In group 1, the rats were injected with vehicle (controls), in group 2 they were injected with gentamicin for 5 days and in group 3 injected with gentamicin plus melatonin for 5 days. At 24 h after the last injection, rats were killed and the renal cortex separated from the medulla. Most of the cortex was homogenized but a small sample was fixed in formaldehyde solution for histological examination by light microscopy. Blood samples were also taken to assess the serum levels of urea, creatinine, Na+, K+ and gamma-glutamyl transpeptidase (gamma-GT); before death, urine samples were analysed for protein content. Crude extracts of the cortex were used to determine lipoperoxides, reduced glutathione (GSH-Px), catalase and superoxide dismutase (SOD). The results were compared using the Mann-Whitney U-test.

RESULTS: Compared with the controls rats, gentamicin caused hyperproteinuria, an increase in the level of gamma-GT in serum, a marked increase in lipoperoxides and a significant decrease of GSH-Px, catalase and SOD activity in the kidney. In the rats in group 3 there was a marked restoration in lipid peroxidation, GSH-Px, catalase, SOD activity and proteinuria, and in gamma-GT in serum. In rats in group 2 there was widespread tubular necrosis (grade 2-4) but in rats in group 3 there was a marked reduction in the extent of tubular damage. There was no significant difference in serum levels of Na+, K+, blood urea nitrogen and creatinine.

CONCLUSION: These results indicate that melatonin prevents the tubular necrosis induced by gentamicin in rats, presumably because it is a potent antioxidant and restores antioxidant enzyme activity in the rat kidney.

Abstract  PURPOSE: To compare histological changes induced by antiglaucoma medications in the rabbit conjunctiva.

METHODS: Fifty New Zealand rabbits were divided in 5 groups of 10 animals. The left eyes were treated daily with one drop of bimatoprost 0.03%, travoprost 0.004%, latanoprost 0.005%, timolol maleate 0.5% or artificial tears containing benzalkonium chloride (BAK) for 30 days. The right eyes served as controls. Superior limbic conjunctival biopsies were performed at the 8th and 30th day in 5 rabbits of each group. The conjunctiva was fixed with 10% formaldehyde, followed by HE and PAS staining. Morphohistometric quantitative analyses were performed to evaluate the following parameters: inflammatory infiltrate, epithelial thickness, number of goblet cells, diameter and number of blood vessels.

RESULTS: At the 8th and 30th posttreatment days, all groups, except one that received artificial tears, exhibited a diffuse inflammatory infiltrate, composed by lymphocytes and neutrophils, which was denser in the timolol group than in the prostaglandin (PG) analogues groups. At the 30th day, the timolol group also showed an increased subepithelial collagen density and a significant increase in epithelial thickness (p=0.0035). The goblet cell density was significantly increased at the 8th day in the group treated with travoprost (p=0.0006), and at the 30th day in those treated with bimatoprost (p=0.0021) and latanoprost (p=0.009).

CONCLUSIONS: Although a moderate, diffuse inflammatory infiltrate was observed in PG-treated eyes, no changes in conjunctival epithelial thickness or subconjunctival collagen density were observed with these medications, suggesting that these drugs induce fewer changes than timolol maleate in the rabbit conjunctiva.

Abstract  Low perinatal lamb loss and fast lamb growth rates are important measures for efficient sheep production. To understand the role of ewe nutrition in late pregnancy, 100 adult Border Leicester x Merino ewes were joined at a synchronised oestrus. Ewes were nutritionally managed to maintain maternal body condition until day 130 of pregnancy at which time 50 twin-bearing ewes entered single pens. Thirteen ewes were allocated as controls and 14, 11 and 12 ewes for the 3 treatments groups. All were fed a base diet of lucerne hay (17.3% crude protein; 9.4 MJ ME/kg DM). Three of the 4 treatment groups were supplemented with oaten grain, formaldehyde-treated sunflower meal or lupin grain at 1 of 3 nominal feeding levels: 250, 500 or 750 g/ewe. day of supplement. Actual intake was less than amounts offered. Intakes measured in the final 5 days prepartum, were used in the analysis. Data were collected on peripheral progesterone and insulin-like growth factor-1 at 4 days prepartum and 50 min postpartum; peripheral oestrone sulfate at 4 and 3 days prepartum and 50 min postpartum; and colostrum weight and score at 50 min postpartum. Feeding level of supplement, but not type of supplement, significantly increased insulin-like growth factor-1 and decreased progesterone and oestrone sulfate levels. Correlations of energy and nitrogen intake with insulin-like growth factor-1, progesterone and oestrone sulfate levels were positive (P<0.01), as were the correlations of colostrum weight with these traits. An unexpected high correlation between energy and nitrogen intake masked any differential effects on colostrum production and hormone response. Nevertheless, the supply of energy and protein supplements were associated with elevated colostrum weights and scores, and lower progesterone concentration. Lowering progesterone levels is considered necessary for successful parturition. Oaten grain was the least desirable grain supplement. These observations support the practical importance of providing adequate nutrition in late pregnancy and its effect on colostrum yield and presumably lamb survival and growth.

Abstract  OBJECTIVE: To investigate whether the kainate (KA) receptor subunit GluR6 is involved in the acute inflammatory pain.

METHODS: Formalin was injected into the mucosa of rectum in Sprague-Dawley rats to induce visceral pain. The antisense oligodeoxynucleotides (ODNs) of GluR6 were injected once per day for 3 d before formalin injection, after which GluR6 protein level was examined by immunoblotting method. The change of visceral pain was also investigated.

RESULTS: The expression of GluR6 in the spinal cord of rats increased after the formalin injection. Moreover, pre-treatment of GluR6 antisense ODNs could suppress GluR6 expression in the spinal cord of rats and decrease the scores of visceral pain at 45 min following formalin injection.

CONCLUSION: Kainate receptor subunit GluR6 plays an important role in the visceral pain induced by injection of formalin into the wall of rectum. GluR6 may serve as a potential target for the treatment of acute inflammatory visceral pain.

Abstract  In this study, the suppressive effects of BmK IT2, a kind of Na+ channel-specific modulator from the venom of the scorpion Buthus martensi Karsch, on biphasic nociceptive behavior in rats and c-Fos expression in rat spinal cord induced by formalin were investigated. Fifty microliters of 2.5% formalin were subcutaneously injected into the rat hind paw; 0.1 and 1 microg doses of BmK IT2 were subcutaneously administered into the rat ipsilateral hind paw 1 min before or 10 min after formalin injection individually, and the number of flinches per 5 min was counted. The detection of c-Fos expression induced by formalin in either the absence or the presence of BmK IT2 was carried out with the ABC method. Biphasic nociceptive behavior in rats was significantly suppressed by pretreatment with BmK IT2. No. of flinches/5 min in the second phase was also decreased by posttreatment with BmK IT2. In addition, c-Fos expression induced by formalin was significantly inhibited in all laminae of L4-5 spinal cord by pre- or posttreatment with BmK IT2. The suppression of BmK IT2 in the first- and second-phase behaviors may be attributed to the anesthesia of the toxin toward nociceptors and primary afferents and its selective modulation of tetrodotoxin-resistant Na+ currents of dorsal root ganglion neurons, respectively. In addition, the nonparallel suppression of BmK IT2 on flinch behavior and c-Fos expression induced by formalin may be ascribed to the different activity patterns of afferent fibers and central neurons.

Abstract  The in situ degradation of the two nitramine explosives, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), was evaluated using a mixture of RDX and HMX, incubated anaerobically at 10 degrees C with marine sediment from a previous military dumping site of unexploded ordnance (UXO) in Halifax Harbor, Nova Scotia, Canada. The RDX concentration (14.7 mg.L-1) in the aqueous phase was reduced by half in 4 days, while reduction of HMX concentration (1.2 mg.L-1) by half required 50 days. Supplementation with the carbon sources glucose, acetate, or citrate did not affect the removal rate of RDX but improved removal of HMX. Optimal mineralization of RDX and HMX was obtained in the presence of glucose. Using universally labeled (UL)-[14C]RDX, we obtained a carbon mass balance distributed as follows: CO2, 48%-58%; water soluble products, 27%-31%; acetonitrile extractable products, 2.0%-3.4%; and products covalently bound to the sediments and biomass, 8.9% (in the presence of glucose). The disappearance of RDX was accompanied by the formation of the mononitroso derivative hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and formaldehyde (HCHO) that subsequently disappeared. In the case of HMX, mineralization reached only 13%-27% after 115 days of incubation in the presence or absence of the carbon sources. The disappearance of HMX was also accompanied by the formation of the mononitroso derivative. The total population of psychrotrophic anaerobes that grew at 10 degrees C was 2.6 x 10(3) colony-forming units.(g sediment dry mass)-1, and some psychrotrophic sediment isolates were capable of degrading RDX under conditions similar to those used for sediments. Based on the distribution of products, we suggest that the sediment microorganisms degrade RDX and HMX via an initial reduction to the corresponding mononitroso derivative, followed by denitration and ring cleavage.

Abstract  A majority (24/32) of the extracellularly recorded dorsal hippocampus field CA1 putative GABAergic interneurons were excited in conjunction with theta activation on formalin injection (5%, 0.05 mi, s.c. into right hind-paw) in urethane (1.0 g/kg, i.p.)-anaesthetized rats. An increase in activity was observed to the 10th minute (n=24) and also at later time-periods at which a few of the neurons were recorded following injection of formalin. The mean peak increase in activity within 5 min of formalin injection was 6.43 +/- 0.81 Hz over the average background activity for these neurons (6.46 +/- 1.04 Hz). Of 24 neurons, 14 exhibited an increase in activity which was rhythmically modulated with theta. With a concurrent administration of formalin and morphine (5 mg/kg, i.p.), the presumed interneurons recorded displayed an initial increase in discharge rate (mean peak increase within 5 min of 6.95 +/- 1.10 Hz) which then declined with a decrease in theta activity. The effect of concurrent morphine was naloxone reversible. Morphine administration alone resulted in an immediate decrease in the interneuronal firing rate. In presence of the medial septal region lesions, formalin did not evoke an excitation of interneurons or theta activation. Further, such lesions prevented the decrease in interneuron activity to morphine administration. The above data are consistent with the notion that (i) the field CA1 interneurons participate in a noxious stimulus-induced and medial septal region mediated pyramidal cell suppression, and (ii) morphine affects CA1 nociceptive responses partly in a fashion consistent with the effect of the drug on septohippocampal neural network processing. (C) 1999 IBRO. Published by Elsevier Science Ltd.

Abstract  Aim: In the present study we evaluated the effects of gastric myenteric denervation using benzalkonium chloride (BAC) on the time for gastric emptying, as well as gastric secretion, and mucosal epithelial cell size and population in rats. Methods and Results: Wistar rats were treated with topical serosal application of BAC to the stomach. Control animals received saline. Ninety days after surgery, gastric emptying time, gastric acid secretion and serum gastrin levels were studied. Next, the animals were sacrificed and the stomachs were removed, fixed in formalin and histologically processed for histomorphometry of the height, area and volume of the glandular portion, and volume and population of mucous, chief, parietal, G- and labelled cells. BAC animals showed a significant delay in gastric emptying and an increase in gastric acid secretion and serum gastrin levels. These animals also presented a significant reduction of myenteric neuron number, hypertrophy of parietal and chief cells, hyperplasia of G cells and an increase in the gastric mucosa area. Conclusion: The absence of the myenteric plexus seems to protect the stomach from the hyperplastic effects of hypergastrinemia. Gastric food stasis may act as a factor triggering morphological and functional alterations of the gastric epithelium. Although gastric food stasis is a common finding in medical practice, its physiopathological consequences are poorly understood and have not been frequently discussed in the literature.

Abstract  Slices of unembedded rat anterior pituitaries, fixed with a periodate-lysine-paraformaldehyde (PLP) fixative, were incubated with guinea pig antiserum to ACTH and stained with a peroxidase-conjugated IgG fraction of anti-guinea pig gamma-globulin serum from rabbits. The fine structure of the stained cells was identical to that of the ACTH-secreting cell, as described by Siperstein and coworkers. Immunoreactive granules were mainly located at the periphery of the cell. Numerous granules of the inner cytoplasm and also the Golgi complex were nonreactive to the antiserum. The differential labeling for granules and Golgi apparatus peptide.

Abstract  A number of cases of paresthesia following the use of N2 or other paraformaldehyde-containing root canal cements have been reported. Since paresthesia is longlasting and not only an inconvenience but also disabling at times, such cements should not be used for obturating root canals.

Abstract  SSPE patients characteristically have high complement-fixing (CF) and neutralizing (N) antibody titers against measles virus in their sera, CSF, and brain. However, using SSPE patients' sera, the immunoperoxidase (IP) labeling of smooth nucleocapsids in SSPE or measles virus infected Vero cells or measles virions has not been achieved using conventional EM fixatives. Using the periodate-lysine-paraformaldehyde (PLP) fixative developed by McLean and Nakane (1974), and the indirect IP technique, antibodies against smooth nucleocapsids in SSPE and measles virus infected Vero cell cultures have been detected in serum from SSPE patients and normal individuals with high measles antibody titers.

Abstract  This report describes an immunoferritin labeling study of mouse H-2 histocompatibility antigens on epithelial cells dissociated from stomach, duodenum-jejunum, ileum, trachea, diestrus uterus, gall bladder, and vas deferens. Before cell dissociation, most of the organs were prefixed in periodate-lysine-paraformaldehyde to preserve the shape of the cells and to immobilize H-2 antigens in their native positions. Five kinds of epithelial cells expressed H-2 antigens on lateral and basal membranes but not on apical membranes. These were the lining cells of the upper intestine, ileum, gall gladder, uterus, and the tracheal brush cell. The antigens were continuously distributed on the lateral and basal membranes of these cells and appeared to be absent from the apical membranes, rather than masked by the fuzzy coat. On four other epithelial cell types H-2 antigens could not be detected. These were the lining cells of the vas deferens, parietal and chief cells from the stomach, and ciliated tracheal cells. It does not seem to be uncommon for normal nucleated cells to lack H-2 antigens. On fixed and labeled epithelial cells from the upper intestine the zonula occludens membranes were unlabeled, while the zonula adherens and desmosome membranes were labeled as densely as the remainder of the lateral membranes. The zonula occludens membrane thus constituted the boundary betewen the unlabeled apical membrane and the labeled lateral membrane of these cells. Intestinal epithelial cells dissociated without prefixation showed a patchy distribution of H-2 antigens on their lateral membranes after indirect labeling, indicating antigen mobility in this membrane. On the same unfixed dissociated cells the antigens were able to migrate from lateral to apical membranes, a movement which appears to be prevented in the intact epithelial layer by the occluding junction. The absence of H-2 antigens from apical membranes and their inability to migrate through an intact zonula occludens suggest that these molecules must reach the lateral membranes of epithelial cells by a pathway which is distinct from that followed by apical membrane components.

Abstract  Nitrogen mustard N-oxide was tried for the fixation of tissue for electron microscopy. A fixative consisting of 1% nitrogen mustard N-oxide, 1% glutaraldehyde and 1% paraformaldehyde buffered at pH 7.4 followed by 1% OsO4 buffered at pH 7.4 was found useful for the tissues examined: thyroid, anterior pituitary, adrenal gland and oviduct of mice. If the tissues are fixed and the sections are stained with uranyl acetate and lead acetate doubly, the follicle colloid, colloid droplets, and secretory granules containing thyroglobulin in the thyroid become higher in electron density. The cisterna of the maturing face of the Golgi apparatus, secretory granules, ribosomes, nucleolus and chromatin in the cells examined are extremely electron dense. Tubular elements of smooth endoplasmic reticulum in the adrenal cortical cell and microtubules in all the cells examined are also well preserved. The fixative containing nitrogen mustard N-oxide is useful also for cytochemistry. Using tissue fixed by this method and stained en bloc by uranyl acetate, the noradrenaline and adrenaline cells in the adrenal medulla are clearly distinguished by light microscopy.

Abstract  A simple implanted device was used to occlude acutely the left middle cerebral artery (MCA) of 16 conscious cats. Eight received no treatment and 8 were given intravenous mannitol (1.2 gm/kg) at the time of occlusion. The initial neurological findings in both groups were similar, that is, agitation, forced circling, and right hemiparesis. The treated cats remained alert but the untreated cats became lethargic and drowsy. Perfusion with a mixture of colloidal carbon and buffered paraformaldehyde was carried out from 30 minutes to 6 hours following MCA occlusion. Results of morphological examination of brains from the treated and untreated groups suggested that mannitol had a protective effect upon cerebral tissue during the primary phase of acute focal ischemia. Light microscopic analysis of neuronal alterations demonstrated considerable preservation of neurons in brains of treated cats. Beneficial effect of mannitol was attributed partly to prevention of capillary narrowing and suppression of ischemic cerebral edema.

Abstract  An approach for testing platelet aggregates by formol fixation is presented. The investigations are made either in vitro by the study of aggregation in the presence of ADP, or in vivo after thrombin perfusion in the rabbit. The calculation of an 'index of aggregability' comparing fixed and non-fixed platelets permits an evaluation of the presence of aggregates.

Abstract  Inasmuch as precise correlations of light- and electronmicroscopy are crucial for understanding biostructure, it seemed necessary to bring together the advantages of the glyoxylic acid (GA) method (for inducing monoamine fluorescence) and electron microscopy. A combined fluorescence and electron microscope method using GA is introduced. The brain is perfused by 2% GA in Krebs-Ringer bicarbonate buffer (pH 7.0) and this solution is followed by 4% paraformaldehyde containing 0.5% glutaraldehyde in Sorensen's phosphate buffer (pH 7.4). Sections are cut by cryostat or by vitratome and incubated in 2% GA in phosphate buffer (pH 7.0). Using fluorescence microscopy, features of interest are sketched and/or photographed. Afterwards, the same or subsequent section is processed for electron microscopy. Since axons of catecholamine-containing neurons (as well as their perikarya and terminals) are visualized by GA, the recommended procedure expands the range of studies concerning monoamine neurons that can now be carried out effectively.

Abstract  A semi-quantitative histochemical assay for noradrenaline was developed, based on the assumption that the rate of reaction of noradrenaline with paraformaldehyde depends on transmitter concentration. Changes in organ noradrenaline content caused by drugs or cold-stress were associated with similar changes in fluorescence intensity of organ samples taken for microscopy. Differences in the fluorescence intensity of experimental and control tissues were also found when there was no change in total noradrenaline content, suggesting that fluorescence intensity is not a simple function of whole organ noradrenaline content. Changes in the relative fluorescence of experimental tissues with different paraformaldehyde exposures suggested that the intraneuronal distribution of noradrenaline may affect the rate of development of fluorescence. Analysis of the time course of the fluorescence reaction showed that this was best described by the sum of two first-order exponential components of different half-life. Further results suggested that the first, fast component represents vesicle-bound noradrenaline, while the slow component represents extrangranular transmitter.

Abstract  The use of thin-layer chromatography has demonstrated that incubations of indoleamines with 5-methyl[14-C]tetrahydrofolic acid and an enzyme previously described as an N-methyltransferase, do not yield Nw, N1, or O-methylated products. Further elucidation by thin-layer chromatography, gas chromatography, mass spectrometry and selected ion monitoring enabled us to identify the reaction products as tetrahydroisoquinolines and tetrahydro-beta-carbolines in mixtures incubated respectively with catecholamines and indoleamines in the presence of 5-methyl[14-C]tetrahydrofolic acid and enzyme. The alkaloids have been shown to originate from a spontaneous condensation of the corresponding amines with formaldehyde, this latter being formed in the first stage of the reaction by enzymatic conversion from 5-methyltetrahydrofolic acid.

Abstract  The formaldehyde-formed autogenous fascia graft represents another step toward more reliable functional restoration of the diseased tympanic membrane. It combines the advantages of the availability and high nonperforation rate of autogenous fascia with the more normal anatomic restoration experienced with homograft tympanic membrane grafts. Its primary indication is in total membrane perforations with intact malleus although the concept can be employed in conjunction with various types of ossicular reconstruction.

Abstract  A mild and versatile method for the synthesis of some novel indole-1-carbinols has been developed via one-pot reaction of indoles and paraformaldehyde in the presence of an excess of CaO, MgO, ZnO or TiO(2). The solvent-free reaction provided all the indole derivatives in moderate to good yields and short reaction times. Moreover, the effect of some selected indole-1-carbinols on cell proliferation of the hepatoma cell line FaO was evaluated.

Abstract  OBJECTIVE: To observe the effect of Ciclosporin (CsP) on apoptosis and expression of the associated protein Bcl-2, Caspase-3 in gingival epithelium of rats in order to approach the mechanism of CsP-induced gingival epithelium overgrowth.

METHODS: Eighty SPF grade male 7-week-old Wistar rats were randomly divided into experimental group and control group, and each group was divided into 4 subgroups according to the duration of treatment (10, 20, 30 and 40 days). The experimental objects were given fresh milk including CsP intragastrically and the control ones were given only fresh milk. After perfusion of 4% paraform for internal fixation, the specimens' bucco-lingual paraffin sections at lower first molar were made. Apoptosis was detected using TdT-mediated dUT nick end labeling (TUNEL) and the expression of Bcl-2 and Caspase-3 using immunohistochemisty of PV. The apoptotic index, positive cell rate of Caspase-3 and average gray scale of Bcl-2 was measured with an image analysis system. Data were analyzed by two-way analysis of variance of factorial design.

RESULTS: The apoptosis index and positive cell rate of Caspase-3 were down-regulated in the experimental group, and were significant difference from the control group (P < 0.05). The average gray scale of Bcl-2 was up-regulated in the experimental group, and was significant difference from the control group (P < 0.05).

CONCLUSION: CsP-induced gingival epithelial overgrowth is likely to associated with interference to the path of mitochondrial apoptosis and inhibition apoptosis.

Abstract  PURPOSE: To quantify the extent of cellular proliferation and immunohistochemically characterize the proliferating cell types in epiretinal membranes (ERMS) from four different conditions: proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, post-retinal detachment, and idiopathic ERM.

METHODS: Forty-six ERMs were removed from patients undergoing vitrectomy and immediately fixed in paraformaldehyde. The membranes were processed whole and immunolabeled with either anti-MIB-1 or anti-SP6 to detect the K(i)-67 protein in proliferating cells, in combination with anti-glial fibrillary acidic protein or anti-vimentin to identify glia, anti-ezrin to identify retinal pigment epithelial cells, Ricinus communis to identify immune cells, and Hoechst to label nuclei. Digital images were collected using a laser scanning confocal microscope. The cell types were identified, their combined proliferative indices were tabulated as the average number of anti-K(i)-67-positive cells/mm(2) of tissue, and the number of dividing cells was related to the specific ocular condition and estimated disease duration.

RESULTS: ERMs of all four types were shown to be highly cellular and contained proliferating cells identified as glia, retinal pigment epithelium, and of immune origin. In general, membranes identified as PVR had many more K(i)-67-positive cells in comparison to those in the other three categories, with the average number of K(i)-67-positive cells identified per mm(2) of tissue being 20.9 for proliferative diabetic retinopathy, 138.3 for PVR, 12.2 for post-retinal detachment, and 19.3 for idiopathic ERM. While all membrane types had dividing cells, their number was a relatively small fraction of the total number of cells present.

CONCLUSIONS: The four ERM types studied demonstrated different cell types actively dividing at the time of removal, confirming that proliferation is a common event and does continue over many months. The low number of dividing cells at the time of removal in comparison to the total number of cells present, however, is an indicator that proliferation alone may not be responsible for the problems observed with the ERMs. Treatment strategies may need to take into consideration the timing of drug administration, as well as the contractile and possibly the inflammatory characteristics of the membranes to prevent the ensuing effects on the retina.