Airway Elastin is increased in severe asthma and relates to proximal wall area: histological and computed tomography findings from the U-BIOPRED severe asthma study.

BACKGROUND: Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype. OBJECTIVE: Within the U-BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions. METHODS: Bronchial biopsies were collected from two severe asthma groups, one non-smoker (SAn, n = 28) and one current/ex-smoker (SAs/ex, n = 13), and a mild-moderate asthma group (MMA, n = 28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n = 33). Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) was counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa was also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry. RESULTS: The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAn, 18.9% SAs/ex) compared with the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n = 18-20, rho=0.544, p = 0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans, it was not feasible to compare airway morphometry between the asthma groups. CONCLUSION: These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma.

A Transcriptome-driven Analysis of Epithelial Brushings and Bronchial Biopsies to Define Asthma Phenotypes in U-BIOPRED.

RATIONALE: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. OBJECTIVES: Using transcriptomic profiling of airway tissues, we sought to define the molecular phenotypes of severe asthma. METHODS: The transcriptome derived from bronchial biopsies and epithelial brushings of 107 subjects with moderate to severe asthma were annotated by gene set variation analysis using 42 gene signatures relevant to asthma, inflammation, and immune function. Topological data analysis of clinical and histologic data was performed to derive clusters, and the nearest shrunken centroid algorithm was used for signature refinement. MEASUREMENTS AND MAIN RESULTS: Nine gene set variation analysis signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper cell type 2 cytokines and lack of corticosteroid response (group 1 and group 3). Group 1 had the highest submucosal eosinophils, as well as high fractional exhaled nitric oxide levels, exacerbation rates, and oral corticosteroid use, whereas group 3 patients showed the highest levels of sputum eosinophils and had a high body mass index. In contrast, group 2 and group 4 patients had an 86% and 64% probability, respectively, of having noneosinophilic inflammation. Using machine learning tools, we describe an inference scheme using the currently available inflammatory biomarkers sputum eosinophilia and fractional exhaled nitric oxide levels, along with oral corticosteroid use, that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. CONCLUSIONS: This analysis demonstrates the usefulness of a transcriptomics-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target T-helper cell type 2-mediated inflammation and/or corticosteroid insensitivity.

The effects of caffeine ingestion on time trial cycling performance.

AIM: The purpose of this work was to determine the effects of caffeine ingestion on cycling time trial (TT) performance in well trained male subjects. METHODS: Eight males, with the following physical characteristics (Mean +/- SD) age 30.2+/-10.1 years, height 180.3+/-7.1 cm, mass 70.4+/-5.1 kg, VO2max 63.6+/-4.4 mL.kg(-1).min(-1) undertook three 1 h TT performances on a VelotronPro cycle ergometer, in a double blind, random fashion. The trials were Control (C), Placebo (Pl) and Caffeine (CAF). The CAF and Pl were given 60 min prior to exercise in a dose of 6 mg.kg(-1) body mass. Prior to ingestion, 60 min post ingestion, and at the end of the TT, subjects gave 10 mL of venous blood which was analysed for lactate, glucose, and free fatty acids. Expired air was collected throughout each test by indirect calorimetry. RESULTS: The cyclists rode significantly further in CAF trial (28.11+/-1.32 km) than they did in the C (26.69+/-1.5 km, P < 0.03) or Pl (27.0+/-1.5 km, P < 0.03) trials. No significant differences were seen between C and Pl trials (P > 0.88). No differences between C and Pl were seen in heart rate data throughout the TT (p > 0.05). The free fatty acid (FFA) concentrations were significantly higher in the CAF trials both post ingestion (P < 0.005) and post exercise (P < 0.0001) than either C or Pl trials. CONCLUSION: We concluded that performance was improved possibly based upon a greater reliance on fat metabolism, as indicated by increased FFA and a lower respiratory exchange ratio (RER).

Is there a risk associated with the insect repellent DEET (N,N-diethyl-m-toluamide) commonly found in aquatic environments?

DEET (N,N-diethyl-m-toluamide) is the active ingredient of most commercial insect repellents. This compound has commonly been detected in aquatic water samples from around the world indicating that DEET is both mobile and persistent, despite earlier assumptions that DEET was unlikely to enter aquatic ecosystems. DEET's registration category does not require an ecological risk assessment, thus information on the ecological toxicity of DEET is sparse. This paper reviews the presence of DEET in aqueous samples from around the world (e.g. drinking water, streams, open seawater, groundwater and treated effluent) with reported DEET concentrations ranging from 40-3000 ng L(-1). In addition, new DEET data collected from 36 sites in coastal waterways from eastern Australia (detections ranging from 8 to 1500 ng L(-1)) are examined. A summary of new and existing toxicity data are discussed with an emphasis on preparing a preliminary risk assessment for DEET in the aquatic environment. Collated information on DEET in the aquatic environment suggests risk to aquatic biota at observed environmental concentrations is minimal. However, the information available was not sufficient to conduct a full risk assessment due to data deficiencies in source characterisation, transport mechanisms, fate, and ecotoxicity studies. These risks warrant further investigation due to the high frequency that this organic contaminant is detected in aquatic environments around the world.

Model describing the relationship between pharmacokinetics and hematologic toxicity of the epirubicin-docetaxel regimen in breast cancer patients.

PURPOSE: The aims of the present study were (1) to characterize the pharmacokinetics of both component drugs and (2) to describe the relationship between the pharmacokinetics and the dose-limiting hematologic toxicity for the epirubicin (EPI)/docetaxel (DTX) regimen in breast cancer patients. PATIENTS AND METHODS: Forty-four patients with advanced disease received EPI and DTX every 3 weeks for up to nine cycles. The initial doses (EPI/DTX) were 75/70 mg/m(2). Based on leukocyte (WBC) and platelet counts, the subsequent doses were, stepwise, either escalated (maximum, 120/100 mg/m(2)) or reduced (minimum, 40/50 mg/m(2)). Hematologic toxicity was monitored in all patients, whereas pharmacokinetics was studied in 16 patients. A semiphysiological model, including physiological parameters as well as drug-specific parameters, was used to describe the time course of WBC count following treatment. RESULTS: In the final pharmacokinetic model, interoccasion variability was estimated to be less than interindividual variability in the clearances for both drugs. The sum of the individual EPI and DTX areas under concentration-time curve correlated stronger to WBC survival fraction than did the corresponding sum of doses. A pharmacokinetic-pharmacodynamic (PK-PD) model with additive effects of EPI and DTX could adequately describe the data. CONCLUSION: The final PK-PD model might provide a tool for calculation of WBC time course, and hence, for prediction of nadir day and duration of leukopenia in breast cancer patients treated with the EPI/DTX regimen.

Population analysis of the pharmacokinetics and the haematological toxicity of the fluorouracil-epirubicin-cyclophosphamide regimen in breast cancer patients.

PURPOSE: The aims of the study were (a) to characterise the pharmacokinetics (PK), including inter-individual variability (IIV) and inter-occasion variability (IOV) as well as covariate relationships and (b) to characterise the relationship between the PK and the haematological toxicity of the component drugs of the fluorouracil (5-FU)-epirubicin (EPI)-cyclophosphamide (CP) regimen in breast cancer patients. PATIENTS AND METHODS: Data from 140 breast cancer patients, either within one of different studies or in routine clinical management, were included in the analyses. The patients were all treated with the fluorouracil-epirubicin-cyclophosphamide (FEC) regimen every third week for 3-12 courses, either in standard doses, i.e. 600/60/600 mg/m(2) of 5-FU, EPI and CP, respectively, or according to a dose escalation/reduction protocol (tailored dosing). PK data were available from 84 of the patients, whereas time-courses of haematological toxicity were available from 87 patients. The data analysis was carried out using mixed effects models within the NONMEM program. RESULTS: The PK of 5-FU, EPI and 4-hydroxy-cyclophosphamide (4-OHCP), the active metabolite of CP, were described with a one-compartment model with saturable elimination, a three-compartment linear model and a two-compartment linear model, respectively. No clinical significant correlation was found between PK across drugs. The unexplained variability in clearance was found to be less within patients, between courses (inter-occasion variability, IOV) than between patients (inter-individual variability, IIV) for EPI and 5-FU. For 4-OHCP, however, the IIV diminished by approximately 45% when significant covariates were included and the final population model predicts an IIV that is equal to IOV. Significant covariates for elimination capacity parameters were serum albumin (5-FU, EPI and 4-OHCP), creatinine clearance (5-FU), bilirubin (EPI) and body surface area (BSA) (4-OHCP). Elimination capacity of 5-FU and EPI was not related to BSA and for none of the studied drugs did body weight explain the PK variability. The time-course of haematological toxicity after treatment was well described by a semi-physiological model that assumes additive haematological toxicity between CP and EPI with negligible contribution from 5-FU. The influence of G-CSF could be incorporated into the model in a mechanistic manner as shortening the maturation time to 43% of the normal duration and increasing the mitotic activity to 269% of normal activity. CONCLUSIONS: The models presented describe the dose-concentration-toxicity relationships for the FEC therapy and may provide a basis for implementation and comparison of different individualisation strategies based on covariates, therapeutic drug monitoring and/or pharmacodynamic (PD) feedback. The PD model extends on previous semi-mechanistic models in that it also takes G-CSF administration into account.

Lack of relationship between systemic exposure for the component drug of the fluorouracil, epirubicin, and 4-hydroxycyclophosphamide regimen in breast cancer patients.

PURPOSE: The aim of this study was to investigate the covariance between the pharmacokinetics of the three components of the FEC regimen, epirubicin (EPI), fluorouracil (5-FU), and the cyclophosphamide (CP) metabolite 4-hydroxycyclophosphamide (4-OHCP), in breast cancer patients. PATIENTS AND METHODS: Data from 21 women were collected over a total of 35 cycles. 5-FU (300 to 600 mg/m2) and CP (300 to 600 mg/m2) were administered as bolus injections, whereas EPI (15 to 60 mg/m2) was administered either as a bolus injection or as an infusion. The pharmacokinetics of the component drugs were monitored using a limited sampling scheme. Population pharmacokinetic models for each of the three drugs were developed using the program NONMEM. RESULTS: The data for 5-FU were best described by a one-compartment model with nonlinear elimination, where the maximal rate of elimination (Vmax) and the concentration at which the elimination was half-maximal (Km) were 105 mg/L.h and 27 mg/L, respectively. EPI concentration-time profiles showed a triexponential decline, with a mean terminal half-life of 24 hours and a clearance (CL) of 59 L/h. The elimination of 4-OHCP was monoexponential, with a mean half-life of 7 hours. The interindividual coefficients of variation (CVs) in CL were 30%, 22%, and 41% for 5-FU, EPI, and 4-OHCP, respectively. The corresponding values for intrapatient course-to-course variability in CL were 11%, 8%, and 27%. No significant correlation in any of the pharmacokinetic parameters between the drugs was found. CONCLUSION: Individualization of dosing of the FEC regimen using therapeutic drug monitoring and attempts to find concentration-response relationships may be successful, but requires that the exposure of all three drugs is considered simultaneously.

Bone-marrow-derived mesenchymal stem cells attenuate cognitive deficits in an endothelin-1 rat model of stroke.

PURPOSE: Stroke is the third leading cause of death and permanent disability in the United States, often producing long-term cognitive impairments, which are not easily recapitulated in animal models. The goals of this study were to assess whether: (1) the endothelin-1 (ET-1) model of chronic stroke produced discernable cognitive deficits; (2) a spatial operant reversal task (SORT) would accurately measure memory deficits in this model; and (3) bone-marrow-derived mesenchymal stem cells (BMMSCs) could reduce any observed deficits. METHODS: Rats were given unilateral intracerebral injections of vehicle or ET-1, a stroke-inducing agent, near the middle cerebral artery. Seven days later, they were given intrastriatal injections of BMMSCs or vehicle, near the ischemic penumbra. The cognitive abilities of the rats were assessed on a novel SORT, which was designed to efficiently distinguish cognitive deficits from potential motoric confounds. RESULTS: Rats given ET-1 had significantly more cognitive errors at six weeks post-stroke on the SORT, and that these deficits were attenuated by BMMSC transplants. CONCLUSIONS: These findings indicate that: (1) the ET-1 model produces chronic cognitive deficits; (2) the SORT efficiently measures cognitive deficits that are not confounded by motoric impairment; and (3) BMMSCs may be a viable treatment for stroke-induced cognitive dysfunction.

p53 splice acceptor site mutation and increased HsRAD51 protein expression in Bloom's syndrome GM1492 fibroblasts.

GM1492 human diploid skin fibroblasts derived from a patient with Bloom's syndrome (BS), lack detectable p53 mRNA and protein as shown by Northern and Western blotting, and express an increased RecA-like activity. Here we demonstrate that the p53 gene is grossly intact in GM1492 cells according to Southern blotting. DNA sequencing did not reveal any mutations in the promoter region of p53. A highly sensitive RT-PCR produced a p53 cDNA fragment that was shorter than expected. DNA sequence analysis of p53 cDNA showed that exon 6 was missing, explaining the shorter PCR product. Furthermore, sequencing of genomic DNA revealed a base substitution at the nucleotide preceding the AG splice acceptor site of intron 5. The omission of exon 6 creates a frameshift at the junction of exons 5 and 7, and a premature stop codon in exon 7. The aberrant transcript is predicted to encode a truncated p53 protein containing 189 amino acid residues. Moreover, Western blotting demonstrated elevated HsRAD51 protein levels in GM1492 cells. The lack of sufficient levels of wild-type p53 and increased levels of HsRad51 protein may contribute to the elevated RecA-like activity in the GM1492 fibroblasts.

Population pharmacokinetic modelling of unbound and total plasma concentrations of paclitaxel in cancer patients.

The aim of this study was to validate and further develop a mechanism-based population pharmacokinetic model for paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ, USA) based on the knowledge of Cremophor EL (CrEL) micelle entrapment and to evaluate the exposure/toxicity relationships. Paclitaxel (total and unbound) and CrEL concentrations were obtained according to a sparse sampling scheme with on average only 3.5 samples per course from 45 patients with solid tumours who received 3-hour infusions of paclitaxel (final dose range 112-233 mg/m(2)). The present data were predicted well by the mechanism-based model. In addition, bilirubin and body size were found to be significant as covariates. A change in body surface area (BSA) of 0.1 m(2) typically caused a change in clearance (CL) of 22.3 l/h and an increase in bilirubin of 10 microM typically caused a decrease in CL of 41 l/h. Toxicity was best described by a threshold model. In conclusion, even with a sparse sampling scheme, the same mechanism-based binding components as in the previously developed model could be identified. Once the CrEL and total paclitaxel plasma concentrations are known, the unbound concentrations, which are more closely related to the haematological toxicity, can be predicted.

Prenatal diagnosis and molecular cytogenetics in a case of partial trisomy 14 and monosomy 21.

We report an unbalanced translocation involving chromosomes 14 and 21 which presented as fetal ventriculomegaly at 33 weeks gestation. Second trimester ultrasound had indicated normal fetal anatomy, including normal intracranial structures. Parental karyotypes showed a paternal balanced translocation: 46,XY,t(14;21)(q12;q21). The unbalanced translocation in the fetus resulted in trisomy for 14pter-->q12 and monosomy for 21pter-->q21. Postnatal examination showed that the male infant had a cleft palate, but no cleft lip, and mild dysmorphic features. Postnatal MRI revealed bilateral and symmetric dilatation of the occipital horns, atria, and temporal horns of the lateral ventricles. Molecular cytogenetic techniques were used to delineate further the breakpoint on chromosome 14 to a site distal of the D14S1071 locus and the breakpoint on chromosome 21 to a region between D21S1918 and D21S1902. More precise definitions of chromosomal breakpoints in such clinical cases should provide more accurate prognosis for individuals with unbalanced karyotypes and assist in the identification of putative developmentally important genes.

c-fos gene expression is induced in a subpopulation of striatal neurons following a single administration of a dopamine D1-receptor agonist in adult rats lesioned with 6-OHDA as neonates.

The effects of the dopamine D1 receptor agonist, SKF-38393, on the levels of mRNAs encoding for the proto-oncogene c-fos and the GABA-synthesizing enzyme glutamate decarboxylase (GAD65) were measured by in situ hybridization histochemistry in the striatum of adult rats depleted of dopamine as neonates. c-fos mRNA levels exhibited a prominent increase following the acute systemic administration of SKF-38393 in dopamine-depleted but not in normal rats. Double-labeling in situ hybridization histochemistry using a radioactive c-fos probe and a digoxigenin-labeled preproenkephalin (PPE) cRNA probe indicated that c-fos mRNA levels were increased by SKF-38393 exclusively in a subpopulation of PPE-unlabeled neurons. Dopamine-depleted rats exhibited an increase in GAD65 mRNA levels relative to control rats. Acute administration of SKF-38393 did not alter GAD65 mRNA levels in control or in dopamine-depleted rats. Our results demonstrate that an acute administration of a D1-receptor agonist induces c-fos but not GAD65 gene expression in a subpopulation of presumed striato-nigral/entopeduncular neurons. They also suggest that the D1-dependent behavioral plasticity exhibited by adult rats depleted of dopamine as neonates is not the result of an altered activation of the two subpopulations of striatal efferent neurons.

The psychosocial work environment and skin symptoms among visual display terminal workers: a case referent study.

BACKGROUND: This study is a part of the interdisciplinary project The Office Illness Project in Northern Sweden, which was initiated with a questionnaire study in late 1988. Previously published results from the project have shown that facial skin symptoms reported among visual display terminal (VDT) workers are associated with a number of exogenous factors. This part of the project investigated the relation between the psychosocial work environment and facial skin complaints. METHODS: From an initial questionnaire study among 4943 office workers, 163 VDT workers were selected for a case referent study of facial skin symptoms. The data comprise a self-administered questionnaire filled out by 149 subjects and interviews with representatives of the organizations concerned. RESULTS: Psychosocial conditions, especially lack of social support from co-workers, were associated with an increased risk of reporting skin symptoms. Stratification by sex showed that the associations between some psychosocial factors and health differed between men and women. The results indicate that there might be an interaction between psychosocial factors and electric fields in the workplace which increases the risk of reporting skin symptoms. CONCLUSIONS: This study supports the idea that the aetiological basis of facial skin symptoms among VDT-workers includes physical as well as psychosocial factors, and that the interaction between such factors might be significant in the understanding of skin complaints among VDT workers.

Facial skin symptoms in visual display terminal (VDT) workers. A case-referent study of personal, psychosocial, building- and VDT-related risk indicators.

BACKGROUND: The Office Illness Project in northern Sweden, comprising both a screening questionnaire study of 4943 office workers and a case-referent study of facial skin symptoms in 163 subjects was recently completed. Previously published results from the survey showed that female gender, asthma/rhinitis, high psychosocial work load, visual display terminal (VDT) and paperwork were related to an increased prevalence of facial skin symptoms. METHODS: The case-referent study presented in this paper used data from the questionnaire supplemented by information from a clinical examination, a survey of psychosocial factors at work, building data and VDT-related factors from inspection and measurements taken at the work site. RESULTS: Psychosocial conditions and exposure to electromagnetic fields or conditions associated with such factors were related to an increased occurrence of skin symptoms. The results also indicated that personal factors such as atopic dermatitis and physical exposure factors influencing indoor air quality, such as paper exposure and cleaning frequency were related to an increased prevalence of symptoms. CONCLUSIONS: The results suggest that skin symptoms reported by VDT users have a multifactorial background.

Busulphan kinetics and limited sampling model in children with leukemia and inherited disorders.

Busulphan pharmacokinetics were investigated in 20 children, who underwent bone marrow transplantation for either leukemia or inherited disorders. Busulphan (1.90-6.02 mg/kg/day) was administered orally as a single dose or twice daily. Busulphan kinetics were found to be linear within the studied range. Children with inherited disorders eliminated busulphan significantly faster after the first and the last dose with half-lives (t1/2) of 1.93 and 1.71 h, respectively compared to children with leukemia (3.16 and 2.70 h, respectively). The area under plasma concentration curves (AUCs, corrected for mg/kg) as an expression for the systemic exposure of busulphan were significantly higher in children with leukemia, 22.4 and 19.04 mumol/l.h (5527 and 4690 ng.h.ml-1) after the first and the last dose, respectively, compared to 11.2 and 8.2 mumol/l.h (2768 and 2029 ng.h.ml-1) found in children with inherited disorders. The present results confirm those reported by others, ie busulphan pharmacokinetics can be influenced by the underlying disease and its status. Our population pharmacokinetic analysis showed a negative correlation between the weight corrected clearance and the age in both groups of children. However, clearance was about 42% higher in children with inherited disorders compared to those with leukemia. To estimate AUC for the first dose, we evaluated a limited sampling model based on three concentrations (1, 3 and 6 h). A high correlation (r = 0.998, P < 0.0001, n = 40) between the estimated and the determined AUC was found. The present model is reliable and adequate for studying more patients, with a long-term follow-up combined with drug monitoring in correlation with drug efficacy and toxicity to define the optimal busulphan dosage required.

Population pharmacokinetic analysis resulting in a tool for dose individualization of busulphan in bone marrow transplantation recipients.

The aims of the present study were (1) to investigate and quantify the pharmacokinetics, including inter-occasion variability and covariate relationships, of busulphan in BMT patients and (2) to develop a user-friendly initial dosing and therapeutic drug monitoring (TDM) strategy for the treatment of those patients with busulphan. The pharmacokinetics of busulphan was studied in 64 adults and 12 children who received busulphan (1 mg/kg) four times daily for 4 days. A one-compartment model with first order absorption and a lag time was sufficient in describing the concentration-time profile. Oral clearance (CL/F) was found to be correlated to weight (+1.2%/kg), ALT (-13%/microcat/l) and concomitant phenytoin treatment (+21%). CL/F and the volume of distribution (V/F) were estimated to 9.23 l/h and 39.3 l, respectively, in a typical individual. Inter-occasion variability (9.4%) in CL/F was estimated to be less than inter-individual variability (28%), a prerequisite for the value of TDM. Bayesian CL/F estimates based on three samples were in good accordance with those based on all samples. The final population model was implemented into the program Excel. The resulting flexible and easy to use dosing program might be used for both initial and, requiring only three plasma samples, maintenance dose individualization of busulphan therapy.

Clinical specular microscopy. I. Optical principles.

The clinical specular microscope yields a corneal endothelial image. Depending on the slit width of the illumination source, a typical endothelial photomicrograph contains three or four distinct zones. The appearance of the boundary between the endothelial cell pattern and the adjacent dark zone, called the dark boundary, reflects the configuration of the endothelial cell-aqueous humor interface and provides important information about the posterior corneal surface.

Clinical specular microscopy. II. Qualitative evaluation of corneal endothelial photomicrographs.

The clinical specular microscope shows the morphological appearance of the endothelium in normal and abnormal corneas. This instrument resolves the endothelial mosaic of the normal cornea into a quasiregular pattern of contiguous cells having well-defined cell boundaries. Cell size varies over a wide range in a number of disorders, and endothelial cells may assume shapes that are substantially different from their usual hexagonal appearance. Cell boundaries are dark and most commonly appear as a straight, narrow line. However, other types of cell boundaries, collectively referred to as doubled boundaries, have been encountered. Cell boundaries normally intersect in a manner that results in three angles of intersection, each approximately 60 degrees, but variations from this pattern are seen. A number of noncellular structures also can be seen in the endothelial zone.

In vivo photomicrography of the corneal endothelium.

A technique and apparatus for observing and photographing the corneal endothelium in vivo at a magnification of approximately times 200 is described. The method is suitable for animal experimentation and for diagnostic observation and clinical research in humans.