A qualitative and quantitative method for evaluating implant success: a 5-year retrospective analysis of the Br?nemark implant

A proposed protocol and differentiated success criteria for long-term evaluation of oral implants are presented. The protocol and criteria were applied to a retrospective patient material treated during a 1-year period and followed for 5 years. The protocol comprised a two-stage analysis of the collected clinical data. First, a quantitative analysis of the outcome was made using a life table. Based on the information obtained during the follow-up, each implant was categorized into one of three groups: unaccounted for, failure, or survival. A qualitative analysis of the survival group was then performed by active testing against defined criteria. Depending on the modes of clinical and radiographic examinations and their results, surviving implants were either further assigned to one of three success grades or remained in the survival group. The data are presented in a four-field table at one level of success. Strict success criteria together with individual stability testing and radiographic examination of each consecutive implant should be used when a new implant system is evaluated or when a new application is explored. Radiography alone and more moderate success criteria may be used to document routine treatments, provided that an already well-documented implant system is studied.     

Usefulness of detection of breast cancer: the part played by the internist

The prognosis of breast cancer is the result of many factors, among which the mass of the tumor at the time of diagnosis remains the most significant: small tumors have a better prognosis than larger ones and are less often accompanied by positive lymph nodes. It is therefore justifiable to search for them systematically by breast examination of all patients over 30. Large-scale mass screening campains in the USA, with clinical and mammographic examination of tens of thousands of women, have proven that it is possible to detect more "early" cancers and reduce general mortality in the groups studied. The number of cancers thus detected is nevertheless so small that it does not justify the investment of so much labour and money in this kind of campaign. Systematic breast examination at regular intervals (6 months to 1 year) with regular mammographies should be confined to patients in the high risk groups: women who have already undergone surgery for cancer of one breast, and patients with a marked family history of breast cancer. For the rest of the female population, the solution seems obvious: every physician should get into the habit of performing regular clinical examination of the breasts. Most gynecologists are already doing so, but they only examine a small part of the population. The most important role in the detection of breast cancer falls to the internists and the general practitioners: they should assume responsibility for all their patients' breasts, in the same manner as they do for heart and lung examinations. They will then request additional examinations (mammography, thermography) as soon as clinical examination reveals a pathological finding. The results of GILBERTSEN [5] confirm that clinical examination remains the most valuable and least expensive method for breast cancer detection.     

Combined neck dissection and postoperative radiation therapy in the management of the high-risk neck: a matched-pair analysis

PURPOSE: Our purpose was to determine the sensitivity, specificity, and receiver operator characteristic (ROC) curve of a fast screening MR protocol in children and adolescents with suspected intracranial tumors. METHODS: One hundred forty-one patients (mean age, 9.7 years; range, 2 months to 23.5 years) with suspected brain tumor were entered in a case-control study. Eighty-seven patients had intracranial tumors (31 suprasellar/hypothalamic, 27 supratentorial, 26 infratentorial, and three pineal) and 54 patients in the control group had other disorders. Two neuroradiologists reviewed blindly a detailed three-sequence conventional protocol (acquisition time, 8 minutes 27 seconds) and a two-sequence fast screening MR protocol (acquisition time, 4 minutes 44 seconds). RESULTS: Sensitivity and specificity of the fast screening protocol for intracranial tumors was 100% and 92.6%, respectively. The areas under the ROC curves were 0.966 for the fast screening and 0.980 for the conventional MR protocol. No diagnostic performance difference was found between the ROC curves using the Az index. A kappa statistic of .93 for both examinations indicated excellent interobserver agreement. Additional MR sequences and other neuroimaging studies were not deemed necessary to exclude the presence of an intracranial tumor. CONCLUSION: A fast dual-plane brain MR protocol may be adequate to screen children and adolescents thought to have an intracranial tumor. The less than 5 minute acquisition time allows a complete examination (including preparation) to be performed in 10 to 15 minutes. Future studies are recommended before this time-efficient neuroimaging examination is incorporated into clinical practice.     

Retropsoas positioned bowel: incidence and clinical relevance

PURPOSE: Our goal was to assess the incidence of retropsoas positioned large or small bowel in the population and to examine factors predisposing to its formation. METHOD: The presence of retropsoas positioned bowel was retrospectively studied in 1,852 abdominal CT examinations of 1,055 men and 797 women, 648 younger and 1,204 older than 50 years. All examinations were considered normal or demonstrated findings that were unrelated to the position of the bowel. RESULTS: Retropsoas positioned colon (RPC) was observed in 51 (2.8%) cases for the ascending and 45 (2.3%) for the descending colon. RPC appeared more frequently in younger (< 50 years) than older patients and in individuals with decreased amount of retroperitoneal fat. Retropsoas position of small bowel loops was observed in 11 (0.6%) patients, all exhibiting paucity of retroperitoneal fat. CONCLUSION: Because of its prevalence, retropsoas positioned bowel should be considered when performing percutaneous diskectomy or other interventional procedures in the posterior retroperitoneum.     

Ten-year risk of false positive screening mammograms and clinical breast examinations

BACKGROUND: The cumulative risk of a false positive result from a breast-cancer screening test is unknown. METHODS: We performed a 10-year retrospective cohort study of breast-cancer screening and diagnostic evaluations among 2400 women who were 40 to 69 years old at study entry. Mammograms or clinical breast examinations that were interpreted as indeterminate, aroused a suspicion of cancer, or prompted recommendations for additional workup in women in whom breast cancer was not diagnosed within the next year were considered to be false positive tests. RESULTS: A total of 9762 screening mammograms and 10,905 screening clinical breast examinations were performed, for a median of 4 mammograms and 5 clinical breast examinations per woman over the 10-year period. Of the women who were screened, 23.8 percent had at least one false positive mammogram, 13.4 percent had at least one false positive breast examination, and 31.7 percent had at least one false positive result for either test. The estimated cumulative risk of a false positive result was 49.1 percent (95 percent confidence interval, 40.3 to 64.1 percent) after 10 mammograms and 22.3 percent (95 percent confidence interval, 19.2 to 27.5 percent) after 10 clinical breast examinations. The false positive tests led to 870 outpatient appointments, 539 diagnostic mammograms, 186 ultrasound examinations, 188 biopsies, and 1 hospitalization. We estimate that among women who do not have breast cancer, 18.6 percent (95 percent confidence interval, 9.8 to 41.2 percent) will undergo a biopsy after 10 mammograms, and 6.2 percent (95 percent confidence interval, 3.7 to 11.2 percent) after 10 clinical breast examinations. For every 100 dollars spent for screening, an additional 33 dollars was spent to evaluate the false positive results. CONCLUSIONS: Over 10 years, one third of women screened had an abnormal test result that required additional evaluation, even though no breast cancer was present. Techniques are needed to decrease false positive results while maintaining high sensitivity. Physicians should educate women about the risk of a false positive result from a screening test for breast cancer.     

Sequence analysis of thyroid transcription factor-1 gene reveals absence of mutations in patients with thyroid dysgenesis but presence of polymorphisms in the 5'' flanking region and intron

The purpose of this study was to determine the optimal scanning technique for lesion detection in a small bowel phantom and to evaluate the virtual endoscopy (VE) technique in patients. A small bowel phantom with a fold thickness of 7 mm and length of 115 cm was prepared with nine round lesions (3 x 1 mm, 2 x 2 mm, 2 x 3 mm, 2 x 4 mm). Spiral CT parameters were 7/7/4, 3/5/2, 3/5/1, 1.5/3/1 (slice thickness/table feed/reconstruction interval). VE was done using volume rendering technique with 1 cm distance between images and 120 degrees viewing angle. Two masked readers were asked to determine the number and location of the lesions. Seven patients underwent an abdominal CT during one breathhold after placement of a duodenal tube and filling of the small bowel with methyl cellulose contrast solution. VE images were compared with the axial slices with respect to detectability of pathology. With the 7/7/4 protocol only the 4-mm lesions were visualised with fuzzy contours. The 3/5/2 protocol showed both 4-mm lesions, one 3-mm lesion and one false positive lesion. The 3/5/1 protocol showed both 4-mm and both 3-mm (one uncertain) lesions with improved sharpness, and no false positive lesions. One 2-mm and one 1-mm lesion were additionally seen with the 1.5/3/1 protocol. Path definition was difficult in sharp turns or kinks in the lumen. In all patients, no difference was found between VE and axial slices for bowel pathology; however, axial slices showed 'outside' information that was not included in VE. We conclude that the 3/5/2 protocol may be regarded as an optimal compromise between lesion detection, coverage during one breathhold, and number of reconstructed images in patients; round lesions of 4 mm in diameter can be detected with high certainty.     

Effects of smoking on the presentation and clinical course of inflammatory bowel disease

OBJECTIVE: To evaluate the influence of regular smoking on the presentation and clinical course of inflammatory bowel disease. METHODS: We performed a case-control study interviewing 160 inflammatory bowel disease patients (63 with Crohn's disease (CD) and 97 with ulcerative colitis (UC)) and 140 first-degree relatives as controls. The risk of developing the disease relative to a smoking habit was calculated as the odds ratio. Furthermore, to evaluate the influence of smoking on the subsequent course of inflammatory bowel disease, we performed a multivariate analysis that included pertinent variables such as the need for surgery, number of hospitalizations and relapses. RESULTS: The pattern of smoking in UC patients was different from that in CD patients. In UC there was a significant predominance of non-smokers and ex-smokers (P = 0.02), whereas smoking habits in CD were not different from those in controls. Giving up smoking was a risk factor to develop UC (odds ratio: 3.2, P = 0.02). In UC, non-smokers and specially ex-smokers need surgery more frequently than smokers (P < 0.01). Otherwise the relapse/year index was not influenced by smoking. In CD there was a non-significant association between smoking habits and the various clinical parameters analysed. UC patients who begin smoking after diagnosis of the disease present a significant reduction in the number of recurrences. CONCLUSION: Smoking habit significantly affects the presentation and clinical course of UC, whereas in CD, a smoking habit does not have any apparent influence on the disease.     

Evaluation of the endomysial antibody for celiac disease: operating properties and associated cost implications in clinical practice

OBJECTIVE: To evaluate the operating properties of endomysial antibodies (EMAs) in the diagnosis of celiac disease and to examine, using a cost minimization model, different strategies used in the diagnosis of celiac disease. METHODS: A total of 248 EMA results were reviewed and compared with small bowel biopsy results in 66 patients who had undergone both tests. Regression analysis was used to look for predictors of positive EMA results and positive biopsy results. A cost minimization model from a societal perspective was used to evaluate the cost differences among three different strategies. RESULTS: EMAs had a sensitivity of 95% and specificity of 64%. The only predictor of a positive biopsy result that reached statistical significance was a positive EMA. The strategy of EMA as a diagnostic test for celiac disease was the most expensive strategy, with a cost of $3,174 per patient assessed. The strategy of small bowel biopsy for all patients had a cost of $997, and a strategy of EMA followed by small bowel biopsy for positive patients had a cost of $866 per patient. The results were sensitive to cost of a gluten-free diet, the specificity of the EMA and the cost of a small bowel biopsy. CONCLUSION: The EMA is best used as a screening test from both a clinical and cost perspective.     

Phase I pilot study of the effects of trovafloxacin (CP-99,219) on the pharmacokinetics of theophylline in healthy men

INTRODUCTION: We report on a cost-effective easy-access software developed for the functional integration of the clinical records and history of oncologic patients with the management of the Day Hospital of the Radiotherapy Department of the University Hospital A. Gemelli, in Rome. MATERIAL AND METHODS: The software was designed to archive the clinical records and history of oncologic patients and the relative chemotherapy, to manage the examination scheduling, to draw up nursing files with the planned therapy and to make statistical analyses of the department activity. Five forms are available: the patient form, recording patient data; the admission form, recording the type of therapy (e.g., chemotherapy, tests, medical examinations, etc.), the relative cost and chemotherapy protocol, detailing for instance the type of drug; the nursing file, detailing chemotherapy schedule and the dilution of each drug; the menu, to select and retrieve any record. The minimum configuration requires a 386 Intel CPU, 4 Mb RAM and 4 Mb free on the hard disk. The software is the File Maker Pro 2.1 for Windows which can interact with Apple Macintosh computers. RESULTS: Since October, 1995, we have saved the clinical records of 272 oncologic outpatients (2415 entries in all), with a mean of 201/month. This computer system permitted us to save and retrieve data for both clinical and didactic purposes and to plan our activity. CONCLUSIONS: One year after it was implemented and used in clinical practice, the system is a cost-effective and user-friendly tool for the management of the Radiochemotherapy Day Hospital of our Radiotherapy Department.     

Predictors of intracranial pathologic findings in patients who seek emergency care because of headache

BACKGROUND: Clinical criteria to select patients with headache in whom structural diagnostic studies (computed tomography) have a high yield disclosing intracranial pathologic findings, independent of abnormal findings on neurologic examination, have not been defined. OBJECTIVE: To determine which clinical characteristics predict the presence of intracranial pathologic findings, independently of neurologic examination, in patients with headache. DESIGN: Case-control, consecutive sample. SETTING: Major metropolitan trauma center emergency department. PATIENTS AND MATERIALS: Hospital records of 139 hospitalized and 329 randomly selected patients from 1720 nonhospitalized adult patients, consecutively evaluated for headache in the emergency department, were reviewed. Demographic data, clinical characteristics of the headache, results of neurologic and physical examinations, and diagnostic radiologic and laboratory results were correlated with final diagnosis and outcome at 6 months after emergency department visit. DATA ANALYSIS: Nonparametric statistical analysis. RESULTS: Intracranial pathologic findings were found in 18 (3.8%) of 468 patients. Acute onset and occipitonuchal location of headache, presence of associated symptoms, and patient age of 55 years or older were significantly associated with the finding of intracranial pathology, independently of the findings from neurologic examination. Abnormal findings on neurologic examination alone, whether focal or nonfocal, had a highly significant association and a positive predictive value for intracranial pathology of 39%. CONCLUSIONS: Abnormal results from neurologic examination are the best clinical parameters to predict structural intracranial pathology; however, in patients 55 years or older with headache of acute onset located in the occipitonuchal region that has associated symptoms, computed tomographic scan of the head is justified as part of their clinical evaluation independently of the findings of the neurologic examination.     

Protection by endoscopy against death from colorectal cancer. A case-control study among veterans

BACKGROUND: Although several clinical and epidemiologic studies suggest that timely diagnostic procedures of the large bowel may reduce mortality from colorectal cancer, the evidence for this relationship is primarily circumstantial. METHODS: A case-control study was conducted among hospitalized US military veterans to investigate whether diagnostic procedures of the large bowel were performed in the period preceding the diagnosis of colorectal cancer less frequently in patients dying of colorectal cancer than in control patients. Data files of a total of 4411 veterans dying of colorectal cancer between 1988 and 1992 were extracted from the records of the US Department of Veterans Affairs, Washington, DC. Data of four living control patients and four dead control patients without colorectal cancer were matched by age, sex, and race to each case patient. The case and the two control populations were compared by conditional logistic regression, calculating odds ratios, and their 95% confidence interval. RESULTS: Diagnostic procedures of the large bowel reduced mortality from colorectal cancer, the odds ratio being 0.41 (range, 0.33 to 0.50) for the comparison with living control patients. The protective effects of proctosigmoidoscopy, colonoscopy, and polypectomy lasted for 5 years. The procedures were protective against death from cancer of the colon, as well as cancer of the rectum. The most protective influence was associated with removal of tissue through biopsy, fulguration, and polypectomy. Similar influences were found comparing case patients with dead control patients. CONCLUSION: Removal of tissue represents the most effective means to reduce mortality from cancers of the large bowel. It retains its efficacy over a time period of 5 years.     

A randomized trial of physicians and physical therapists as instructors of the musculoskeletal examination

OBJECTIVE: To evaluate the effectiveness of physicians vs physical therapists as instructors of the musculoskeletal examination to second year medical students. METHODS: A randomized trial conducted over 3 consecutive years in a physical diagnosis course at The University of North Carolina. During the first (baseline) year, medical students received education about the musculoskeletal examination from a lecture and supervision by clinical preceptors. This increased in the second and third (intervention) years where random halves of each class received supplementary clinical instruction which included a structured manual, a videotape, and supervised practice with either general internal medicine physicians or physical therapists. Outcomes were measured from student performance on a practical test of clinical skills, and by written student evaluations of the supplementary instruction. RESULTS: As measured on the clinical examination, performance during the intervention years improved over that during the baseline year in both intervention groups. Measures of medical students' clinical skills did not correlate with measures of academic aptitude. CONCLUSIONS: Clinical education about the musculoskeletal examination should be structured and systematic. Medical students prefer clinical education that is active, provides clear directions, and gives them performance feedback.     

Nonradiographic assessment of enteral feeding tube position

OBJECTIVE: To determine whether a clinical, nonradiographic criterion can be used to predict when the tip of a blindly placed feeding tube is in the small intestine. DESIGN: Prospective sample. SETTING: Pediatric intensive care unit at a tertiary care children's hospital. PATIENTS: Critically ill children requiring transpyloric feeding. INTERVENTIONS: The small bowel was intubated, using a blind, bedside transpyloric feeding tube placement protocol. The feeding tube was considered to be in the small bowel when <2 mL of a 10- mL aliquot of insufflated air could be aspirated from the feeding tube. This clinical criterion was confirmed with an abdominal radiograph. MEASUREMENTS AND MAIN RESULTS: Patient age ranged from 1 month to 19 yrs (median 6 months). Weight ranged from 2.2 to 60 kg (median 4.9). Median time to feeding tube placement was 10 mins (range 5 to 60). Eighty-nine percent of the patients were mechanically ventilated, while 28% of these patients were pharmacologically paralyzed. Seventy-five feeding tubes were inserted. There were no known complications. Ninety-nine (74/75) percent of the feeding tubes were positioned in the small bowel. The inability to aspirate insufflated air correctly predicted small bowel intubation with 99% certainty (Sequential Probability Ratio Test, p = .05 and power = .80). This test incorrectly predicted the position of only one feeding tube, the 26th, which was in the stomach. Of the 74 feeding tubes positioned in the small bowel, 13 feeding tubes were in the duodenum and 61 were in the jejunum. CONCLUSIONS: The inability to aspirate insufflated air confirms the transpyloric position of a feeding tube. Other clinical criteria did not successfully predict small bowel intubation. Use of this single test may obviate confirmatory abdominal radiographs in carefully selected patients and may lead to more cost-effective and timely initiation of enteral feedings.     

Epidemiological aspects of inflammatory bowel disease in a north Italian population: a 4-year prospective study

OBJECTIVE: To determine the incidence and clinical characteristics at presentation of inflammatory bowel disease (IBD) in a defined area of north Italy. DESIGN: A 4-year prospective population-based epidemiological study. SETTING: An area in Lombardia defined by the National Health Service scheme with about 294,000 inhabitants, two referral hospitals and 259 general practitioners (GPs). PATIENTS: Subjects presenting to a GP with symptoms compatible with IBD underwent a diagnostic work-up at one of the referral hospitals. Those with ulcerative colitis (UC), Crohn's disease (CD) or indeterminate colitis diagnosed according to a defined protocol were included, as were residents of the area with IBD diagnosed elsewhere. Rigid case ascertainment methods were used. Patients were followed for one year; 125 patients were identified. RESULTS: The patient ascertainment rate was constant over the 4 years; UC was diagnosed in 82 patients, CD in 40, and indeterminate colitis in three. The mean annual incidence of IBD for the whole period was 10.6/10(5) inhabitants (95% confidence limits, 7.2-15.1), 7.0/10(5) for UC (4.3-10.7) and 3.4/10(5) (1.6-6.3) for CD. The mean interval between onset of symptoms and diagnosis was under 6 months. The clinical characteristics of our patients were similar to those of north European and American series. CONCLUSION: The incidence of IBD was higher than previously observed in Italy but was still lower than in some north European countries and in the USA. Our data could be used as a basis for future longitudinal studies and in international comparative investigations.     

Mesenteric vasculitis associated with Sézary syndrome

A 71 year old lady with Sézary syndrome presented with chronic diarrhoea and cramping abdominal pains. A small bowel meal x ray examination showed two mid-ileal strictures. At laparotomy the small intestine was found to be sub-acutely obstructed and resection of a 15 cm ileal stricture and stricturoplasty of a second, 10 cm stricture were performed. Histological examination of the stricture revealed a mesenteric vasculitis with secondary ischaemic changes in the small bowel wall. Mesenteric vasculitis causing small bowel stricture may be associated with Sézary syndrome.     

Uterine artery embolization for the treatment of uterine fibroids

Masking bias is hypothesized to explain associations between breast density and breast cancer risk. Tumours in dense breasts may be concealed at the initial examination, but manifest themselves in later years, suggesting an increase in breast cancer incidence. We studied the association between breast density and breast cancer risk in 0, 1-2, 3-4 and 5-6 year periods between initial examination and diagnosis. We studied 359 cases and 922 referents, identified in a breast cancer screening programme in Nijmegen, The Netherlands. Breast density was assessed at the initial examination and classified as 'dense' (if > 25% of the breast was composed of density) or 'lucent' (< or = 25% density). In women examined with mid-1970s film screen mammography, we found that at time 0 the odds ratio (OR) for women with dense breasts compared to those with lucent breasts was 1.4 (95% confidence interval (CI): 0.7-6.2). After a 3-4 year period the risk was increased to 3.3 (95% CI: 1.5-7.1). Then, the risk decreased again (OR: 1.2, 95% CI: 0.6-2.7). This rise and decline in risk are in accordance with the masking hypothesis. The observation, however, that the risk at time 0 does not appear to be lower for women with dense breasts than for those with lucent breasts, seems to be inconsistent with the masking hypothesis and may be indicative of causality. The same analysis were performed in women whose initial screening examination was done with current high-quality mammography. Due to the small size of this study group no firm conclusions could be drawn, but it seems as if masking bias could still play a role with high-quality mammography.     

Impalpable breast cysts: utility of cytologic examination of fluid obtained with radiologically guided aspiration

PURPOSE: To evaluate the utility of cytologic analysis of fluid obtained from impalpable breast cysts by means of radiologically guided aspiration. MATERIALS AND METHODS: The authors retrospectively reviewed the reports of cytologic examinations of fluid obtained with sonographically or mammographically guided aspiration of 660 impalpable breast cysts in 583 women during 3 1/2 years. RESULTS: No malignant cells (541 cysts) or insufficient cellular material (86 cysts) was seen with cytologic examination of 95% of the aspirates. Atypical cells were seen with cytologic examination of fluid from 33 (5%) lesions. None of these 33 lesions were found to represent malignancy at the time of surgical excision (n = 9) or during clinical follow-up (n = 24). CONCLUSION: Routine cytologic examination is unnecessary if the fluid obtained with radiologically guided aspiration from impalpable breast cysts is not bloody.     

Computer aided, examiner independent screening for inapparent eye misalignment among 590 infants and preschoolers--a pilot study with an orthoptic gold standard

BACKGROUND: The purpose of the study was to investigate the computer aided screening method using Purkinje image I and IV reflection patterns for the detection of inapparent eye misalignment and to compare this to an orthoptic examination. MATERIALS AND METHODS: 590 subjects up to 72 months of age with inapparent eye misalignment were recruited from the orthoptic outpatient department and externally. The computer aided screening consisted of taking a series of still video pictures with Purkinje reflection patterns. These were evaluated in an examiner independent way to reach a recommendation whether the child needed an ophthalmological referral or not. As gold standard, an orthoptic examination was performed. For analysis, the data were split by age groups. The orthoptic results were tested for certainty and repeatability. RESULTS: The computer aided examination had the highest sensitivity of 0.82 in the age group up to 2.5 years of age, and a specificity of 0.90. With an estimated prevalence for microtropia of 0.01, the extrapolated positive predictive value was 0.08, and the negative predictive value was 0.998. In the age group up to 2.5 years of age, the percentage of orthoptic examinations without clear result (neither non-referral, nor strabismic) was 22.4%, and 6.1% in the screening examination. Among the cases which were examined repeatedly, some were classified as "strabismic" in the beginning, and as "non-referral" in the end in the orthoptic examinations. CONCLUSIONS: The examiner independent, computer aided screening method is a cost effective option for the screening for inapparent eye misalignment, especially in the age group up to 2.5 years of age. If an orthoptic examination was carried out for screening, one should expect a higher rate of false positives, which entails more costly ophthalmological checks. Future studies should assess the validity of the single ortoptic examination as the gold standard in this age group.     

Central corneal endothelial cell changes over a ten-year period

PURPOSE: To obtain longitudinal data to estimate long-term morphometric changes in normal human corneal endothelia. METHODS: Ten years after an initial study, the authors rephotographed the central corneal endothelium of 52 normal subjects with the same contact specular microscope. The findings for the 10 subjects younger than 18 years of age at the initial examination were considered separately. For the remaining 42 adult subjects, the time between examinations averaged 10.6 +/- 0.2 years (range, 10.1 to 11 years). At the recent examination, these subjects' ages averaged 59.5 +/- 16.8 years (range, 30 to 84 years). Outlines of 100 cells for each cornea were digitized. RESULTS: For the 42 adult subjects, the mean endothelial cell density decreased during the 10.6-year interval from 2715 +/- 301 cells/mm2 to 2539 +/- 284 cells/mm2 (P < 0.001). The calculated exponential cell loss rate over this interval was 0.6% +/- 0.5% per year. There was no statistically significant correlation between cell loss rate and age. During the 10.6-year interval, the coefficient of variation of cell area increased from 0.26 +/- 0.05 to 0.29 +/- 0.06 (P < 0.001), and the percentage of hexagonal cells decreased from 67% +/- 8% to 64% +/- 6% (P = 0.003). For the 10 subjects 5 to 15 years of age at the initial examination, the exponential cell loss rate was 1.1% +/- 0.8% per year. CONCLUSIONS: Human central endothelial cell density decreases at an average rate of approximately 0.6% per year in normal corneas throughout adult life, with gradual increases in polymegethism and pleomorphism.