Miriam B. Zimmerman

The agility total ankle arthroplasty seven to sixteen-year follow-up

BACKGROUND We previously reported the intermediate-term results with the early version of the Agility total ankle replacement, a unique design that takes advantage of arthrodesis of the tibiofibular syndesmosis for tibial component support. The purpose of this study was to report longer-term results of this procedure in the treatment of disabling ankle arthritis. METHODS We conducted an independent review of all Agility total ankle replacements performed by a single surgeon between 1984 and 1994. Follow-up evaluation consisted of completion of a validated ankle osteoarthritis scale and a short questionnaire and a review of the radiographs. All radiographs were evaluated for evidence of the development of progressive hindfoot arthritis, nonunion of the tibiofibular syndesmosis, progressive radiolucent lines, osteolysis, and component subsidence. RESULTS One hundred and thirty-two arthroplasties were performed in 126 patients. After a mean follow-up period of nine years, thirty-three patients (thirty-six implants) had died, fourteen patients (11%) had a revision of the implant or an ankle arthrodesis, and one had the leg amputated because of an unrelated cause. Of the remaining seventy-eight patients (eighty-one ankles), sixty-seven (sixty-nine ankles) were followed clinically. More than 90% of them reported that they had decreased pain and were satisfied with the outcome of the surgery. We found modest differences in a comparison of the pain and disability scores with those of age-matched controls. Of the 117 ankles that had been followed radiographically for a minimum of two years, twenty-two (19%) had progressive subtalar arthritis, seventeen (15%) had progressive talonavicular arthritis, and nine (8%) had a syndesmosis nonunion. Eighty-nine (76%) of the 117 ankles had some evidence of peri-implant radiolucency. CONCLUSIONS Arthrodesis of the tibiofibular syndesmosis impacts the radiographic and clinical outcomes with the Agility total ankle replacement. The relatively low rates of radiographic hindfoot arthritis and revision procedures at an average of nine years after the arthroplasty are encouraging. Agility total ankle replacement is a viable and durable option for the treatment of ankle arthritis in selected patients.

Role of Nocturnal Arterial Hypotension in Optic Nerve Head Ischemic Disorders

Objective: To investigate the role of nocturnal arterial hypotension, intraocular pressure (IOP) and heart rate in optic nerve head (ONH) ischemic disorders, and the effects of systemic factors and topical β-blocker eye-drops on nocturnal arterial hypotension and heart rate. Methods: We investigated prospectively, by 24-hour ambulatory blood pressure (BP) monitoring and diurnal curve of the IOP, 275 white patients with anterior ischemic optic neuropathy (AION – 114), normal tension glaucoma (NTG – 131) and primary open angle glaucoma (POAG – 30). Results: Hourly average BP data analyses showed a significantly greater drop in mean diastolic BP (p < 0.009) at night in NTG than AION. Cases with visual field deterioration had significantly (p = 0.05) lower minimum nighttime diastolic BP. Arterial hypertensives on oral hypotensive therapy showed a significantly lower mean nighttime systolic BP (p = 0.006) and larger mean percentage drop in systolic (p < 0.0001), diastolic (p = 0.0009) and mean (p < 0.0001) BPs. Normotensives and hypertensives without therapy had no such difference. IOP showed no significant correlation with visual field deterioration in any of these conditions. Patients using β-blocker eyedrops, compared with those not using them, had greater percentage drop in diastolic BP (p = 0.028), lower minimum nighttime diastolic BP (p = 0.072) and lower minimum nighttime heart rate (p = 0.002). Conclusions: Findings of our study suggest that nocturnal hypotension, by reducing the ONH blood flow below a crucial level during sleep in a vulnerable ONH, may play a role in the pathogenesis of AION and glaucomatous optic neuropathy (GON) and progression of visual loss in them. Thus, nocturnal hypotension may be the final insult in a multifactorial situation.

MENOPAUSE AND TEAR FUNCTION : THE INFLUENCE OF PROLACTIN AND SEX HORMONES ON HUMAN TEAR PRODUCTION

PURPOSE The onset of dry eye is very common during menopause and may result from the loss of hormonal support. The purpose of this study was to assess the effect that changes in sex hormone and prolactin levels have on tear function in premenopausal and menopausal woman. METHODS Women between the ages of 30 and 60 were solicited to participate in a study concerning menopause and tear function. One-hundred and ten women were given tear function tests (osmolarity, tear volume, tear flow, Schirmers test) and serum levels were measured for total testosterone, estradiol, prolactin, and follicle stimulating hormone. RESULTS For all women on hormone replacement therapy, we found a strong negative correlation between serum prolactin level and tear function. For women in menopause, total testosterone correlated positively with tear function, whereas for premenopausal women there was a negative correlation between total testosterone and tear function. Serum estradiol levels correlated positively with tear function for women 30-39 years of age, whereas for menopausal women the correlation was negative. CONCLUSIONS This is the first demonstration in humans that tear production is correlated with serum prolactin and sex hormone levels prior to and during the menopause.

Model for ocular tear film function

Blepharitis patients have a number of disturbances in their tear film associated with meibomian gland dysfunction that affect evaporation and tear osmolarity. We tested a series of 156 consecutive patients, with a presumed diagnosis of blepharitis, dry eye, or allergic disease, and a series of 72 normals. We compared their tear film characteristics using tear osmolarity, tear volume, tear production (fluorophotometric and Schirmer test), tear turnover (decay constant), tear evaporation, and meibomian gland function evaluated by gland drop-out, expressed lipid viscosity, and volume. Of the 156 patients tested, we found 37 had only dry eye, 10 had only allergic disease, 73 had meibomian gland dysfunction and dry eye, and 36 had only meibomian gland dysfunction. We created a model of the relative influence some of these factors had on each other using their correlation coefficients. The highest correlations for osmolarity were Schirmer test (-0.44), lipid volume low (-0.44), lipid viscosity high (0.39), gland drop-out (0.39), and tear evaporation (0.36). With regression analysis we accounted for 47% of the total variation in osmolarity, but only 17% of the variation in tear evaporation. We also present our classification system for blepharitis and dry eye patients based on our measurable physiologic parameters.

Natural history of pelvic organ prolapse in postmenopausal women

OBJECTIVE: To describe the natural history of pelvic organ prolapse and risk factors for changes in vaginal descent in older women. METHODS: This 4-year prospective observational study included 259 postmenopausal women with a uterus enrolled at one Women’s Health Initiative clinical site who completed at least two annual pelvic organ prolapse quantification (POP-Q) examinations. We calculated 1-year and 3-year incidence and resolution risks for prolapse (defined as maximal vaginal descent to or beyond the hymen) and estimated progression and regression rates (1 cm or greater and 2 cm or greater changes in maximal vaginal descent) and risk factors. RESULTS: Mean age was 68.1±5.5 years, and median vaginal parity was 4. Seventy-three (28%) women had four exams, 128 (49%) had three exams, and 58 (22%) had two exams. Prolapse waxed and waned yearly in individual women. Overall 1-year and 3-year prolapse incidences were 26% (95% confidence interval [CI] 20–33%) and 40% (95% CI 26–56%); 1-year and 3-year prolapse resolution risks were 21% (95% CI 11–33%) and 19% (95% CI 7–39%). Rates of any change in maximal vaginal descent over time varied depending on baseline measurements. Over 3 years, the maximal vaginal descent increased by at least 2 cm in 11.0% (95% CI 4.9–20.5%) of the women and decreased by at least 2 cm in 2.7% (95% CI 0.3–9.5%). Increasing body mass index and grand multiparity increased the risk for vaginal descent progression. CONCLUSION: Prolapse progresses and regresses in older women, although rates of vaginal descent progression are slightly greater than regression overall. Obesity is a risk factor for progression in vaginal descent. LEVEL OF EVIDENCE: III

Effects of transcutaneous electrical nerve stimulation on pain, pain sensitivity, and function in people with knee osteoarthritis: a randomized controlled trial.

Background Transcutaneous electrical nerve stimulation (TENS) is commonly used for the management of pain; however, its effects on several pain and function measures are unclear. Objective The purpose of this study was to determine the effects of high-frequency TENS (HF-TENS) and low-frequency TENS (LF-TENS) on several outcome measures (pain at rest, movement-evoked pain, and pain sensitivity) in people with knee osteoarthritis. Design The study was a double-blind, randomized clinical trial. Setting The setting was a tertiary care center. Participants Seventy-five participants with knee osteoarthritis (29 men and 46 women; 31–94 years of age) were assessed. Intervention Participants were randomly assigned to receive HF-TENS (100 Hz) (n=25), LF-TENS (4 Hz) (n=25), or placebo TENS (n=25) (pulse duration=100 microseconds; intensity=10% below motor threshold). Measurements The following measures were assessed before and after a single TENS treatment: cutaneous mechanical pain threshold, pressure pain threshold (PPT), heat pain threshold, heat temporal summation, Timed “Up & Go” Test (TUG), and pain intensity at rest and during the TUG. A linear mixed-model analysis of variance was used to compare differences before and after TENS and among groups (HF-TENS, LF-TENS, and placebo TENS). Results Compared with placebo TENS, HF-TENS and LF-TENS increased PPT at the knee; HF-TENS also increased PPT over the tibialis anterior muscle. There was no effect on the cutaneous mechanical pain threshold, heat pain threshold, or heat temporal summation. Pain at rest and during the TUG was significantly reduced by HF-TENS, LF-TENS, and placebo TENS. Limitations This study tested only a single TENS treatment. Conclusions Both HF-TENS and LF-TENS increased PPT in people with knee osteoarthritis; placebo TENS had no significant effect on PPT. Cutaneous pain measures were unaffected by TENS. Subjective pain ratings at rest and during movement were similarly reduced by active TENS and placebo TENS, suggesting a strong placebo component of the effect of TENS.

Morphologic Changes in Chronic High-pressure Experimental Glaucoma in Rhesus Monkeys

PURPOSE To investigate morphologic changes in the posterior segment of the eye and optic nerve head (ONH) in rhesus monkeys with experimental glaucoma, and to evaluate the effect of age and vascular disease on the glaucomatous damage. METHODS This study was conducted in 36 eyes of rhesus monkeys 11 to 24 years of age. Experimental glaucoma was produced by laser photocoagulation of the anterior chamber angle in 28 eyes, and the remaining 8 eyes served as the nonglaucomatous group. Of the 28 glaucomatous eyes, 19 belonged to animals with experimental atherosclerosis and chronic arterial hypertension (A-H group); the remaining 9 had no A-H (non-AH group). Among the 8 eyes without glaucoma, 5 belonged to A-H animals and the remaining 3 to animals without A-H. All eyes underwent IOP measurements and fundus photography before laser photocoagulation and serially thereafter for 4 to 60 months (median 22.5 months). After enucleation, eyes were fixed in formalin for light microscopic studies. Morphologic abnormalities were evaluated and graded. Correlation analyses between morphologic parameters and clinical data were performed. RESULTS The highest IOP ranged from 44 to 80 mmHg, but during the follow-up period median IOP was mostly 28 mmHg (mean 27+/-4.8 mmHg). On histopathologic examination, the eyes showed moderate to severe atrophy of the temporal peripapillary choroid (67%), choriocapillaris (70%), and RPE (12%); axonal atrophy in the retinal nerve fiber layer (85%), prelaminar region (69%), lamina cribrosa (66%), and retrolaminar region (82%); fibrous septal thickening in the lamina cribrosa (77%) and retrolaminar region (86%); bowing backward of the lamina cribrosa (77%); overall tissue atrophy in the prelaminar region (81%); and retinal ganglion cell atrophy (74%). The data showed a positive correlation between the ONH damage and atrophic changes in the temporal peripapillary choroid, and suggested greater damage in animals with A-H than in those without A-H. CONCLUSION Vascular disease may influence glaucomatous damage in the ONH, as damage in the ONH was greater in animals with A-H than in those without A-H. A similar relationship also may exist between age and glaucomatous damage, but this needs to be investigated further in a larger study. It is postulated that the bowing back of the lamina cribrosa seen in optic disc cupping is produced by retrolaminar septal fibrosis and axonal loss. Although elevated IOP no doubt played an important role, the data suggest that the glaucomatous changes that were observed in this study are not simply mechanical in nature (due to the raised IOP), but may represent a multifactorial phenomenon.

Role of thrombocytosis in diagnosis of giant cell arteritis and differentiation of arteritic from non-arteritic anterior ischemic optic neuropathy.

Purpose To investigate the role of thrombocytosis in the diagnosis of giant cell arteritis (GCA), and differentiation of arteritic (A-AION) from non-arteritic (NA-AION) anterior ischemic optic neuropathy; and comparison of the sensitivity and specificity of platelet count to that of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and some other hematologic variables in the diagnosis of GCA. METHODS This retrospective study is based on 121 temporal artery biopsy confirmed GCA patients and 287 patients with NA-AION seen in our clinic. For inclusion in this study, all GCA patients, at their initial visit, prior to the initiation of corticosteroid therapy, must have had ESR (Westergren), platelet count and complete blood count, and temporal artery biopsy. From 1985 onwards CRP estimation was done. For inclusion in this study, all NA-AION patients at the initial visit must have undergone evaluation similar to that described above for GCA, except for temporal artery biopsy. Wilcoxon rank-sum test and the two-sample t-test were used to compare hematologic variables between GCA patients with and without visual loss, between those with and without systemic symptoms, and also between GCA and NA-AION patients. Pearson correlation coefficient was computed to measure the association of platelet counts and the other hematologic variables with ESR. Receiver operating characteristic (ROC) curves were constructed for ESR, CRP, platelet count, combinations of ESR and platelet count, and CRP and platelet count, hemoglobin, hematocrit, and white blood cell (WBC) count and the area under the curve (AUC) were compared. Results Comparison of ESR, CRP, and hematologic variables of GCA patients and of A-AION with the NA-AION group, showed significantly (p <0.0001) higher median levels of ESR, CRP, platelet count, and WBC count and lower levels of hemoglobin and hematocrit in the GCA patients and A-AION than in NA-AION. Comparing AUC of the ROC curve between ESR and platelet count, ESR was a better predictor of GCA compared to platelet count (AUC of 0.946 vs. 0.834). There was a slight improvement in prediction of GCA using the combination of ESR and platelet count (AUC=0.953). The other hematologic variables had an AUC that was smaller than platelet count (0.854 for hemoglobin; 0.841 for hematocrit), with WBC being the least predictive of GCA (AUC=0.666). The AUC of the ROC curve for CRP was 0.978. There was no improvement in prediction of GCA using platelet count in combination with CRP (AUC=0.976). CONCLUSIONS Patients with GCA had significantly (p <0.0001) higher values of platelet count, ESR, CRP and WBC but lower values for hemoglobin and hematocrit compared to the NA-AION group. Predictive ability of an elevated platelet count did not surpass elevated ESR or CRP as a diagnostic marker for GCA. Thrombocytosis may complement ESR. Hemoglobin, hematocrit and WBC were much less predictive of GCA. Elevated CRP had a greater predictive ability for GCA compared to ESR or the other hematologic parameters; thrombocytosis in combination with CRP did not yield an improvement in prediction of GCA.

Assessment of the tear film with tandem scanning confocal microscopy.

Purpose: To evaluate the confocal microscopic appearance of the tear film by correlating the interference pattern created by the lipid surface with physiologic measurements of tear function and with clinic diagnosis. Methods A series of 53 patients was examined with a battery of tests to evaluate the tear film and with confocal microscopy to evaluate the interference pattern created by the lipid surface of the tear film. Assessment of the tear-film appearance involved five nonparametric scales: degree of debris in the tear film, variability of the interference pattern over time, linearity of the interference pattern, number of dry spots seen, and relative thickness of the lipid layer. For 10 other subjects, the confocal appearance of the tear film and evaporation from the ocular surface was tested for before and after meibomian gland expression. Results The confocal appearance correlated with multiple physiologic variables and clinical diagnosis. Patients with seborrheic meibomian gland dysfunction had a thicker lipid layer, greater variability, and more debris than did patients with obstructive meibomian gland dysfunction. After meibomian gland expression, lipid thickness and linearity increased, whereas pattern variability and evaporation decreased significantly. The mean reduction in evaporation was 48%. Conclusions Confocal microscopy can be used to examine the tear film, and its appearance correlates significantly with physiologic variables in normal individuals and in disease states. The confocal appearance of the lipid interference patterns and evaporation from the ocular surface are altered after lipid expression from meibomian glands.

Achievement test performance in children conceived by IVF

BACKGROUND Long-term follow-up studies of children conceived by IVF are limited. We examine academic performance on standardized tests [Iowa Tests of Basic Skills/Educational Development (ITBS/ITED)] of children conceived by IVF. METHODS Parents of children 8-17 years of age at the onset of the study (March 2008) who were conceived by IVF at the University of Iowa Hospitals and Clinics and living in the state of Iowa were contacted by mail. Parents completed questionnaires on their childs health and education and parental education. ITBS/ITED scores from school grades 3-12 were obtained on IVF children and a group of anonymous children matched by grade, year, gender and school district. Scores were analyzed using linear mixed models. RESULTS Four hundred and ninety-seven couples were contacted. Two hundred and ninety-five couples (463 children) agreed to participate (59.4% of parents), with ITBS/ITED scores available on 423 children (91.4% of participants). IVF children scored higher than the national mean (P < 0.0001) across all grades and subtests and higher than their matched peers for grades 3-11. A trend toward lower test scores in multiple gestations was present (but not significant). Factors found to affect test scores included parental level of education, maternal age, divorce and childs BMI. Cryopreservation, length of embryo culture and method of insemination did not affect scores. CONCLUSIONS IVF children scored higher on standardized tests than their matched peers, suggesting that IVF does not have a negative effect on cognitive development. However, long-term follow-up of IVF children is still limited. Further research should be performed on the effect of multiple gestation on academic performance.