Diagnostic delay in patients with FKRP-related muscular dystrophy.

Diagnostic journey for people with FKRP mutations participating in a dystroglycanopathy natural history study (n = 68; NCT00313677) was analyzed. Earliest symptoms and age at muscular dystrophy diagnosis were abstracted from subject-reported medical history and record review. Initial signs/symptoms were classified as chronic motor dysfunction (e.g., delayed motor milestones, weakness, falling; n = 40, 59%), elevated transaminases (n = 7, 10%), or acute/intermittent symptoms (myoglobinuria, myalgia, febrile illness-associated acute weakness; n = 21, 31%). Median time from sign/symptom onset to diagnosis was 6.5 years and differed by symptom group: 7.5 years for motor group, 9 years for acute/intermittent group, and 4 years for elevated transaminases group. The sign/symptom category that most commonly resulted in a diagnosis was chronic motor dysfunction (n = 45). Of those without clear weakness as first symptom (n = 55), 36.4% were not diagnosed with MD until weakness became apparent. Median time to diagnosis was shortest for those with febrile illness-associated acute weakness (0.25 years). Median time from first sign/symptom to MD diagnosis has decreased incrementally from 18.8 years for those with onset in the 1970s to < 10 years for symptom onset occurring after 2000. Awareness of disease presentation variability will aid in earlier diagnosis, which is increasingly important with treatments in development.

Efficacy of Alveolar Ridge Preservation: A Randomized Controlled Trial.

Alveolar ridge preservation (ARP) therapy is indicated to attenuate the physiologic resorptive events that occur as a consequence of tooth extraction with the purpose of facilitating tooth replacement therapy. This randomized controlled trial was primarily aimed at testing the efficacy of ARP as compared with unassisted socket healing. A secondary objective was to evaluate the effect that local phenotypic factors play in the volumetric reduction of the alveolar bone. A total of 53 subjects completed the study. Subjects were randomized into either the control group, which involved only tooth extraction (EXT n = 27), or the experimental group, which received ARP using a combination of socket grafting with a particulate bone allograft and socket sealing with a nonabsorbable membrane (dPTFE) following tooth extraction (ARP n = 26). A set of clinical, linear, volumetric, implant-related, and patient-reported outcomes were assessed during a 14-wk healing period. All linear bone assessments (horizontal, midbuccal, and midlingual reduction) revealed that ARP is superior to EXT. Likewise, volumetric bone resorption was significantly higher in the control group (mean ± SD: EXT = -15.83% ± 4.48%, ARP = -8.36% ± 3.81%, P < 0.0001). Linear regression analyses revealed that baseline buccal bone thickness is a strong predictor of alveolar bone resorption in both groups. Interestingly, no significant differences in terms of soft tissue contour change were observed between groups. Additional bone augmentation to facilitate implant placement in a prosthetically acceptable position was deemed necessary in 48.1% of the EXT sites and only 11.5% of the ARP sites (P < 0.004). Assessment of perceived postoperative discomfort at each follow-up visit revealed a progressive decrease over time, which was comparable between groups. Although some extent of alveolar ridge remodeling occurred in both groups, ARP therapy was superior to EXT as it was more efficacious in the maintenance of alveolar bone and reduced the estimated need for additional bone augmentation at the time of implant placement (ClinicalTrials.gov NCT01794806).

Nasotracheal intubation over a bougie vs. non-bougie intubation: a prospective randomised, controlled trial in older children and adults using videolaryngoscopy.

Conventionally, nasotracheal intubation has consisted of blind nasal passage and external manipulation of the tube through the glottis ('conventional technique'), a technique associated with a high incidence of nasal trauma. We evaluated a novel technique for routine asleep (i.e. post-induction) nasotracheal intubation using a bougie ('bougie technique'), which uses a nasopharyngeal airway to guide a paediatric bougie nasotracheally for use as a Seldinger tracheal intubation guide. Two hundred and fifty-seven older children (> 8 years) and adults were randomly assigned to videolaryngoscopy-assisted nasotracheal intubation using either the conventional or the bougie technique. The hypothesis was that the bougie technique would result in less nasopharyngeal trauma. The bougie technique was associated with significantly less nasopharyngeal bleeding than the conventional technique at both 60-90 s (55% vs. 68%; p = 0.033) and 5 min (51% vs. 70%; p = 0.002). The severity of bleeding was also significantly less with the bougie technique, with an OR for active bleeding of 0.42 (95%CI 0.20-0.87; p = 0.020) at 60-90 s and 0.15 (95%CI 0.06-0.37; p < 0.0001) at 5 min. Magill forceps were needed significantly less often with the bougie technique (9% vs. 28%, p = 0.0001) and there was no difference in first attempt and overall success rates between the two techniques (p = 0.133 and p = 0.750, respectively). Not only is nasal intubation over a bougie as successful as the conventional technique, it also significantly decreases both the incidence and severity of nasopharyngeal trauma, as well as the need for the use of Magill forceps.

Altered ADAR 2 equilibrium and 5HT(2C) R editing in the prefrontal cortex of ADAR 2 transgenic mice.

Modulation of serotonin signaling by RNA editing of the serotonin 2C receptor (5HT(2C) R) may be relevant to affective disorder as serotonin functions regulate mood and behavior. Previously, we observed enhanced endogenous behavioral despair in ADAR2 transgenic mice. As the transcript of the 5HT(2C) R is a substrate of ADAR2, we hypothesized that perturbed ADAR2 equilibrium in the prefrontal cortex of ADAR2 transgenic mice alters the normal distribution of edited amino acid isoforms of the 5HT(2C) R and modifies the receptor function in downstream basal extracellular signal-regulated kinase (ERK) signaling. We examined groups of naive control and ADAR2 transgenic mice and found significantly increased ADAR2 expression, increased RNA editing at A, C, D and E sites and significantly altered normal distribution of edited amino acid isoforms of the 5HT(2C) R with increased proportions of valine asparagine valine, valine serine valine, valine asparagine isoleucine, isoleucine asparagine valine and decreased isoleucine asparagine isoleucine amino acid isoforms of the 5HT(2C) R in ADAR2 transgenic mice. Localized serotonin levels (5-HT) were unchanged and perturbed ADAR2 equilibrium coincides with dysregulated edited amino acid isoforms of the 5HT(2C) R and reduced basal ERK signaling. These results altogether suggest that altered 5HT(2C) R function could be contributing to enhanced depression-like behavior of ADAR2 transgenic mice and further implicate ADAR2 as a contributing factor in cases of affective disorder.

Ankle fractures in patients with diabetes mellitus.

Diabetes mellitus is considered an indicator of poor prognosis for acute ankle fractures, but this risk may be specific to an identifiable subpopulation. We retrospectively reviewed 42 patients with both diabetes mellitus and an acute, closed, rotational ankle fracture. Patients were individually matched to controls by age, gender, fracture type, and surgical vs non-surgical treatment. Outcomes were major complications during the first six months of treatment. We contrasted secondarily 21 diabetic patients with and 21 without diabetic comorbidities. Diabetic patients and controls did not differ significantly in total complication rates. More diabetic patients required long-term bracing. Diabetic patients without comorbidities had complication rates equal to their controls. Diabetic patients with comorbidities had complications at a higher rate (ten patients; 47%) than matched controls (three patients; 14%, p = 0.034). A history of Charcot neuroarthropathy led to the highest rates of complication. An increased risk of complications in diabetic patients with closed rotational fractures of the ankle are specific to a subpopulation with identifiable related comorbidities.

Vitreous and retinal amino acid concentrations in experimental central retinal artery occlusion in the primate.

PURPOSE: Vitreous and retinal amino-acid concentrations were evaluated in a primate model of central retinal artery occlusion (CRAO) to study the role of glutamate excitotoxicity in acute retinal ischaemia. METHODS: Unilateral, acute CRAO was produced by temporary clamping of the central retinal artery for 190 min in four elderly rhesus monkeys. Fundus photography, fluorescein angiography, and electroretinogram were performed before and during CRAO, and after unclamping the artery. Vitreous samples were obtained before and after CRAO in both eyes, and analysed for 13 amino-acid concentrations using high-pressure liquid chromatography. The animals were killed 350 min after retinal reperfusion, and the retinal tissue was submitted for amino-acid analysis. RESULTS: In all four eyes, the macula showed the 'cherry red spot'. The CRAO was confirmed by fluorescein angiography and decreased b-wave on electroretinogram. Retinal histology confirmed ischaemic changes in the inner retina. Changes in all 13 vitreous amino-acid concentrations after CRAO (including glutamate) were not significantly different between study and control eyes (P = 0.09 to 0.82). All retinal amino-acid concentrations (including glutamate) were not significantly different between two eyes (P = 0.07-0.93). CONCLUSIONS: In the primate model of acute inner retinal ischaemia induced by transient CRAO, we were unable to detect significantly elevated concentrations of vitreous and retinal glutamate. Our primate model has the advantage of closely modelling the CRAO in humans. Further basic and clinical studies are needed to elucidate the role of glutamate excitotoxicity in retinal ischaemia.

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.

Rate of visual field loss and long-term visual outcome in primary open-angle glaucoma.

PURPOSE: To evaluate long-term visual field outcome in primary open-angle glaucoma. METHODS: In this retrospective cohort study, 40 eyes of 40 patients with primary open-angle glaucoma with elevated intraocular pressure and a minimum of 8-year longitudinal series of visual fields were plotted with Goldmann perimeter. Eyes with any other ocular disease except cataract were excluded. Manual grid templates were used to quantify the visual fields. Linear regression was performed to estimate the rate of visual field decline. Pertinent clinical factors were evaluated for statistical association with the rate of decline. Long-term clinical outcome including visual acuity, rate of legal blindness, and rate of medical and surgical interventions was also measured. RESULTS: In the 40 eyes studied, with a mean follow-up of 14 years, the visual field score decreased at the rate of -1.5% per year. Overall, 68% showed significant decrease, and the rate of decrease among these eyes was -2.1% per year. Five eyes became legally blind from glaucoma; the cumulative rate of blindness from glaucoma was 19% at 22 years. Higher intraocular pressure and greater number of antiglaucoma medications on initial presentation were associated with faster and slower deterioration of visual field (compared with the average), respectively. CONCLUSIONS: With standard glaucoma therapy, the rate of visual field loss in primary open-angle glaucoma is slow. Lower intraocular pressure and more antiglaucoma medications are associated with slower visual field decline. Legal blindness from glaucoma is 19% over a follow-up of 22 years.

Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis.

It is not known if a surgical lung biopsy is necessary in all patients for the diagnosis of idiopathic pulmonary fibrosis (IPF). We conducted a blinded, prospective study at eight referring centers. Initially, cases were evaluated by clinical history and examination, transbronchial biopsy, and high-resolution lung computed tomography scans. Pulmonologists at the referring centers then assessed their certainty of the diagnosis of IPF and provided an overall diagnosis, before surgical lung biopsy. The lung biopsies were reviewed by a pathology core and 54 of 91 patients received a pathologic diagnosis of IPF. The positive predictive value of a confident (certain) clinical diagnosis of IPF by the referring centers was 80%. The positive predictive value of a confident clinical diagnosis was higher, when the cases were reviewed by a core of pulmonologists (87%) or radiologists (96%). Lung biopsy was most important for diagnosis in those patients with an uncertain diagnosis and those thought unlikely to have IPF. These studies suggest that clinical and radiologic data that result in a confident diagnosis of IPF by an experienced pulmonologist or radiologist are sufficient to obviate the need for a lung biopsy. Lung biopsy is most helpful when clinical and radiologic data result in an uncertain diagnosis or when patients are thought not to have IPF.

Consumption of carrageenan and other water-soluble polymers used as food additives and incidence of mammary carcinoma.

This study examined the hypothesis that the increasing incidence of mammary carcinoma in the USA in the twentieth century may be related to the consumption of carrageenan and possibly other water-soluble polymers. Widely used as food additives in the Western diet, the water-soluble polymers, also known as gums, are generally regarded as inert. However, the gum carrageenan which is comprised of linked, sulfated galactose residues has potent biological activity and undergoes acid hydrolysis to poligeenan, an acknowledged carcinogen. A time-trend analysis using age-adjusted incidence data and consumption data from established sources tested the hypothesis that increased consumption of the gums may be associated with increased incidence of mammary carcinoma. Correlations were determined using Pearson and Spearman correlation coefficients, incorporating lag intervals of 10 to 35 years. This analysis demonstrated that increasing consumption of several gums correlates positively with increased incidence of breast carcinoma.

Long-term results of eyes with penetrating keratoplasty and glaucoma drainage tube implant.

PURPOSE: To present long-term results of eyes with penetrating keratoplasty (PK) and glaucoma tube implant. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: We retrospectively reviewed medical records of all patients who underwent both PK and glaucoma tube implant (Baerveldt or Ahmed) at the University of Iowa between July of 1988 and December of 1997 (55 eyes). METHODS: Success of the tube implant or PK was evaluated using Kaplan-Meier survival analysis. Association of relevant clinical factors with glaucoma or corneal graft outcome was evaluated using log-rank test or Cox proportional hazard regression analysis. The factors evaluated were glaucoma and cornea diagnoses; prior, simultaneous, and subsequent surgeries; type of tube implant; relative timing of surgeries; and postsurgical complications. MAIN OUTCOME MEASURES: Glaucoma outcome was assessed by postoperative intraocular pressure (IOP), number of medications, and need for further glaucoma surgery. Corneal outcome was assessed by graft rejection, failure, and Snellen visual acuity. Surgical procedures before and during the study period, and their complications were evaluated. RESULTS: The mean preoperative intraocular pressure was 29.8 mmHg with an average of 2.9 medications. At last postoperative follow-up, the mean IOP decreased to 14.3 mmHg with 0.7 medication. The tube implant successfully controlled glaucoma in 45 eyes (82%) at 3 years. More severe postsurgical complications were associated with greater glaucoma failure. Graft rejection occurred in 17 eyes, and 7 of these progressed to failure. Nonimmunologic graft failure occurred in an additional 17 eyes (31%). The remaining 31 eyes (56%) had a clear graft. The corneal grafts remained clear in 70% and 55% of eyes at 2 and 3 years, respectively. Corneal graft failure was associated with glaucoma and cornea diagnoses groups, type of tube implant, and relative timing of the two surgeries. Complications occurred in 23 eyes (42%), and 10 of these were serious. CONCLUSIONS: A drainage tube implant can successfully control glaucoma in a majority (82%) of keratoplasty eyes at 3 years. However, the success of corneal grafts is low (55%) at 3 years. Postsurgical complications are not uncommon and are associated with poor glaucoma outcome. Other clinical factors are associated with poor graft outcome.

Comparison of appropriateness ratings for cataract surgery between convened and mail-only multidisciplinary panels.

BACKGROUND: In this article, the authors determine the reproducibility of appropriateness ratings for cataract surgery between a multidisciplinary physician panel that convened and a multidisciplinary physician panel that completed ratings by mail. METHODS: Eighteen panelists, who constituted 2 distinct multidisciplinary panels, rated 2894 clinical scenarios as an appropriate, inappropriate, or uncertain indication to perform cataract surgery. Each panel's summary score for each scenario was calculated. Weighted kappa values were determined to assess the level of agreement between the ratings of the 2 panels. RESULTS: The panels had a substantial level of agreement overall, with a weighted kappa statistic of 0.64. There was agreement on about 68% of the scenarios, and serious disagreement, in which one panel rated an indication appropriate and the other rated it inappropriate, occurred in only 1% of the ratings. CONCLUSION: There was substantial agreement about the ratings by the 2 panels. The panel that convened rated fewer scenarios uncertain and more appropriate, suggesting the impact of group dynamics and face-to-face discussion on resolution of uncertainty.

Physician use of and attitudes regarding the minimum data set.

OBJECTIVE: To determine physician use of the Minimum Data Set (MDS), part of the Resident Assessment Instrument (RAI). DESIGN: A population-based survey. SETTING: The United States. PARTICIPANTS: A total of 2223 physicians listing geriatrics as their primary specialty, 1921 of whom are internists and 302 family physicians. MEASUREMENTS: A 34-item questionnaire asking nine physician-specific demographic questions; nursing home caseload; percent time spent reviewing MDS and care plan; how the information on the MDS was used. Physicians were also asked to describe their attitudes about the MDS. RESULTS: Among the 472 physicians who completed the survey and cared for nursing home patients, 357 were internists and 107 were family physicians. Ninety-one percent of the physicians were board certified, 76% had certificate of added qualifications in geriatrics,65% oversaw 20 nursing home patients. Only 11% of physicians reported reviewing the entire MDS, and 21% part of the MDS for all of their patients. Nineteen percent of physicians did not review the care plan for any of their patients. Fifty-six percent of 461 comments made by physicians regarding the MDS were negative or derogatory. CONCLUSIONS: Many practicing geriatricians are not using MDS to facilitate medical decisions. If this physician population is not using the MDS, there is a need to improve the information transfer from the MDS form to the busy clinician.

Phlebotomy overdraw in the neonatal intensive care nursery.

OBJECTIVE: Because blood loss attributable to laboratory testing is the primary cause of anemia among preterm infants during the first weeks of life, we quantified blood lost attributable to phlebotomy overdraw, ie, excess that might be avoided. We hypothesized that phlebotomy overdraw in excess of that requested by the hospital laboratory was a common occurrence, that clinical factors associated with excessive phlebotomy loss would be identified, and that some of these factors are potentially correctable. DESIGN, OUTCOME MEASURES, AND ANALYSIS: Blood samples drawn for clinical purposes from neonates cared for in our 2 neonatal special care units were weighed, and selected clinical data were recorded. The latter included the test performed; the blood collection container used; the infant's location (ie, neonatal intensive care unit [NICU] and intermediate intensive care unit); the infant's weight at sampling; and the phlebotomist's level of experience, work shift, and clinical role. Data were analyzed by univariate and multivariate procedures. Phlebotomists included laboratory technicians stationed in the neonatal satellite laboratory, phlebotomists assigned to the hospital's central laboratory, and neonatal staff nurses. Phlebotomists were considered experienced if they had worked in the nursery setting for >1 year. Blood was sampled from a venous or arterial catheter or by capillary stick from a finger or heel. Blood collection containers were classified as tubes with marked fill-lines imprinted on the outside wall, tubes without fill-lines, and syringes. Infants were classified by weight into 3 groups: <1 kg, 1 to 2 kg, and >2 kg. The volume of blood removed was calculated by subtracting the weight of the empty collection container from that of the container filled with blood and dividing by the specific gravity of blood, ie, 1.050 g/mL. The volume of blood withdrawn for individual laboratory tests was expressed as a percentage of the volume requested by the hospital laboratory. RESULTS: The mean (+/- standard error of the mean) volume of blood drawn for the 578 tests drawn exceeded that requested by the hospital laboratory by 19.0% +/- 1.8% per test. The clinical factors identified as being significantly associated with greater phlebotomy overdraw in the multiple regression model included: 1) collection in blood containers without fill-lines; 2) lighter weight infants; and 3) critically ill infants being cared for in the NICU. Because the overall R(2) of the multiple regression for these 3 clinical factors was only.24, the random factor of individual phlebotomist was added to the model. This model showed that there was a significant variation in blood overdraw among individual phlebotomists, and as a result, the overall R(2) increased to.52. An additional subset analysis involving 2 of the 3 groups of blood drawers (ie, hospital and neonatal laboratory phlebotomists) examining the effect of work shift, demonstrated that there was significantly greater overdraw for blood samples obtained during the evening shift, compared with the day shift when drawn using unmarked tubes for the group of heavier infants cared for in the NICU. CONCLUSION: Significant volumes of blood loss are attributable to overdraw for laboratory testing. This occurrence likely exacerbates the anemia of prematurity and may increase the need for transfusions in some infants. Attempts should be made to correct the factors involved. Common sense suggests that blood samples drawn in tubes with fill-lines marked on the outside would more closely approximate the volumes requested than those without. Conversely, the use of unmarked tubes could lead to phlebotomy overdraw because phlebotomists may overcompensate to avoid having to redraw the sample because of an insufficient volume for analysis. We were surprised to observe that the lightest and most critically ill infants experienced the greatest blood overdraw. (ABSTRACT TRUNCATED)

Laryngeal cancer cost analysis: association of case-mix and treatment characteristics with medical charges.

OBJECTIVES: To examine the relationship of various pretreatment case-mix characteristics and treatment modalities with medical charges incurred during diagnosis, treatment, and 2-year follow-up for patients with laryngeal cancer. DESIGN: Retrospective chart review and billing record analysis. METHODS: The charts and billing records of patients diagnosed with laryngeal cancer at the University of Iowa Hospitals and Clinics (UIHC) between January 1, 1991 and December 31, 1994 were reviewed. The independent variables included various pretreatment patient-mix and tumor characteristics (age, AJCC TNM clinical stage, smoking history, ASA class, and comorbidity as defined by Kaplan-Feinstein grade) as well as type of treatment. The dependent variables included total physician, office, and university hospital-based charges incurred during the pretreatment evaluation and 0- to 3-, 3- to 12, and 12- to 24-month billing periods after the initiation of cancer-directed therapy. Total 1-year and 2-year charges were also evaluated. Univariate and multivariate analyses were used to investigate the relationships between dependent and independent variables and to develop models predictive of management charges during the individual and total billing periods. RESULTS: Pretreatment charges showed no significant associations (P < .05) with any of the independent variables. Multiple regression analyses indicated that comorbidity, stage, and initial treatment modality were significant variables in one or more of the models predicting charges incurred during the 0- to 3-month, 3- to 12-month, total 1-year, and total 2-year billing periods. The models yielded R2 values for the total 1- and 2-year billing periods of 0.5246 and 0.5055, respectively. CONCLUSIONS: This work supports continued study of measures that may result in earlier detection of laryngeal cancer as a potential means of reducing management charges. These results also indicate that a more accurate method of stratifying the disease severity of laryngeal cancer patients for reimbursement purposes would include measurements of the severity of the index disease as well as comorbid diseases.

Administration of recombinant human granulocyte-macrophage colony-stimulating factor to children undergoing allogeneic marrow transplantation: a prospective, randomized, double-masked, placebo-controlled trial.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered to 40 pediatric patients undergoing partially matched related, or closely matched unrelated, allogeneic marrow transplants. This trial was set up in a prospective, randomized, double-masked, placebo-controlled manner to establish if the administration of GM-CSF to such patients enhanced neutrophil recovery in this allogeneic transplant setting. The GM-CSF group had a significantly shorter time to neutrophil recovery to > 500 x 10(9) cells/L (15 days) than the placebo group (p = 0.0036). In addition, the GM-CSF group had a significantly shorter neutrophil recovery time to > 1,000 x 10(9) cells/L (18 days) than the placebo group (p = 0.0053). The primary objective of this study was met by showing that GM-CSF enhanced neutrophil recovery in this allogeneic setting. However, within the study group of patients, there was no effect of GM-CSF on the incidence or severity of graft-vs.-host disease (GvHD), one of the secondary end-points of the study. With regard to the other secondary end-points, there was no effect of GM-CSF on marrow cellularity, duration of systemic antibiotics given for real infections or as prophylaxis to prevent infections, risk of significant infections (as defined by systemic culture of virus, fungus, or bacteria), and duration or cost of hospitalization, platelet recovery, and nutritional support. With the secondary end-points, it will be necessary to study larger numbers of pediatric patients to identify differences that are small in this study group. In conclusion, GM-CSF can be safely administered to children with few, if any, significant side-effects. Additional work remains to facilitate earlier discharge of patients and decreased antibiotic usage, to offset the cost of using a neutrophil growth factor.

Ocular and optic nerve head ischemic disorders and hearing loss.

PURPOSE: To investigate in an exploratory study whether any evidence suggests that ophthalmic ischemic disorders, particularly of the optic nerve head, are associated with hearing loss. METHODS: We investigated prospectively 583 consecutive patients in eight primary ocular diagnostic groups for associated hearing loss: nonarteritic anterior ischemic optic neuropathy (n = 81), normal-tension glaucoma (n = 36), primary open-angle glaucoma (n = 138), other types of glaucoma (n = 142), ocular arterial occlusive disorders (n = 22), retinal vein occlusion (n = 89), ocular vasculitis (n = 42), and a miscellaneous group (n = 33). The patients and their relatives were questioned in detail for any evidence of hearing loss in the patients. RESULTS: In the logistic regression model, with presence or absence of hearing loss as the dependent variable and gender, age, and diagnosis as independent variables, gender (P = .003) and age (P<.0001) were found to be significantly associated with hearing loss. No significant association was found with any of the ophthalmic disease groups evaluated in this study. Whenever any significant association with any ophthalmic disease group was seen, this result could be explained by examination of the association between diagnosis and age, which showed a significant (P<.001) association. CONCLUSIONS: This study showed that there is a significant (P<.001) relationship between hearing loss and aging-the older the population, the higher the incidence of hearing loss-but the study showed that there is no association between hearing loss and ocular and optic nerve head ischemic disorders. The two represent unrelated and independent disorders.

Beta-blocker eyedrops and nocturnal arterial hypotension.

PURPOSE: To investigate the effects of topical beta-blocker eyedrops on nocturnal arterial hypotension and heart rate and on visual field deterioration. METHODS: We prospectively investigated 275 white patients, 161 with glaucomatous optic neuropathy and 114 with nonarteritic anterior ischemic optic neuropathy, by 24-hour ambulatory blood pressure monitoring and diurnal curve of intraocular pressure, in addition to detailed ophthalmic evaluation. Of the patients with glaucomatous optic neuropathy, 131 had normal-tension glaucoma and 30 had primary open-angle glaucoma. Of the 275 patients, 114 were using topical beta-blocker eyedrops twice daily (76 with normal-tension glaucoma, 26 with primary open-angle glaucoma, and 12 with anterior ischemic optic neuropathy). RESULTS: Hourly average blood pressure data analyses showed overall a drop in blood pressure as well as heart rate during sleep, and a significantly greater drop in mean diastolic blood pressure (P = .009) at night in normal-tension glaucoma than in anterior ischemic optic neuropathy. Also, patients using beta-blocker eyedrops experienced a significantly greater percentage drop in diastolic blood pressure at night (P = .028), lower minimum nighttime diastolic blood pressure (P = .072), and lower minimum nighttime heart rate (P = .002) than did those not using them. In normal-tension glaucoma, eyes receiving beta-blocker eyedrops showed visual field progression significantly (P = .0003) more often than those not receiving beta-blockers. CONCLUSIONS: The findings of our studies, as well as those of others, suggest that any factor that increases nocturnal arterial hypotension is a potential risk factor in vulnerable individuals with glaucomatous optic neuropathy or anterior ischemic optic neuropathy. The present study suggests that the use of beta-blocker eyedrops, by aggravating nocturnal arterial hypotension and reducing the heart rate, may be a potential risk factor in susceptible individuals.

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.