Analysis of risk factors associated with radiosurgery for vestibular schwannoma.

OBJECT: The aim of this study was to identify factors associated with delayed cranial neuropathy following radiosurgery for vestibular schwannoma (VS or acoustic neuroma) and to determine how such factors may be manipulated to minimize the incidence of radiosurgical complications while maintaining high rates of tumor control. METHODS: From July 1988 to June 1998, 149 cases of VS were treated using linear accelerator radiosurgery at the University of Florida. In each of these cases, the patient's tumor and brainstem were contoured in 1-mm slices on the original radiosurgical targeting images. Resulting tumor and brainstem volumes were coupled with the original radiosurgery plans to generate dose-volume histograms. Various tumor dimensions were also measured to estimate the length of cranial nerve that would be irradiated. Patient follow-up data, including evidence of cranial neuropathy and radiographic tumor control, were obtained from a prospectively maintained, computerized database. The authors performed statistical analyses to compare the incidence of posttreatment cranial neuropathies or tumor growth between patient strata defined by risk factors of interest. One hundred thirty-nine of the 149 patients were included in the analysis of complications. The median duration of clinical follow up for this group was 36 months (range 18-94 months). The tumor control analysis included 133 patients. The median duration of radiological follow up in this group was 34 months (range 6-94 months). The overall 2-year actuarial incidences of facial and trigeminal neuropathies were 11.8% and 9.5%, respectively. In 41 patients treated before 1994, the incidences of facial and trigeminal neuropathies were both 29%, but in the 108 patients treated since January 1994, these rates declined to 5% and 2%, respectively. An evaluation of multiple risk factor models showed that maximum radiation dose to the brainstem, treatment era (pre-1994 compared with 1994 or later), and prior surgical resection were all simultaneously informative predictors of cranial neuropathy risk. The radiation dose prescribed to the tumor margin could be substituted for the maximum dose to the brainstem with a small loss in predictive strength. The pons-petrous tumor diameter was an additional statistically significant simultaneous predictor of trigeminal neuropathy risk, whereas the distance from the brainstem to the end of the tumor in the petrous bone was an additional marginally significant simultaneous predictor of facial neuropathy risk. The overall radiological tumor control rate was 93% (59% tumors regressed, 34% remained stable, and 7.5% enlarged), and the 5-year actuarial tumor control rate was 87% (95% confidence interval [CI] 76-98%). Analysis revealed that a radiation dose cutpoint of 10 Gy compared with more than 10 Gy prescribed to the tumor margin yielded the greatest relative difference in tumor growth risk (relative risk 2.4, 95% CI 0.6-9.3), although this difference was not statistically significant (p = 0.207). CONCLUSIONS: Five points must be noted. 1) Radiosurgery is a safe, effective treatment for small VSs. 2) Reduction in the radiation dose has played the most important role in reducing the complications associated with VS radiosurgery. 3) The dose to the brainstem is a more informative predictor of postradiosurgical cranial neuropathy than the length of the nerve that is irradiated. 4) Prior resection increases the risk of late cranial neuropathies after radiosurgery. 5) A prescription dose of 12.5 Gy to the tumor margin resulted in the best combination of maximum tumor control and minimum complications in this series.

Cytoskeletal and kinetic epithelial differences between NSAID gastropathy and Helicobacter pylori gastritis: an immunohistochemical determination.

AIMS: Distinguishing histological features between non-steroidal anti-inflammatory drug (NSAID) gastropathy and Helicobacter pylori gastritis have been accepted. However, the molecular basis explaining these dissimilar histologies has not been elucidated. In an attempt to clarify this question we investigated the differences in the structural cytoskeleton and proliferative activity of these two gastropathies. METHODS AND RESULTS: We assessed the distribution of five cytokeratins (CK) (CK7, 8, 18, 19 and 20) and Ki67 for the ability to distinguish NSAID from H. pylori gastropathies. In H. pylori gastritis, CK7, 8, 18 and 19 were expressed comparably to normal mucosa from the deep foveolae up to the tips of the glands. The detection of CK20, normally expressed in the upper foveolar region and surface, was decreased with only an epithelial surface reaction. In NSAID gastropathy, CK expression was increased in intensity, with normal distribution for CK8, 18 and 19. Modification of localization was noted for CK7 and 20, with labelling extending toward the deep foveolar region. Unlike H. pylori gastritis, no surface epithelial labelling with Ki67 was noted with NSAID gastropathy but downward elongation of the proliferative zone occurred instead. CONCLUSIONS: Contrasting cytostructural alterations and distinct proliferative patterns distinguish NSAID gastropathy from H. pylori gastritis, possibly reflecting different injury pathways.

Axial characteristics of circular external skeletal fixator single ring constructs.

OBJECTIVE: Evaluate the effects of varying ring diameter, wire tension, and wire-divergence angle on the axial stiffness characteristics of circular external skeletal fixator single-ring constructs. Study Design-Biomechanical evaluation using circular fixator components and a Delrin cylinder bone model. METHODS: Single ring constructs using two 1.6 mm diameter Kirschner wires to secure a 19 mm Delrin cylinder centered within the ring were examined. Component variables evaluated were ring diameter (50 mm, 66 mm, 84 mm, and 118 mm), wire-divergence angle (30 degrees, 60 degrees, and 90 degrees ), and wire tension (0 kg, 30 kg, 60 kg, and 90 kg). A total of 48 constructs were examined. Rings were rigidly mounted on a universal testing system and the cylinder loaded in axial compression (7.4 N/s) to 220 N. Load/displacement curves were analyzed to determine the following: the displacement (mm) that occurred before the slope of each load/displacement curve became linear, the stiffness (N/mm) of the linear portion of each load/deformation curve, and the total displacement (mm) produced at maximal load. Least-squares linear regression was used to model response variables as linear functions of ring diameter, wire divergence angle, and wire tension. Three-way interactions and 2-way interactions among independent component variables were evaluated first in the modeling process and included in a best model if response variables were found to have statistically significant regression coefficients. The regression coefficients and corresponding standard errors and covariances were used to estimate the maximal effect and standard error attributable to wire divergency angle (change from 30 degrees to 90 degrees ) and wire tension (change from 0 to 90 kg) for each ring diameter. RESULTS: All load/deformation curves had an initial exponential increase in stiffness, with the slope becoming linear at higher loads. The exponential phase was more pronounced in larger-diameter ring constructs and was mitigated by tensioning the wires. Ring diameter had the greatest influence on displacement that occurred before the curve became linear (semipartial r(2) [sp-r2] = .89), stiffness (sp-r2 = .94), and total displacement (sp-r2 = .93). Wire tension exerted a smaller influence on displacement that occurred before the curve became linear (sp-r2 =.06), stiffness (sp-r2 = .03), and total displacement (sp-r2 = .05). Wire divergence angle had a nominal effect on displacement that occurred before the curve became linear (sp-r2 = .0001), on stiffness (sp-r2 = .004), and on total displacement (sp-r2 =.003). CONCLUSIONS: Ring diameter had a profound effect on the axial stiffness characteristic of single ring constructs. Tensioning of the fixation wires can improve the axial stiffness characteristics of these constructs, particularly in larger diameter ring constructs, by mitigating the initial exponential phase of the load/deformation curve. Wire divergence angle had only a nominal differential effect on axial stability. CLINICAL RELEVANCE: Understanding how individual component variables and their interactions influence bone segment stability should help surgeons to optimize interfragmentary strain. Tensioning fixation wires is probably unnecessary in 50 mm diameter ring constructs, but assumes greater importance as ring diameter increases.

Acetabular component orientation as an indicator of implant luxation in cemented total hip arthroplasty.

OBJECTIVE: To determine the sensitivity and specificity with which acetabular component angles of inclination and version could be used, alone or in combination, to predict luxation of cemented total hip arthroplasties (THA). STUDY DESIGN: Comparison of retrospectively selected cases and controls SAMPLE POPULATION: All THA performed at the University of Florida between 1991 and 1998 with the BioMedtrix system and for which at least 2 months of radiographic follow-up were available. All THA performed at the University of Georgia with the BioMedtrix system which subsequently luxated. METHODS: Acetabular component inclination angle (IA) and acetabular version angle (VA) were determined for each THA. Data were grouped according to outcome - luxation or no luxation - with the luxated cases from the 2 institutions pooled. Receiver operator characteristic (ROC) analysis was used to evaluate decision rules for using IA and VA as tests for detecting postoperative luxation. Sensitivity and specificity for luxation and 95% confidence bounds were computed with selected values of IA and VA as cut-points. RESULTS: The nonluxation group consisted of 68 THA with a median follow-up time of 5 months (range, 2-60 months). The luxation group consisted of 12 THA with a mean time to luxation of 36 days. The nonluxation group had a mean +/- standard deviation (SD) IA and VA of 40.3 degrees +/- 8.9 degrees and 71.1 +/- 13.6 degrees, respectively, whereas the luxation group had a mean +/- SD IA and VA of 34.7 degrees +/- 12.6 degrees and 72.9 degrees +/- 16.6 degrees, respectively. An IA cut-point of 37.8 degrees achieved 58.3% sensitivity and 57.4% specificity. A VA cut-point of 73 degrees achieved 75.0% sensitivity and 51.5% specificity. IA and VA considered simultaneously achieved a 50.0% sensitivity and 88.2% specificity. CONCLUSIONS AND CLINICAL RELEVANCE: ROC analysis indicated that both IA and VA considered individually or simultaneously were poor indicators of luxation. Although extreme values of IA may predict luxation with high specificity, the potential for luxation cannot be excluded based on apparently appropriate values of IA and VA. The results of this study also indicate that a successful outcome is possible with a wide range of acetabular component positions.

Evaluation of four interfragmentary Kirschner wire configurations as a component of screw/wire/polymethylmethacrylate fixation for acetabular fractures in dogs.

The biomechanical contribution of the interfragmentary Kirschner wire as a component of composite fixation for acetabular fracture repair was subjectively and objectively evaluated. Acetabular osteotomies were repaired using the screw/wire/polymethylmethacrylate (SWP) composite fixation with or without one of three configurations of Kirschner wire in 32 hemipelves obtained from 16 dogs. Reduction, assessed objectively and subjectively, was unaffected by Kirschner wire placement. Hemipelves repaired with Kirschner wire(s) were subjectively more stable prior to application of polymethylmethacrylate when manually assessed in multiple planes. Consistent incremental increases in stiffness, yield load, and maximum load sustained that were observed during biomechanical testing were not significant, with the exception that hemipelves repaired with two Kirschner wires had significantly greater yield loads than hemipelves repaired without Kirschner wires. The subjective results of this study support the use of at least one interfragmentary Kirschner wire to maintain reduction prior to polymethylmethacrylate application; however, fracture configuration and location may dictate the number and pattern of interfragmentary Kirschner wires used to maintain reduction prior to application of the polymethylmethacrylate. The objective results and observations made during biomechanical testing suggest that use of one or more interfragmentary Kirschner wires may enhance stability after polymethylmethacrylate application.

Development of glaucoma after cataract surgery in dogs: 220 cases (1987-1998).

OBJECTIVE: To examine postoperative ocular hypertension (POH) and other variables as predictors of the risk of developing glaucoma after cataract surgery in dogs. DESIGN: Retrospective study. ANIMALS: 220 dogs that had cataract surgery. PROCEDURE: Medical records of 220 dogs (346 eyes) that had extracapsular cataract removal or phacoemulsification of cataracts were reviewed. With respect to glaucoma development, 8 variables were analyzed, which included development of POH, breed, sex, age at time of surgery, eye (right vs left), phacoemulsification time, intraocular lens (IOL) placement (yes or no), and stage of cataract development. Eyes developed glaucoma within 6 or 12 months of surgery or did not have signs of glaucoma at least 6 or 12 months after cataract surgery. RESULTS: Of 346 eyes, 58 (16.8%) developed glaucoma after surgery. At 6 months, 32 of 206 (15.5%) eyes examined had glaucoma; at 12 months, 44 of 153 (28.8%) eyes examined had glaucoma. Median follow-up time was 5.8 months (range, 0.1 to 48 months). Mixed-breed dogs were at a significantly lower risk for glaucoma, compared with other breeds. Eyes with IOL placement were at a significantly lower risk for glaucoma, compared with eyes without IOL placement. Eyes with hypermature cataracts were at a significantly higher risk for glaucoma, compared with eyes with mature or immature cataracts. CONCLUSIONS AND CLINICAL RELEVANCE: Multiple factors appear to contribute to the onset of glaucoma in dogs after cataract surgery. Complications prohibiting IOL placement during cataract surgery may lead to a high risk of glaucoma development.

Risk factors affecting the outcome of surgery for atlantoaxial subluxation in dogs: 46 cases (1978-1998).

OBJECTIVE: To identify risk factors for successful surgical management of dogs with atlantoaxial subluxation (AAS). DESIGN: Retrospective study. ANIMALS: 46 dogs managed surgically for AAS. PROCEDURE: Age at onset of clinical abnormalities, duration of clinical abnormalities prior to surgery, radiographic appearance of the dens, type (dorsal or ventral procedure) and number (1 or 2) of surgeries performed, grade of postoperative atlantoaxial joint reduction, and neurologic status prior to surgery (preoperative), when dogs were discharged from the hospital (postoperative), and during a follow-up evaluation (final) were obtained from the dogs' medical records. Risk factors for surgical success and degree of neurologic improvement were identified and analyzed for predictive potential. RESULTS: Age at onset of clinical abnormalities < or = 24 months was significantly associated with greater odds of a successful first surgery and final outcome and a lower postoperative neurologic grade. Duration of clinical abnormalities < or = 10 months was significantly associated with greater odds of a successful final outcome and a lower final neurologic grade. A preoperative neurologic grade of 1 or 2 was significantly associated with a lower final neurologic grade. Potential risk factors that did not affect odds of a successful outcome included type of surgery performed, grade of atlantoaxial joint reduction, radiographic appearance of the dens, or need for a second surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Age at onset of clinical abnormalities, duration of clinical abnormalities prior to surgery, and preoperative neurologic status are risk factors for success of surgical management of AAS in dogs.

Exercise training in the debilitated aged: strength and functional outcomes.

OBJECTIVE: Resistance and endurance training result in gains in fitness in the aged. It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength, endurance, and function in this population. DESIGN: Randomized, controlled trial. SETTINGS AND PATIENTS: Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home. They were older than 60 yrs with impairment in at least one physical activity of daily living. Seventy-eight subjects volunteered and 58 (mean age, 75 yrs; 9 women, 49 men) completed the intervention and initial posttest. Only one subject withdrew because of injury or disinterest. INTERVENTION: Thrice-weekly resistance training (using an isokinetic dynamometer) and twice-weekly endurance training for 4 to 8 weeks. MAIN OUTCOMES: Isometric strength in dominant arm and leg, heart rate response to timed endurance test, and activities of daily living score. RESULTS: The mean change in isometric strength across the muscle movements tested was 32.8% in the training group and 10.2% in the control group (difference, 22.6%; 95% confidence interval, 6.2% to 39.0%). No change in heart rate during exercise was seen in the training group. Trained subjects tended to have a greater improvement in functional activity than control subjects, which was statistically significant (p = .04) for those subjects who at enrollment were most dysfunctional (i.e., activities of daily living score less than 13 [maximum score 26]). CONCLUSION: This group of debilitated elderly patients effectively performed resistance training and increased their strength, with the most impaired gaining the most function. Few in the group could effectively perform endurance training.

Performance of serologic tests used to detect heartworm infection in cats.

OBJECTIVE: To compare heartworm serum antibody (Ab) and antigen (Ag) test results, using commercial laboratories and in-house heartworm test kits, with necropsy findings in a population of shelter cats. DESIGN: Prospective study. ANIMALS: 330 cats at an animal shelter. PROCEDURE: Between March and June 1998, 30 ml of blood was collected from the cranial and caudal venae cavae of 330 cats that were euthanatized at a local animal shelter. Results of heartworm Ab and Ag serologic tests for heartworm infection were compared with necropsy findings in this population of cats, using commercial laboratories and in-house test kits to measure serum Ab and Ag concentrations. RESULTS: On necropsy, adult Dirofilaria immitis were found in 19 of 330 (5.8%) cats. Combining results from serum Ab and Ag tests achieved higher sensitivities than using serum Ab and Ag test results alone (i.e., maximum sensitivities of 100% vs 89.5%, respectively, whereas use of serum Ag and Ab test results alone achieved higher specificities compared with the use of a combination of serum Ab and Ag results (i.e., maximum specificities of 99.4% vs 92.9%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of our findings, if a cat has clinical signs that suggest heartworm disease despite a negative heartworm serum Ab test result, an alternative heartworm Ab test, a heartworm Ag test, thoracic radiography, or two-dimensional echocardiography should be performed.

Upper gastrointestinal bleeding in patients with hepatic cirrhosis: clinical course and mortality prediction.

OBJECTIVE: We conducted this study to describe the complications and validate the accuracy of previously reported prognostic indices in predicting the mortality of cirrhotic patients hospitalized for upper GI bleeding. METHODS: This prospective, observational study included 111 consecutive hospitalizations of 85 cirrhotic patients admitted for GI bleeding. Data obtained included intensive care unit (ICU) admission status, Child-Pugh score, the development of systemic inflammatory response syndrome (SIRS), organ failure, and inhospital mortality. The performances of Garden's, Gatta's, and Acute Physiology and Chronic Health Evaluation (APACHE) II prognostic systems in predicting mortality were assessed. RESULTS: Patients' mean age was 48.7 yr, and the median APACHE II and Child-Pugh scores were 17 and 9, respectively. Their ICU admission rate was 71%. Organ failure developed in 57%, and SIRS in 46% of the patients. Nine patients had acute respiratory distress syndrome, and three patients had hepatorenal syndrome. The inhospital mortality was 21%. The APACHE II, Garden's, and Gatta' s predicted mortality rates were 39%, 24%, and 20%, respectively, and their areas under the receiver operating characteristic curve (AUC) were 0.78, 0.70, and 0.71, respectively. The AUC for Child-Pugh score was 0.76. CONCLUSIONS: SIRS and organ failure develop in many patients with hepatic cirrhosis hospitalized for upper GI bleeding, and are associated with increased mortality. Although the APACHE II prognostic system overestimated the mortality of these patients, the receiver operating characteristic curves did not show significant differences between the various prognostic systems.

Immunohistochemical detection of p53 tumor-suppressor protein is a poor indicator of prognosis for canine cutaneous mast cell tumors.

Eighty-three canine cutaneous mast cell tumors were graded histologically and evaluated immunohistochemically for p53 tumor-suppressor protein expression. An avidin-biotin immunohistochemical protocol incorporated a rabbit polyclonal antibody (CM-1) directed against normal and mutant p53 protein. Positive staining was observed in 44.6% (37/83) of tumors and included 50% (12/24) of grade I (well differentiated) tumors, 46.9% (23/49) of grade II (intermediate differentiation) tumors, and 20% (2/10) of grade III (poorly differentiated) tumors. A statistically significantly higher proportion (P < 0.019) of tumors from the head and neck (83.3%, 10/12), stained positive for p53 than tumors from the thorax, back, abdomen, and axilla (39.4%, 13/33), legs (35.7%, 10/28), or prepuce, scrotal, or inguinal areas (44.4%, 4/9). No statistically significant difference between p53 labeling and histologic grade, breed, or tumor size was present. Survival data were available for 53/83 (63.9%) of dogs. Positive reactivity for p53 was observed in 47% (25/53) of tumors within this group, with 57.9% (11/19) of grade I, 43.3% (13/30) of grade II, and 25% (1/4) of grade III tumors labeled. Mean survival time for the 53 dogs was 12.1 months. The median survival time for dogs with grade III tumors or tumors >5 cm was statistically significantly shorter (P < 0.0001) than for dogs with grades I and II or smaller tumors. Although p53 protein abnormalities may play a role in tumor development or behavior in some canine cutaneous mast cell tumors, immunoreactivity was not associated with lack of tumor differentiation, tumor locations previously shown to demonstrate aggressive biological behavior, breed predisposition, or survival times.

A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team.

Our aim was to identify financial and outcome benefits of therapeutic intervention by a multidisciplinary antimicrobial treatment team composed of pharmacists, a clinical microbiologist, and an infectious disease specialist. Of 252 consecutive inpatients receiving suboptimal intravenous antibiotics identified by the clinical pharmacist, 127 were prospectively randomized to intervention and 125 to a control group. The groups were similar with regard to severity of illness, infection type, and time from admission to randomization. Physicians received timely, detailed reviews of relevant microbiologic and clinical data with recommendations of possible optimal antibiotic choices, dosages, and rationales. Median length of stay after randomization for control and intervention groups was 9.0 days and 5.7 days, respectively (3.3-day difference, p=0.0001). Fifteen (12.0%) and eight patients (6.3%), respectively, died, although the time-specific mortality risk was not significantly different when length of postrandomization follow-up and time to death were taken into account. Physician acceptance of suggestions was 89%. Median patient charges for radiology, laboratory, pharmacy, and room were reduced by $4404/intervention, and median hospital costs were reduced by $2642/intervention. A multidisciplinary antimicrobial therapy team can be a useful information source for physicians, improve outcomes in hospitalized patients receiving intravenous antimicrobials, and result in substantial cost savings.

Pre- and post-radiotherapy computed tomography in laryngeal cancer: imaging-based prediction of local failure.

PURPOSE: To determine if pre-radiotherapy (RT) and/or post-radiotherapy computed tomography (CT) can predict local failure in patients with laryngeal carcinoma treated with definitive RT. METHODS AND MATERIALS: The pre- and post-RT CT examinations of 59 patients (T3 glottic carcinoma [n = 30] and T1-T4 supraglottic carcinoma [n = 29]) were reviewed. For each patient, the first post-RT CT study between 1 and 6 months after irradiation was used. All patients were treated with definitive hyperfractionated twice-daily continuous-course irradiation to a total dose of 6,720-7,920 cGy, and followed-up clinically for at least 2 years after completion of RT. Local control was defined as absence of primary tumor recurrence and a functioning larynx. On the pre-treatment CT study, each tumor was assigned a high-or low-risk profile for local failure after RT. The post-RT CT examinations were evaluated for post-treatment changes using a three-point post-RT CT-score: 1 = expected post-RT changes; 2 = focal mass with a maximal diameter of < 1 cm and/or asymmetric obliteration of laryngeal tissue planes; 3 = focal mass with a maximal diameter of > 1 cm, or < 50% estimated tumor volume reduction. RESULTS: The local control rates at 2 years post-RT based on pre-treatment CT evaluation were 88% for low pre-treatment risk profile patients (95% CI: 66-96%) and 34% (95% CI: 19-50%) for high pre-treatment risk profile patients (risk ratio 6.583; 95% CI: 2.265-9.129;p = 0.0001). Based on post-treatment CT, the local control rates at 2 years post-RT were 94% for score 1, 67% for score 2, and 10% for score 3 (risk ratio 4.760; 95% CI: 2.278-9.950 p = 0.0001). Post-RT CT scores added significant information to the pre-treatment risk profiles on prognosis. CONCLUSIONS: Pre-treatment CT risk profiles, as well as post-RT CT evaluation can identify patients, irradiated for laryngeal carcinomas, at high risk for developing local failure. When the post-RT CT score is available, it proves to be an even better prognosticator than the pre-treatment CT-risk profile.

Impact of resistant pneumococcus on rates of acute mastoiditis.

OBJECTIVE: To determine whether the rate of acute mastoiditis is rising, specifically as a result of antibiotic-resistant strains of Streptococcus pneumoniae. METHODS: A retrospective chart review of all patients with a discharge diagnosis of acute mastoiditis between July 1, 1987, and June 30, 1997, was performed at our academic, tertiary-care medical center. There were no interventions, and the main outcome measures included the number of cases of acute or coalescent mastoiditis, stratified by pathogen, per year. RESULTS: The rate of acute mastoiditis as a proportion of yearly otorhinolaryngology admissions increased linearly over time (P = 0. 024). Pneumococcal-related rates of acute mastoiditis, expressed as a proportion of yearly hospital and otorhinolaryngology admissions, increased linearly over time (P = 0.002, P = 0.002). All but 1 case of pneumococcal mastoiditis during the past 3 years were caused by penicillin-resistant strains. CONCLUSIONS: The emergence of antibiotic-resistant S pneumoniae may be responsible for an increasing rate of acute mastoiditis.

Tacrolimus-based triple-drug immunosuppression minimizes serum lipid elevations in pediatric cardiac transplant recipients.

BACKGROUND: Immunosuppression with corticosteroids and cyclosporine has been associated with hyperlipidemia, a risk factor for post-transplant coronary artery disease. The recent development of tacrolimus has created an alternative to cyclosporine-based triple drug immunotherapy. One potential benefit that has been reported in patients receiving tacrolimus is a minimization of elevation of both total and LDL cholesterol, compared to those increases observed in patients receiving cyclosporine-based immunosuppression. It is unclear in previous studies whether this beneficial effect is related to tacrolimus directly or to its corticosteroid sparing potential. To study this relationship, we compared lipid profiles from pediatric cardiac transplant recipients treated with corticosteroids, and either cyclosporine or tacrolimus. METHODS: The study group consisted of 23 patients (mean age = 12.3 years) with pre-transplant and serial post-transplant determinations of total cholesterol, LDL, HDL, and triglycerides. Patients were separated into 4 study groups, defined by immunosuppressive regimen (cyclosporine vs. tacrolimus) and prednisone dose (>0.10 mg/kg/day vs. < or =0.10 mg/kg/day). RESULTS: Patients who received cyclosporine and higher doses of prednisone experienced a mean 74 mg/dl increase from baseline in total cholesterol (p = .0001). None of the other 3 treatment groups demonstrated a statistically significant elevation. Similar trends were observed in LDL and triglyceride alterations between the 4 study groups. Interestingly, patients treated with tacrolimus and higher doses of prednisone demonstrated a significant rise in HDL from baseline (p = .0001), although those who received cyclosporine and higher dose prednisone failed to exhibit this rise. CONCLUSION: The minimal degree of lipid alteration seen in patients receiving tacrolimus and higher doses of prednisone indicates that this effect was not solely based upon the steroid-sparing properties of tacrolimus therapy. The data also suggests a possible synergistic effect between cyclosporine and higher doses of prednisone on hyperlipidemia. Therefore, in pediatric patients requiring higher corticosteroid doses late after transplantation, use of tacrolimus rather than cyclosporine may lead to more favorable lipid profiles and help minimize the risk of post-transplant coronary arteriopathy.

Evaluation of gastric biopsies for neoplasia: differences between Japanese and Western pathologists.

Cited variations in the evaluation of gastric endoscopic biopsies for neoplasms between pathologists in Japan and those in the United States and Europe (the West) may have stemmed from several causes. The five-tiered group classification of the Japanese Research Society for Gastric Cancer (JRSGC) for interpretation of biopsies is not used in the West. Some differences may also exist in the morphologic criteria to reach a diagnosis of dysplasia or carcinoma. The goals of this study were to test the Western and Japanese classifications of gastric dysplasia and adenocarcinoma and to assess the differences between four Japanese and seven Western pathologists. One hundred biopsies, 20 from each of the five categories of the JRSGC scheme as determined by one observer, were collected. The Japanese observers used the JRSGC system, expressed in Roman numerals, whereas Western pathologists used a five- or six-tiered scheme expressed in diagnostic terms. Pairwise agreement was evaluated using k statistics within both groups. Consensus diagnosis on each biopsy was accepted as the opinion of the majority. The sensitivity and specificity of each reviewer for a certain diagnosis were also assessed. The intragroup agreements were moderate for both the Japanese (mean k = 0.663) and the Westerners (mean k = 0.652). The pairwise agreements between Japanese and Western observers were low (mean k = 0.542). Overall, the sensitivity was low for all Japanese observers for the diagnosis of dysplasia (38.7% vs 92.5%), and the sensitivity for the diagnosis of adenocarcinoma was high in both groups but higher among the Japanese observers (93.9% and 85.2%, respectively). Overall, the Japanese-Western interobserver agreement was moderate. The JRSCG scheme did not translate into higher interobserver agreement among Japanese observers. The sensitivity for the diagnosis of gastric adenocarcinoma was high for both groups, but the specificity was low among the Japanese. The cause seemed to be centered around the diagnosis of dysplasia in the Western system, which was a lesion frequently interpreted as carcinoma in Japan because of the different definitions of carcinoma in each system. Such a discrepancy might be important because it may explain some of the differences in the prevalence and prognosis of early gastric cancer between Japan and the West. An international effort is needed to harmonize morphologic criteria and analyze whether therapeutic consequences may stem from such discrepancies.

Recent advances in the treatment and outcome of locally advanced rectal cancer.

OBJECTIVE: To compare the outcomes of treatment of locally advanced rectal cancer of the early era (1975-1990) with those of the late era (1991-1997). BACKGROUND: Preoperative therapy has been used in locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. At the University of Florida, preoperative radiation has been used since 1975, and it was combined with chemotherapy beginning in 1991. METHODS: The records of 328 patients who underwent preoperative radiation or chemoradiation followed by complete resection for locally advanced rectal cancer defined as tethered, annular, or fixed tumors were reviewed. The clinicopathologic characteristics, adjuvant treatment administered, surgical procedures performed, and local recurrence-free and overall survival rates were analyzed. RESULTS: There were 219 patients in the early era and 109 in the late era. No significant differences were seen in patients (age, gender, race) or tumor characteristics (mean distance from the anal verge, annularity, fixation). Preoperative radiation regimens were radiobiologically comparable. No patient in the early era received preoperative chemotherapy, compared with 64 in the late era. Of those receiving any pre- or postoperative chemotherapy, three patients received chemotherapy in the early era, compared with 76 in the late era. Sphincter-preserving procedures increased from 13% in the early era to 52% in the late era. Pathologic downstaging for depth of invasion increased from 42% to 58%, but lymph node negativity remained similar. The 1-, 3-, and 5-year local recurrence-free survival rates were comparable. However, in the late era, 1-, 3-, and 5-year overall survival rates improved significantly compared with those of the early era, and also compared with each of the preceding 5-year intervals. CONCLUSION: The addition of a chemotherapy regimen to preoperative radiation therapy improves survival over radiation therapy alone. Likewise, an improvement in downstaging is associated with an increase in sphincter-preserving procedures.

Pediatricians' and social workers' knowledge and opinions of Florida's religious immunity laws.

BACKGROUND: Florida laws grant exemption from prosecution to parents who choose spiritual healing rather than conventional medical therapy for their children. Despite the American Academy of Pediatrics' policy statement supporting repeal of such laws, we believe pediatricians are not aware of existing statutes. METHODS: A survey to assess understanding of Florida's religious exemption laws was distributed to pediatric house staff, faculty, and clinical social workers at a large teaching hospital and to community pediatricians in private practice. RESULTS: Eighty-four percent of respondents were unaware of Florida statutes, and physicians were significantly less knowledgeable than social workers. Of those who understood the statutes, 92% believed physicians should overrule parents' decisions. Significantly more social workers than physicians believed that parents should be prosecuted for child abuse or neglect when medical treatment is withheld for religious reasons. CONCLUSIONS: Further education of pediatric health care workers is required before repeal of these laws will become a priority for legislators.

Usefulness of acute phase reactants in the diagnosis of acute infections in HIV-infected children.

BACKGROUND: Children infected with the human immunodeficiency virus (HIV) often have hypergammaglobulinemia, causing elevation of the erythrocyte sedimentation rate (ESR). This study was done to determine whether C-reactive protein (CRP) is a better indicator of acute infection than ESR in HIV-infected children. METHODS: Erythrocyte sedimentation rate, CRP, and immunoglobulin G (IgG) levels were measured in sick and otherwise healthy HIV-infected children. McNemar's test was used to compare ESR and CRP. RESULTS: In 22 of the 26 cases (85%), the IgG level was elevated, and in all cases ESR was elevated. In 20 of these 22 (91%), both ESR and CRP were elevated. Of the 18 controls, 17 (94%) had elevated IgG, 14 of 17 (82%) had elevated ESR, and 1 (7%) had elevated CRP. The sensitivity for ESR and CRP was 96% and 92%, respectively, and the specificity for ESR and CRP was 17% and 94%, respectively. CONCLUSIONS: Since CRP is more specific than ESR in predicting acute infection in HIV-infected children, it should be used in the evaluation of acute infection in this population.

Computed tomography and the diagnosis of coalescent mastoiditis.

OBJECTIVE: To evaluate the sensitivity and accuracy of temporal bone CT findings for the diagnosis of acute coalescent mastoiditis. DESIGN: CT scans were blindly scored for mastoid bone integrity (air cell septae, sigmoid cortical plate, and lateral cortical wall) by an otologist and 2 neuroradiologists. Scores were analyzed to determine their sensitivity and specificity for acute coalescent mastoiditis. SUBJECTS: Twenty-one patients with acute coalescent mastoiditis or acute noncoalescent mastoiditis and 12 patients with chronic mastoiditis. SETTING: Academic tertiary care facility. RESULTS: Pair-wise interobserver agreement was good to excellent (kappa = 0.4 to 0.83) for the sigmoid plate, the lateral cortex, and the septae. Scores for the sigmoid plate were significantly greater (indicative of greater bone destruction) in the coalescent group than in either the noncoalescent group or the chronic group (P < 0.05). Within the coalescent group, scores were highest for the sigmoid plate, followed by the septae and the lateral wall. Sensitivity and specificity for coalescent mastoiditis were both highest for the sigmoid plate (67% and 90%, respectively). CONCLUSIONS: Erosion of the cortical plate overlying the sigmoid sinus is the most sensitive and specific CT finding for distinguishing coalescent from noncoalescent acute mastoiditis.