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Biomedical subjects

S E Brooks

Publications and source records attributed to S E Brooks.

At least 19 recordsLinked to original sources

Health care cost and utilization project analysis of comorbid illness and complications for patients undergoing hysterectomy for endometrial carcinoma.

OBJECTIVE: The objective was to study the association of race, comorbid illness, and lymph node dissection (LND) with complications in patients undergoing hysterectomy for endometrial carcinoma. METHODS: The Health Care Cost Utilization Project analysis studied women undergoing hysterectomy for endometrial carcinoma in 1996. Chi-square and Student t tests were used to determine differences in means or proportions. Linear, stepwise, and three-stage regression analyses were used to build predictive models for charges and lengths of stay (LOS). RESULTS: The mean age of the 5730 patients was 64.5 (standard deviation, 12.37); 72% of the patients were white, 5% were African American, and 23% were classified as "other." Ninety percent underwent total abdominal hysterectomy, 5% total vaginal hysterectomy (TVH), 4% radical abdominal hysterectomy, and 1% TVH/laparoscopy. Thirty-eight percent also underwent LND. Lymph node dissection was performed more frequently at teaching hospitals (P = 0.0000) and was associated with more complications. Comorbid illness (i.e., diabetes, heart disease) was documented in 51% of admissions, and > or = 1 comorbidity was documented in 21.5%. African Americans were more likely to have one or more comorbid illnesses, underwent more LNDs (P = 0.02), suffered more complications (P = 0.0001), and were more likely to die in the hospital compared with whites or others (P = 0.000). Although LND, complications, and longer LOS were more likely to occur in teaching hospitals (P = 0.0005), total charges and inpatient death were not higher in teaching hospitals. CONCLUSIONS: The higher frequency of comorbid illness, complications, LND, and inpatient death in African Americans reflects severity of medical illness and cancer in these patients. Teaching hospital admission was associated with more complications and longer LOS, but not a higher death rate.

Black or African American↗

Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice.

PURPOSE: Exposure of premature human infants to hyperoxia results in the obliteration of developing retina capillaries, leading to a vision-threatening retinopathy termed retinopathy of prematurity (ROP). The authors hypothesized that this process may be mediated in part by endothelial nitric oxide (NO)-derived oxidants such as peroxynitrite and tested this hypothesis in a mouse model of ROP. METHODS: Normal mice, mice treated with the nitric oxide synthase (NOS) inhibitor N:(G)-nitro-L-arginine (L-NNA), and knockout mice carrying a homozygous targeted disruption of the gene for endothelial NOS (eNOS) were studied in an experimental model of ROP. Retinas were compared for extent of capillary obliteration in hyperoxia, vascular endothelial growth factor (VEGF) expression, nitrotyrosine formation, and vitreous neovascularization. RESULTS: Oxygen-induced retinal vaso-obliteration was significantly reduced by L-NNA treatment (43% decrease from controls). The eNOS-deficient mice showed a similar reduction in vaso-obliteration (46% decrease from controls), and vitreous neovascularization was also substantially reduced (threefold decrease). Retinal nitrotyrosine formation, a measure of in situ peroxynitrite modification of proteins, was significantly elevated in normal mice during hyperoxia, in a spatial and temporal pattern consistent with a role in oxygen-induced vaso-obliteration. This was not seen in eNOS-deficient mice. VEGF expression was similar in both groups of mice, although suppression in hyperoxia was slightly blunted in eNOS-deficient mice. CONCLUSIONS: These data suggest a role for NO and peroxynitrite in the pathogenesis of ROP. Therapies aimed at modulation of eNOS activity may have therapeutic potential for preventing ROP.

Animals↗

Orbital cellulitis due to occult orbital lymphangioma.

A 12-year-old female patient with atypical orbital and periorbital cellulitis was found to have an occult lymphangioma of the orbit. Recognition of this entity provided an explanation for the atypical features of the case and guided appropriate medical management.

Cellulitis↗

Vascular endothelial growth factor activates STAT proteins in aortic endothelial cells.

Vascular endothelial growth factor (VEGF) intracellular signaling in endothelial cells is initiated by the activation of distinct tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR). Because the tyrosine kinase-dependent transcription factors known as STAT (signal transducers and activators of transcription) proteins are important modulators of cell growth responses induced by other growth factor receptors, we have determined the effects VEGF of on STAT activation in BAEC (bovine aortic endothelial cells). Here, we show that VEGF induces tyrosine phosphorylation and nuclear translocation of STAT1 and STAT6. VEGF also stimulates STAT3 tyrosine phosphorylation, but nuclear translocation does not occur. We found that placenta growth factor, which selectively activates VEGFR1, has no effect on the STATs. However, upon VEGF stimulation, STAT1 associates with the VEGFR2 in a tyrosine kinase-dependent manner, indicating that VEGF-induced STAT1 activation is mediated primarily by VEGFR2. Thus, our study shows for the first time that VEGF activates the STAT pathway through VEGFR2. Because the growth-promoting activity of VEGF depends upon VEGFR2 activation, these findings suggest a role for the STATs in the regulation of gene expression associated with the angiogenic effects of VEGF.

Animals↗

Pharmacokinetic and pharmacodynamic study of the combination of docetaxel and topotecan in patients with solid tumors.

PURPOSE: The sequence in which chemotherapeutic agents are administered can alter their pharmacokinetics, therapeutic effect, and toxicity. We evaluated the pharmacokinetics and pharmacodynamics of docetaxel and topotecan when coadministered on two different sequences of administration. PATIENTS AND METHODS: On cycle 1, docetaxel was administered as a 1-hour infusion at 60 mg/m(2) without filgrastim and at 60, 70, and 80 mg/m(2) with filgrastim on day 1, and topotecan was administered at 0.75 mg/m(2) as a 0.5-hour infusion on days 1 to 4. On cycle 2, topotecan was administered on days 1 to 4, and docetaxel was administered on day 4. Cycles were repeated every 21 days. Blood samples for high-performance liquid chromatography measurement of docetaxel (CL(DOC)) and topotecan (CL(TPT)) total clearance were obtained on day 1 of cycle 1 and day 4 of cycle 2. CL(DOC) and CL(TPT) were calculated using compartmental methods. RESULTS: Mean +/- SD CL(DOC) in cycles 1 and 2 were 75.9 +/- 79.6 L/h/m(2) and 29.2 +/- 17.3 L/h/m(2), respectively (P: <.046). Mean +/- SD CL(TPT) in cycles 1 and 2 were 8.5 +/- 4.4 L/h/m(2) and 9.3 +/- 3.4 L/h/m(2), respectively (P: >. 05). Mean +/- SD neutrophil nadir in cycles 1 and 2 were 4,857 +/- 6, 738/microL and 2,808 +/- 4,518/microL, respectively (P: =.02). CONCLUSION: Administration of topotecan on days 1 to 4 and docetaxel on day 4 resulted in an approximately 50% decrease in docetaxel clearance and was associated with increased neutropenia.

Adult↗

Cervical cancer outcomes analysis: impact of age, race, and comorbid illness on hospitalizations for invasive carcinoma of the cervix.

OBJECTIVE: The aim of this study was to evaluate the association of age, race, and comorbid illness with procedures and complications in hospitalized patients with invasive carcinoma of the cervix in a statewide population-based database over a 3-year period. METHODS: Hospitalizations were classified into homogeneous subgroups based on a diagnosis of invasive cervical cancer. Cancer-related complications and comorbid diseases were evaluated. chi(2) and t tests determined differences in means or proportions. Linear regression techniques were applied to build models for hospitalization charges and lengths of stay (LOS). RESULTS: There were 1009 admissions. The mean age was 49.5, with a median age of 46 (21-100, SD 15.4). Of the total, 606/1009 (60%) were white, 354/1009 (35%) were African-American (AA), and 5% were "other" races. AAs were more likely to have Medicaid or be uninsured (44% vs 23%, P = 0. 001) and were more likely to be admitted for an emergency (unadjusted odds ratio (OR) = 1.6; 1.2-2.2), to have a comorbid illness (P = 0.001), to be admitted for a cancer-related complication (P = 0.036), to be admitted for a transfusion (P = 0. 01), and to be admitted for radiation therapy rather than surgery (P = 0.001). The following were associated with LOS and higher hospital costs: emergency admissions for complications of cancer, comorbid illness, and older age. CONCLUSIONS: Racial differences exist in patterns of admission, type of therapy, and severity of illness; however, there were no differences in charges or LOS for similar procedures. The large percentage of African-Americans uninsured or insured by government-supported programs indicates the potential impact of public policy on the care of these patients. Socioeconomic status rather than phenotypic appearance may be a more important determinant of outcome.

Adult↗

Cervical cancer--the impact of clinical presentation, health and race on survival.

This study evaluated the association of race, comorbid illness, insurance status, and other prognostic factors on treatment and survival of patients with invasive carcinoma of the cervix, using as its methodology a retrospective study of patients with invasive carcinoma of the cervix treated from 1991 to 1998 at the University of Maryland. Of 161 such patients, 153 met the study criteria. Of these 153 women, 83 (54%) were African Americans and 70 (46%) were white. The mean (+/- SE) age of African American women was 52 +/- 1.8 years and that of white women was 50 +/- 1.8 years. African American women were more likely to present with stages II-IV disease (P = 0.01) and, as a consequence, underwent radiation therapy rather than surgery (P = 0.04). The survival of African American women with stage I-II disease was significantly lower than for white women. In the final regression model, stage III-IV disease (hazard ratio 3.2, 95% (CI 1.7, 6.1) African American race, (hazard ratio 1.9; 95% CI 1.0, 3.3) and comorbid illnesses (hazard ratio 2.3; 95% CI 1.3-4.0) were associated with poor survival. Adverse outcomes of African American women with cervical cancer persist after adjustment for stage of disease and other factors and are particularly apparent in stage I-II disease. The role of comorbid illness is deserving of further study.

Black or African American↗

Treatment outcome in fellow eyes after laser photocoagulation for retinopathy of prematurity.

PURPOSE: To determine the concordance in structural outcome between fellow eyes in patients undergoing diode laser peripheral retinal photocoagulation for threshold retinopathy of prematurity. METHODS: Records from 103 patients undergoing bilateral diode laser peripheral retinal photocoagulation for retinopathy of prematurity at three academic medical centers were reviewed. Information regarding infant gestational ages, birth weights, characteristics of retinopathy of prematurity, laser treatment variables, complications, and structural outcomes were obtained. The data were analyzed to determine the rate of successful structural outcomes among all eyes as well as the interocular outcome concordance. RESULTS: A successful structural outcome was observed in 182 (88%) of the 206 eyes. Eighty-eight patients (85.4%) had bilateral favorable outcomes. Nine patients (8.7%) had bilateral unfavorable outcomes, and six patients (5.8%) had one favorable and one unfavorable eye. The outcome was concordant between fellow eyes in 94.2% of patients. This rate was higher than predicted if fellow-eye outcomes were truly independent (P < .00001) and did not depend on study center, laser settings, or location of the retinopathy of prematurity. Serious complications related to treatment were uncommon. CONCLUSIONS: Diode laser peripheral retinal photocoagulation is a safe and effective procedure for treating threshold retinopathy of prematurity. The concordance of structural outcomes between fellow eyes is higher than expected by chance and suggests that patient-specific factors play a key role in treatment response.

Birth Weight↗

Discordant retinoblastoma in monozygotic twins.

PURPOSE: We report cases of discordant retinoblastoma in twins confirmed to be monozygotic by DNA analysis. METHODS: Twin A demonstrated severe, bilateral, multifocal retinoblastoma, which was recalcitrant to external beam irradiation and chemoreduction. Twin B has not demonstrated retinoblastoma. DNA analysis was performed with polymorphic microsatellite markers to confirm monozygosity. Single-stranded conformation polymorphism and Southern blot analysis of the retinoblastoma gene were performed. RESULTS: Molecular genetic analyses confirmed monozygosity but failed to disclose a retinoblastoma gene mutation in either twin. CONCLUSIONS: The extreme phenotypic discordance may best be explained by an unidentified, postzygotic retinoblastoma gene mutation in early embryonic development of the affected twin.

Blotting, Southern↗

Cluster of diplopia cases after periocular anesthesia without hyaluronidase.

PURPOSE: To describe a cluster of cases of iatrogenic diplopia after cataract surgery that occurred in 1998, when hyaluronidase was unavailable for use in periocular anesthetic regimens. SETTING: The clinical practices of the authors. METHODS: This study comprised a retrospective chart review. RESULTS: Twenty-five cases of transient or permanent diplopia were reported. Of these, 13 eyes had retrobulbar and 10 had peribulbar injections; in 2 cases the injection technique was unknown. The inferior rectus was affected in 19 eyes; of these, 1 had a temporary palsy and 18 had permanent restriction. Temporary paresis developed in the lateral rectus in 5 cases and the superior rectus in 2. Eleven cases were submitted by 4 anterior segment surgeons, who collectively had a zero incidence of iatrogenic postoperative diplopia in the preceding 4 to 11 years of practice (approximately 6900 cases). CONCLUSION: Hyaluronidase may be more important than previously suspected in preventing anesthetic-related damage to the extraocular muscles. The inferior rectus muscle is particularly vulnerable, presumably because of the injection technique.

Aged↗

The negative psychosocial impact of strabismus in adults.

INTRODUCTION: The goal in the treatment of strabismus is to realign the visual axes to eliminate diplopia, produce or restore binocular vision, expand the binocular visual field, and/or provide a normal appearance. The treatment of strabismus in adults who do not experience diplopia or who do not have binocular potential has sometimes been regarded as "cosmetic." Many adults with strabismus have stated that it has had a negative effect on their lives. This study was designed to ascertain whether there is a negative social bias against adult patients with strabismus that could affect interpersonal relationships and limit employment opportunities. METHODS: An orthotropic person was photographed in primary, right, and left gaze. These photographs were then digitally altered to produce an esotropia and exotropia of similar magnitude. Subjects were then asked to evaluate a single photograph with reference to personality characteristics that are important for social interaction and employment capability. RESULTS: Overall, the strabismic faces were judged significantly more negatively, across 11 descriptive characteristics, than the nonstrabismic face. The effect of esotropia was worse than exotropia. CONCLUSION: Strabismus creates a significant negative social prejudice. These biases can have a detrimental impact on socialization and employability. Treatment of strabismus may positively alter perceived characteristics of individuals and improve their ability to socialize normally and obtain employment. Therefore, the treatment of strabismus should not be considered cosmetic even when there is no hope of improving binocular vision.

Adolescent↗

Current trends in the management of carcinoma of the cervix, vulva, and vagina.

In this review, current basic and clinical literature that describes innovative strategies for staging diagnosis and management of cancers of the cervix, vulva, and vagina are reviewed. The reviewed literature includes investigations of viral oncogenesis, the role of angiogenesis in tumor development, pretreatment staging, and the emerging role of chemotherapy in the treatment of locally advanced disease.

Female↗

Artifact in cervical LLETZ specimens: correlation with follow-up.

The effect of cautery artifact on the ability to accurately diagnose dysplasia and predict abnormal follow-up in large loop excision specimens of the transformation zone (LLETZ) has not been adequately addressed in the pathology literature. One hundred consecutive conization specimens with cytologic and/or histologic follow-up were studied. Indications for the procedure were high-grade squamous intraepithelial lesion (on Pap smear and/or biopsy) in 64 cases, low-grade squamous intraepithelial lesion in 28, atypical squamous cells of unknown significance (ASCUS) in 3, atypical glandular cells of unknown significance in 2, adenocarcinoma in situ, squamous carcinoma in situ, and invasive squamous carcinoma in 1 each. Twenty-four specimens were cold-knife conizations (CKCs) and 76 LLETZs. All LLETZs had at least 1+ artifact, and in 46 cases (61%) it interfered with at least one aspect of evaluation. In 21 cases (28%), 1+ artifact interfered only with margin assessment. In 25 cases (33%), there was 2+ or 3+ artifact precluding not only margin assessment, but also diagnosis and grading of dysplasia. Of the 43 LLETZs received in more than one piece, 33 (77%) had interfering artifact, and in 21 (49%) it was 2+ or 3+, at least focally interfering with diagnosis and grading. In contrast, of 33 LLETZs received in a single piece, only 13 (39%) had interfering artifact, which was 2+ or 3+ in 4 (12%), (p < 0.05). Positive follow-up (including ASCUS, favor dysplasia, and ASCUS, not otherwise specified) was found in 6 of 7 CKCs with positive margins (86%), 10 of 16 LLETZs with positive margins (63%), and 4 of 7 LLETZs with unassessable margins (57%). In cases with negative cone margins, positive follow-up was found in 2 of 17 CKCs (12%), and 18 of 53 LLETZs (34%), p < 0.05; a higher frequency of interfering artifact (p < 0.05) was seen in these cases. LLETZ margin status and postprocedure endocervical curettage (ECC) specimens were not good predictors of residual disease, unlike margin status in CKC. Post-CKC ECC was a better predictor of subsequent abnormal follow-up than post-LLETZ ECC (p < 0.05). The presence of interfering artifact was only rarely mentioned in the original pathology report. In conclusion, the status of margins is a better predictor of abnormal follow-up in CKC than in LLETZ specimens. Fragmentation of the specimen is an additional factor, compounding the inevitable artifact. Postprocedure ECC is not a useful indicator of residual dysplasia. The pathologist should not hesitate to comment on specimen adequacy in surgical pathology reports.

Adult↗

Treatment of posttraumatic ocular dysmotility using autogenous buccal fat grafts in a porcine model.

Diplopia occurring after orbital trauma is a complex and difficult clinical problem. Numerous potential mechanisms exist by which it may occur. Restrictive ocular dysmotility caused by intraorbital scarring is a major component in diplopia's pathogenesis. The current large animal study was conducted to develop an experimental model of restrictive ocular dysmotility that would quantitatively characterize the biomechanical properties of the globe rotations. Using this model, a novel method of restoring the low-friction milieu within the orbit by interposing a buccal fat graft was tested. In the initial stage, the baseline force duction was measured in 20 pig eyes using a highly sensitive, digital tensiometer. Traumatic violation of Tenon's fascia with electrocautery into the extraconal fat and the periorbita was followed by direct suturing of the extraocular muscle to the nearest orbital periosteum. After 6 weeks, the measurements (again in the field of the traumatized muscle) were repeated, and the eyes were divided into two treatment groups (n = 10 eyes per group). The left eye received the standard lysis of adhesion, whereas the right eye received lysis and buccal fat interposition grafting. The third and final force measurements were performed 6 weeks after treatment. The results showed a baseline linear load-displacement curve of 0 to 8 mm, with the globe rotating 400 microm for every 1000 mg of tensile load. Surgical trauma increased the slope as defined by load/displacement but, surprisingly, the relationship remained linear in the entire range from 2 to 8 mm. This linear relationship was seen in all stages: baseline, after trauma to Tenon's fascia, after surgical lysis alone, and after lysis with buccal fat interposition. The difference was in the slope, or stiffness. Lysis alone partially reduced the slope, but it was still higher than baseline. Lysis and buccal fat grafting returned the slope to near baseline. This, however, did not reach the level of statistical significance. It seems that a focal intervention along the course of an extraocular muscle altered the composite behavior of orbital resistance to globe rotation. Although buccal fat grafting did not significantly improve motility, it did not worsen it.

Adipose Tissue↗

The effect of blood transfusion protocol on retinopathy of prematurity: A prospective, randomized study.

OBJECTIVE: Controversy exists regarding the potential influence of anemia and blood transfusions on the rate of retinopathy of prematurity (ROP) in premature infants. A prospective, randomized, masked trial was performed to determine the influence of red blood cell transfusion protocol on ROP incidence and severity in a population of high-risk infants. METHODS: A total of 50 infants with birth weights <1251 g were divided randomly into two groups beginning on day of life 29. Group 1 (n = 24) received red cell transfusions during the 6-week study period, only if certain symptom-based guidelines were met. Group 2 (n = 26) received red cell transfusions to maintain the hematocrit level above 40% for the entire 6 weeks. Infants were monitored for ROP, growth, and associated morbidity. Serial measurements of serum glucose, lactate, ferritin, total iron-binding capacity, and iron were performed. RESULTS: ROP occurred in 83% of infants in group 1, and 73% of infants in group 2. There were no statistically significant differences in ROP severity, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or any of the laboratory values except hemoglobin (10.8 vs 13.2 g/dL) and hematocrit (33.9% vs 41.8%) between the groups. Combining data from both groups, there was no association between hemoglobin or hematocrit ratios and ROP incidence or severity. CONCLUSIONS: A transfusion policy aimed at limiting the amount of blood given to premature infants (symptom-based) during the neonatal period does not impart a significantly different risk for ROP or other associated conditions, than does a policy in which transfusions are given more liberally for replacement purposes.

Erythrocyte Transfusion↗

Profile of women 45 years of age and younger with endometrial cancer.

OBJECTIVE: The clinical characteristics and outcomes of endometrial cancer patients 45 years of age and younger were compared with those of patients older than 45 years of age. METHODS: We performed a cross-sectional study of 301 consecutive endometrial cancer patients referred to our center from 1989 to 1994. Of the 289 patients eligible for study, 40 were 45 years of age or younger (group A) and 249 were older than 45 years of age (group B). RESULTS: The majority of patients in both groups presented with stage I disease. Of the women with stage I disease, patients in group A were more likely than those in group B to have low-grade disease localized to the endometrium (P < .001; relative prevalence 3.39; confidence interval [CI] 1.88, 6.12). However, the distribution of stages I to IV overall was the same for the two groups (P = .269). Although univariate analysis revealed that 11% of the patients in group A and 2% in group B had synchronous ovarian malignancies (P = .007; relative prevalence 5.42; CI 1.39, 21.14), multivariate logistic regression found that nulliparity, not age, was an independent risk factor for synchronous ovarian malignancy (P = .017; relative prevalence 6.15; CI 1.52, 25.61). There were no statistically significant differences by age in the prevalence of high-risk endometrial histology (serous and clear cell carcinoma) or in survival. CONCLUSION: The overall distribution of tumor stage and survival were the same for the younger and older women; this finding contradicts previous reports that suggest that young women with endometrial cancer are at lower risk. Additionally, nulliparity, which occurs with a higher prevalence in younger women who develop endometrial cancer, is associated statistically with the development of synchronous ovarian malignancies.

Adult↗