Treatment of oropharyngeal squamous cell carcinoma with external beam radiation combined with interstitial brachytherapy

BACKGROUND: We reviewed the outcomes of oropharyngeal squamous cell carcinoma treated with external beam radiation and interstitial brachytherapy. METHODS: Ninety patients with squamous cell carcinoma of the oropharynx were treated with interstitial brachytherapy at the University of Utah between 1984 and 2001. Seventy-two patients received external beam radiotherapy (EBRT) followed by brachytherapy boost, 11 had surgery followed by EBRT and brachytherapy, 4 had surgery and brachytherapy, and 3 were treated with brachytherapy alone. Median doses for EBRT and brachytherapy were 50 and 24 Gy, respectively. RESULTS: Median follow-up after brachytherapy was 48.3 months for all patients. Five-year local control, disease-free survival, and overall survival were 76%, 61%, and 55%. For T1, T2, T3, and T4, 5-year local control rates were 83%, 79%, 79%, and 64%, respectively. Severe complications occurred in 13 patients, including 2 treatment-related deaths. CONCLUSIONS: EBRT combined with interstitial brachytherapy provide good local control rates for locally advanced oropharyngeal squamous cell carcinoma.     

Early results of immediate repair of obstetric third-degree tears: 65% are completely asymptomatic despite persistent sphincter defects in 61%

OBJECTIVE: The outcome of immediate repair of obstetric third-degree tears is poorly documented. Immediate repair may give better functional results than delayed repair because scarring is reduced. This aim of this prospective study was to examine the early outcome of immediate repair of third-degree tears. METHOD: A total of 121 women who had immediate repair of obstetric third-degree tears underwent interview, anal ultrasonography and anorectal physiology. RESULTS: At review, 79 (65%) were completely asymptomatic (score = 0), 23 (19%), had minor flatus incontinence or mild urgency causing no compromise to their quality of life (score 1-4), and 19 (16%) had clinically embarrassing faecal incontinence (score 5-24). Thirty-nine (32%) had an intact internal anal sphincter (IAS) and external anal sphincter (EAS) (i.e. a successful repair), eight (7%) had a defect in the IAS alone but the EAS was intact (i.e. a successful repair but a residual IAS defect), 43 (35%) had a residual defect in the EAS alone (IAS intact) and 31 (26%) had a persistent defect in the IAS and EAS. Residual defects in either or both of the sphincters were associated with a significantly higher incidence of abnormal resting and squeeze anal pressures. Anal manometry had no correlation with symptoms. The highest proportion of severe incontinence was in those with an IAS defect alone (37%) and when there was a residual IAS and EAS defect (24%). Only 2 of 39 (5%) with an intact IAS and EAS had severe incontinence and only 8 of 43 (18%) with a residual EAS defect alone had severe faecal incontinence. CONCLUSION: These results indicate a good outcome following immediate repair of third-degree obstetric tears and emphasize the role of the IAS in providing continence.     

Evaluation of magnification and paddle compression techniques in the assessment of mammographic screening detected abnormalities

Between February 1988 and December 1989, 8.6% of all women who presented to the South East London Breast Screening Centre for mammography were recalled for assessment. Magnification or paddle compression techniques were used in the assessment of 39% of these patients. The aim of the study was to evaluate the improvement in mammographic specificity provided by these 'special views'. Three hundred and thirty cases were reviewed. The basic mammograms were assessed both alone and together with the special views, and the mammographic findings were scored according to the index of suspicion for malignancy. Special views were felt to be helpful when they led to an increase in mammographic specificity. It was found that special views increased mammographic specificity in 50.8% of cases. Sixteen 'equivocal' diagnoses became 'normal' or 'benign' and 15 of these patients avoided surgical biopsy. Twelve 'equivocal' diagnoses became 'malignant', which helped surgical planning, and in all 12 cases, histology confirmed the diagnosis of malignancy. It is felt that 'special views' are necessary for the complete mammographic assessment of many screen-detected abnormalities.     

Effects of injury severity on regional and temporal mRNA expression levels of calpains and caspases after traumatic brain injury in rats

Despite a preponderance of studies demonstrating gene expression and/or enzymatic activation of calpain and caspase proteases after traumatic brain injury (TBI), no studies have examined the effects of injury magnitude on expression levels of these cell death effectors after TBI. Determination of the degree to which injury severity affects specific expression profiles is critical to understanding the relevant pathways contributing to post-trauma pathology and for developing targeted therapeutics. This investigation tested the hypothesis that different injury magnitudes (1.0, 1.2, and 1.6 mm) cause alterations in the regional and temporal patterns of mRNA expression of calpain-related (calpain-1 and -2, calpastatin) and caspase-related (caspases -3, -8, -9, BID) gene products after cortical impact in rats. Quantitative RT-PCR was used to compare effects of injury severity on mRNA levels in ipsilateral (injured) cortex and hippocampus, 6 h to 5 days post-injury. TBI caused increases in mRNA expression of all proteins examined, with the highest expression detected in the cortex. Generally, injury magnitude and levels of gene expression were positively correlated. High levels of gene induction were observed with BID, caspase-3, and -8, while caspase-9 mRNA had the lowest level of induction. Interestingly, although calpains are activated within minutes of TBI, calpain mRNA expression was highest 72 h to 5 days post-TBI. This study is the first analysis of the regional and temporal expression of calpains and caspases after TBI. These data provide insight into the inter-relationship of these two protease families and on the distinct but overlapping cascades of cell death after TBI.     

Techniques for high-resolution MR imaging of atherosclerotic plaque

Atherosclerotic cardiovascular disease is the most common cause of death in the United States. Investigation of atherosclerotic plaque morphology and composition is important because the findings may be useful in predicting prognosis or response to therapy. This study presents high-resolution magnetic resonance (MR) imaging techniques developed on a 1.5-T whole-body imager with a custom-built surface coil, for characterizing the composition and morphology of plaque removed at carotid endarterectomy. The initial comparison of MR imaging and histologic results showed good correlation. In conjunction with MR angiography, these techniques could be used in in vivo imaging to define the size, location, and contents of atherosclerotic plaque at the carotid bifurcation.     

Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis

Hypercalcemia and hypercalciuria in sarcoidosis are thought to result from the endogenous overproduction of an active vitamin D metabolite. We employed primary cultures of pulmonary alveolar macrophages from two patients with biopsy-proven pulmonary sarcoidosis and a recent or current clinical abnormality in calcium metabolism to synthesize in vitro a 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-like metabolite from 25-hydroxyvitamin D3 (25OHD3). The macrophage metabolite cochromatographed with [3H]1,25-(OH)2D3 on normal phase and reverse phase high performance liquid chromatography and was bound with high affinity by the chick intestinal receptor for 1,25-(OH)2D3. On UV spectroscopy, the metabolite possessed the carbon-5,7,10 (19) cis-triene chromophore characteristic of a vitamin D sterol. Electron impact mass spectrometry of trimethylsilyl ether derivatives of the metabolite revealed a mass fragmentation pattern similar to that of the trimethylsilyl ether derivative of authentic 1,25-(OH)2D3. The incubation of cultured macrophages from two patients with idiopathic pulmonary fibrosis and two with scleroderma with [3H]25OHD3 did not result in production of a metabolite with the chromatographic identity of 1,25-(OH)2D3. These data indicate that the metabolite of 25OHD3 synthesized by sarcoid macrophages in vitro is 1,25-(OH)2D3 and that the macrophage is a synthetic source of the sterol metabolite in sarcoidosis.     

Cardiac arrhythmias in patients with surgical repair of Ebstein's anomaly

Preoperative, perioperative and postoperative arrhythmias in 52 consecutive patients who underwent operation for Ebstein's anomaly were reviewed. There were 25 male and 27 female patients (mean age 18 years, range 11 months to 64 years). Thirty-four patients had one or more documented arrhythmias preoperatively (18 had paroxysmal supraventricular tachycardia, 10 had paroxysmal atrial fibrillation or flutter, 13 had ventricular arrhythmia and 3 had high grade atrioventricular block). Seven patients without documented arrhythmias had a history typical of tachyarrhythmias. During the perioperative and early postoperative periods, 14 patients had atrial tachyarrhythmias and 8 had ventricular tachycardia or ventricular fibrillation. There were seven deaths between day 1 and 27 months after operation. Five of these deaths were sudden (all in male patients, aged 12 to 34 years), and four of the patients had had perioperative ventricular tachycardia or ventricular fibrillation. One patient was taking one antiarrhythmic agent and another patient was taking two at the time of sudden death. Of the 18 patients with paroxysmal supraventricular tachycardia and 9 patients with paroxysmal atrial fibrillation or flutter preoperatively who were followed up for a mean of 40 and 36 months, respectively, 22 and 33% continued to have symptomatic tachycardia. Of the 11 patients (mean age 9 years) without preoperative documentation or symptoms of arrhythmia, follow-up data were obtained (range 1 to 144 months, mean 31) in 9 patients. None died suddenly or developed symptomatic arrhythmia.