Primary closure versus radial forearm flap reconstruction after hemiglossectomy: functional assessment of swallowing and speech

The authors compared the postoperative speech and swallowing function of six patients who underwent free radial forearm flap reconstruction after hemiglossectomy with that of six control patients who underwent primary closure of the defect. Clinical speech pathologic evaluations included the Fletcher time-to-time maximum repetition rate of syllables, multiple rhyme test, and overall quality and intelligibility of the patients' speech. Evaluation of swallowing included the duration of deglutition, bolus volume, and ingestion rate. Speech quality, including intelligibility and articulation, was better in patients with primary closure. However, the bolus volume and ingestion rate in deglutition were better in those with flap reconstruction. These results suggest that the flap adds bulk, thus improving pharyngeal clearance by maintaining the tongue-to-mouth roof contact that is necessary in the swallowing process. The nonfunctional flap, however, hinders articulation by restricting the mobility of the remaining portion of the normal tongue.     

Hypoglossal schwannoma in the submandibular space

Most schwannomas of the hypoglossal nerve originate from the intracranial portion, but they may extend extracranially. Solitary and extracranial schwannomas are extremely rare. We report a case of submandibular hypoglossal schwannoma along with its clinical course and management.     

Efficacy and safety of losartan in patients with proteinuria

The renoprotective effect and safety of an angiotensin II receptor blocker, losartan, were studied in 11 diabetic and 14 nondiabetic patients with a daily urinary protein excretion >500 mg. Once-daily losartan was administered to all patients for 16 weeks without diuretics or other antihypertensive agents. A daily dose of 50 mg was given to those patients with a sitting systolic blood pressure of between 130 and 170 mm Hg; 25 mg was given to patients with a systolic blood pressure of between 110 and 130 mm Hg. Sixteen patients (6 diabetic and 10 nondiabetic patients) had a more than 25% decrease of their daily urinary protein excretion (response rate 64%). The mean decrease in these 16 patients was 57 +/- 17% (p < 0.05). Two patients (1 diabetic and 1 nondiabetic) had more than a 25% increase of their urinary protein excretion. The trough sitting systolic blood pressure of all patients (n = 25) decreased from 142 +/- 17 to 125 +/- 13 mm Hg (p < 0.05) and the trough sitting diastolic blood pressure from 87 +/- 11 to 78 +/- 11 mm Hg (p < 0.05). Serum uric acid was measured in 16 patients; a decrease from 7.3 +/- 1.6 to 6.6 +/- 1.4 mg/dl (a 9.6% decrease, p < 0.05) was found after 16 weeks. Our study showed that in both diabetic and nondiabetic proteinuric patients once-daily losartan, given as monotherapy at doses of 25 or 50 mg, was effective in reducing blood pressure, serum uric acid levels, and daily urinary protein excretions.     

Body fat standards and individual physical readiness in a randomized Army sample: screening weights,methods of fat assessment,and linkage to physical fitness

Body fat standards have been used by the military services since the early 1980s to prevent obesity and motivate good fitness habits. The Army Weight Control Program has continued to undergo evaluation and incorporate improvements based on emerging scientific findings. Recently drafted revisions of Department of Defense-wide procedures address issues of consistency and validity raised by external oversight groups. This study evaluated the impact of three proposed refinements of the Army Weight Control Program. Anthropometric measurements and fitness test performance were obtained in a randomized sample of 1,038 male and 347 nonpregnant female soldiers at three Army posts. Of this sample, 11% of men and 17% of women were overweight and overfat; 6.3 and 9.8%, respectively, were currently on the Army Weight Control Program. Screening weight tables that ensure women are not inappropriately striving to meet weights more stringent than "healthy" weight (i.e., body mass index < 25 kg/m2) still correctly identified all women for evaluation for the age-specific body fat standards. Body fat estimation using more valid DoD body fat equations that include an abdominal circumference for women reduced the number of female soldiers currently classified as exceeding fat standards, coincidentally resulting in a comparable prevalence of male and female soldiers over the fat standards (12%). A body fat allowance for young soldiers who scored very well on the physical fitness test could have benefited one-fourth of the soldiers exceeding fat standards and acknowledges biological variability in body fat thresholds. Whereas this linkage may motivate fitness habits, it complicates enforcement of reasonably achievable body fat standards. The proposed changes in fat screening and measurement methods are appropriate, but the impact to health and physical readiness of the Force cannot be accurately predicted or measured because of the absence of comprehensive baseline data and tracking mechanisms.     

Anti-tumour activity and toxicity of the new prodrug 9-aminocamptothecin glucuronide (9ACG) in mice

Cancer chemotherapy is limited by the modest therapeutic index of most antineoplastic drugs. Some glucuronide prodrugs may display selective anti-tumour activity against tumours that accumulate beta-glucuronidase. We examined the toxicity and anti-tumour activity of 9-aminocamptothecin glucuronide, a new glucuronide prodrug of 9-aminocamptothecin, to evaluate its potential clinical utility. 9-aminocamptothecin glucuronide was 25-60 times less toxic than 9-aminocamptothecin to five human cancer cell lines. Beta-glucuronidase activated 9-aminocamptothecin glucuronide to produce similar cell killing as 9-aminocamptothecin or topotecan. The in vivo toxicity of 9-aminocamptothecin glucuronide in BALB/c mice was dose-, route-, sex- and age-dependent. 9-aminocamptothecin glucuronide was significantly less toxic to female than to male mice but the difference decreased with age. 9-aminocamptothecin glucuronide and 9-aminocamptothecin produced similar inhibition (approximately 80%) of LS174T human colorectal carcinoma tumours. 9-aminocamptothecin glucuronide cured a high percentage of CL1-5 human lung cancer xenografts with efficacy that was similar to or greater than 9-aminocamptothecin, irinotecan and topotecan. The potent anti-tumour activity of 9-aminocamptothecin glucuronide suggests that this prodrug should be further evaluated for cancer treatment.     

Improvement of local control of T3 and T4 nasopharyngeal carcinoma by hyperfractionated radiotherapy and concomitant chemotherapy

PURPOSE: When the primary tumor of nasopharyngeal carcinoma (NPC) is treated at the base of skull and intracranium with conventional radiotherapy, the result is generally poor. In this report, we investigated whether hyperfractionated radiotherapy (HFRT) and concomitant chemotherapy (CCT) could achieve better local control and survival in NPC patients with T3 and T4 lesions. PATIENTS AND METHODS: Forty-eight patients (11 T3 and 37 T4 NPC) were treated with HFRT and CCT. HFRT was administered at 1.2 Gy per fraction, two fractions per day, Monday-Friday for 62 fractions for a total dose of 74.4 Gy. Concomitant chemotherapy consisting of cis-diamino-dichloroplatinum (CDDP) alone or CDDP and 5-fluorouracil was delivered simultaneously with radiotherapy during Weeks 1 and 6. Adjuvant chemotherapy consisted of CDDP and 5-fluorouracil for 2 to 3 cycles and was given monthly beginning 1 month after completion of radiation. RESULTS: With a median follow-up of 57 months (range: 28-94 months), the 3-year locoregional control rate was 93%, the disease-free survival rate was 71%, and the overall survival rate was 72%. For T4 patients, the 3-year locoregional control rate was 91%, disease-free survival was 62%, and overall survival was 63%. The major acute toxicity was Grade 3 mucositis in 73% and Grade 2 weight loss in 31% of patients. Fifty percent of patients were tube fed. Most patients tolerated the combined modality treatments relatively well; 88% of patients completed their radiation treatment within 8 weeks. CONCLUSION: HFRT and CCT for T3 and T4 NPC were associated with excellent local control and improved survival. The treatment-related toxicity was acceptable and reversible. We would recommend using HFRT with CCT for advanced T-stage NPC if the three-dimensional conformal radiation planning shows a significant portion of the brainstem to be inside the treatment field.     

Mapping geographic zones of cancer risk with epigenetic biomarkers in normal breast tissue.

PURPOSE: Genetic alterations were previously identified in normal epithelia adjacent to invasive cancers. The aim of this study was to determine DNA methylation in histologically normal tissues from multiple geographic zones adjacent to primary breast tumors. EXPERIMENTAL DESIGN: First, methylation status of a 4-kb region of RASSF1A promoter was interrogated using oligonucleotide-based microarray in 144 samples (primary tumors, 47; adjacent normals, 69; reduction mammoplasty tissues, 28). Second, allelic imbalance (AI)/loss of heterozygosity (LOH) surrounding RASSF1A promoter were analyzed in 30 samples (tumors, 8; adjacent normals, 22). Third, global methylation screening of 49 samples (tumors, 12; adjacent normals, 25; reduction mammoplasty, 12) was done by differential methylation hybridization. Real-time quantitative methylation-specific PCR was used to validate the microarray findings. RESULTS: DNA methylation in the core RASSF1A promoter was low in reduction mammoplasty tissues (P=0.0001) when compared with primary tumors. The adjacent normals had an intermediate level of methylation. The regions surrounding the core were highly methylated in all sample types. Microsatellite markers showed AI/LOH in tumors and some of the adjacent normals. Concurrent AI/LOH and DNA methylation in RASSF1A promoter occurred in two of six tumors. Global methylation screening uncovered genes more methylated in adjacent normals than in reduction mammoplasty tissues. The methylation status of four genes was confirmed by quantitative methylation-specific PCR. CONCLUSIONS: Our findings suggest a field of methylation changes extending as far as 4 cm from primary tumors. These frequent alterations may explain why normal tissues are at risk for local recurrence and are useful in disease prognostication.     

银屑病和日光性角化病皮损应用氨基-γ-酮戊酸荧光染色后肉眼荧光强度与原卟啉Ⅸ含量的相互关系

应用5-氨基-γ-酮戊酸（ALA）诱导的卟啉荧光诊断（FDAP）中，肉眼可观察到原卟啉IX（PpIX）沉积。因操作重复性低，且涉及PpIX肿瘤选择的机制知之甚少，所以解释荧光数据仍有些困难。本研究中，作者要研究FDAP后银屑病和日光性角化病（AK）患者皮损的PpIX沉积情况。基于此目的，将患者脱屑区皮损和无皮损正常皮肤用20％ALA油孵育3h，进行FDAP，取强荧光区皮损和无皮损处皮肤活检。从活检标本中提取PpIX、蛋白质和双链DNA行荧光分光光度法定量，用图像分析软件分析由FDAP获得的数字图像。     

Estrogen blocks parathyroid hormone-stimulated osteoclast-like cell formation in modulating differentiation of mouse marrow stromal cells in vitro.

BACKGROUND AND PURPOSE: During skeletal development and bone remodeling, bone marrow stromal cells give rise to osteoblasts and provide a critical microenvironment to support osteoclast formation. Estrogen is important for the maintenance of bone balance in adult animals by either increasing bone mass or inhibiting osteoclastic bone resorption. This study sought to determine the role that estrogen plays in coordinating osteogenic differentiation of bone marrow stromal cells and the ability of these cells to support osteoclast formation. METHODS: A conditionally immortalized mouse bone marrow stromal cell line, MS1, was used to examine the effects of estrogen on stromal cell differentiation and on stromal cell-supported osteoclast formation. RESULTS: On treatment of MS1 cells with 17 beta-estradiol (E2) (10(-12)-10(-8) M), alkaline phosphatase activity and bone nodule formation were increased in a dose-dependent manner, while the proliferation of MS1 cells was dose-dependently inhibited. 17 beta-E2 (10(-12)-10(-8) M) also caused a concentration-dependent inhibition of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation in parathyroid hormone (PTH)-stimulated MS1 and spleen cell cocultures. Furthermore, estrogen pretreatment of MS1 cells also decreased the number of TRAP-positive MNCs in cocultures. Culturing in PTH-treated conditioned media did not rescue the loss of activity supporting osteoclast-like cell formation in MS1 cells. CONCLUSION: These results indicate that 17 beta-E2-stimulated osteoblastic differentiation of mouse marrow stromal cells results in bone matrix mineralization and a decrease in activity of supporting PTH-induced osteoclast-like cell formation.