Hemopericardium and cardiac tamponade as presenting findings of dexamethasone-induced hypertrophic cardiomyopathy complicated by transmural myocardial infarction.

This is the first report of dexamethasone-induced left ventricular outflow obstruction causing decreased coronary artery perfusion and apical transmural cardiac infarct that resulted in hemopericardium and rapid cardiac tamponade. The differential diagnosis of hemorrhagic pericardial effusion must now include dexamethasone-induced hypertrophic cardiomyopathy.

Methylene blue staining of dysplastic and nondysplastic Barrett's esophagus: an in vivo and ex vivo study.

BACKGROUND AND STUDY AIMS: Methylene blue selectively stains specialized columnar epithelium in Barrett's esophagus with high accuracy. We prospectively evaluated the methylene blue staining properties of dysplastic and nondysplastic Barrett's esophagus and the association of these properties with the risk for dysplasia and cancer. PATIENTS AND METHODS: In a ex vivo study, we mapped, photographed, and sampled esophagectomy specimens with high grade dysplasia and/or early adenocarcinoma before and after methylene blue staining. In a concurrent in vivo study, we performed methylene blue staining and characterized methylene blue stain characteristics. Pathologists estimated the proportion of specialized columnar epithelium in each specimen and graded dysplasia. RESULTS: We examined 551 biopsies from 47 patients with biopsy-proven Barrett's esophagus and 48 sections from five surgical specimens with Barrett's esophagus and dysplasia and early adenocarcinoma. The accuracy of ex vivo and in vivo methylene blue staining for specialized columnar epithelium was 87% and 90%, respectively. It was influenced by the length of Barrett's esophagus, biopsy location, and the presence of esophagitis and/or dysplasia. Light to absent staining (p = 0.01) and moderate to marked heterogeneity (p = 0.01) were significantly associated with high grade dysplasia or cancer in the univariate analysis and in a multivariate model that adjusted for the length of Barrett's esophagus and the presence of a lesion. These staining characteristics were present in all patients with severe dysplasia and/or adenocarcinoma. CONCLUSIONS: Highly dysplastic or malignant Barrett's esophagus stains differently with methylene blue. Increased heterogeneity and decreased methylene blue stain intensity are significant independent predictors of high grade dysplasia and/or cancer. These features may help to direct biopsies in patients without a lesion.

Methylene blue-directed biopsies improve detection of intestinal metaplasia and dysplasia in Barrett's esophagus.

BACKGROUND: Endoscopically applied methylene blue selectively stains specialized columnar epithelium in Barrett's esophagus. METHODS: The diagnostic yield and cost of cancer surveillance in patients with Barrett's esophagus using methylene blue-directed biopsies (MBDB) were compared with surveillance using a "jumbo" random biopsy technique in a prospective, sequential, controlled trial. Esophagogastroduodenoscopy was performed with either MBDB or random biopsy in a randomized sequence. The proportions of various types of epithelia in each biopsy were estimated and dysplasia was graded in a blinded fashion. RESULTS: Forty-three patients with short- (n = 8), limited- (n = 10), and long-segment (n = 25) Barrett's esophagus were studied. Using MBDB technique, the average number of biopsies obtained per patient was significantly lower and the proportion of specialized columnar epithelium in each specimen was significantly higher compared with random biopsy. Dysplasia or cancer was diagnosed in significantly more MBDB specimens (12% vs. 6%, p = 0.004). Despite fewer biopsies per patient using MBDB, dysplasia or cancer was diagnosed in significantly more patients (44% vs. 28%, p = 0.03) than by random biopsy technique. MBDB cost less and detected more cancers than random biopsy. CONCLUSIONS: MBDB is a more accurate and cost-effective technique than random biopsy for diagnosing specialized columnar epithelium and dysplasia/cancer, particularly in long-segment Barrett's esophagus.

Diffuse stromal Leydig cell hyperplasia: a unique cause of postmenopausal hyperandrogenism and virilization.

A 60-year-old woman presented with diffuse scalp alopecia, hirsutism, and clitorimegaly, and the mean serum testosterone levels were greater than 200 ng/dL. Findings on computed tomography of both adrenal glands were normal. After bilateral oophorectomy, a unique histological picture consisting of diffuse stromal Leydig cell hyperplasia was found. Reinke crystals were present, but neither hilus cell hyperplasia nor stromal hyperthecosis was noted. Sequencing of the 11 exons of the gene for the luteinizing hormone receptor revealed no abnormality. Relevant data suggest that treatment of the postmenopausal woman with hyperandrogenism and virilization is bilateral laparoscopic oophorectomy if she has no pronounced ovarian enlargement or adrenal tumor on imaging. In this setting, an intensive endocrine evaluation or a search for metastatic disease seems to be unnecessary.

Lipoinjection in the paralyzed feline vocal fold: study of graft survival.

Six adult domestic strain cats were used to study the long-term histologic outcome of injected autologous fat for augmentation of the paralyzed vocal fold. Each animal had surgically induced left vocal cord paralysis via sectioning of the recurrent laryngeal nerve, followed by injection of 0.1 to 0.2 ml of autologous fat into the paralyzed vocal fold. The animals were killed at 6 weeks, and at 4, 6, 8, and 12 months after the injection. Photographic and videolaryngoscopic data were obtained. Histologic studies of the larynges were performed. The results documented histologic viability and persistence of a portion of the injected adipose tissue graft at 8 months after the injection, but only minimal graft survival at 12 months. The outcome suggests that autologous lipoinjection has potential use for short-term (several months) augmentation of the paralyzed vocal cord. Further investigation is warranted before recommending this technique for such use or as an alternative to currently available long-term injectable laryngeal biomaterials.

Predictors of invasion in ductal carcinoma in Situ of the breast: The value of a scoring system.

Ductal carcinoma in situ (DCIS) of the breast shows unpredictable association with invasive ductal carcinoma (IDC). Comedo DCIS (CDCIS) is more frequently associated with IDC than noncomedo DCIS (NCDCIS). We studied prognostic variables in 64 cases of DCIS to identify predictors of invasion. These factors included DCIS type and nuclear grade and two counts of the AgNOR silver staining technique for identification of ploidy and proliferative activity (PA) using two counts: mAgNOR for ploidy and pAgNOR for PA. The other factors included immunostaining of the lesions for epidermal growth factor receptors (EGFR), cathepsin-D (C-D), and the c-erbB-2 oncogene. The 34 cases associated with ICD had pAgNOR ranging from 3% to 36% (median 11%), whereas cases not associated with IDC had a pAgNOR range of 0% to 25% (median 5%; P=0.0001). The correlation between mAgNOR and the development of IDC was less statistically significant. The DCIS type and staining pattern for EGFR, C-D, and c-erbB-2 showed no statistical correlation of individual variables with the development of IDC. A scoring system adding the values of the seven variables was used. A score of 1-2 was given to each variable, depending on whether it was positive or negative. Lesions associated with IDC had a median total score of 8 (+/- 1.35 SD), whereas those lesions not associated with invasion had a median score of 4 (+/- 1.45 SD; P=0.0002). We conclude that proliferative activity analysis may play a significant role in predicting the invasive potential of DCIS. The use of a scoring system adding the sum of single prognostic indicators may provide more useful information regarding the prediction of invasive potential of DCIS than single indicators.

Methylene blue selectively stains intestinal metaplasia in Barrett's esophagus.

BACKGROUND: Specialized columnar epithelium in Barrett's esophagus resembles gastric intestinal metaplasia, which selectively stains with methylene blue. METHODS: We prospectively evaluated the safety, accuracy, reproducibility, cost, and diagnostic yield of methylene blue-directed biopsy in detecting specialized columnar epithelium and dysplasia in Barrett's esophagus. We performed upper endoscopy with methylene blue-directed biopsy and obtained 236 large cup biopsy specimens (145 stained, 91 unstained) from 14 patients with Barrett's esophagus of any length (Group 1) and 12 control patients. Biopsy specimens were independently examined by two pathologists unaware of the endoscopic results. RESULTS: Methylene blue stained specialized columnar epithelium in 18 of the 26 patients, including those with intramucosal carcinoma (1), high-grade dysplasia (1), and indefinite/low-grade dysplasia (6). Methylene blue staining pattern, which was focal in 72% and diffuse in 28% of patients, was reproduced in 8 patients who had repeat staining within 4 weeks. The overall accuracy of methylene blue staining for detecting specialized columnar epithelium was 95%. The diagnostic yield of methylene blue staining for specialized columnar epithelium in "control" patients was 42%. The risk for dysplasia in stained biopsy specimens was greater than in unstained ones (odds ratio 17.7, p = .0004). CONCLUSIONS: Methylene blue mucosal staining is a safe, inexpensive, reproducible, and highly accurate method of diagnosing specialized columnar epithelium in Barrett's esophagus.

Topoisomerase I activity in squamous cell carcinoma of the head and neck.

In recent preclinical and clinical trials, topoisomerase I inhibitors have shown great promise as antitumor agents. These agents are most effective against tumors with high topoisomerase I activity. Therefore, determining topoisomerase I activity in advance may predict response to topoisomerase I inhibitors. Squamous cell carcinoma of the head and neck and normal tissue samples were obtained from 12 patients. Cellular extracts were prepared, and topoisomerase I activity assays were performed. The results suggest that topoisomerase I activity in squamous cell carcinoma of the head and neck is increased approximately sixtyfold compared to normal tissue. Increased activity often correlates with clinical responsiveness; these results predict that topoisomerase I inhibitors should be effective and selective against squamous cell carcinoma of the head and neck.

Metastatic calcification of the true vocal cords as a cause of hoarseness.

Visceral soft tissue calcification is common in patients with end-stage renal disease. However, metastatic calcification of the true vocal cords has not been described. We present a patient with chronic renal failure and hoarseness in whom an exophytic true vocal cord mass was diagnosed as a metastatic calcification.

The argyrophilic nucleolar organizer regions in ductal carcinoma in situ of the breast. The significance of ploidy and proliferative activity analysis using this silver staining technique.

BACKGROUND: Two interphase argyrophilic nucleolar organizer region (AgNOR) counts have been correlated with ploidy and proliferative activity in patients with ductal carcinoma in situ (DCIS) of the breast. The first is the mean number of AgNORs (mAgNOR); it reflects ploidy. The second is the percentage of nuclei with greater than or equal to five AgNORs/nucleus (pAgNOR); it correlates with proliferative activity. DCIS of the breast is a heterogeneous group of lesions that is not associated uniformly with invasive ductal carcinoma. A significant number of patients with DCIS will, however, progress to invasive ductal carcinoma. Factors identifying the invasive potential of DCIS in these patients have not been defined clearly. The authors postulated that pAgNOR in DCIS may predict the invasive potential of these lesions. METHODS: The authors studied 86 cases of DCIS of the breast by the AgNOR silver stain using the two above-mentioned counts. RESULTS: There were 54 comedo and 32 noncomedo DCIS cases. Forty-one cases (47%) were associated with invasive ductal carcinoma. Thirty cases of comedo DCIS (55%) showed mAgNOR counts suggestive of aneuploidy (> or = 2.4/nucleus), whereas only seven cases of noncomedo DCIS (22%) showed such counts (P = 0.001). Cases associated with invasion had higher incidence of aneuploid mAgNOR counts (P = 0.0003). The pAgNOR counts in comedo DCIS ranged from 1% to 36% (median, 11%), whereas in noncomedo DCIS pAgNOR counts ranged from 0% to 22% (median, 7%) (P = 0.007). The 41 cases associated with invasion had pAgNOR counts ranging from 3% to 36% (median, 12%), whereas those not associated with invasion had pAgNOR counts ranging from 0% to 24% (median, 5%) (P = 0.000001). This difference was irrespective of the type of DCIS or mAgNOR counts. CONCLUSIONS: Comedo DCIS of the breast may show a higher incidence of aneuploidy and increased proliferative activity and invasive ductal carcinoma than does noncomedo DCIS. Ploidy and proliferative activity, measured by AgNOR staining in DCIS, may have a significant predictive value in identifying the invasive potential of these lesions.

Growth stimulation of ovarian and extraovarian mesothelial cells by corpus luteum extract.

Ovarian (OM) and extraovarian (EM) mesothelia represent a common source of gynecologic malignancies with yet unclear pathogenesis. Ovulation triggers a finite wave of DNA synthesis and morphogenesis only in native OM cells, probably through the activation of intraovarian growth factors. To evaluate their growth response to such factors, OM and EM cells were obtained from estrous New Zealand white rabbits by enzymatic dispersion and unit gravity sedimentation. Cell cultures were maintained in serumless, fibronectin-rich, HL-1 medium without or with rabbit corpora lutea tissue extracts (CLE). The growth effects of CLE were evaluated by measuring percent changes in cell number relative to controls (CCN), cell population doublings (CPD), cell population doubling time in hours (CPDT). After 7.5 days, CLE enhance (P < 0.001) the growth of both OM and EM cells, which exhibited, respectively, a CCN of 214 and 257%; a CPD of 2.89 and 2.87; and a CPDT of 54.39 and 59.49. CLE-treated OM and EM cells were smaller, formed more cohesive monolayers, and exhibited more frequent and diffuse microvilli than control cells. These data show a similar in vitro response of OM and EM cells to luteal growth factors, suggesting that the lack of postovulatory morphogenesis in native extraovarian mesothelia is due to the spatially restricted activity of intraovarian growth factors.

Photodynamic therapy of human squamous cell carcinoma in vitro and in xenografts in nude mice.

Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systematically administered photosensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photosensitizer was 1.6 or 1.5, respectively. Administration of Pf-II (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm2, 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo.

Intraabdominal desmoplastic small round cell tumor. Report of a case diagnosed by fine needle aspiration cytology.

In this report, fine needle aspiration (FNA) findings in a case of intraabdominal desmoplastic small round cell tumor (IADSRCT) are presented. Computed tomographic scan-guided FNA performed on a right upper abdominal mass on a 20-year-old man produced a cellular specimen consisting of monomorphic small round cells with scant cytoplasm and ovoid nuclei. FNA cytology and immunocytochemistry suggested the diagnosis of IADSRCT. Surgical removal of the tumor and detailed histology and ultrastructural studies confirmed the cytologic findings.

[Evaluation of functional reserves of the oxygen transport system in cardiac surgery patients]. / Otsenka funktsional'nykh rezervov sistemy transporta kisloroda u kardiokhirurgicheskikh bol'nykh.

The informative value of determination of the restoration rate of spiroergometric parameters was examined in cardiosurgical patients who had undergone exercise testing. All the patients were divided into 3 homogeneous groups: (1) those without disorders; (2) those with moderate restoration; and (3) pronounced restoration. There was a moderate relationship between the restoration rate and the function of the oxygen transport system (OTS) and a high relationship between the rate and exercise tolerance in decompensated metabolic acidosis and left ventricular function. Analysis of the restoration of spiroergometric parameters provided a final assessment of the functional reserves of OTS in cardiosurgical patients and serves as a non-invasive technique to study left ventricular function in the patients.

[Physical exercise tolerance in heart surgery patients during decompensated metabolic acidosis]. / Perenosimost' fizicheskoi nagruzki v usloviiakh dekompensirovannogo metabolicheskogo atsidoza kardiokhirurgicheskimi bol'nymi.

Spiroergometric findings obtained before and in different periods (1 month to 8 years) after surgical correction were analyzed in 373 patients with congenital and acquired heart diseases. This allowed the patients to be divided into two groups in terms of their exercise tolerance in decompensated metabolic acidosis. The division should be used to assess the function of the oxygen transport system in cardiac surgical patients who have failed to achieve the "plateau" of oxygen uptake.

[The spiroergometric assessment of the level of exercise hyperventilation in patients with heart defects before and after their surgical correction]. / Spiroérgometricheskaia otsenka urovnia nagruzochnoi giperventiliatsii u bol'nykh s porokami serdtsa do i posle khirurgicheskoi korrektsii.

The paper is concerned with elaboration of criteria for spiroergometric assessment of the level of load hyperventilation (LHV) in patients with heart diseases before and after surgical correction. Study of the dynamics of the correlation between CO2 production and ventilation underlies the method suggested. Four grades of LHV are distinguished: mild, moderate, pronounced and dramatic. It is shown that the pronounced and dramatic grades of LHV may provide indirect evidence for high pulmonary hypertension (stage II or III).