A vacuum-compatible cylindrical inertial rotation sensor with picoradian sensitivity.

We describe an inertial rotation sensor with a 30-cm cylindrical proof-mass suspended from a pair of 14 µm thick BeCu flexures. The angle between the proof-mass and support structure is measured with a pair of homodyne interferometers, which achieve a noise level of ∼5prad/Hz. The sensor is entirely made of vacuum compatible materials, and the center of mass can be adjusted remotely.

Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs with myxomatous mitral valve disease: a pilot study.

OBJECTIVES: To describe pulmonary transit time (nPTT) and myocardial perfusion (nMP) normalised to heart rate in dogs with stable ACVIM stage C myxomatous mitral valve disease (MMVD) and to assess short-term effects of pimobendan on these variables. We hypothesised that nPTT and nMP would increase in dogs with MMVD compared with normal dogs. Additionally, we hypothesised that treatment with pimobendan would decrease nMP and nPTT in dogs with MMVD. DESIGN: Prospective, single-blind study involving 6 normal dogs and 12 dogs with MMVD. METHODS: Dogs with MMVD were treated with enalapril and furosemide for at least 1 month prior to examination. All dogs underwent standard and contrast echocardiographic examinations at the beginning of the study (T0). At this time, MMVD dogs were randomly assigned to receive either pimobendan (0.4-0.6 mg/kg) or not. All dogs with MMVD were re-evaluated by standard and contrast echocardiography after 1 week (T1) and nPTT and nMP were measured. RESULTS: nPTT was significantly increased in dogs with MMVD (P = 0.0063), compared with normal dogs. It was significantly decreased at T1 in dogs receiving pimobendan (P = 0.0250). The nMP was not significantly different in dogs with MMVD, compared with healthy dogs (P = 0.2552), and it was not significantly different at T1 in the treatment group (P = 0.8798). CONCLUSIONS: Contrast echocardiography was a valid, complementary tool for echocardiographic analysis of dogs with MMVD. Pimobendan decreased nPTT in dogs affected by MMVD. Myocardial perfusion was not different in dogs with severe MMVD.

How do we measure a residual tumor size in histopathology (the gold standard) after neoadjuvant chemotherapy?

Accurate reporting of the residual tumor size by pathologists after neoadjuvant chemotherapy is an important component of a breast cancer. Recent literature reported comparisons regarding the accuracy of clinical and radiological residual tumor size findings using the histopathology as a "gold standard". However, the histopathological methods of measuring the residual tumor size are not standardized. Most pathologists use the tumor size measured by the gross examination. We collected 32 patient samples and compared the residual tumor size by gross and microscopic pathologic examinations. Using microscopic tumor size as the gold standard, our study showed gross tumor size is overestimated in 25%, underestimated in 56% and correlated to the final microscopic tumor size in 19% of the cases after neoadjuvant chemotherapy. Determining accurate residual tumor size to estimate pathologic response to chemotherapy is essential. We attempted to provide guidelines for pathology reporting post-neoadjuvant chemotherapy on breast cancers.

A systematic approach to pacemaker assessment.

Despite the increasing use of pacemaker therapy, assessment of pacemaker function and electrocardiogram (ECG) interpretation continue to challenge even experienced critical care nurses. Accurate assessment of pacemaker function is essential in the evaluation of patients, especially patients with symptoms that may be related to pacemaker malfunction such as syncope or palpitations. This article will review pacing concepts and pacing system components. A systematic approach to ECG interpretation will be presented that can be used in a variety of clinical settings.

Technique for neurosurgically relevant CT image transfers using inexpensive video digital technology.

OBJECTIVE: To examine and document neurosurgically relevant CT image transfers using inexpensive video digital technology. METHODS: Thirty abnormal CT scans were evaluated on a personal computer monitor following their digital image creation and transfer by electronic mail (e-mail). These were compared with the radiologist's interpretation of a hard copy of the CT scan originals. Any change in diagnosis based on the CT scan or e-mail image was assessed after completion of the comparison. RESULTS: A total of 30 CT scans were successfully transferred and reviewed. On only one image was there disagreement between the neurosurgeon's and the radiologist's interpretations of the image. This resulted in a change in the radiologist's diagnosis after digital image transfer occurred and the neurosurgeon diagnosed an isodense subdural hematoma, which was later confirmed at the time of surgical decompression. CONCLUSIONS: A hand-held, inexpensive digital camera may serve neurosurgeons as a helpful alternative to expensive, labor-intensive teleradiology systems. It should be considered as an adjunctive option for small community-based hospitals unable to financially support more sophisticated teleradiology techniques, which have been shown to provide a significant benefit in the management and outcome of head trauma patients.

Comparative polymerase chain reaction analysis of c-myc amplification on archival breast fine-needle aspiration materials.

The oncogene c-myc is a key regulator of cell cycle progression (from G1 to S phase). The amplification of c-myc can either induce cell proliferation or apoptosis. As a part of our ongoing effort to develop methods for multiple tumor marker analysis, this study was carried out to determine whether biomarkers such as c-myc amplification could be analyzed on genetic materials collected from archival fine-needle aspiration (FNA) smears. A novel comparative PCR analysis was used to analyze c-myc amplification semiquantitatively. Genomic DNA was prepared using cells obtained from archival FNA materials that had undergone quantitative fluorescence image analysis (QFIA) for other biomarkers. Of the 72 cases selected from 1995 for this study, 53 had an adequate amount of DNA for analysis. A novel comparative PCR analysis was used to analyze c-myc amplification quantitatively. For each batch of experiments, DNA from the high c-myc expressing cells, HL-60, and DNA from the low expressing cells, K562, were served as positive and negative controls, respectively. c-myc amplification was observed in 16 (94.1%) of 17 malignant lesions, 5 (41.7%) of 12 proliferative breast diseases with nuclear atypia, and 4 (16.7%) of 24 other benign lesions (fibroadenoma or fibrocystic disease). The overall difference of c-myc expression among these groups was highly significant by chi2 analysis (P = 0.0002). We conclude that multiple phenotypic markers and genotypic markers may be combined in a risk assessment biomarker profile on small FNA samples that can be obtained on multiple occasions relatively noninvasively from the patient. The results of this study suggest that c-myc amplification may be a biomarker of breast cancer risk. However, additional large, prospective studies are needed to confirm the current observation.

Behavioral sensitization following repeated intravenous nicotine administration: gender differences and gonadal hormones.

Repeated intermittent administration of stimulants is well known to produce behavioral sensitization in male animals. The present studies explored whether 1) behavioral sensitization occurred with the i.v. route of administration, 2) sensitization was greater in females than in males, 3) sensitization was modulated by gonadectomy, 4) intact adult female rats maintained normal estrous cytology patterns in response to repeated nicotine administration, and 5) the pharmacokinetics of i.v. nicotine dosing. Adult male, female, castrated, and ovariectomized Sprague-Dawley rats (n = 48) were surgically implanted with an intravenous access port. Animals received 50 microg/kg i.v. nicotine once/day for 14 days. Immediately after the initial nicotine injection and the final day 14 nicotine injection, animals were placed in IR photocell activity chambers for 60 min. Observational time sampling of behavior was also simultaneously performed by an observer blind to treatment condition. An increase in behavioral activity of greater than 120% occurred across the 14-day time course of i.v. nicotine injections. The magnitude of the increase, however, varied as a function of component of activity, gender, and gonadectomy. The behavioral observation data further suggested that the females demonstrated an increased sensitivity to repeated nicotine, as evidenced in a more rapid response, for example, grooming. These behavioral observations were associated with peak arterial levels of nicotine (approximately 25 ng/ml) no greater than the average venous levels of nicotine commonly maintained by cigarette smokers. Repeated i.v. nicotine, at a dose of 50 microg/kg, did not interfere with intact female vaginal cytology or body weight; the failure to detect such alterations were not due to inadequate statistical power. Moreover, no nicotine-treated animals displayed persistent vaginal estrous or were acyclic. Collectively, these data suggest that the i.v. nicotine model may be particularly useful in exploring the gender-dependent effects of nicotine.

Triple test approach to inadequate fine needle aspiration biopsies of palpable breast lesions.

OBJECTIVE: To perform a retrospective study evaluating the triple test for inadequate fine needle aspiration (FNA) biopsies of palpable breast lesions with a two-year clinical follow-up. STUDY DESIGN: All aspirates were reviewed and assessed for cellular adequacy in a one-year period. Specimen adequacy was based on the most stringent criteria, the presence of six or more epithelial cell clusters composed of at least six cells each. In all cases, clinical and radiologic results were reviewed and compared with the histologic outcome. RESULTS: Aspirates from 61 of 263 (23%) patients with palpable breast lesions that yielded nondiagnostic results were examined. The study showed a misdirected FNA rate of 21% and a misinterpreted rate of 1.6%. The other 77% of cases had benign surgical biopsies and/or clinical follow-up. Three of 61 (4.9%) cases with nondiagnostic smears were found to have cancer; two were inadequate due to misdirected aspirates, and one was misinterpreted microscopically. All cancer cases underwent surgical removal of the mass as a result of clinical or radiologic suspicion. CONCLUSION: We recommend utilizing the three diagnostic parameters of cytology, clinical findings and radiology, the "triple test," to achieve the best diagnostic accuracy in breast FNAs and to enhance patient management.

Immunohistochemical evaluation of K-ras, p53, and HER-2/neu expression in hyperplastic, dysplastic, and carcinomatous lesions of the pancreas: evidence for multistep carcinogenesis.

The pathobiology of precursor lesions leading to invasive pancreatic adenocarcinoma remains a controversial area, but knowledge of the mechanisms of tumorigenesis may lead to possibly earlier detection, prevention, and treatment in the future. We hypothesize that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions and are part of a continuous developmental spectrum evolving into ductal adenocarcinoma of the pancreas. To further define this sequence, we studied the immunohistochemical markers HER-2/neu, K-ras, and p53 in 15 adenocarcinomas and 15 nonmalignant specimens of the pancreas. The 15 nonmalignant specimens of the pancreas included both normal pancreas and chronic pancreatitis. Overall, HER-2/neu was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 30, 11 of 20 (55%), 10 of 15 (67%), and 12 of 15 (80%), respectively, with progressive increase in the intensity of staining; p53 was positive in 1 of 30 (3%), 0 of 20, 3 of 15 (20%), and 13 of 15 (80%), respectively, and K-ras was positive in 1 of 30 (3%), 6 of 20 (30%), 11 of 15 (73%), and 8 of 15% (53%), respectively. These data support the hypothesis that ductal hyperplasia and dysplasia of the pancreas represent precursor lesions, and, in a fashion similar to that in colorectal tumorigenesis, pancreatic cancer seems to accumulate progressive genetic alterations.

Single cell multiple biomarker analysis in archival breast fine-needle aspiration specimens: quantitative fluorescence image analysis of DNA content, p53, and G-actin as breast cancer biomarkers.

Fine-needle aspiration (FNA) is a sensitive and cost-effective method for evaluating breast lesions. However, the diagnosis of early premalignant lesions is less reliable by FNA because of a lack of distinctive cytological features. Accurately defining the risk of such lesions at the individual level may have significant impact in breast cancer prevention and management. The main objective of this preliminary study was to develop a method to study multiple biomarkers on archival FNA slides using quantitative fluorescence image analysis (QFIA). Biomarkers p53, G-actin, and DNA content were labeled with an immunofluorescence technique and measured by QFIA simultaneously on a single cell basis. QFIA allows the labeling and measurement procedures to be carried out in situ, without the need to remove cells from the slide while preserving the morphology of the cells. FNA slides from 72 incident patients were obtained for this study. Fifty-six cases had an adequate number of cells for the actual analysis (25 benign breast lesions, 14 proliferative breast diseases with nuclear atypia, and 17 malignant lesions). The DNA content (> or = 5c) and G-actin (average gray mean, > 90) were positive in 81% and 88% of malignant lesions, respectively. These were significantly higher than the corresponding positive rates in benign lesions (7% and 15%, respectively; P <0.01 for both). None of the benign cases were positive for G-actin and DNA simultaneously, and none of the malignant cases were negative for G-actin and DNA together. p53 was positive in 33% of malignant lesions and 8% of benign lesions (P >0.05). Our study demonstrates the feasibility of evaluating multiple biomarkers by QFIA on archival FNA-fixed specimens. The G-actin and DNA content assayed by QFIA may be potential intermediate end point markers for breast cancer individual risk assessment.

Treatment in patients with glioblastoma multiforme and poor performance status: is it worthwhile?

It has not been ascertained that treatment of glioblastoma multiforme of the brain (GMB) favorably alters the prognosis in patients with poor pretreatment performance status (PPS). We report on 52 patients with GMB and PPS. The mean survival of 43 treated persons was 19 +/- 12 months (95% confidence interval) and of nine untreated individuals, 2 +/- 1 months (p > 0.50); the corresponding survival rates at 1 year were 39 +/- 16% and 0% (p > 0.05) and at 2 years, 15 +/- 12% and 0% (p > 0.40). We recommend active treatment of patients with GMB even when they present with poor functional status.

Spinal epidural compression complicating cancer of the cervix: review of seven cases.

Records of women with newly diagnosed cancer of the cervix during a 16-year period were reviewed retrospectively for the development of spinal epidural compression by metastatic tumor (SECMT). Of the 361 cases studied, seven patients (2%) experienced SECMT. Epidural compression often involved the lumbar segment, tended to occur in the nonelderly population, and was relatively protracted in onset following the diagnosis of cervical cancer in cases of metachronous presentations. Although the prognosis was generally poor, the application of therapy may have promoted a better quality of remaining life by relieving pain or restoring the ability to walk.

Small cell cancer of the cervix presenting as compression of the spinal cord and cauda equina.

Spinal cord or cauda equina compression by metastatic cancer usually occurs months or even years after the diagnosis of the primary tumor. We describe the unusual simultaneous presentation of small cell cancer of the cervix and metastatic tumor compressing the spinal cord and cauda equina.

Fine needle aspiration biopsy of solitary fibrous tumor of the pleura. A report of two cases with a discussion of diagnostic pitfalls.

BACKGROUND: The diagnosis of a peripheral pulmonary nodule presents a challenge due to many diagnostic possibilities and pitfalls. We describe the cytologic features of solitary fibrous tumor of the pleura, differential diagnoses, pertinent immunohistochemical stains and histogenesis. CASES: Two cases of solitary fibrous tumor of the pleura showed two cell populations on cytologic preparations; mesothelial cells and spindle cells. The neoplastic spindle cell component was positive for CD-34 and vimentin but not for cytokeratin. CONCLUSION: Solitary fibrous tumor of the pleura is rare but should be included in the differential diagnosis of a peripheral pulmonary nodule. Fine needle aspiration biopsy is a safe and rapid method of providing a confirmatory diagnosis.

Fine needle aspiration diagnosis of fibromatosis colli. A report of three cases.

BACKGROUND: Fibromatosis colli, a common cause of congenital muscular torticollis, should be differentiated from other neck masses in infants. Invasive diagnostic and therapeutic measures should be avoided. CASES: Three infants under the age of 2 months presented with neck masses--a clinical suspicion of malignancy, lymphadenopathy and teratoma. The cytologic findings included dyshesive multinucleated skeletal muscle fragments showing degenerative and atrophic changes within a background of scattered reactive fibroblasts. CONCLUSION: Fine needle aspiration biopsy is a safe and rapid method of providing a confirmatory diagnosis of neck masses in infants.

Jejunal lymphangioma. An unusual cause of chronic gastrointestinal bleeding.

We discuss a case of lymphangioma of the small bowel that caused chronic anemia secondary to gastrointestinal blood loss. We believe that this is the first jejunal lymphangioma to be diagnosed by Sonde endoscopy. There are several other lymphatic abnormalities of the small intestine that are briefly discussed. In the Western literature, anemia or chronic gastrointestinal blood loss is an unusual presentation of lymphangioma of the small bowel.

Polymerase chain reaction-based K-ras mutation detection of pancreatic adenocarcinoma in routine cytology smears.

The cytologic diagnosis of pancreatic carcinoma is notoriously difficult, particularly in distinguishing benign atypia from well-differentiated adenocarcinoma. Mutation of codon 12 in the K-ras oncogene is frequently found with pancreatic cancers. Detection by polymerase chain reaction (PCR) followed by restriction endonuclease digestion can provide a powerful tool to improve and confirm diagnosis. The authors examined the utility of PCR-based detection in the diagnosis of pancreatic carcinoma using routinely obtained cytology smears that could be collected at most hospitals. Pancreatic cytology smears were collected retrospectively from 60 patients. DNA was extracted from the slides and amplified by PCR using mismatched primers that generated a Bst-N1 recognition site with the wild type codon 12 but not with the mutant allele. Results were compared with clinical follow-up. K-ras codon 12 mutations were observed in 44 of 46 (95.7%) cases of pancreatic cancer, but not in 12 benign cases nor in 2 cases of islet cell tumor. The amplification and digestion steps proved robust and sensitive, capable of detecting mutant K-ras alleles from cytology smears that contained only small foci of suspicious cells. Our results indicate that K-ras mutation analysis can be done reliably within 1 to 2 days from routine cytology slides without special handling, increasing the sensitivity of diagnosis in ambiguous cases while maintaining cost-effective and relatively noninvasive sampling strategy.