Cytopathology in Europe: on seeing what the neighbours do.
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Cervix Uteri↗
Biomedical subjects
W Gray
Publications and source records attributed to W Gray.
Factors predicting successful DNA recovery from archival cervical smear samples.
Polymerase chain reaction (PCR)-based DNA testing of archival cervical smear slides is a useful method of retrospectively establishing the presence of the human papillomavirus (HPV) in cervical cells. A cellular DNA recovery test is performed in parallel to HPV DNA testing to ensure that sufficient cells are present and purification of sample DNA has been successfully performed. Previous studies have not comprehensively assessed DNA recovery rates in slides older than 13 years. We undertook a study to determine the factors impacting DNA recovery in 436 UK slides dating from 11 to 33 years prior to testing. Overall, a low cellular DNA recovery success rate of 29% was obtained but a strong trend was observed with increasing recovery rates the older the slides (P < 0.001). Recovery rates increased from 22% in the most recent slides collected from 1988 to 1992, to 61% in the oldest slides, collected in 1970-72. It is likely that fixation compounds incorporating acetic acid, introduced in the UK through the 1980s, have compromised subsequent attempts at PCR amplification. These findings emphasize the importance of the original fixation method in the success of DNA recovery from archival smear samples.
DNA, Viral↗
Macroscopic assessment of pulmonary fine needle aspiration biopsies: correlation with cytological diagnostic yield.
Fine needle aspiration biopsy (FNAB) is widely used in the diagnosis of pulmonary neoplasia. Previous studies have advocated the use of immediate cytological review at the time of biopsy to reduce the number of needle passes performed, whilst stating that in the absence of this, simple macroscopic assessment of sample quality was used. This latter practice is widespread, but there is no data regarding its accuracy or the level of intra-observer consistency. We assessed the degree of correlation between a macroscopic grading of the FNAB sample at the time of lung biopsy by the radiologist performing the procedure and subsequent diagnostic yield. 45 consecutive patients in whom pulmonary neoplastic disease was strongly suspected were included. Macroscopic sample appearances were graded on a five-point scale from 1 (blood with no particulate material) to 5 (solid tissue pieces). The positivity rate increased stepwise along with macroscopic grading from 50% for samples graded 1 to 100% for samples graded 5. Grouping the predominately haemorrhagic samples (graded 1-2) together and comparing them with the particulate samples (graded 3-5) demonstrates a statistically significant difference in diagnostic yield (p<0.001). This small study shows that a simple macroscopic grading of pulmonary FNAB samples can provide a good indication of likely cytological diagnostic yield and that radiologists can develop a degree of consistency in their assessment. In the absence of direct cytological input, this may provide a basis for decisions on the number of passes performed.
Adult↗
Discovery of 12 satellites of Saturn exhibiting orbital clustering.
The giant planets in the Solar System each have two groups of satellites. The regular satellites move along nearly circular orbits in the planet's orbital plane, revolving about it in the same sense as the planet spins. In contrast, the so-called irregular satellites are generally smaller in size and are characterized by large orbits with significant eccentricity, inclination or both. The differences in their characteristics suggest that the regular and irregular satellites formed by different mechanisms: the regular satellites are believed to have formed in an accretion disk around the planet, like a miniature Solar System, whereas the irregulars are generally thought to be captured planetesimals. Here we report the discovery of 12 irregular satellites of Saturn, along with the determinations of their orbits. These orbits, along with the orbits of irregular satellites of Jupiter and Uranus, fall into groups on the basis of their orbital inclinations. We interpret this result as indicating that most of the irregular moons are collisional remnants of larger satellites that were fragmented after capture, rather than being captured independently.
Journal Article↗
Percutaneous image-guided cutting needle biopsy of the pleura in the diagnosis of malignant mesothelioma.
STUDY OBJECTIVES: Pleural fluid cytology and non-image-guided Abrams or Cope biopsies have sensitivities of approximately 30% for detecting malignant mesothelioma, and thoracoscopic biopsy has a sensitivity of approximately 90%. The difference between these two probably relates to obtaining adequate tissue. The use of immunohistochemical stains allows a firm diagnosis to be made from relatively small samples. This study explores whether percutaneous image-guided cutting needle biopsy (CNB) combined with immunohistochemistry is accurate in diagnosing pleural thickening due to mesothelioma. DESIGN: Retrospective review of image-guided CNB of pleural thickening performed on consecutive patients over 7 years by a single radiologist. SETTING: Teaching hospital chest radiology department. PATIENTS: Twenty-one adult patients with a final diagnosis of malignant mesothelioma were identified from 53 consecutive patients who underwent percutaneous image-guided CNB. All 21 patients had pleural thickening identified on contrast-enhanced CT, and all had a final histologic diagnosis of mesothelioma confirmed by postmortem examination or thoracoscopy. INTERVENTIONS: Fourteen-gauge and 18-gauge cutting needles were used. Biopsy guidance was by ultrasound in 6 patients and by CT in 15 patients. MEASUREMENTS AND RESULTS: A correct histologic diagnosis of malignant mesothelioma was made by CNB in 18 patients (86% sensitivity and 100% specificity). Complications included one chest wall hematoma and a small hemoptysis. Four patients with a pleural thickness of < or = 5 mm underwent biopsy, and all specimens were diagnostic for mesothelioma. CONCLUSIONS: Image-guided percutaneous CNB of pleural thickening is a safe procedure, with 86% sensitivity for detecting malignant mesothelioma. Pleural thickening of < or = 5 mm may be successfully sampled.
Aged↗
Is endometrial pre-treatment of value in improving the outcome of transcervical resection of the endometrium?
The aim of this study was to determine whether or not the use of medical pre-treatment of the endometrium improves the outcome of transcervical resection of the endometrium with regards to long-term operative outcome, histological findings and patient satisfaction. A prospective randomized trial comparing three endometrial pre-treatment agents (danazol, medroxyprogesterone acetate or nafarelin) with no pre-treatment was conducted. The main outcome measures were: (i) thickness of the endometrium and myometrium resected; (ii) histological stage of the endometrium at the time of operation; (iii) the presence or absence of menses and (iv) patient satisfaction 1 year post-operatively. Of the three pre-treatments studied, danazol produced a lower median endometrial thickness than the control, showed the greatest ability to induce atrophy of the endometrial glands and stroma (not statistically significant) and produced the highest rate of amenorrhoea (not different to the control). Danazol and nafarelin produced significantly lower median endometrial thickness than no pre-treatment. There were, however, no significant differences in the rates of amenorrhoea in any of the pre-treatment groups compared with that in the control group. No improvement in clinical outcome or patient satisfaction is conferred by the use of medical pre-treatments if transcervical resection of the endometrium is performed in the proliferative phase of the menstrual cycle.
Amenorrhea↗
Lymphoid interstitial pneumonitis associated with common variable hypogammaglobulinaemia treated with cyclosporin A.
Lymphoid interstitial pneumonitis (LIP) is a rare clinicopathological entity that may be associated with common variable immune deficiency (CVID) and may lead to respiratory failure and death. Some patients may respond to prolonged corticosteroid treatment. We hypothesised that, in view of the predominant T cell nature of LIP, cyclosporin A would be a more appropriate choice of immunosuppressive agent and report the first case of its successful use in a woman with LIP associated with CVID.
Adult↗
Xanthoma disseminatum with respiratory tract involvement and fatal outcome.
Xanthoma disseminatum (XD) is a rare mucocutaneous xanthomatosis classified as a benign form of non-Langerhans' cell histiocytosis. The case history is presented of a 61 year old woman with XD who developed dyspnoea and spirometric features of airflow obstruction. Bronchoscopy and computed tomography confirmed involvement of the large and medium sized bronchi and she subsequently died from acute respiratory failure. The post-mortem findings and the importance of respiratory tract disease in this unusual condition are discussed.
Airway Obstruction↗
Angiectatic nasal polyps that clinically simulate a malignant process: report of 2 cases and review of the literature.
BACKGROUND: Approximately 5% of inflammatory or allergic sinonasal polyps develop extensive vascular proliferation and ectasia with deposition of pseudoamyloid. These so-called angiectatic nasal polyps (ANPs) can grow rapidly and exhibit an aggressive clinical behavior that could simulate malignancy preoperatively. OBJECTIVE: To systematically address the differential histologic diagnosis of ANPs. METHODS: We evaluated by light microscopy, immunohistochemistry, and electron microscopy biopsy and resection specimens from 2 large ANPs (8 and 10 cm in diameter) that presented in 2 adult men with life-threatening epistaxis and facial deformity, respectively. RESULTS: The tumors were firm, lobulated, and covered by smooth, partially ulcerated mucosa. Histologically, clusters of dilated, thin-walled blood vessels embedded in pools of Congo red-negative eosinophilic material, associated with patchy necrosis and atypical stromal spindle cells, were seen. Electron microscopy and immunohistochemistry (CD34, factor VIII) confirmed the endothelial nature of the cells lining the spaces, whereas the atypical stromal cells were classified as myofibroblasts. CONCLUSIONS: These 2 cases represent extreme examples of ANPs that clinically simulate a malignant process. Awareness of the histological features of ANPs should prevent confusion of such lesions with other vascular or spindle cell lesions of the nasopharynx that would require different treatment and carry a different prognosis.
Angiofibroma↗
Spontaneous regression of pulmonary metastases demonstrated by CT.
Two cases of disappearing or spontaneous regression of pulmonary metastases on CT are presented. In both cases, cytological proof was obtained by radiologically guided fine needle aspiration. The lesions subsequently regressed on follow-up CT studies without recognized systemic treatment.
Aged↗
Regulation of ecdysis-triggering hormone release by eclosion hormone.
Ecdysis behavior in the tobacco hornworm Manduca sexta (Lepidoptera: Sphingidae) is triggered through reciprocal peptide signaling between the central nervous system and the epitracheal endocrine system. Recent evidence indicates that eclosion hormone may initiate endocrine events leading to ecdysis through its action on epitracheal glands to cause the release of ecdysis-triggering hormone (ETH). Here, we report that direct exposure of epitracheal glands to eclosion hormone in vitro leads to secretion of ETH. The threshold concentration of eclosion hormone needed to evoke release of ETH is approximately 3 pmol l-1. Eclosion hormone also induces elevation of cyclic GMP, but not cAMP, concentration in epitracheal glands at concentrations similar to those causing release of ETH. Both cGMP and 8-Br-cGMP mimic the secretory action of eclosion hormone. The sensitivity of the secretory response to eclosion hormone occurs during a narrow window of development, beginning approximately 8 h prior to pupal ecdysis. However, eclosion hormone can cause elevation of cGMP levels in epitracheal glands long before they acquire competence to release ETH, showing that the initial portion of the signal transduction cascade is in place early in development, but that the absence of a downstream step in the cascade prevents secretion. Measurements of cGMP levels in epitracheal glands during the ecdysis sequence show a sudden elevation some 30 min after the onset of pre-ecdysis, well after ETH secretion has been initiated. ETH secretion can therefore be viewed as a two-step process, beginning at pre-ecdysis when cGMP levels are relatively low, followed by a massive release resulting from a logarithmic elevation of cGMP levels.
Animals↗
Benefits and pitfalls of telemedicine in neurosurgery.
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Adult↗
Tinnitus Habituation Therapy: The University of Maryland Tinnitus and Hyperacusis Center Experience.
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Journal Article↗
A pilot trial of paclitaxel, carboplatin, and concurrent radiotherapy for unresectable squamous cell carcinoma of the head and neck.
Combined chemoradiotherapy is superior to radiotherapy alone for stage III and IV squamous cell carcinoma of the head and neck, and concurrent use of both offers the advantage of synergistic interactions. Our prior trial demonstrated the ease and convenience of administering carboplatin during radiotherapy. Since paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has activity in squamous cell carcinoma of the head and neck and can act synergistically with both radiotherapy and platinum drugs, we initially added paclitaxel at 45 mg/m2/wk to carboplatin given at 100 mg/m2 during radiotherapy given at conventional fractions. The initial dose of paclitaxel was subsequently reduced to 40 mg/m2/wk. Thirteen of 18 patients entered so far have sufficient follow-up data; 12 are assessable for toxicity and 11 are assessable for response. One died early of progressive disease, two achieved a complete response, six achieved a partial response, and two had stable disease. Toxicities have so far been manageable for the 76 weekly doses administered. Chemotherapy dose reduction was needed in 10 patients. For the planned 100 doses of chemotherapy, 53 (53%) were administered as planned, 23 (23%) were reduced, and 24 (24%) were withheld due to neutropenia or mucositis. There were no toxic deaths, and no patient stopped therapy for toxicity. Paclitaxel/carboplatin can be administered during radiotherapy for squamous cell carcinoma of the head and neck with acceptable toxicities, and further accrual is needed to evaluate the effect of this combination.
Aged↗
HPV testing in patients with low grade cervical cytological abnormalities: a follow up study.
AIM: To assess the diagnostic performance of human papillomavirus (HPV) analysis in predicting cervical intraepithelial neoplasia (CIN) grades 2 and 3 in patients with persistent low grade cervical cytological abnormalities. METHODS: Cervical smears from 167 women referred for colposcopy with persistent borderline, wart virus or mildly dyskaryotic changes on cervical screening were analysed by Papanicolaou staining, non-isotopic in situ hybridisation and generic and type specific polymerase chain reaction (PCR) amplification of HPV sequences. Follow up was by cytological and, where appropriate, histological analysis. RESULTS: CIN grade 2 or 3 was identified in 46 patients after a median follow up of 27 months. HPV positivity by both techniques was associated with high grade CIN and with age less than 30 years (median age 33 years). Non-isotopic in situ hybridisation was more predictive but less sensitive than either generic or type specific PCR, but prediction was greater using either molecular technique in women over 30 years of age. CONCLUSIONS: Although the degree of prediction found is of only limited clinical value, the strong association of HPV positivity with both high grade CIN and patient age suggests that further studies of HPV testing in this patient group are warranted.
Adult↗
Temperature-sensitive yeast GPI anchoring mutants gpi2 and gpi3 are defective in the synthesis of N-acetylglucosaminyl phosphatidylinositol. Cloning of the GPI2 gene.
To identify genes required for the synthesis of glycosyl phosphatidylinositol (GPI) membrane anchors in yeast, we devised a way to isolate GPI anchoring mutants in which colonies are screened for defects in [3H]-inositol incorporation into protein. The gpi1 mutant, identified in this way, is temperature sensitive for growth and defective in vitro in the synthesis of GlcNAc-phosphatidylinositol, the first intermediate in GPI biosynthesis (Leidich, S. D., Drapp, D. A., and Orlean, P. (1994) J. Biol. Chem. 269, 10193-10196). We report the isolation of two more conditionally lethal mutants, gpi2 and gpi3, which, like gpi1, have a temperature-sensitive defect in the incorporation of [3H]inositol into protein and which lack in vitro GlcNAc-phosphatidylinositol synthetic activity. Haploid Saccharomyces cerevisiae strains containing any pairwise combination of the gpi1, gpi2, and gpi3 mutations are inviable. The GPI2 gene, cloned by complementation of the gpi2 mutant's temperature sensitivity, encodes a hydrophobic 269-amino acid protein that resembles no other gene product known to participate in GPI assembly. Gene disruption experiments show that GPI2 is required for vegetative growth. Overexpression of the GPI2 gene causes partial suppression of the gpi1 mutant's temperature sensitivity, a result that suggests that the Gpi1 and Gpi2 proteins interact with one another in vivo. The gpi3 mutant is defective in the SPT14 gene, which encodes a yeast protein similar to the product of the mammalian PIG-A gene, which complements a GlcNAc-phosphatidylinositol synthesis-defective human cell line. In yeast, at least three gene products are required for the first step in GPI synthesis, as is the case in mammalian cells, and utilization of several different proteins at this stage is therefore likely to be a general characteristic of the GPI synthetic pathway.
Amino Acid Sequence↗
Morphological correlation of human papillomavirus infection of matched cervical smears and biopsies from patients with persistent mild cervical cytological abnormalities.
Human papillomavirus (HPV) analysis of cytological material has been advocated for determining those patients with low-grade cervical cytological abnormalities who have current high-grade squamous intraepithelial lesions (SILs). In this study, we analyzed concurrent cervical smears and biopsies from 167 patients with Papanicolaou (Pap) smears showing persistent atypical squamous cells of uncertain significance (ASCUS) or low grade SILs (1) to compare the detection of HPV by nonisotopic in situ hybridization (NISH) on matched smears and biopsies; (2) to analyze the type and distribution of NISH signal within lesions; and (3) to define further the ability of NISH techniques to distinguish between patients with low- and high-grade SIL. Whether present in cervical smears or biopsies, high-risk HPV types (16, 18, 31, 33, and related types) were significantly associated with high-grade SILs (P < .001) but were found in 15% of low-grade SILs. Ninety percent of high grade lesions were directly infected by these HPV types, and good concordance (92.2%) was found between NISH analysis of matched cervical smears and biopsies, indicating accurate colposcopic targetting of biopsies and excision specimens. Punctate signal morphology, which correlates with viral integration, was associated with high-grade SILs but was also observed in two low-grade SILs. Although the presence of high-risk HPV types in low-grade SILs limits the predictive ability of HPV testing by this means in this group of patients, those patients with high-risk HPV infection of low-grade SILs may be a greater risk of progression to high-grade SIL or invasive carcinoma. If this were the case, HPV testing would be of potential value in the management of patients with low-grade cytological abnormalities.
Biopsy↗
Human papillomavirus status in the prediction of high-grade cervical intraepithelial neoplasia in patients with persistent low-grade cervical cytological abnormalities.
The role of human papillomavirus (HPV) detection in the management of patients with persistent low-grade (mild dyskaryosis or less) cervical cytological abnormalities is unclear. We have analysed cytological material from 167 such patients both cytologically and by non-isotopic in situ hybridisation (NISH) for HPV 16, 18, 31 and 33 and consensus primer polymerase chain reaction (PCR) amplification followed by both generic and specific typing for these HPV types. Cervical intraepithelial neoplasia (CIN) 2 or 3 was present in 40 of 167 patients (23.9%), and the positive predictive values (PPVs) for the presence of CIN 2 or 3, of moderate or severe dyskaryosis at repeat cytology and an HPV-positive NISH and generic PCR signal were 100%, 66% and 42% respectively. The corresponding sensitivities were 48%, 68% and 87%. Addition of cytology to molecular analysis improved both PPV and sensitivity, the best combination being NISH and cytopathology (PPV 71%, sensitivity 87%). These data demonstrate that the presence of CIN 2 or 3 in patients with mild cytological abnormalities can be predicted by molecular detection of HPV in some cases, particularly when combined with cytological analysis. However, the magnitude of this prediction is dependent on the population of patients studied, and the clinical role of this approach therefore remains to be defined.
Cervix Uteri↗