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C S Herrington

Publications and source records attributed to C S Herrington.

At least 19 recordsLinked to original sources
PubMed2006

Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation.

BACKGROUND: A scoring system was recently proposed to grade the severity of primary graft dysfunction (PGD), a frequent early complication of lung transplantation. The purposes of this study are to: (1) validate the PGD grading system with respect to patient outcomes; and (2) compare the performance of criteria employing the arterial oxygenation to fraction of inspired oxygen (P/F) ratio to an alternative grading system employing the oxygenation index (OI). METHODS: We retrospectively reviewed the medical records of 402 patients having undergone lung transplantation at our institution from 1992 through 2004. The ISHLT PGD grading system was modified and grades were assigned up to 48 hours post-transplantation as follows: Grade 1 PGD, P/F > 300; Grade 2, P/F 200 to 300; and Grade 3, P/F < 200. A worst score T(0-48) was also assigned, which reflects the highest grade recorded between T0 and T48. RESULTS: The prevalence of severe PGD (P/F Grade 3) declined after transplant, from 25% at T0 to 15% at T48. Grouping patients by P/F grade at T48 demonstrated the clearest differentiation of 90-day death rates (Grade 1, 7%; Grade 2, 12%; Grade 3, 33%) (p = 0.0001). T48 OI grade also differentiates 90-day death rates. There was no difference in longer-term survival between patients with PGD Grades 1 and 2. OI grade at T0 qualitatively improved differential mortality between Grades 1 and 2; however, the differences did not reach statistical significance. Patients with a worst score T(0-48) of Grade 3 PGD did have significantly decreased long-term survival, as well as longer ICU and hospital stay, when compared with Grades 1 and 2 PGD. Significant risk factors for short- and long-term mortality in our multivariate model were P/F Grade 3 [worst score T(0-48) as well as T0 grade], single-lung transplant, use of cardiopulmonary bypass and high pre-operative mean pulmonary artery pressure. CONCLUSIONS: There is an increased risk of short- and long-term mortality and length of hospital stay associated with severe (Grade 3) PGD. The proposed ISHLT grading system can rapidly identify patients with poor outcomes who may benefit from early, aggressive treatment. Refinement of the scoring system may further improve patient risk stratification.

Adolescent↗
PubMed2006

Genomic integration of oncogenic HPV and gain of the human telomerase gene TERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer.

Recently proposed events associated with the progression of cervical intraepithelial neoplasia (CIN) 2/3 to cervical carcinoma include integration of human papillomavirus (HPV) into the host genome, genomic instability, and an increase in chromosome 3q copy number. In particular, the gene coding for the RNA component of telomerase (TERC) at 3q26 has been implicated as a possible candidate gene. Since it is not known to date how these events are temporally related during cervical carcinogenesis, the aim of the present study was to assess the correlation between TERC gene copy number and the physical status of HPV during progression in cervical neoplasia. Solitary precursor lesions of the uterine cervix (CIN 2/3, n = 17), lesions associated with a micro-invasive carcinoma (CIN 3&mCA, n = 13), and advanced invasive carcinomas (invCA, n = 7) were analysed by fluorescence in situ hybridization (FISH) to determine the physical status of the virus and TERC gene copy number. The TERC gene was increasingly gained with progression of CIN 2/3 (3 of 17) through CIN 3&mCA (7 of 13) to invCA (5 of 7). In the lesions exhibiting gain of TERC, the virus was predominantly integrated. This was seen in eight of ten diploid lesions, indicating that these events can occur prior to aneuploidization and are strongly associated with the progression of CIN 3 to mCA and invCA (p < 0.001). With progression to carcinoma, a number of these lesions show polyploidization, resulting in aneuploidy and high TERC gene copy numbers. In conclusion, genomic integration of oncogenic HPV and gain of the human telomerase gene TERC appear to be important associated genetic events in the progression of uterine cervical dysplasia to invasive cancer.

Cell Transformation, Neoplastic↗
PubMed2005

Villoglandular adenocarcinoma of the cervix: clarity is needed on the histological definition for this difficult diagnosis.

BACKGROUND: Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. CASES: We present two cases histologically reported as a villoglandular adenocarcinoma of the cervix that have recurred and progressed rapidly since initial treatment. External histopathological review suggested both had a prominent villoglandular pattern but with an associated underlying well-differentiated adenocarcinoma. CONCLUSION: The diagnosis of VGA is difficult. Current literature is not entirely consistent in the presented definition, and further clarity is needed. Because of the rarity of VGA and the difficulty but importance of the diagnosis, we would feel that a central review of all cases of VGA is warranted. This would assist in diagnosis and also in obtaining accurate follow-up data.

Adenocarcinoma↗
PubMed2005

Effect of preoperative pulmonary artery pressure on early survival after lung transplantation for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the second largest indication for lung transplantation worldwide. Average 90-day mortality rates for this procedure are 22%. It is unclear what factors predispose patients with IPF to this increased early posttransplant mortality. Pulmonary hypertension may increase the risk of development of early posttransplant complications through several mechanisms. We examined the effect of secondary pulmonary hypertension on 90-day mortality after lung transplantation for IPF. METHODS: An International Society for Heart and Lung Transplant Registry cohort study of 830 patients with IPF transplanted from January 1995 to June 2002 was undertaken. Risk factors were assessed individually and adjusted for confounding by a multivariable logistic regression model. RESULTS: In the univariate analysis, pulmonary hypertension and bilateral-lung transplantation were significant risk factors for increased 90-day mortality. Multivariate analysis confirmed that mean pulmonary artery pressure and bilateral procedure remain independent risk factors after adjustment for potential confounders. Recipient age, ischemia time, cytomegalovirus status mismatch, and donor age were not independent risk factors for early mortality. CONCLUSIONS: Bilateral-lung transplantation carries a greater risk of early mortality than single-lung transplantation for IPF. Increasing pulmonary artery pressure is a risk factor for death after single-lung transplantation in IPF. Mean pulmonary artery pressure should be included in the overall risk assessment of patients with IPF evaluated for lung transplantation.

Adult↗
PubMed2004

Induction of tetrasomy by human papillomavirus type 16 E7 protein is independent of pRb binding and disruption of differentiation.

We have demonstrated previously that high-risk human papillomaviruses (HPVs) induce tetrasomy in low-grade squamous intraepithelial lesions of the cervix. In this study we show that the E6 and E7 genes of high-risk HPV-16, but not those of low-risk HPV-6, are independently able to induce tetrasomy when constitutively expressed in proliferating monolayer cultures of primary human keratinocytes. Of seven HPV-16 E7 mutants analysed (H2P, Delta6-10, Delta21-24, C24G, S31G/S32G, A50S and S71I), five were severely impaired in their ability to induce tetrasomy in monolayer and raft culture. Only mutant C24G induced tetrasomy to levels comparable with wild-type E7 in monolayer and raft culture. This mutant shows strongly reduced binding to the retinoblastoma gene product pRb. The casein kinase II phosphorylation defective mutant S31G/S32G induced tetrasomy to levels comparable with wild-type E7 in raft culture, but not in monolayer culture, and induction of tetrasomy did not correlate with raft morphology. These results indicate that pRb protein binding is not required for HPV-16 E7 associated tetrasomy and that tetrasomy is not directly related to the ability of this protein to disrupt keratinocyte differentiation.

Aneuploidy↗
PubMed2004

Medium-term results of extracorporeal membrane oxygenation for severe acute lung injury after lung transplantation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used successfully for early, severe reperfusion injury after lung transplantation. The purposes of this study are to: (1) document the medium-term survival of patients treated with ECMO; and (2) assess the extent of recovery of their pulmonary function. METHODS: We retrospectively reviewed charts of 172 patients having lung transplants at our institution from 1997 through 2002. The group included 16 patients (9% of total; 10 bilateral, 5 single, 1 living lobar) treated with ECMO for primary allograft failure after single or bilateral single-lung transplantation. Survival and bronchiolitis obliterans syndrome (BOS)-free survival rates were calculated. Pulmonary function was assessed at 2 months, 1 year and 2 years post-transplant. RESULTS: Median hospital stay was 48 days for the ECMO group and 16 days for the overall group (p < 0.05). The 90-day survival was 60% in the ECMO group, and 90% in the overall group. The 2-year survival was 46% in the ECMO group, and 69% in the overall group. Mean forced expiratory volume in 1 second (FEV(1)) in the ECMO group at 1 year was 59 +/- 13% of predicted, and at 2 years 60 +/- 15% of predicted; it was not significantly different for the overall group. CONCLUSIONS: Patients treated with ECMO for primary allograft failure after lung transplantation showed acceptable medium-term survival and pulmonary function.

Adult↗
PubMed2004

A retrospective clinical audit of cervical smears reported as 'glandular neoplasia'.

The aims of this study were to review the diagnostic pathway of women with smears reported as 'glandular neoplasia' and to outline the management, colposcopy findings, treatment and final histological diagnosis in these women. The design was a retrospective review. A total of 114 women were identified over a 5-year period from the cytology database at the Royal Liverpool University Hospital Cytology Department, whose hospital case notes were available for review. Methods included a review of the case notes for the demographic details, indication for smear, colposcopic findings, investigation and/or treatment procedures, histology, final diagnosis and current disease status. Of 114 smears reported as 'glandular neoplasia', 67 were reported as consistent with cervical glandular intra-epithelial neoplasia (CGIN), six with endocervical adenocarcinoma, 36 with endometrial adenocarcinoma and five with other glandular neoplastic abnormalities. The average age was 46.5 years. 79 (69.3%) smears were routine call/recall and 36 (30.7%) women were symptomatic. The positive predictive value (PPV) for a significant histological abnormality in the CGIN smear group was 80.6% (23.9% invasive carcinomas, 43.3% CGIN and 13.4% CIN) and the PPV of an 'endometrial adenocarcinoma' smear was 86.1%. Smears indicating glandular neoplasia are associated with a high probability of clinically significant lesions, the PPV of a CGIN smear being over 80%. Immediate referral for colposcopy and assessment by an experienced colposcopist is recommended.

Clinical Laboratory Techniques↗
PubMed2004

Use of the nested reverse transcription-polymerase chain reaction for the detection of human papillomavirus 16 E6 transcriptional activity in cervical cancer: a technical perspective.

AIM: The aim of this study was to evaluate HPV 16 E6 expression using nested RT-PCR in cervical tumour tissue and compare this technique with standard RT-PCR in a group of patients using injectable contraceptive steroids. PATIENTS AND METHODS: Tumour DNA was analysed for the presence and type of HPV by polymerase chain reaction (PCR) from 120 cervical cancer samples. Ribonucleic acid (RNA) was extracted from cervical tissue samples and cell-lines. Reverse transcription was carried out on all samples using reverse transcriptase enzyme to form single-stranded cDNA. The GAPDH (glyceraldehyde-3-phosphate dehydrogenase) housekeeping gene was used. RESULTS: The majority of patients had squamous cell carcinoma. Of 120 cervical tissue samples, there were 111 samples with confirmed HPV 16 infection. RNA was extracted in only 86 samples. Of these, 23 samples contained genomic DNA. Of the remaining 63 patients, there were 53 patients who had expression of HPV-type 16. E6 full-length gene expression. In total there were 25 patients (40%) with expression of the HPV 16 E6*I gene and 30 patients with expression of the E6*II gene. The nested PCR method using S1/S2 primers detected 54 patients with the E6*I & E6*II transcripts in comparison to classical PCR which detected only 31 such transcripts. CONCLUSION: Nested RT-PCR is the method of choice to determine the role of different E6/E7 splice products in HPV-associated carcinogenesis.

Carcinoma, Squamous Cell↗
PubMed2003

CD10 and calretinin staining of endocervical glandular lesions, endocervical stroma and endometrioid adenocarcinomas of the uterine corpus: CD10 positivity is characteristic of, but not specific for, mesonephric lesions and is not specific for endometrial stroma.

AIMS: In the female genital tract CD10 has been used to assist in the evaluation of mesenchymal tumours of the uterus and in determining whether endometrial stroma is present. CD10 positivity has also been shown in cervical mesonephric remnants and this antibody has been suggested as a useful immunohistochemical marker of mesonephric lesions in the female genital tract. Calretinin has also been shown to be positive in mesonephric lesions. In this study the specificity of these two antibodies in evaluating cervical and uterine glandular lesions and the value of CD10 in determining whether stroma is endometriotic or not were investigated. METHODS AND RESULTS: Cases of cervical tubo-endometrial metaplasia (TEM) (n = 11), microglandular hyperplasia (MGH) (n = 10), endometriosis (n = 8), mesonephric remnants/hyperplasia (n = 12), endocervical adenocarcinoma, usual type (n = 15), mucinous variant of minimal deviation adenocarcinoma (MDA) (n = 7) and mesonephric adenocarcinoma (n = 3) were stained with antibodies against CD10 and calretinin. Nine cases of endometrial adenocarcinoma of endometrioid type were also stained. In all the cervical cases normal endocervical glands were negative with both antibodies except for one case with strong positive luminal staining with CD10. All cases of TEM, MGH and endometriosis were negative with CD10 and calretinin except for focal staining with CD10 in one case each of MGH (cytoplasmic staining) and endometriosis (luminal staining). Most usual endocervical adenocarcinomas were negative with both antibodies, although one exhibited focal cytoplasmic staining with calretinin and five exhibited limited luminal positivity with CD10. All MDAs were negative with both antibodies. Ten of 12 mesonephric remnants/hyperplasia showed luminal positivity with CD10 and one exhibited cytoplasmic and nuclear staining with calretinin. Two of three mesonephric adenocarcinomas showed luminal positivity with CD10 and nuclear and cytoplasmic positivity with calretinin. Seven of nine endometrial adenocarcinomas were positive with CD10 (four cytoplasmic, two membranous and cytoplasmic, one luminal and cytoplasmic) and three with calretinin (two cytoplasmic, one nuclear and cytoplasmic). Positive staining of endometriotic stroma with CD10 was present in all endometriosis cases but normal cervical stroma was also strongly positive, especially around glands. Endometriotic stroma and cervical stroma were negative with calretinin. CONCLUSIONS: We conclude that most endocervical glandular lesions, including mesonephric remnants/ hyperplasia, are negative with calretinin. However, the focal nuclear and cytoplasmic positivity with calretinin in two of three mesonephric adenocarcinomas suggests that this may be a useful indicator of a mesonephric origin of a cervical adenocarcinoma. Most mesonephric remnants/hyperplasias exhibit luminal positivity with CD10, although this is not invariable and staining is usually focal. Positive luminal staining of a benign endocervical glandular lesion with CD10 may help confirm mesonephric remnants. Although positive staining with CD10 was found in two of three mesonephric adenocarcinomas, the observed immunoreactivity of several conventional cervical adenocarcinomas limits the diagnostic value of CD10 in confirming a mesonephric origin for an adenocarcinoma. Since all cervical MDAs were negative with CD10, positivity with this antibody may be of value in distinguishing mesonephric hyperplasia from MDA, although this distinction rarely necessitates immunohistochemistry. Most endometrial adenocarcinomas of endometrioid type stain with CD10 and thus positivity with this antibody is not specific for a mesonephric origin of an endometrial adenocarcinoma. Positivity of normal cervical stroma limits the value of CD10 staining in confirming a diagnosis of cervical endometriosis.

Biomarkers, Tumor↗
PubMed2001

Tetrasomy is induced by human papillomavirus type 18 E7 gene expression in keratinocyte raft cultures.

We have demonstrated previously that oncogenic human papillomaviruses (HPVs) induce basal cell tetrasomy in low-grade squamous intraepithelial lesions of the cervix. To identify HPV genes and growth conditions involved in this process, we analyzed: (a) organotypic raft cultures of primary human keratinocytes transfected with whole HPV-18 genomes; and (b) organotypic raft cultures acutely infected with recombinant retroviruses expressing the HPV-18 E6, E7, or E6/E7 genes from the differentiation-dependent HPV-18 enhancer-promoter. Cultures were examined for HPV DNA by in situ hybridization and for karyotype by interphase cytogenetics. Tetrasomy occurred in the suprabasal strata of raft cultures expressing E7 and E6/E7 but not in those expressing E6 alone or in a control culture. These data indicate that suprabasal tetrasomy occurs in association with expression of the E7 gene alone. Basal cell tetrasomy was additionally observed in the raft culture transfected with whole HPV-18 genomes, consistent with observations in low-grade squamous intraepithelial lesions. The distribution of tetrasomic cells in these raft cultures may reflect the involvement of additional viral genes or possibly differences in the pattern of viral oncogene and host gene expression.

Chromosome Aberrations↗
PubMed2001

Variation in the E2-binding domain of HPV 16 is associated with high-grade squamous intraepithelial lesions of the cervix.

Human papillomaviruses (HPV) are strongly associated with cervical intraepithelial neoplasia (CIN) and invasive cancer mainly through the action of the E6 and E7 viral proteins, transcription of which is down-regulated by the E2 protein. To test the hypothesis that HPV 16 E2 variation is important in the development of high-grade squamous neoplasia of the cervix, we carried out a cross-sectional analysis of low-grade and high-grade squamous intraepithelial lesions (SILs) for specific mutations in the HPV 16 E2 gene and for E2 gene disruption in these regions. Isolates were also analysed for the HPV 16 350T-G variant. 22 of 178 low-grade SILs and 43 of 61 high-grade SILs examined, contained HPV 16. No relationship was found between the E6 350T-G variant, or the E2 hinge region 3410C-T variant, and lesion grade. However, disruption of the regions of E2 analysed was significantly more frequent in high-grade lesions, and there was a significant association between the 3684C-A variant in the E2 DNA binding domain and high-grade histology suggesting that this variant may be important in progression to high-grade intraepithelial disease.

Binding Sites↗
PubMed2001

Human papillomavirus variants and squamous neoplasia of the cervix.

Human papillomaviruses (HPVs) play a central role in the aetiology of cervical neoplasia. However, only a small proportion of cervical intraepithelial lesions infected with high-risk HPVs will progress to invasive cervical carcinoma, which indicates the involvement of additional factors. An important emerging viral factor is naturally occurring intratypic sequence variation. Such variation has been used to study the geographical spread of HPVs, but there is increasing evidence that it may be important in determining the risk of development of neoplastic disease. The collected data indicate that different HPV variants have altered biochemical and biological properties and represent an additional risk factor in the development of squamous intraepithelial lesions and invasive carcinoma of the cervix. This may be relevant not only to the biology of HPV infection and its association with squamous neoplasia, but also to the use of HPV typing in clinical practice.

Female↗
PubMed2001

Allelic imbalance is not restricted to numerically abnormal chromosomes in epithelial ovarian tumours.

In this study, 23 low malignant potential (LMP) and 27 invasive epithelial ovarian tumours have been examined by microdissection and microsatellite polymerase chain reaction (PCR) for allelic imbalance (AI) at loci on the p and q arms of chromosomes 1, 11, 17, and X, and the data have been compared with interphase cytogenetics for numerical abnormalities (aneusomy) of these chromosomes. AI was uncommon in LMP tumours (5 of 23 at 9 of 146 informative loci) but was significantly more common (p<0.001) in invasive carcinomas (21 of 27 at 47 of 168 informative loci). This difference remained when LMP tumours were compared specifically with stage I carcinomas (p<0.001). A greater number of loci were involved in AI amongst serous than amongst mucinous carcinomas (p=0.015). AI was present at significantly more loci in carcinomas showing aneusomy by interphase cytogenetics than in those showing no numerical chromosome abnormalities (p<0.001). However, amongst the carcinomas showing aneusomy, AI was as frequent at loci on chromosomes with no numerical abnormality as at those with the numerical changes. These data demonstrate that aneusomy and AI are interrelated phenomena but that AI does not occur simply as a consequence of numerical chromosome changes.

Allelic Imbalance↗
PubMed2001

Loss of cytokeratin 14 expression is related to human papillomavirus type and lesion grade in squamous intraepithelial lesions of the cervix.

In a recent study of low-grade cervical squamous intraepithelial lesions (SILs), we reported that infection with both low- and high-risk human papillomaviruses (HPVs) upregulated cyclin A, B, E, and Ki67 expression in basal and suprabasal cells. In view of the intricate link between cell cycle exit, proliferation, and differentiation, we examined the morphologic distribution of cytokeratins 13 and 14 and involucrin expression in 49 low-grade SILs infected with HPV types 6, 11, 16, 18, 31, 33, 39, 42, 43, 44, 45, 51, 52, 56, 58, and 66; 2 lesions contained both low- and high-risk HPVs. The findings were compared with 30 high-grade SILs infected with HPV types 16, 31, 33, 51, 58, 66, and 67; 3 of these were infected with 2 different HPVs. In low-grade lesions, the differentiation markers were expressed normally, showing that differentiation proceeds despite upregulation of cell cycle--associated proteins. Loss of involucrin (3 of 33) and cytokeratin 13 (8 of 33) expression occurred only in the high-grade lesions and was therefore related to lesion grade. Loss of cytokeratin 14 expression was also significantly more frequent in high-grade than in low-grade lesions (19 of 33 v 12 of 51; P < .01). In addition, cytokeratin 14 expression was significantly less frequent in the intermediate and superficial layers of low-grade SILs infected with high-risk HPVs than in those infected with low-risk HPVs (3 of 27 v 14 of 24; P < .001). These findings are consistent with in vitro data and suggest that abnormalities of both cell cycle control and squamous differentiation are important in HPV-associated neoplastic transformation.

DNA, Viral↗
PubMed2001

Human papillomavirus in pterygium.

AIM: To determine the prevalence and significance of human papillomaviral types in conjunctival pterygia. METHODS: Polymerase chain reaction technology was used to identify the presence of human papillomavirus (HPV) in 10 formalin fixed paraffin embedded pterygia samples. 10 conjunctival papillomas were used as positive controls. 20 conjunctival samples, 10 with primary acquired melanosis and 10 with malignant melanoma, were used as negative controls. Sample subgroups were of equal sex, race, and age distribution to eliminate bias. All samples were further analysed (for 21 HPV types) using dot-blot hybridisation techniques. RESULTS: HPV was identified in 90% of the conjunctival papillomas, 50% of the pterygia samples, but no HPV was detected in the negative control group. Two pterygia showed type 6, two type 11, and one type 16. These three HPV types were also detected in papillomas. CONCLUSION: These results suggest that HPV may be involved in the pathogenesis of pterygia and that broadly the same HPV types are found in pterygia and in papillomas. Persistent conjunctival HPV may possibly play a part in the recurrence of pterygia post excision but further larger studies are required to elucidate this hypothesis.

Adult↗