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Biomedical subjects

H Rowley

Publications and source records attributed to H Rowley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism.

CONTEXT: Intravenous tissue-type plasminogen activator can be beneficial to some patients when given within 3 hours of stroke onset, but many patients present later after stroke onset and alternative treatments are needed. OBJECTIVE: To determine the clinical efficacy and safety of intra-arterial (IA) recombinant prourokinase (r-proUK) in patients with acute stroke of less than 6 hours' duration caused by middle cerebral artery (MCA) occlusion. DESIGN: PROACT II (Prolyse in Acute Cerebral Thromboembolism II), a randomized, controlled, multicenter, open-label clinical trial with blinded follow-up conducted between February 1996 and August 1998. SETTING: Fifty-four centers in the United States and Canada. PATIENTS: A total of 180 patients with acute ischemic stroke of less than 6 hours' duration caused by angiographically proven occlusion of the MCA and without hemorrhage or major early infarction signs on computed tomographic scan. INTERVENTION: Patients were randomized to receive 9 mg of IA r-proUK plus heparin (n = 121) or heparin only (n = 59). MAIN OUTCOME MEASURES: The primary outcome, analyzed by intention-to-treat, was based on the proportion of patients with slight or no neurological disability at 90 days as defined by a modified Rankin score of 2 or less. Secondary outcomes included MCA recanalization, the frequency of intracranial hemorrhage with neurological deterioration, and mortality. RESULTS: For the primary analysis, 40% of r-proUK patients and 25% of control patients had a modified Rankin score of 2 or less (P = .04). Mortality was 25% for the r-proUK group and 27% for the control group. The recanalization rate was 66% for the r-proUK group and 18% for the control group (P<.001). Intracranial hemorrhage with neurological deterioration within 24 hours occurred in 10% of r-proUK patients and 2% of control patients (P = .06). CONCLUSION: Despite an increased frequency of early symptomatic intracranial hemorrhage, treatment with IA r-proUK within 6 hours of the onset of acute ischemic stroke caused by MCA occlusion significantly improved clinical outcome at 90 days.

Aged↗
PubMed1998

p53 expression and p53 gene mutation in oral cancer and dysplasia.

BACKGROUND: The aim of the current study was to examine the possible association of the p53 tumor suppressor gene with the development of oral cancer. We examined biopsy material from patients with oral squamous cell carcinoma for p53 protein expression and p53 mutations. METHODS: Eighteen samples were analyzed. These comprised oral squamous cell carcinoma biopsy samples and oral dysplastic biopsy material taken from nine patients. An immunohistochemical technique was used to determine p53 protein expression. A direct sequencing technique was used to detect mutations in the p53 gene itself. RESULTS: Overall seven of nine (77%) oral squamous cell carcinomas and seven of nine (77%) oral dysplastic lesions analyzed showed evidence of p53 protein over-expression. Mutations in exons 5 and 6 of the p53 gene were detected in five of nine (55%) oral squamous cell carcinomas and four of nine (44%) dysplastic lesions analyzed. CONCLUSIONS: Both p53 protein over-expression and p53 mutations were noted in dysplastic oral lesions. Over-expression of the p53 protein and p53 gene mutations were not always coexistent, however, suggesting that gene mutation may be only one of the mechanisms responsible for stabilization of the p53 protein.

Carcinoma, Squamous Cell↗
PubMed1998

p53 protein expression in tumours from head and neck subsites, larynx and hypopharynx, and differences in relationship to survival.

The present study involves an immunohistochemical analysis of p53 protein expression in head and neck tumours located at two separate subsites, the larynx and hypopharynx. It attempts to relate differences in expression to differences in the behaviour of these tumours. Detection of the p53 protein was performed using immunohistochemistry on 32 specimens of hypopharyngeal squamous cell carcinoma and 35 specimens of laryngeal squamous cell carcinoma. p53 overexpression was found in 66% of the hypopharyngeal tumours and in 51% of the laryngeal specimens analysed. Some differences between the two tumour types were noted in the pattern staining. p53 staining in those with hypopharyngeal tumours was associated with a statistically significant increased survival. For laryngeal carcinoma the converse was true but did not reach statistical significance. Differences in the behaviour of different head and neck tumour types may be reflected in differences in expression of the p53 protein. While p53 protein expression does not appear to be a useful prognostic indicator in laryngeal carcinoma it might be a useful prognostic indicator in tumours of the hypopharynx. Moreover, it may help predict those tumours which are radioresistant, thus suggesting other modes of treatment for these tumours. Of particular importance is the molecular basis for the observed differences in survival associated with p53 expression in the two tumour sites. This is under further investigation.

Biomarkers, Tumor↗
PubMed1998

Radical radiotherapy for squamous cell carcinoma of the larynx, oropharynx and hypopharynx: patterns of recurrence, treatment and survival.

The present study investigates 1085 previously untreated patients with squamous cell carcinoma of the head and neck for factors that influence recurrence following treatment with definitive radiotherapy. In the second part of this study, those diagnosed with recurrence were studied with regard to treatment and were further analysed with regard to identification of prognostic factors which may affect outcome in the patient who actually develops a recurrence.

Adult↗
PubMed1997

Adenoid cystic carcinoma of the head and neck.

Adenoid cystic carcinoma has a long natural history but frequently proves fatal. The present study describes 108 patients with an adenoid cystic carcinoma of the head and neck seen over a 30-year period. Analysis of the data utilized both univariate and multivariate methods. Forty per cent of patients had tumours arising from the oral cavity and half of these were in the hard palate; 29% occurred in the major salivary glands; 41% of tumours were locally advanced at presentation and 11% had lymph node metastases at this time. The histological pattern was solid in 25%, cribriform in 40% and tubular in 20%. In addition, 15% of patients had a polymorphous low-grade adenocarcinoma and these were analysed separately. Primary site recurrence was more common in the presence of locally advanced tumours at presentation (T3-4) (P = 0.0093). Only six patients had surgery with adjuvant radiotherapy. Six patients had no curative treatment, 21 had primary radiotherapy, 39 had local excision and 42 radical excision. The actuarial primary site recurrence rate was 100% at 30 years. The neck node recurrence rate was 23% at 15 years. Tumour specific survival was 40% at 20 years. Solid histology had a worse prognosis than other histological types (P = 0.0429) but those patients with polymorphous low-grade adenocarcinomas fared very well. Patients with tumours of the hard palate fared better than those patients with tumours at other sites (P = 0.0301). Early disease at the primary site (T1-2) was a good prognostic sign (P = 0.0013). Patients with neck node metastases at presentation tended to do badly (P = 0.009).

Carcinoma, Adenoid Cystic↗
PubMed1997

An immunohistochemical analysis of p53 protein expression in pre-malignant and malignant tissues of the oral cavity.

This study looks at p53 protein expression in dysplastic and malignant lesions of the oral cavity using an immunohistochemical staining technique. Archival biopsy specimens of oral dysplasia of squamous cell carcinoma from 64 patients were analysed immunohistochemically. Sections from 90 oral biopsy specimens were examined in all. Positive immunohistochemical detection of the p53 protein, demonstrated by brown nuclear staining, was detectable in over 80% of mild, moderate and severe dysplastic tissues as well as carcinoma-in-situ and squamous carcinoma specimens. We concluded that p53 protein expression occurs frequently in both malignant and dysplastic lesions of the oral cavity, suggesting that abnormally detectable p53 protein is present at the very early stages of development of oral squamous carcinoma. Oral cancer may provide a good model for the study of multistage tumorigenesis in head and neck cancer as the lesions are frequently detected at the pre-invasive stage and are accessible to biopsy.

Carcinoma, Squamous Cell↗
PubMed1996

Definition of a tumor suppressor gene locus on the short arm of chromosome 3 in squamous cell carcinoma of the head and neck by means of microsatellite markers.

BACKGROUND: Tumor suppressor genes are important in the development of head and neck cancer. Using microsatellite markers that map close to the region 3p24-pter, we determined the frequency of allele loss close to this site with a view to narrowing the search for a putative tumor suppressor gene involved in the development of squamous cell carcinoma of the head and neck, which may facilitate future positional cloning techniques. DESIGN: Laboratory-based project with tumor and normal specimens subjected to molecular genetic analysis. Tumor-normal tissue DNA pairs were analyzed for allelic imbalance and microsatellite instability on chromosome 3p in the region 3p24-pter by the polymerase chain reaction and microsatellite markers D3S1304, D3S656, D3S1252, D3S1293, THRB, and D3S1266. SETTING: Molecular genetics and oncology research laboratory. PATIENTS: Paired tumor-normal DNA samples were obtained from 46 patients with tumors of the head and neck. MAIN OUTCOME MEASURES: Detection of loss of heterozygosity and microsatellite instability on chromosome 3 in the region 3p24-p25.1. RESULTS: We found loss of heterozygosity with at least one marker in 48% of informative cases and loss of heterozygosity or microsatellite instability in 57% of informative cases. The minimal region of loss was found in the region bounded by D3S656 and D31293. CONCLUSION: A putative tumor suppressor gene in head and neck cancer lies between D3S656 and D3S1293 in the 3p25.1 region.

Alleles↗
PubMed1996

MIB-1 and involucrin expression in laryngeal squamous carcinoma: the relationship to host and tumour factors and survival.

MIB-1 is an antibody which attaches to the Ki67 antigen expressed by proliferating cells. MIB-1 immunoreactivity may be used to quantify the proliferative component of a tumour. Involucrin is a protein expressed by mature keratinocytes and may be used as a marker of differentiation. The present paper studies the expression of these two markers in a group of patients with squamous carcinoma of the larynx. Tumour cell kinetics were studied in 49 patients with squamous cell carcinoma of the larynx using antibodies to "Ki67' and involucrin. The median potential follow-up for the group was 8.1 years with a minimum follow-up of 5 years. The median MIB-1 index was 32%. The median involucrin index was 56%. Fifteen patients had no or only slight involucrin staining whereas 34 stained intensely for this protein. Involucrin expression was found to be associated with histological grade with those patients expressing involucrin tending to have well differentiated tumours and those not expressing this parameter tending to have poorly differentiated tumours (P = 0.045). There were no other associations between host and tumour factors and the various biological parameters. Survival analysis demonstrated that patients with an involucrin count above the median value had a better 5-year survival than those below the median (89% and 56% respectively) (P < 0.05). In addition, patients with no (or poor) involucrin expression had an increased risk of developing a recurrence at the primary site (P < 0.05). Involucrin appears to be a promising marker of tumour differentiation and survival in squamous carcinoma of the larynx.

Biomarkers, Tumor↗
PubMed1996

Malignant tumours of the cervical oesophagus.

Forty-seven patients with malignancy of the cervical oesophagus are described and compared with a group of 647 patients with hypopharyngeal malignancy. There was a higher proportion of non-squamous malignancy in cervical oesophageal cancer compared with hypopharyngeal cancer. Cervical oesophageal malignancy tended to present earlier with significantly lower T stage and neck node metastases were relatively unusual at presentation. Patients with cervical oesophageal malignancy were frequently incurable at the time they are first seen and 21 had palliative treatment only, 26 patients had curative treatment, 12 underwent radical radiotherapy and 14 had surgery. Cervical oesophageal malignancy had a significantly worse prognosis than hypopharyngeal malignancy with an 18% 3 year survival compared with a 33% 3 year survival (chi (1)2 = 7.1089, P < 0.01). Those patients with oesophageal malignancy who were treated fared considerably better than the whole group with 30% being alive at 3 years (chi (1)2 = 10.5185, P < 0.01).

Carcinoma, Squamous Cell↗
PubMed1995

Chondroradionecrosis of the larynx: still a diagnostic dilemma.

Following radiation treatment for carcinoma of the larynx it may be very difficult to differentiate between persistent or recurrent tumour and severe radiation effects particularly chondroradionecrosis. Despite repeated negative biopsy it may be necessary to perform total laryngectomy where the concern about persistent cancer remains and the larynx is non-functioning. We report nine cases presenting as chondroradionecrosis over a five-year period. Two patients settled on medical treatment. Of seven patients treated with laryngectomy the histology on two revealed residual or recurrent carcinoma. We outline the dilemmas in diagnosis and propose management strategies to deal with this condition including recommendations for prevention and treatment.

Adult↗
PubMed1995

Allelotype of squamous cell carcinoma of the head and neck: fractional allele loss correlates with survival.

Allelic imbalance or loss of heterozygosity (LOH) studies have been used extensively to identify regions on chromosomes that may contain putative tumour-suppressor genes. We have undertaken an extensive allelotype of 80 specimens of squamous cell carcinoma of the head and neck (SCCHN) using 145 polymorphic microsatellite markers on 39 chromosome arms. Allelic imbalances were found most frequently on chromosome arms 3p, 9p, 17p and 18q with over 45% LOH and imbalances on 1p, 1q, 2p, 5q, 6p, 6q, 8p, 8q, 9q, 11q, 13q, 17q and 19q were found in more than 20% of SCCHN. These LOH data were analysed against a range of clinicopathological parameters which included previously untreated and previously treated tumours; correlations were found between LOH on 9q and nodes at pathology (P = 0.02) and between histopathological grade and LOH on 12q (P = 0.02) and 13q (P = 0.01). In the group of previously untreated tumours, a correlation was found between site of tumour and LOH on 3p (P = 0.019), and 8p (P = 0.029), while TNM staging correlated with LOH on 3p (P = 0.019) and 17p (P = 0.016). Fractional allele loss (FAL) was calculated for 52 tumours with LOH data on nine or more chromosomal arms and found to have a median value of 0.22 (range 0.0-0.80). Correlations were found between FAL > median value and nodes at pathology (P = 0.01) and tumour grade (P = 0.06), demonstrating that advanced tumours with lymph node metastasis often had LOH at multiple sites. FAL > median value was found to correlate with a poor survival (P < 0.03) and, furthermore, FAL > median value correlated with poor survival in the previously untreated patients (P < 0.019). These results indicate that assessment of the accumulation of genetic damage, as provided by allelotype data, provides a useful molecular indicator of the tumour behaviour and clinical outcome.

Alleles↗
PubMed1995

Lymphoma presenting to a head and neck clinic.

Lymphomas generally have a good prognosis compared with squamous carcinomas. The present study investigates a series of 185 lymphomas of the head and neck seen over a 30-year-period. The records of 236 patients were examined and the histology slides reviewed. The lymphomas were classified according to the working formulation method and staged using the Ann Arbor system. A total of 185 patients had a non-Hodgkin's lymphoma, of those 43 were low grade, nine intermediate and 103 high grade. The histology slides of 30 patients were not available for review. In addition, 51 patients had Hodgkin's disease. One hundred and fifty patients were stage 1 or 2 and 74 stage 3 or 4. In 12 patients insufficient data was available for staging; 152 were extranodal and 84 nodal. The 5-year survival of those patients with Hodgkin's disease was 73%. For the patients with non-Hodgkin's lymphoma the 5-year survival was 43% for low grade and 48% for high grade lesions. The survival of patients with Hodgkin's disease was significantly better than for non-Hodgkin's lymphoma (P < 0.01). The 5-year survival of patients with extranodal disease was 54% and for patients with nodal disease 65% (P = NS). Treatment was by irradiation for localized lesions and by chemotherapy or a combination for more advanced lesions. Lymphomas have a relatively good prognosis in the head and neck as elsewhere in the body and every effort should be made to provide adequate diagnosis and treatment in combined clinics.

Aged↗
PubMed1995

Chromosome 18: a possible site for a tumour suppressor gene deletion in squamous cell carcinoma of the head and neck.

The present study analyses tumour samples from 41 patients with squamous cell carcinoma of the head and neck (SCCHN) using the polymerase chain reaction (PCR) to detect genetic alterations on chromosome 18. Microsatellite markers were used to examine each sample for loss of heterozygosity (LOH) and microsatellite instability. Genetic alterations were most commonly noted on the long arm of chromosome 18 (18q). LOH/microsatellite instability occurred on 18q in 20/41 (49%) of patients. The highest single incidence of LOH was found at 18q21.1-21.3 using the microsatellite marker D18S35. LOH occurred in 10/30 (33%) informative cases while LOH/microsatellite instability occurred in 13/30 (43%) informative cases using this marker. Interestingly the tumour suppressor gene known as the 'deleted in colonic carcinoma' (DCC) gene is located in this region at 18q21.3 but is not commonly lost. This suggests that the marker D18S35 is mapping close to a second as yet unidentified tumour suppressor gene in this area.

Adult↗
PubMed1995

Pharyngeal perforation: an easily missed finding following intra-oral injury.

A 2-year-old child presented with pharyngeal perforation following a peroral injury with a toothbrush. Direct force applied to an object such as a toothbrush in the mouth may cause either superficial or penetrating injury within the oropharynx. A high index of suspicion is sometimes necessary to identify a pharyngeal perforation and if this is diagnosed we would advocate admission to hospital, restriction of oral intake, intravenous fluids and antibiotics, with close observation to ensure that healing occurs without development of further complications.

Child, Preschool↗
PubMed1995

Reversible MRI abnormalities following seizures.

We describe eight patients with reversible MRI changes following seizures. The patients were mostly young with a serious underlying medical problem; MRI abnormalities were localized primarily in the posterior vascular boundary zones. A likely mechanism for these lesions is edema secondary to disruption in the blood-brain barrier. Recognition of the transient radiologic changes may aid in the diagnostic and therapeutic management of seizures.

Adolescent↗
PubMed1995

The natural history of globus pharyngeus.

While globus pharyngeus is a common disorder, accounting for 3% to 4% of new otolaryngology outpatient referrals, few long-term follow-up studies have been conducted on patients with this condition. The authors of this study followed 74 patients with a diagnosis of globus pharyngeus for an average of 7 years, 7 months (range: 7 years to 8 years, 10 months). During the follow-up period, 55% of patients were asymptomatic and 45% of patients had persistent symptoms. An in-depth analysis of features at clinical presentation failed to reveal any reliable prognostic indicators. A number of patients developed other conditions during the follow-up period, but no patient developed upper aerodigestive tract malignancy. This study represents the longest follow-up of globus patients to date and, to the authors' knowledge, is the first to address the issue of malignancy in globus.

Adolescent↗