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P Blake

Publications and source records attributed to P Blake.

At least 37 records · Page 2Linked to original sources
PubMed2000

An audit of outcome of adjuvant post-operative radiotherapy for 52 women with stage II carcinoma of the endometrium.

A retrospective review was undertaken of the medical records of 52 women with stage II carcinoma of the endometrium who received adjuvant radiotherapy following surgery. The information was obtained from medical notes and a hospital database. Actuarial disease-free survival was 68% at 5 years for those women with stage IIA disease, and 70% at 5 years for those women with stage IIB disease. 6 of the women (11.5%) had side effects from treatment. In contrast to the literature, the only statistically significant prognostic factor in this study was histological differentiation; patients with poorly differentiated tumours fared worse (p = 0.05). This may indicate that a greater number than 52 women is needed to demonstrate weaker prognostic factors such as substage. A larger review is being undertaken of the remaining women recorded on the database, with stage I, III and IV disease.

Adult↗
PubMed1999

Pro-1 of macrophage migration inhibitory factor functions as a catalytic base in the phenylpyruvate tautomerase activity.

Macrophage migration inhibitory factor (MIF) is an important immunoregulatory molecule with a unique ability to suppress the anti-inflammatory effects of glucocorticoids. Although considered a cytokine, MIF possesses a three-dimensional structure and active site similar to those of 4-oxalocrotonate tautomerase and 5-carboxymethyl-2-hydroxymuconate isomerase. Moreover, a number of catalytic activities have been defined for MIF. To gain insight into the role of catalysis in the biological function of MIF, we have begun to characterize the catalytic activities in more detail. Here we report the crystal structure of MIF complexed with p-hydroxyphenylpyruvate, a substrate for the phenylpyruvate tautomerase activity of MIF. The three binding sites for p-hydroxyphenylpyruvate in the MIF trimer lie at the interface between two subunits. The substrate interacts with Pro-1, Lys-32, and Ile-64 from one subunit and Tyr-95 and Asn-97 from an adjacent subunit. Pro-1 is positioned to function as a catalytic base. There is no functional group that polarizes the alpha-carbonyl of the substrate to weaken the adjacent C-H bond. Mutation of Pro-1 to glycine substantially reduces the catalytic activity. The insertion of an alanine between Pro-1 and Met-2 essentially abolishes activity. Structural studies of these mutants define a source of the reduced activity and provide insight into the mechanism of the catalytic reaction.

Amino Acid Substitution↗
PubMed1999

Self-assessment of morbidity following radical hysterectomy for cervical cancer.

The aim of this study was to assess the magnitude of the morbidity following radical surgery for early stage cervical cancer. We performed a retrospective survey of all women who had undergone a radical hysterectomy and lymphadenectomy between the months of July 1995 and December 1996 inclusive at either the Royal Marsden or St George's Hospital (n =38), using a detailed questionnaire on bladder, ano-rectal and sexual function, both before and after treatment. Sixteen women (44.4%) received adjuvant radiotherapy. The mean interval between surgery and inquiry was 16.4% months (range 8-25 months). The mean age at the time of surgery was 40.5 years. Thirty-six out of 38 women contacted responded (94.7%). Overall 33 women (91.7%) reported new bladder, ano-rectal or sexual symptoms. Complaints of urinary incontinence, particularly of urge incontinence, and of voiding difficulties increased significantly after surgery (P <0.05). However, only 5.3% of women had sought treatment. Tenesmus increased significantly (P <0.05), while increases in diarrhoea and faecal incontinence were not statistically significant (P =0.051). Although 12.9% of women stated an improvement in their sex lives, 54.8% thought that their sex life was worse after treatment, and 12.9% of women had ceased sexual activity altogether. Of women of childbearing age 53.8% felt adversely affected by their loss of fertility. Bladder, ano-rectal and sexual symptoms are very common following radical hysterectomy for cervical cancer, with adverse effect on quality of life, and persist into the second year after treatment.

Journal Article↗
PubMed1999

Escherichia coli O157:H7 outbreak associated with an improperly chlorinated swimming pool.

A cluster of gastrointestinal illnesses, including one case of hemolytic-uremic syndrome and one culture-confirmed Escherichia coli O157:H7 infection, followed a trailer park pool party. We interviewed a cohort of party attendees and park residents. A primary case was defined as the first gastrointestinal illness within a household between 5 July and 20 July in which the titer of IgG antibody to E. coli O157 (if determined) was elevated. Of 51 party attendees and trailer park residents, 18 developed a gastrointestinal illness, including 10 who met the definition of a primary case. Swimming in the pool significantly increased the risk of primary illness (relative risk = 6.3; 95% confidence interval = 1.8-18.9). No other exposure was significantly associated with primary illness, after pool exposure was controlled for. The implicated pool had little to no chlorine added during the period of 4-10 July. This outbreak provides new evidence of the importance of proper pool maintenance in controlling the spread of E. coli O157:H7.

Chlorides↗
PubMed1999

Family-of-origin characteristics in bipolar disorder: a controlled study.

OBJECTIVE: To assess the family-of-origin characteristics of patients with bipolar disorder relative to those of control subjects. METHOD: Fifty-six euthymic patients meeting research diagnostic criteria for bipolar disorder and 21 control subjects completed the Family Environment Scale (FES) for the family they grew up with. RESULTS: The 2 groups showed strikingly similar profiles on 10 indices of family functioning or structure. CONCLUSIONS: The results do not support the hypothesis that specific family attributes contribute to the development of bipolar disorder.

Adult↗
PubMed1999

Natural history of stage IV epithelial ovarian cancer.

PURPOSE: In this report we present the natural history, prognostic factors, and therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: We reviewed 192 patients with stage IV EOC as defined in 1985 by the International Federation of Gynecology and Obstetrics. RESULTS: The site of stage IV-defining disease was cytologically positive pleural effusion in 63 patients, liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other sites in 15 patients, and disease at multiple stage IV-defining metastatic sites in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25 patients (14.8%) were left with only microscopic residual disease or less than 2 cm of macroscopic residual disease. The overall response rate to chemotherapy was 56%; the complete response rate was 18%. The median progression-free survival was 7.1 months, and the median overall survival was 13.4 months. The median overall survival of patients with positive pleural effusions only was 13.4 months as compared with 10.5 months for patients with visceral disease only, but this difference was not statistically significant. The 5-year survival rate was 7.6%, with only six patients surviving more than 5 years. Univariate and multivariate analysis showed that two parameters were associated with a shorter survival time: visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION: Patients with stage IV EOC initially respond to chemotherapy as often as those with less advanced disease, but the long-term prognosis is very poor. The size of residual disease is not a prognostic factor in this group of patients, and, therefore, the role of debulking surgery in these patients needs to be reconsidered.

Adult↗
PubMed1999

Stage IV endometrial carcinoma: a 10 year review of patients.

Stage IV endometrial cancer is uncommon, often occurs in elderly patients and has a poor prognosis, which makes the choice of treatment difficult. 18 patients with stage IV endometrial cancer presenting over a 10 year period, between 1987 and 1997, were reviewed with regard to mode of treatment and response. The mean age was 65 years. Five had disease confined to the pelvis and 13 had extra pelvic disease. 15 of 18 patients had a total abdominal hysterectomy (TAH). One patient received radiotherapy alone and five received post-operative radiotherapy. Overall freedom from pelvic symptoms was achieved in seven of 18 patients. All seven had undergone TAH and two had received post-operative radiotherapy. Progestogens were given to 13 patients. Six received progestogens alone, without radiotherapy or chemotherapy. Of these, two responded, one for 9 months and one with verified lung metastases, who had a complete response, is still alive at 6.5 years. Eight patients received chemotherapy, with single agent cisplatin or carboplatin AUC 6. Three patients responded, one for 4.5 years. The overall median survival was 12 months from diagnosis. Actuarial 5 year survival was 15% (CI 3-36). There was no significant survival difference for, hormone therapy or chemotherapy. Stage IV endometrial cancer has a poor prognosis but durable response can be achieved in some patients.

Adult↗
PubMed1998

When not to syringe an ear.

This article reviews the potential hazards of ear syringing and the Accident Compensation Corporation Medical Misadventure Unit's experience of alleged iatrogenic injury over a 17-month period. Syringing claims account for about 25% of the total claims received by the ACC ENT Medical Misadventure Committee. Forty-seven claims were accepted as either mishap or error, and 63 claims were declined. Perforation of the drum was by far the commonest injury resulting in significant disability. Severe iatrogenic otitis externa accounted for most of the remainder. Practice nurses had syringed the ears of approximately two-thirds of the claimants with significant disability. The contraindications to ear syringing are listed and discussed. The correct technique, with a few "do and don't" pointers, is briefly reviewed. Management of the unintentional injury is discussed.

Adult↗
PubMed1998

Macrophage migration inhibitory factor interactions with glutathione and S-hexylglutathione.

Macrophage migration inhibitory factor (MIF) has been reported to interact with glutathione and S-hexylglutathione and to possess glutathione S-transferase activity. However, contrary to these reports, a recent NMR study concluded that MIF shows no affinity for glutathione. Re-examination of the glutathione-MIF interactions indicates that the reported increase in fluorescence upon addition of glutathione is because of pH-induced unfolding of the protein and not to any direct interactions. Circular dichroism shows that MIF remains folded from pH 4.5-7.5 but is 50% unfolded at pH 2.9 +/- 0.2. The reported increase in fluorescence can be achieved by acid titration. Under strongly buffered conditions, no fluorescence change is observed upon addition of glutathione. In contrast to the results with glutathione, MIF binds S-hexylglutathione with a Kd of 2.5 +/- 0.6 mM. Using NMR spectroscopy, a binding site which clusters around the N-terminal proline was identified. These data indicate that the binding site for S-hexylglutathione is the same as the catalytic site for the dopachrome tautomerase activity of MIF. Consequently, the binding of S-hexylglutathione as well as hexanethiol inhibits this catalytic activity.

Binding Sites↗
PubMed1998

Granulosa cell tumours of the ovary: demographics, survival and the management of advanced disease.

Ovarian granulosa cell tumours (OGCT) are rare, accounting for only 3%-5% of primary ovarian tumours. As a result of oestrogen production OGCTs tend to present with early stage disease, which has a good prognosis. For patients with advanced disease, surgery and radiotherapy have been the major modalities of treatment. More recently, platinum-based chemotherapy has been shown to have important activity in advanced disease. In this retrospective study, we have reviewed the results of 62 patients who were treated for adult OGCT at the Royal Marsden Hospital between 1969 and 1995, with particular emphasis on the management of advanced disease. The median age at primary diagnosis was 53 years (range 13-77). Sixty-one per cent of these patients had Stage I disease, 21% Stage II disease, 16% Stage III and 2% Stage IV. Stage I patients had a good prognosis with 5- and 10-year overall survival rates of 95% and 90%. Eleven Stage I patients received adjuvant pelvic radiotherapy, with no apparent benefit to recurrent rate or overall survival. Disease progression occurred in 40% of Stage I patients at a median interval of 76 months (range 12-240), and in 62% of the Stage II patients, at a median interval of 31 months (range 2-57). The median interval from progression of Stage I/II disease to death was 22 months (range 3-144). For patients with inoperable disease, radiotherapy produced a number of long-term remissions with an overall response rate of 50%. Platinum-based chemotherapy also appears active, with responses documented in four out of five patients treated with the PVB regimen (cisplatin, vinblastine, bleomycin) as first line therapy. There were no responses documented to non-platinum chemotherapy or to hormonal manipulation. The results from this study confirm the activity of platinum-containing chemotherapy regimens in OGCT and support the need for further trials to optimize the management of this rare tumour.

Adolescent↗
PubMed1998

Detection of chlamydiosis in a shipment of pet birds, leading to recognition of an outbreak of clinically mild psittacosis in humans.

Avian chlamydiosis was detected in a shipment of > 700 pet birds from a Florida bird distributor that were sold to nine Atlanta-area pet stores in August 1995. Respiratory illness among persons who had recently acquired birds from this shipment was reported to local public health officials. The attack rate of acute respiratory illness was 10.7% among persons in households exposed to birds from the implicated flock vs. 1.8% among control households (odds ratio, 6.60; 95% confidence interval, 1.39-31.2). Illness and serological evidence of infection in the absence of symptoms were more common among persons in households with recently purchased birds that were sick or that had died and among persons who had had direct contact with the birds. Clinical psittacosis or serological evidence of Chlamydia psittaci infection was found in 30.7% of households with birds from the infected flock. Mild illnesses and asymptomatic infections in exposed persons were unusual features of this outbreak.

Animals↗
PubMed1998

Pitfalls in placebo-controlled trials in palliative care: dexamethasone for the palliation of malignant bowel obstruction.

To determine the effect of dexamethasone when treating malignant bowel obstruction, 35 patients were randomized to receive intravenous dexamethasone or a placebo, crossing over to the alternate treatment arm if there had been no resolution of obstruction by day 5. This was done in two consecutive studies. Patients were stratified according to whether or not they had received specific anticancer therapy within 28 days of study. In trial 1, 15 out of 22 patients 'responded' (resolution of obstruction by day 5; 10 on dexamethasone, five on placebo). Eleven out of 15 patients were 'on treatment'. In trial 2, six out of 13 responded (three on dexamethasone, three on placebo); three out of six were 'on treatment'. When both studies are combined, 60% (21/35) patients responded (13 on dexamethasone, eight on placebo). Poor patient accrual terminated both studies. Numbers are too small to allow a combination of studies or formal statistical analysis. We are unable to make any conclusion as to the effectiveness of dexamethasone in the palliation of malignant bowel disease.

Adult↗
PubMed1998

Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group.

PURPOSE: We have examined the role of an increase in cisplatin dose-intensity in patients with advanced epithelial ovarian cancer by means of single-agent carboplatin therapy. PATIENTS AND METHODS: Two hundred twenty-seven patients were randomized to treatment and eligible for analysis. The dose of carboplatin was calculated according to the Calvert formula. One hundred seventeen patients received carboplatin at an area under the concentration time curve (AUC) of 6 for six courses, administered every 28 days, and 110 patients received carboplatin at an AUC of 12 for four courses, administered every 28 days. Patients were eligible provided they had not received prior chemotherapy or radiotherapy and had International Federation of Gynecology and Obstetrics stages II to IV or relapsed stage I epithelial ovarian cancer. RESULTS: The planned total-dose increase was 33% for the patients treated with carboplatin AUC 12, but the received percentage total-dose increase was 20%. There were no differences in progression-free or overall survival between the two treatment arms; the overall survival rate at 5 years was 31% and 34% of patients treated at AUCs 6 and 12, respectively. There was significantly more toxicity associated with carboplatin AUC 12, which resulted in more treatment delays and/or dose reductions (52% v 18%; P < .001). CONCLUSION: We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs. Nonhematologic toxicities were not clinically significant. Carboplatin offers an opportunity to intensify cisplatin therapy, but a greater than two-fold increase in dose-intensity probably needs to be achieved before significant effects on survival will be produced and hematologic support will be required.

Adult↗
PubMed1997

Contribution of BRCA1 mutations to ovarian cancer.

BACKGROUND: Inherited mutations in the BRCA1 gene confer a high risk of breast and ovarian cancer in some families. To determine the contribution of BRCA1 mutations to ovarian cancer in the general population, we analyzed DNA samples from a consecutive series of women with ovarian cancer seen at one center. METHODS: We studied 374 women who received a diagnosis of epithelial ovarian cancer before the age of 70 years and were treated at the Royal Marsden Hospital between July 1993 and September 1995. Genomic DNA was analyzed by multiplex heteroduplex analysis. Variants were further identified by sequencing. RESULTS: Probable germ-line BRCA1 mutations were identified in 13 of the 374 women (3 percent; 95 percent confidence interval, 2 to 6 percent). Six of the variants have not been described previously. Of the 13 mutations, 12 are predicted to result in a truncated protein product. An additional variant results in an in-frame deletion just outside the putative zinc-finger domain. Nine of the 12 women with truncating mutations had family histories of breast or ovarian cancer or both. CONCLUSIONS: Assuming that our method has a sensitivity of 70 percent, mutations in BRCA1 occur in approximately 5 percent (95 percent confidence interval, 3 to 8 percent) of women in whom ovarian cancer is diagnosed before the age of 70 years.

Adenocarcinoma, Clear Cell↗
PubMed1997

Performance of a neural-network-based determination of amino acid class and secondary structure from 1H-15N NMR data.

A neural network which can determine both amino acid class and secondary structure using NMR data from 15N-labeled proteins is described. We have included nitrogen chemical shifts, 3JHNH alpha coupling constants, alpha-proton chemical shifts, and side-chain proton chemical shifts as input to a three-layer feed-forward network. The network was trained with 456 spin systems from several proteins containing various types of secondary structure, and tested on human ubiquitin, which has no sequence homology with any of the proteins in the training set. A very limited set of data, representative of those from a TOCSY-HSQC and HNHA experiment, was used. Nevertheless, in 60% of the spin systems the correct amino acid class was among the top two choices given by the network, while in 96% of the spin systems the secondary structure was correctly identified. The performance of this network clearly shows the potential of the neural network algorithm in the automation of NMR spectral analysis.

Amino Acids↗
PubMed1997

A study to ascertain gynaecological patients' perceived levels of embarrassment with physical and psychological care given by female and male nurses.

The Sex Discrimination Act lifted the barriers which prevented men from training and practising as midwives. However, cultural attitudes perceive nursing to be a female profession, and whilst care from a male doctor is considered to be acceptable, care from a male nurse is said to be embarrassing. The purpose of the study was to identify if there was any relationship between the intimacy of a nursing interaction and the patient's level of embarrassment. Data collection was by questionnaires with rating scales. Demographic data was obtained from nursing and medical notes. Statistical analysis was performed by non-parametric methods using Mini-tab. Ninety-one questionnaires were returned from a convenience sample of patients on a gynaecological oncology ward. Analysis of the data indicates that in a population of patients who have no prior experience of hospital admission, or of being cared for by a male nurse, there is a preference for care by a female nurse. However, this preference is not demonstrated in patients who have undergone previous hospital admission within the last five years or who have been cared for by a male nurse. These findings would indicate a cultural preference for care by a female nurse in patients with gynaecological cancer that is changed by experience during hospital admission.

Attitude to Health↗
PubMed1996

The increasing incidence of hospital admission for acute tonsillitis: a 5 year review of the Wellington experience.

AIM: To document the number of admissions with acute tonsillitis over a 5 year period, 1990-4. METHOD: Information was retrieved by retrospective case note review. RESULTS: A total of 198 patients were admitted. The admission rate increased each year from 17 in 1990 to 79 in 1994, and this was statistically significant. Length of stay, average patient age and proportion with glandular fever did not change. The highest admission rate was in the 16 to 20 years age group. Demography remained constant. CONCLUSION: No explanation for the increase was found. Changes in the microbiology of acute tonsillitis, increasing virulence of the causative organisms and primary care factors are possible explanations.

Acute Disease↗