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P Harper

Publications and source records attributed to P Harper.

At least 55 records · Page 3Linked to original sources
PubMed2001

Avascular necrosis of bone: the hidden risk of glucocorticoids used as antiemetics in cancer chemotherapy.

The role of antiemetics is invaluable in allowing cancer patients to complete otherwise potentially intolerable chemotherapy. Corticosteroids have an established place in the prevention and treatment of nausea and vomiting due to emetogenic cytotoxic agents. Avascular necrosis of bone is a recognised complication of glucocorticoid treatment--the risk of this increasing with higher doses and longer duration of use. This report details a case of bilateral avascular necrosis of the femoral heads in a patient receiving 'standard' doses of dexamethasone as part of the antiemetic regimen used in cisplatin-based combination chemotherapy.

Adult↗
PubMed2000

Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

Adult↗
PubMed2000

Randomized trial of a specialist genetic assessment service for familial breast cancer.

BACKGROUND: Because of the growing demand for genetic assessment, there is an urgent need for information about what services are appropriate for women with a family history of breast cancer. Our purpose was to compare the psychologic impact and costs of a multidisciplinary genetic and surgical assessment service with those of current service provisions. METHODS: We carried out a prospective randomized trial of surgical consultation with (the trial group) and without (the control group) genetic assessment in 1000 women with a family history of breast cancer. All P: values are from two-sided tests. RESULTS: Although statistically significantly greater improvement in knowledge about breast cancer was found in the trial group (P: =.05), differences between groups in other psychologic outcomes were not statistically significant. Women in both groups experienced statistically significant reductions in anxiety and found attending the clinics to be highly satisfying. An initial specialist genetic assessment cost pound 14.27 (U.S. $22.55) more than a consultation with a breast surgeon. Counseling and genetic testing of affected relatives, plus subsequent testing of family members of affected relatives identified as mutation carriers, raised the total extra direct and indirect costs per woman in the trial group to pound 60.98 (U.S. $96.35) over costs for the control subjects. CONCLUSIONS: There may be little benefit in providing specialist genetics services to all women with a family history of breast cancer. Further investigation of factors that may mediate the impact of genetic assessment is in progress and may reveal subgroups of women who would benefit from specialist genetics services.

Adult↗
PubMed2000

A comparison of methods currently used in clinical practice to estimate familial breast cancer risks.

BACKGROUND: With the identification of genes predisposing to hereditary breast cancer, the accurate and consistent estimation of a woman's risk of developing breast cancer based on her family history is of paramount importance if national service guidelines are to be developed. PATIENTS AND METHODS: The residual lifetime risk of developing breast cancer was estimated for 200 women attending a breast cancer genetic assessment clinic by three different methods currently in use in the UK. Risks were computed on the basis of the Cancer and Steroid Hormone (CASH) study data and were classified as 'low/moderate' (<20%) or 'high' (>20%). These risk categories are representative of those currently used to allocate surveillance and genetic testing. Risks were then compared to estimates derived by other methods used in current clinical practice, including those of Houlston and Murday. RESULTS: The CASH data-based method ascribed 27% to the high risk category, as compared to 53% for the combined Houlston and Murday methods. A method based on the number of affected relatives alone ascribed only 14% to the high risk category. Overall, 108 (54%) women were placed in the same risk category by all three methods. CONCLUSIONS: This study demonstrates that there is a significant degree of variability between methods currently used to estimate breast cancer risk which has serious implications for individual patient management, service provision and multicentre studies evaluating the benefits of genetic testing for breast cancer susceptibility.

Adult↗
PubMed2000

A randomized phase III study comparing dacarbazine, BCNU, cisplatin and tamoxifen with dacarbazine and interferon in advanced melanoma.

The purpose of this study was to compare the response rate, overall and 1-year survival in patients with advanced melanoma treated with a standard therapy, dacarbazine and interferon-alpha (DTIC/IFN), or combination chemotherapy, consisting of dacarbazine, BCNU, cisplatin and tamoxifen (DBCT). Treatment toxicity and time spent in hospital were secondary end points. One hundred and five patients (of whom 100 were eligible) were randomized to receive either DTIC/IFN or DBCT. The trial was designed to detect a 25% absolute difference in response rate or in 1-year survival with 80% power. There was no significant difference in response rate: this was 17.3% with DTIC/IFN and 26.4% with DBCT. Median overall survival was similar at 199 and 202 days respectively. One-year survival rate favoured standard treatment (30.6 vs 22.6%), but did not differ significantly between arms. DBCT was associated with significantly greater haematological toxicity, and a greater need for time spent in hospital (5.75 days/treatment cycle vs 2.29 with dacarbazine and interferon). DBCT combination therapy cannot be recommended as standard treatment for advanced melanoma. Dacarbazine remains the standard chemotherapy for this condition.

Adult↗
PubMed2000

Male cancer: a qualitative study of male breast cancer.

Breast cancer is a rare condition in males. There is a dearth of information about the psychological and social impact of this condition. Data from six in-depth interviews with men who had breast cancer identified seven major issues. These were associated with delay in diagnosis, shock, stigma, body image, causal factors, the provision of information and emotional support. The findings from this small study suggest that there are psychological and social factors for men diagnosed with breast cancer which have implications for their care and management. The recommendations arising from this study are the development of a structured education programme aimed at all primary health-care professionals; with availability of pre and postoperative gender-specific information to alleviate the potential psychological problems associated with the diagnosis; and provision of appropriate support/counselling services for partners of patients.

Journal Article↗
PubMed2000

Seroprevalence of Neospora caninum infection following an abortion outbreak in a dairy cattle herd.

OBJECTIVE: To investigate the seroprevalence of Neospora caninum infection in a commercial dairy cattle herd, 15 months after detection of an abortion outbreak. PROCEDURE: Sera from the whole herd (n = 266) were examined for N caninum antibodies by indirect fluorescent antibody test (IFAT) and immunoblot analysis. Herd records were reviewed to collate serological results with abortion history, proximity to calving, and pedigree data. RESULTS: The seroprevalence of N caninum infection was 24% (63/266) for IFAT titre > or = 160, 29% (78/266) for immunoblot positive (+ve), and 31% (82/266) for IFAT > or = 160 and/or immunoblot +ve; 94% (59/63) of animals with IFAT > or = 160 were immunoblot +ve. The association between seropositivity (IFAT > or = 160 and/or immunoblot +ve) and history of abortion was highly significant (P < 0.001); the seroprevalence was 86% (18/21) in aborting cows, compared with 30% (50/164) in non-aborting animals. The abortion rate for seropositive cows was 26% (18/68) compared with 3% (3/117) for seronegative animals. IFAT titres of infected cows were higher within 2 months of calving than at other times (P < 0.001). The association between seropositivity in dams and daughters was highly significant (P = 0.009). CONCLUSIONS: The abortions were associated with N caninum infection and there was evidence of reactivation of latent infection close to calving and congenital transmission of infection. Immunodominant antigens identified by immunoblots may prove useful for improved diagnostic tests.

Abortion, Veterinary↗
PubMed2000

A model protocol evaluating the introduction of genetic assessment for women with a family history of breast cancer.

Randomised controlled trials allow comparisons to be made between different models of service delivery, but have not been used in the field of clinical genetics. With the advent of clinical governance, the evidence provided by such trials will be increasingly important in informing and shaping clinical genetics practice. The TRACE project (Trial of genetic assessment in breast cancer) is a randomised controlled trial of genetic assessment for women who are at increased risk of breast cancer because of their family history. The absence of cancer genetics service provision in Wales before this study gave a window of opportunity in which this important trial could be conducted. The present paper describes how TRACE will provide crucial evidence regarding the psychosocial as well as resource implications of adding individualised genetic assessment, genetic counselling, and (where appropriate) gene testing to typical advice and surveillance from a hospital breast clinic. In addition, it is anticipated that TRACE will represent a model for future trials of service delivery in the increasing number of complex genetic disorders where evidence on the economic implications of screening and management is currently limited.

Adult↗
PubMed2000

Why do women attend familial breast cancer clinics?

The increasing demand for genetic assessment for familial breast cancer has necessitated the development of cancer genetics services. However, little is known about the factors motivating the client population likely to approach these services. A cross sectional questionnaire survey of 1000 women with a family history of breast cancer was conducted to identify self-reported reasons for attending a familial breast cancer clinic and possible differences in the characteristics of women who were attending for diverse reasons. Before attendance at clinic, 833 women completed a baseline questionnaire (83% response rate). Women who gave personal risk (n=188), awareness of a family history (n=120), risk to family members (n=84), reassurance (n=69), genetic testing (n=65), breast screening (n=46), or prevention (n=39) as their main reason for attending were compared on demographic and medical variables, and on psychological variables including general anxiety, cancer worry, perceived risk, and attitudes towards prophylactic surgery and genetic testing. Important differences in the psychological characteristics of these groups were found, which were unrelated to reported family history. In particular, women who primarily wanted genetic testing felt extremely vulnerable to developing breast cancer, were more likely to be considering prophylactic surgery, and perceived fewer limitations of testing. Those who primarily wanted reassurance were highly anxious about the disease. We recommend that cancer genetics services take into consideration the informational and psychological needs and concerns of their client group.

Ambulatory Care Facilities↗
PubMed2000

Porphyrins, porphyrin metabolism and porphyrias. II. Diagnosis and monitoring in the acute porphyrias.

The acute porphyrias constitute a group of metabolic disorders engaging enzymes in the haem synthetic chain and generally following dominant inheritance patterns. Some gene carriers are vulnerable to a range of exogenous and endogenous factors, which may trigger neuropsychiatric symptoms. Early diagnosis is of prime importance since it makes way for counselling with the aim to block the development of acute, as well as late, disease. The medical and psycho-social consequences of a porphyria diagnosis are considerable and the freedom for maldiagnosis correspondingly small. The strain imposed upon the diagnostic process makes management in specialized laboratories necessary. Inadvertent handling of the diagnostic procedures in laboratories lacking in knowledge, experience and technical competence is repeatedly the reason for harmful underdiagnosis and overdiagnosis. Gene diagnosis of the carrier condition, principally within reach in all types of acute porphyria, is of incomparable versatility and accuracy. However, despite recent great achievements in the molecular biology of porphyric disease, genomic procedures cannot replace biochemical methods in monitoring the activity and progress of the disease, or the effects of therapy. The classical methods are also useful when it comes to screening for the associated disease states. In these tasks, professional handling of the methods and skillful interpretation of the results are of paramount importance. Knowledge of the limitations and pitfalls of the procedures is a guard against maldiagnosis, which may be fatal. In the article the main diagnostic challenges are discussed; the strategy for early detection of the gene carrier state, the recognition and surveillance of the acute porphyric crisis, the evaluation of subacute/subchronic symptoms, the differential diagnoses of the cutaneous porphyrias and the monitoring of late complications.

Acute Disease↗
PubMed2000

Porphyrins, porphyrin metabolism, porphyrias. III. Diagnosis, care and monitoring in porphyria cutanea tarda--suggestions for a handling programme.

Deficiency of the fifth enzyme in haem synthesis, uroporphyrinogen decarboxylase (UPGD), may give rise to accumulation and excretion of poly-carboxylated porphyrins, as well as to clinical manifestations in the form of a phototoxic skin reaction and liver engagement leading to cirrhosis and hepatocellular cancer. The cutaneous reaction, presenting as skin fragility and blisters on areas exposed to sun--porphyria cutanea tarda (PCT)--develops only in individuals with a remaining hepatic UPGD activity less than 20% of normal. Experimental results and clinical observation give evidence that PCT is a multifactorial disease. In some individuals a 50%, decrease in UPGD activity is a consequence of inheritance of an allele with a mutation in the gene programming for the enzyme, but in these gene carriers, as well as in the other patients with overt PCT, the activity of the hepatic enzyme is reduced below the critical level by the action of specific inhibitors. In the generation of the enzyme inhibitors, iron plays a central role by promoting the formation of reactive oxygen species, a process where a specific class of cytochrome enzymes; cytochrome P450 1A (CYP4501A), participates. The varying individual susceptibility to development of the disease can be discussed in terms of differences in a spectrum of factors that affect the availability of the free form of this element in the liver, or its pathogenic action. In the article the roles of chronic viral infection, alcohol abuse and exposition to polyhalogenated cyclic hydrocarbons are considered in the light of effects on the availability of iron in the liver. Some genetic prerequisites for susceptibility to PCT-inducing agents are included in a tentative model for the disease, i.e. mutations in the UPGD gene and in the HFE gene affected in haemochromatosis, as well as genetically steered inducibilities of the genes programming for CYP4501A and the rate-limiting enzyme in haem synthesis, 5-aminolevulinate synthase. With the pathogenic model as a basis the different therapeutic strategies that can be applied are discussed, and suggestions for a handling programme for the patient presenting with PCT put forward.

Humans↗
PubMed2000

Porphyrins, porphyrin metabolism and porphyrias. IV. Pathophysiology of erythyropoietic protoporphyria--diagnosis, care and monitoring of the patient.

An extremely painful cutaneous condition with no or only slight visible skin changes, presenting in a child or an adult as an acute reaction to sun light, is probably a manifestation of the porphyrin metabolic disorder erythropoietic protoporphyria (EPP). The disease is the result of a genetically determined condition where a mutation in the gene for the final enzyme in the haem synthetic chain, ferrochelatase, results in impaired activity of the enzyme. In some predisposed individuals, the condition is accompanied by heavy accumulation of the substrate for the deficient enzyme, i.e. of protoporphyrin. Distributing to the skin, and there absorbing light of certain wavelengths, the metabolite generates free radicals that give rise to photodynamic cell injury. The primary event takes place in the endothelial cells of the superficial skin capillaries, but complement activation and mast cell degranulation in the surrounding tissue follow in the process. Even if the disease is primarily dermatological the hepatic and psychosocial complications are features requiring close attention by the physician. In order to provide a basis for suggestions regarding lege artis protocols for the diagnosis, treatment and monitoring of the patient with EPP, the pathophysiology of the cutaneous and hepatic manifestations are discussed in some detail in the article.

Humans↗
PubMed1999

Treatment of nondysgerminomatous ovarian germ cell tumors: an analysis of 69 cases.

BACKGROUND: Combination chemotherapy has dramatically improved the prognosis of patients with nondysgerminomatous ovarian germ cell tumors (NDOGCT). However, guidelines are needed for the identification of patients at risk of relapse. METHODS: The authors performed a retrospective analysis of women with NDOGCT managed during the period 1970-1994 at the Royal Marsden Hospital and other hospitals of the London Gynaecological Oncology Group. RESULTS: Sixty-nine women were included; their median follow-up was 5.7 years (minimum, 12 months). The median age was 21 years (range, 4-44 years), with a histology of immature teratoma (IT) for 17 patients, endodermal sinus tumor (EST) for 20 patients, and mixed tumors for 32 patients. Thirty-five patients (51%) had Stage I disease. Nine patients with Stage I tumors were observed without further therapy (six with IT and three with mixed tumors), and one relapsed. Seven patients received non-platinum-based chemotherapy, and four relapsed. A total of 52 patients were treated with platinum-based chemotherapy, with relapse free and overall survival rates of 87% (95% confidence interval [CI], 73-93%) and 84% (95% CI, 70-91%), respectively. Of these patients, relapse was seen in 0 of 9 IT patients, 1 of 25 patients with mixed tumors, and 6 of 18 EST patients. With alpha-fetoprotein (AFP) > 1000 kU/L, relapse was seen in 6 of 18 patients compared with 1 of 33 relapses with lower AFP levels. In multivariate analysis, including all patients who received chemotherapy, AFP >1000 kU/L (P = 0.001) and non-platinum-based chemotherapy (P = 0.005) were associated with relapse. When only patients given platinum-based treatment were considered, EST histology (P = 0.003) and AFP >1000 kU/L (P = 0.003) were associated with relapse in univariate analysis; however, these factors were linked. No malignant tumor was found at second-look surgery performed on 24 patients. Of 26 women assessable for fertility, 24 subsequently recommenced regular menstrual function, and 11 patients had pregnancies. CONCLUSIONS: Platinum-based chemotherapy has been confirmed to be effective in the management of patients with NDOGCT. Relapses were principally seen among patients with AFP >1000 kU/L or pure EST histology. Efforts to improve outcome need to focus on patients with EST, whereas less intensive management strategies may be appropriate for some patients with IT.

Adolescent↗
PubMed1999

Self-expanding metallic stents in the management of pyloric dysfunction after gastric pull-up operations.

The purpose of this paper is to report the use and benefits of self-expanding metallic stents employed in pyloric dysfunction. Four patients treated with oesophagectomy and gastric pull-up for oesophageal carcinoma failed to respond to balloon dilatation for pyloric dysfunction. Three of the patients were thought to have residual tumour at sites remote from the pylorus prior to stenting, but the fourth, who had undergone surgery 8 years previously, was thought to be cured. All were treated with self-expanding metallic stents. All four patients responded well with resolution of their symptoms. Over a mean follow-up of 6 months there has been no recurrence of symptoms. Stent insertion represents a potentially valuable method of treatment in patients with post-surgical pyloric dysfunction in whom simple balloon dilatation has failed.

Aged↗
PubMed1999

Intergroup collaboration in ovarian cancer: a giant step forward.

The rather slow evolution of so-called "optimal chemotherapy" for ovarian cancer is the result of suboptimal randomised clinical trials, not having the statistical power to identify truly superior regimens, and of the lack of systematic comparisons of new agents with relevant control arms. There is little doubt that we need international collaboration to move the field forward in a timely and coherent manner. European and transatlantic collaboration represents the beginning of the process and point to the success that can await us if the drive to work together remains strong. A similar organisation as for breast cancer (Breast International Group, BIG) needs to be established for ovarian cancer.

Clinical Trials as Topic↗
PubMed1999

Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial.

We report the final results of a prospectively randomized study that compared the combination of epirubicin, cisplatin and protracted venous infusion fluorouracil (5-FU) (ECF regimen) with the standard combination of 5-FU, doxorubicin and methotrexate (FAMTX) in previously untreated patients with advanced oesophagogastric cancer. Between 1992 and 1995, 274 patients with adenocarcinoma or undifferentiated carcinoma were randomized from eight oncology centres in the UK and analysed for response and survival. The overall response rate was 46% (95% confidence interval (CI), 37-55%) with ECF, and 21% (95% CI, 13-28%) with FAMTX (P = 0.00003). The median survival was 8.7 months with ECF and 6.1 months with FAMTX (P = 0.0005). The 2-year survival rates were 14% (95% CI, 8-20%) for the ECF arm, and 5% (95% CI, 2-10%) for the FAMTX arm (P = 0.03). Histologically complete surgical resection following chemotherapy was achieved in ten patients in the ECF arm (three pathological complete responses to chemotherapy) and three patients in the FAMTX arm (no pathological complete responses). The ECF regimen resulted in a response and survival advantage compared with FAMTX chemotherapy. The probability of long-term survival following surgical resection of residual disease is increased by this treatment. The high response rates seen with ECF support its use in the neoadjuvant setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity.

Cloning, expression and phenotype studies of the defective gene for delta-aminolaevulinate dehydratase (ALAD) in a family with an asymptomatic girl who had ALAD deficiency were carried out. The proband was identified by neonatal ALAD screening, and had erythrocyte ALAD activity at 12% of the normal control. She was heterozygous for ALAD deficiency, which was inherited from her father. Nucleotide sequence analysis of the cloned ALAD cDNA revealed C36 to G and T168 to C mutations on the same allele. The former mutation resulted in F12L substitution, whereas the latter was a silent mutation. All family members who had decreased ALAD activity had the same mutation. Expression of the mutant ALAD cDNA in Chinese hamster ovary cells produced an ALAD protein without significant enzyme activity. Additionally, the mutant ALAD cDNA which encodes F12L substitution produced an aberrant migration pattern in polyacrylamide gel electrophoresis under denaturing conditions. This finding probably reflects an abnormal folding of the F12L protein, since the mutation occurred in the alpha1 helix of the N-terminal arm of the enzyme, which is involved in the extensive quaternary interactions among the subunits. This is also the first report of ALAD gene mutation in an asymptomatic subject.

DNA, Complementary↗