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Biomedical subjects

A Webb

Publications and source records attributed to A Webb.

At least 55 records · Page 3Linked to original sources
PubMed2000

Are 18fluorodeoxyglucose positron emission tomography and magnetic resonance imaging useful in the prediction of relapse in lymphoma residual masses?

Treatment of both Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) frequently results in a residual mass visible radiologically. Such patients may receive radiotherapy unnecessarily because the residual mass may represent benign fibrotic tissue rather than residual active lymphoma. Radiotherapy has been shown to have significant short and more worrying long-term toxicity. Refining the criteria for its use would be a major advance. A number of clinical investigations have been evaluated to more accurately determine the nature of such lesions, including erythrocyte sedimentation rate (ESR), magnetic resonance imaging (MRI) and high-dose gallium-67 scanning (HDGS) but none has proven utility. 18[F]-fluorodeoxyglucose positron emission tomography (FDG-PET) is an imaging technique that has been shown to be useful in distinguishing fibrosis from residual active disease in solid tumours. The aim of this study was to compare FDG PET and MRI in the assessment of residual masses following treatment for lymphoma. Patients with NHL/HD who had a residual mass following chemotherapy were eligible for this study. Patients had a combination of MRI and/or PET. All scans were completed within 5 months of the end of treatment. Patients were followed-up for relapse. 56 patients had an MRI scan, 24 had a PET scan and 22 patients had both investigations. Overall sensitivity and specificity, respectively, were for MRI 45% and 74%, PET 50% and 69%, and PET/MRI concurring 50% and 67%. There was a trend for improved relapse-free survival (RFS) with a negative result of both MRI and PET, but this was not statistically significant. The predictive value for both tests failed to reach statistical significance. Subgroup analysis suggests that PET may be better at predicting relapse in patients with NHL, especially those with masses above the diaphragm. There is no convincing evidence that either MRI or PET or the combination can reliably predict relapse within residual masses after treatment for lymphoma. A negative PET scan however appears to be more informative than a positive result and may well aid clinical decision making. There are a number of factors that may produce false-positive results, including post-treatment inflammatory changes, the sensitivity of the test in the setting of minimal residual disease and the heterogeneity of the histological subtypes studied. A negative PET (or MRI) result in lymphoma residual masses following therapy may negate the necessity for further therapy such as chemotherapy or radiotherapy and their concomitant toxicities.

Adolescent↗
PubMed2000

FDG-PET in the prediction of survival of patients with cancer of the pancreas: a pilot study.

Carcinoma of the pancreas is an aggressive tumour with an extremely poor prognosis. Recent studies have shown that chemotherapy can improve survival as well as quality of life. Since the prognosis is generally poor, the identification of early responders to chemotherapy is important to avoid unnecessary toxicity in patients who are not responding. Response assessment by conventional radiographic methods is problematical because treatment induces fibrosis and makes tumour measurements difficult. The aim of this pilot study was to assess 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET) as an early marker of the benefit of chemotherapy. Eleven patients with histologically proven adenocarcinoma of the pancreas were treated with protracted venous infusional 5-fluorouracil (PVI 5-FU) alone or PVI 5-FU and mitomycin C (MMC). FDG-PET scans were performed prior to and at 1 month following the commencement of chemotherapy. FDG uptake was compared with the tumour dimensions measured on a computer tomographic (CT) scan. Patients were followed up for relapse, death and symptomatic response. Three of the 11 patients had no measurable FDG uptake prior to chemotherapy. Of the eight patients who had measurable uptake prior to treatment, seven had a reduction in uptake at 1 month. Six out of the 11 patients had no measurable FDG uptake at 1 month. The overall survival (OS) in these patients ranged from 124 to 1460 days, with a median of 318.5 days. This was superior in comparison to patients who had residual FDG uptake at 1 month (median survival 318.5 days vs 139 days; P = 0.034) and there was a trend to improved symptoms (84% [5/6] vs 20% [1/5]; P = 0.13). There was no statistically significant correlation between best CT response and FDG uptake at 1 month. These results suggest that the absence of FDG uptake at 1 month following chemotherapy for carcinoma of the pancreas is an indicator of improved overall survival. This suggests that FDG-PET may be superior to response assessment by conventional radiographic methods and FDG-PET may have the potential to help make difficult treatment decisions in the management of pancreatic cancer. Larger prospective studies are required to confirm this finding.

Antineoplastic Agents↗
PubMed2000

A randomized phase II study of SRL172 (Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma.

Mycobacterial preparations have been used with limited success against cancer apart from superficial bladder cancer. Recently, a therapeutic vaccine derived from Mycobacterium vaccae has been given to patients with prostate cancer and melanoma indicating a possible beneficial effect on disease activity in such patients. We have recently initiated a series of randomized studies to test the feasibility and toxicity of combining a preparation of heat-killed Mycobacterium vaccae (designated SRL172) with a multidrug chemotherapy regimen to treat patients with inoperable non-small cell lung cancer (NSCLC) and mesothelioma. 28 evaluable patients with previously untreated symptomatic NSCLC and mesothelioma were randomized to receive either 3 weekly intravenous combination chemotherapy alone, or chemotherapy given with monthly intra-dermal injections of SRL172. Safety and tolerability were scored by common toxicity criteria and efficacy was evaluated by survival of patients and by tumour response assessed by CT scanning. The toxicity of chemotherapy was similar in the two groups. SRL172 caused mild inflammation at the injection site. In the group of patients randomized to receive chemotherapy combined with SRL172, there was a trend towards improved response rate (54% vs. 33%) with more patients in the combined arm receiving radical surgery and radiotherapy, improved median survival (9.7 months vs. 7.5 months) and improved 1 year survival (42% vs. 18%). SRL172 appeared to improve sleep (P = 0.08) and improved appetite (P = 0.01). There was no detectable change in serum cytokine levels for gamma-interferon and TNF-alpha before and after treatment. In patients with NSCLC and mesothelioma, there may be a beneficial interaction when chemotherapy is administered in combination with SRL172. Confirmation of this effect and further investigation is underway in a randomized phase III trial and in laboratory models.

Adjuvants, Immunologic↗
PubMed2000

Protracted venous infusion 5-fluorouracil in combination with subcutaneous interleukin-2 and alpha-interferon in patients with metastatic renal cell cancer: a phase II study.

Our purpose was to assess the activity of alpha-interferon (IFN-alpha), interleukin-2 (IL-2) and 5 fluorouracil (5FU) administered by protracted venous infusion (PVI) as opposed to bolus injection. 55 patients with advanced renal cell cancer were treated as follows: IL-2 and IFN-alpha according to the schedule originally described by Atzpodien, with PVI 5FU 200 mg m(-2)day(-1)during weeks 5-9. 42 patients (76%) were of moderate or poor prognosis as defined by previous studies. The response rate by intention to treat was 31% (17 of 55, three complete response, 14 partial response; 95% CI = 19-45%) and in evaluable patients (completed one cycle, n = 42), it was 40% (95% CI = 26-57%). In addition, 24% (13 of 55) patients achieved disease stabilization. The overall median survival was 11 months with a 1-year survival of 45%. The median survival for evaluable patients was 18 months with 1- and 2-year survivals of 60% and 40% respectively. The median survival of responding patients was 31 months and the three patients achieving complete response remain progression-free at 14+, 18+ and 23+ months. Evaluable patients with poor prognostic features achieved a response rate of 54% and median survival of 18 months. Toxicity was significant yet manageable with 12 patients unable to complete one cycle due to side-effects and 36% experiencing grade 3-4 toxicities. The three on-treatment deaths were considered unlikely to be due to toxicity. The schedule of IFN-alpha, IL-2 and PVI 5FU has significant activity in advanced renal cell cancer with manageable toxicity. It is of particular interest that this regimen appears to have high activity in fit patients with poor prognostic features.

Adult↗
PubMed2000

Paralysis of the marginal mandibular branch of the facial nerve: treatment options.

Isolated paralysis of the marginal mandibular branch of the facial nerve results in an asymmetrical smile with elevation of the lower lip on the affected side. We discuss the surgical options for its correction and present a series of 26 patients who underwent either botulinum toxin injection, anterior belly of digastric transfer or free extensor digitorum brevis transfer as treatment. Botulinum toxin injection provided satisfactory results although these were temporary. Anterior belly of digastric transfer was the surgical procedure of choice. It yielded superior cosmetic results, less donor-site morbidity and required a shorter operating time. In more complex congenital facial hypoplastic syndromes, or following extensive surgery in the digastric triangle, the anterior belly of the digastric muscle may be absent or damaged. Extensor digitorum brevis transfer is the preferred option in these cases.

Adolescent↗
PubMed2000

Changing screening strategies for genital chlamydia in family planning clinics: a good public health strategy?

OBJECTIVE: To estimate the prevalence and factors associated with genital chlamydia in 1996 and to evaluate the introduction of restricted screening criteria based on diagnostic testing and prevention of iatrogenic pelvic inflammatory disease in 1997. PATIENTS: Women attending Liverpool family planning clinics. METHOD: Clinical and demographic data were recorded at routine clinic consultations. Data were analyzed using logistic regression. RESULTS: In 1996, a 5.7% (123/2165) chlamydial prevalence was detected. A significantly lower prevalence was observed in the over-25-year-old age group compared to those aged 16-19 years old (p < 0.0001), and in those with an interval of over 11 months since the last new sexual partner compared to those with a new partner in the past 1-3 months (p < 0.05). A significantly higher prevalence was detected in those only presenting with signs of infection alone compared to those presenting with either symptoms or both signs and symptoms of infection (p < 0.05). Those requesting a termination of pregnancy were at higher risk of genital chlamydia than those attending for contraceptive advice (odds ratio 1.97; 95% confidence interval 1.14-3.39). Using the restricted screening criteria, prevalences of 5.4% (78/1438) and 3.7% (60/1641) were found for 1996 and 1997, respectively. Prevalences were significantly higher in 1996 than 1997 when adjusted for the other factors (p < 0.05). CONCLUSION: The study raised awareness of genital chlamydia among women attending family planning clinics and showed that primary care could make a significant contribution to the prevention of chlamydial infection. It is only by initiating intervention strategies in such settings that genital chlamydia will be controlled effectively in the UK.

Adolescent↗
PubMed2000

Congenital portosystemic shunts in toy and miniature poodles.

Three male Poodles (two Toy, one Miniature) were presented to their veterinarians for evaluation of urolithiasis and varying degrees of hepatic encephalopathy. All three dogs were diagnosed as having intrahepatic shunts and referred for surgical correction. In each case, shunts arose from the right branch of the portal vein and were amenable to perivascular dissection caudal to where the vessel entered the hepatic parenchyma and to placement of perivascular cellophane bands to achieve shunt attenuation. During the same period, a female Miniature Poodle also presented for treatment of a congenital portosystemic shunt discovered during evaluation for generalised motor seizures. This animal had an extrahepatic portoazygous shunt that was completely ligated. Congenital portosystemic shunts have not previously been identified in Toy and Miniature Poodles at the University Veterinary Centre, Sydney and the anatomical types of shunt seen in this breed have not previously been reported in a consecutive series of cases. The three male dogs are noteworthy for a number of reasons: all had intrahepatic shunts, despite being small breed dogs; all three presented in a similar fashion, and all had shunts of an anatomical type amenable to placement of cellophane bands. One male dog died within 12 hours of surgery, the remaining three dogs survived and their liver function was normal at follow-up between 2 and 3 months after surgery. Use of cellophane bands for successful attenuation of intrahepatic shunts has not been previously reported.

Animals↗
PubMed2000

fMri studies of Stroop tasks reveal unique roles of anterior and posterior brain systems in attentional selection.

The brain's attentional system identifies and selects information that is task-relevant while ignoring information that is task-irrelevant. In two experiments using functional magnetic resonance imaging, we examined the effects of varying task-relevant information compared to task-irrelevant information. In the first experiment, we compared patterns of activation as attentional demands were increased for two Stroop tasks that differed in the task-relevant information, but not the task-irrelevant information: a color-word task and a spatial-word task. Distinct subdivisions of dorsolateral prefrontal cortex and the precuneus became activated for each task, indicating differential sensitivity of these regions to task-relevant information (e.g., spatial information vs. color). In the second experiment, we compared patterns of activation with increased attentional demands for two Stroop tasks that differed in task-irrelevant information, but not task-relevant information: a color-word task and color-object task. Little differentiation in activation for dorsolateral prefrontal and precuneus regions was observed, indicating a relative insensitivity of these regions to task-irrelevant information. However, we observed a differentiation in the pattern of activity for posterior regions. There were unique areas of activation in parietal regions for the color-word task and in occipitotemporal regions for the color-object task. No increase in activation was observed in regions responsible for processing the perceptual attribute of color. The results of this second experiment indicate that attentional selection in tasks such as the Stroop task, which contain multiple potential sources of relevant information (e.g., the word vs. its ink color), acts more by modulating the processing of task-irrelevant information than by modulating processing of task-relevant information.

Adult↗
PubMed2000

Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma.

PURPOSE: To evaluate the pharmacokinetics and toxicity of an antisense oligonucleotide targeting bcl-2 in patients with non-Hodgkin's lymphoma (NHL) and to determine efficacy using clinical and biologic end points. PATIENTS AND METHODS: Twenty-one patients with Bcl-2-positive relapsed NHL received a 14-day subcutaneous infusion of G3139, an 18-mer phosphorothioate oligonucleotide complementary to the first six codons of the bcl-2 open reading frame. Plasma pharmacokinetics were measured by anion exchange high-performance liquid chromatography. Response was assessed by computed tomography. Changes in Bcl-2 expression were measured by fluorescence-activated cell sorting of patients' tumor samples. RESULTS: Eight cohorts of patients received doses between 4. 6 and 195.8 mg/m(2)/d. No significant systemic toxicity was seen at doses up to 110.4 mg/m(2)/d. All patients displayed skin inflammation at the subcutaneous infusion site. Dose-limiting toxicities were thrombocytopenia, hypotension, fever, and asthenia. The maximum-tolerated dose was 147.2 mg/m(2)/d. Plasma levels of G3139 equivalent to the efficacious plasma concentration in in vivo models were produced with doses above 36.8 mg/m(2)/d. Plasma levels associated with dose-limiting toxicity were greater than 4 microg/mL. By standard criteria, there was one complete response, 2 minor responses, nine cases of stable disease, and nine cases of progressive disease. Bcl-2 protein was reduced in seven of 16 assessable patients. This reduction occurred in tumor cells derived from lymph nodes in two patients and from peripheral blood or bone marrow mononuclear cell populations in the remaining five patients. CONCLUSION: Bcl-2 antisense therapy is feasible and shows potential for antitumor activity in NHL. Downregulation of Bcl-2 protein suggests a specific antisense mechanism.

Adult↗
PubMed2000

Oral immunization of mice with a glycoconjugate vaccine containing the O157 antigen of Escherichia coli O157:H7 admixed with cholera toxin fails to elicit protection against subsequent colonization by the pathogen.

It has been postulated that a humoral immune response directed against the O157 antigen of Escherichia coli O157:H7, and expressed in the intestine, might afford protection from colonization and consequent infection by this enteric pathogen. The present study was conducted to determine whether such an immune response can be experimentally generated in mice. To this end, mice were orally immunized with a glycoconjugate vaccine consisting of horse serum albumin and the O157 polysaccharide admixed with the mucosal adjuvant, cholera toxin. Mice consistently developed robust local and systemic immune responses to the cholera toxin adjuvant, but were far from uniformly reactive to the test vaccine. Moreover, vaccinated mice were as susceptible to transient intestinal colonization following challenge with an isolate of E. coli O157:H7 as unvaccinated control mice. These results indicate that this vaccination approach is unlikely to be straightforward in target bovine or human hosts.

Animals↗
PubMed2000

Chlamydia trachomatis screening in young people in Merseyside.

OBJECTIVES: To evaluate the acceptability to young people of proactive Chlamydia trachomatis (CT) information and urine test. To discover the extent of CT infection and the practical implications for completing treatment and partner notification. DESIGN: Prospective screening with sexual health questionnaire. SETTING: Three family planning clinics for young people in Liverpool and South Sefton. PARTICIPANTS: Nine hundred and five women and 53 men had urine tests and answered the questionnaire. All aged 20 years or under attending the clinics were given information about CT and safer sex. MAIN OUTCOME MEASURES: The acceptability of proactive information and screening for CT using a urine test. Prevalence of CT infection. The time and effort incurred informing and managing those testing positive. RESULTS: The information and urine test were readily accepted. Prevalence of CT was 8.5% in women and 5.7% in men. More than three-quarters of those testing positive were treated, but it took much time and effort, as follow-up attendance was poor. CONCLUSIONS: The prevalence of CT was high in this population. Young people participated in screening readily. They are interested in this health issue, but it was difficult to hold their attention long enough to complete the process of treatment and contact tracing. Completing this successfully either needs a huge input of resources or a new approach. These results have led to the piloting of an outreach health adviser administering treatment and carrying out partner notification at the screening site. Some of the questions raised by the CMO have been addressed.

Adolescent↗
PubMed1999

Critical issues in adolescent substance use assessment.

Despite advances in methodology and instrumentation, the assessment of adolescent drug and alcohol involvement remains a complex clinical and practical process. It requires the careful and skillful implementation of procedures across a wide range of service systems and providers. While the literature identifies and provides information on singular aspects of the assessment of adolescents, few sources furnish an integrated overview of the key issues necessary for appropriate and accountable assessment. Consequently, this paper synthesizes theoretical, research, and clinical issues into a practical framework that can be used by clinical and research staff making assessment decisions. Issues discussed have been informed by the literature and by our collective experience during the 8-year development and testing of the Comprehensive Adolescent Severity Inventory (CASI).

Adolescent↗
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

Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania.

OBJECTIVE: Case series and follow-up studies suggest that clozapine may have mood-stabilizing properties in addition to antipsychotic action in patients with schizoaffective disorder, bipolar type, and bipolar I disorder, but the generalizability of these findings is limited. This article describes a randomized, open study of clozapine add-on therapy versus treatment as usual for patients with treatment-resistant illness and a history of mania. METHOD: Thirty-eight patients meeting the DSM-IV criteria for schizoaffective or bipolar disorder that was deemed treatment-resistant were randomly assigned to clozapine add-on treatment (N = 19) or treatment as usual (no clozapine) (N = 19) and followed up for 1 year. Patients received monthly ratings on the Brief Psychiatric Rating Scale, Clinical Global Impression scale, Bech-Rafaelsen Mania Scale, Hamilton Depression Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Abnormal Involuntary Movement Scale, and a 40-item side effect checklist. Differences between treatment groups were assessed according to a pattern-mix random-regression model. An additional analysis compared group differences in rating scale scores against relative time in the study. RESULTS: Significant between-group differences were found in scores on all rating scales except the Hamilton depression scale. Total medication use over 1 year significantly decreased in the clozapine group. No significant differences between groups in somatic complaints were noted. The subjects with nonpsychotic bipolar I disorder who received clozapine showed a degree of improvement similar to that of the entire clozapine-treated group. Clozapine dose was significantly higher for the patients with schizoaffective illness than for those with bipolar disorder. CONCLUSIONS: The results of this study support clozapine's independent mood-stabilizing property. They demonstrate that clozapine use was associated with significant clinical improvement relative to treatment as usual.

Adult↗
PubMed1999

GyneFIX. The frameless intrauterine contraceptive implant--an update for interval, emergency and postabortal contraception.

This article reviews the clinical experience with the GyneFix intrauterine implant system for interval, emergency and post-abortal contraception. The relatively high rate of unintended pregnancies and abortions in the world signifies that greater access to contraception is necessary. Unwanted pregnancies and abortions could be avoided by widening the range of effective and acceptable contraceptive methods for use in situations where current methods are far from optimal. High effectiveness, protection against sexual transmitted infections, long duration of action, reversibility and safety are some of the most important attributes of contraceptives valued by women. The development of the frameless intrauterine device is a response to the need to develop contraceptives with high user continuation rate. GyneFix has the lowest failure rate of all copper IUDs currently available. Its performance is further optimised by the atraumatic frameless design which minimises the side effects and discomfort experienced with conventional IUDs. GyneFix could, therefore, be a useful new contraceptive option in looking at ways to reduce the number of unwanted pregnacies and induced abortions.

Abortion, Induced↗
PubMed1999

Parenteral immunization with a glycoconjugate vaccine containing the O157 antigen of Escherichia coli O157:H7 elicits a systemic humoral immune response in mice, but fails to prevent colonization by the pathogen.

The results of the present study show that whereas both BALB/c and C57BL/6 mice parenterally inoculated with a horse serum albumin-Escherichia coli O157 antigen conjugate vaccine develop systemic, specific antibodies to the carrier protein, only the former mice routinely develop antibodies to the carbohydrate O157 moiety. However, little convincing evidence was found to show that these antibodies transuded into the intestinal tract either naturally or in response to an oral inoculum of the pathogen. Moreover, this vaccination procedure failed to protect mice against intestinal colonization following oral challenge with the pathogen. Thus, the results of this study suggest that parenteral vaccination might be an unsuitable strategy for combatting E. coli O157:H7 organisms located in the gut.

Animals↗