Biomedical subjects

P Patel

Publications and source records attributed to P Patel.

At least 109 records · Page 6Linked to original sources

PubMed1998

Metal stents improve dysphagia, nutrition and survival in malignant oesophageal stenosis: a randomized controlled trial comparing modified Gianturco Z-stents with plastic Atkinson tubes.

OBJECTIVE: To compare modified Gianturco metal stents with plastic Atkinson tubes in the palliation of malignant dysphagia. DESIGN: Patient single-blind, multi-centre prospective, randomized trial. SETTING: Three district general hospitals in the Wessex region. PARTICIPANTS: Thirty one consecutive patients with inoperable malignant oesophageal stenosis causing dysphagia and suitable for treatment with an endoprosthesis. INTERVENTIONS: Patients were randomized to receive either a modified Gianturco metal stent or a plastic Atkinson tube. Sedation was similar and patients were given identical dietary advice. Data were collected after insertion until the patients' death. MAIN OUTCOME MEASURES: Procedural mortality/morbidity; hospital stay; weight loss; quality of life (Nottingham Health Profile, Spitzer QL index and specific questions about dysphagia and enjoyment of food); duration of survival after insertion; cost effectiveness of each intervention. RESULTS: Overall complication rates were similar in the two groups. Compared with Atkinson tubes, patients with Gianturco stents had better palliation of dysphagia (median dysphagia score 1 vs 2, P = 0.04), maintained their weight longer (median percent weight loss 0.66 vs 6.51, P = 0.007), enjoyed food more (enjoyment score 2 vs 1, P = 0.03) and survived longer (log rank P < 0.025). Patients with metal stents were discharged from hospital earlier (Gianturco 4 days, Atkinson 10 days, P = 0.001), and initial treatment cost was lower if the cost of hospital stay exceeded pound sterling 120 per day. CONCLUSION: Gianturco stents are superior to Atkinson tubes in the palliation of malignant oesophageal stenosis.

Deglutition Disorders↗

PubMed1997

Efficacy of postoperative radiation therapy for recurrent squamous cell carcinoma of the head and neck.

PURPOSE: Postoperative radiation therapy (RT) following surgical resection is often the recommended treatment for recurrent squamous cell carcinoma (SCC) of the head and neck. Despite common use, there are few published series evaluating such a management approach. METHODS AND MATERIALS: We evaluated the efficacy of postoperative RT in 31 patients with recurrent SCC of the head and neck treated between 1981 and 1993. None of the patients had prior RT. All had complete resection of recurrent gross disease and no distant metastases. Maximum postoperative RT doses ranged from 59.4-70 Gy (median = 66 Gy). RESULTS: The 5-year disease-specific survival (DSS) and local control (LC) rate for all patients were 32 and 46%, respectively. Several prognostic factors were analyzed including site and stage of original primary tumor, disease-free interval, site of recurrence, status of surgical margins, and dose. Only site of recurrence significantly influenced both DSS and LC. Patients whose recurrence was limited to previously undissected tissue had 5-year DSS and local control rates of 60 and 74%, respectively, as compared to 19 and 29%, respectively, for patients whose recurrence was within previously dissected tissue (p = 0.05). CONCLUSIONS: Patients with recurrent SCC of the head and neck treated with standard postoperative RT following surgical resection do relatively well if the recurrence is within previously undissected tissue (i.e., nodal only); however, patients whose recurrence is within previously dissected tissue do poorly. Every effort to prevent locoregional disease recurrence at the time of primary therapy should be emphasized.

Adult↗

PubMed1997

Classification of Vibrio vulnificus strains by the carbohydrate composition of their capsular polysaccharides.

Pathogenic bacteria are often classified on the basis of the complex polysaccharides found on the surface, usually capsular polysaccharides or lipopolysaccharides. It is common in clinical practice to use reactivity with antisera specific to the various cell surface carbohydrates for this purpose. In this work, we describe a chemotyping method for bacterial capsular polysaccharides which is based on a carbohydrate analysis of an acid hydrolysate of the capsule. High-performance anion-exchange chromatography at high pH (HPAE) with electrochemical detection, which is used for analysis of the hydrolysate, shows preferential sensitivity for sugars. A single acid hydrolysis condition is chosen for screening a large collection of bacterial isolates and a computerized autosampler is used to make possible a large number of rapid analyses. This procedure does not yield a quantitative carbohydrate analysis for the sample but produces a fingerprint which can be used to discriminate among isolates which have different capsular polysaccharide structures. The procedure has been applied to a collection of 120 isolates of Vibrio vulnificus, a water-born species common in shellfish which causes septicemia in immunocompromised individuals, most often from eating of raw oysters. The collection of bacterial isolates includes strains from both clinical cases of septicemia and from such environmental sources such as sea water, sediments, and shellfish. Our results show that a number of unusual sugars including many amino sugars are found in these polysaccharides and that a wide variety of capsular carbotypes in V. vulnificus may be readily distinguished by the HPAE fingerprint.

Anion Exchange Resins↗

PubMed1997

Irradiated NC adenocarcinoma cells transduced with both B7.1 and interleukin-2 induce CD4+-mediated rejection of established tumors.

Previous studies have shown that expression of the immune co-stimulator B7.1 reduces the tumorigenicity of some, but not all, malignant cell lines. However, B7.1-expressing tumor cells are not very effective in inducing the rejection of established tumors. This may in part be due to induction of anergy in the potentially reactive T cells. Previous studies have shown that IL-2 can reverse the anergic state both in vitro and in vivo. Therefore, we have examined the effect of retrovirus-mediated delivery and expression of murine B7.1 and interleukin-2 on tumor formation and rejection of established MHC class I+/II- NC adenocarcinomas. Neither the expression of B7.1 nor IL-2 alone had a significant effect on NC tumorigenicity. In contrast, combined expression of B7.1 and IL-2 substantially decreased the tumorigenicity of these cells in the immunecompetent syngeneic hosts. T-cell depletion studies show this to be dependent primarily on the activation of CD4+ cells. Furthermore, distant subcutaneous injection of irradiated NC/IL-2/B7.1 can induce, much more effectively than NC/B7.1 or NC/IL-2, the rejection of small NC tumors, and prevent the recurrence of large surgically resected tumors. Together, these results suggest that tumor cells genetically modified to express B7.1 and IL-2 can induce the immune-mediated rejection of established class II- tumors by a mechanism involving CD4+ cells.

Adenocarcinoma↗

PubMed1997

Validity of the PAS-ADD for detecting psychiatric symptoms in adults with learning disability (mental retardation).

The Psychiatric Assessment Schedule for Adults with Developmental Disability (PAS-ADD) is a semi-structured interview for use with respondents who have learning disability and for key informants. This report investigates the ability of the instrument to detect symptoms that had been found to exist during routine clinical assessment of the patients. Field trials involved 95 referred patients with learning disability and a key informant for each sample member. Clinical opinions of the referring psychiatrists were sought using a symptom checklist. Referrer checklist symptoms and PAS-ADD data were both factor analysed. Validity testing involved (a) computation of correlations between PAS-ADD factors and checklist data and (b) comparison of PAS-ADD and referrers' diagnoses. Results indicated good validity for the PAS-ADD in relation to psychotic symptoms and depressive symptoms. Anxiety symptom identification was not well validated, probably due to small numbers. Expansive mood identified by the referrers was not detected by the PAS-ADD because there is currently no corresponding section in the interview. Where the PAS-ADD produced a diagnosis (in 58 members of the sample), 44 were in agreement with the referrer. Probability of diagnosis by PAS-ADD increased with the number of relevant active symptoms identified by the referrer. The PAS-ADD has been shown in a previous report to have the sensitivity to detect mental disorders not known to psychiatric services. For psychotic and depressive conditions, our results showed that symptom detection was in good agreement with the information provided by the referring psychiatrists on their patients. The PAS-ADD needs a section on hypomania and further investigation of its detection of anxiety disorders.

Adolescent↗

PubMed1997

Organization and expression of human telomere repeat binding factor genes.

The ends of mammalian chromosomes terminate in structures called telomeres. Recently a human telomere repeat binding factor (TRF1) that binds the vertebrate TTAGGG telomeric repeat in situ was isolated by Chong et al. (1). TRF1 regulates telomere length (2), which is often altered in cancer cells. To understand their genetic organization, TRF1 genes were localized to human chromosomes 13cen, 21cen, and Xq13 by analysis of human monochromosomal hybrids, and by fluorescent in situ hybridization. We also confirmed the recent localization of a human TRF1 gene to chromosome 8, and provide evidence that this locus is alternatively spliced. In contrast to the TRF1 genes on chromosomes 8 and X, the chromosomes 13 and 21 TRF1 genes contained a 60 bp deletion in the coding region. The results suggest that two distinct forms of TRF1 are expressed and that the TRF1 gene family includes at least three pseudogenes whose dispersal in the human genome may have occurred via cDNA intermediates.

Alternative Splicing↗

PubMed1997

Treatment of metastatic renal cell carcinoma with subcutaneous interleukin 2: evidence for non-renal clearance of cytokines.

The circulating cytokine concentrations following administration of subcutaneous recombinant interleukin 2 (IL-2) in combination with interferon alpha and 5-fluorouracil used to treat advanced renal cancer were studied. One patient was anephric and on dialysis, and seven had normal biochemical renal function, although five had undergone single nephrectomy. The pharmacokinetics of IL-2 and changes in IL-6 and tumour necrosis factor (TNF)-alpha were essentially similar in all patients including the anephric patient, irrespective of the periods of dialysis, although at some time points, IL-2 concentrations were slightly higher in the anephric patient than in the others. These results show that for subcutaneous administration of low-dose IL-2, renal clearance of IL-2 is not important. This contrasts with high-dose, intravenous IL-2 where blood concentrations are higher and renal clearance seems to occur, perhaps because of saturation of the non-renal mechanisms of clearance. The subcutaneous route is certainly preferred if IL-2 is used in anephric patients and in those with impaired renal function, and it may be generally preferred for most purposes.

Adult↗

PubMed1997

Gastric mucosal hydrophobicity in duodenal ulceration: role of Helicobacter pylori infection density and mucus lipids.

BACKGROUND & AIMS: Gastric mucosal hydrophobicity is reduced in Helicobacter pylori infection. Infection density is increased in duodenal ulcer (DU) compared with H. pylori gastritis alone, but it is unknown whether there is a corresponding difference in hydrophobicity or whether hydrophobicity is related to infection density or to mucus lipids. The aim of this study was to determine the relationship between H. pylori infection density and mucosal hydrophobicity, and between mucus lipids and hydrophobicity, and to compare results in patients with H. pylori-induced gastritis with and without DU. METHODS: Fifty-four patients, including 29 H. pylori-positive (15 with DU and 14 with gastritis alone) and 25 H. pylori-negative controls, were studied. Hydrophobicity was determined by goniometry and infection density by histology. Mucus lipids were determined by colorimetry and phospholipase A2 activity by radioenzymatic assay. RESULTS: Hydrophobicity was reduced in DU compared with gastritis alone (39 degrees vs. 48 degrees; P < 0.05) and with healthy controls (39 degrees vs. 60 degrees; P < 0.0001). Hydrophobicity correlated with infection density (Rs = -0.55; P < 0.01). Mucus triglyceride level was modestly increased with infection, but mucus phospholipids or lipolysis were unrelated to H. pylori and hydrophobicity. CONCLUSIONS: Mucosal hydrophobicity is reduced in H. pylori-positive patients with DU compared with those having gastritic only. Hydrophobicity correlates with infection density but not with mucus lipid levels.

Adult↗

PubMed1997

The TWIST gene, although not disrupted in Saethre-Chotzen patients with apparently balanced translocations of 7p21, is mutated in familial and sporadic cases.

The TWIST gene maps to 7p21 and mutations in the gene have been reported in the Saethre-Chotzen form of craniosynostosis. The position of the Saethre-Chotzen gene has previously been refined by FISH analysis of four patients carrying balanced translocations involving 7p21 which suggested that it was located between D7S488 and D7S503. We report here that the breakpoints in four translocation patients do not interrupt the coding sequence of the TWIST gene and thus most likely act through a positional effect. Twelve Saethre-Chotzen cases were found to have TWIST mutations. Four of these families had been used as part of the linkage study of the Saethre-Chotzen locus. The mutations detected included missense and nonsense mutations and three cases of a 21 bp duplication. Although phenotypically diagnosed as having Saethre-Chotzen syndrome, three families were found to have a pro250arg mutation of FGFR3.

Acrocephalosyndactylia↗

PubMed1997

Dementia in older people with intellectual disability: symptoms of physical and mental illness, and levels of adaptive behaviour.

Detailed data on health and functional ability of 101 people with intellectual disability over 50 years of age are presented. Using a combination of informant interviewing, observation and measurement of cognitive change over a 3-year period, 12 of these individuals were identified as suffering from dementia. Their data are compared to those of the non-dementia sufferers. The people suffering from dementia had a greater number of chronic physical health problems and chronic disability resulting from physical health problems. Their capacity for self-directed activity was lower. The subjects had a reduced capacity to enjoy things, and were more irritable and more prone to violence. However, the outlook is somewhat different from a strategic perspective. The population of people with intellectual disability shows considerable epidemiological changes across the lifespan because of the effects of differential survival. The interaction of these factors tends to mask the impact of dementia-related skill loss in this population.

Adaptation, Psychological↗

PubMed1997

Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.

OBJECTIVE: To determine whether serum concentrations of the cytokines tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. DESIGN: A population based cross sectional study. SUBJECTS AND METHODS: 198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. RESULTS: Serum TNF alpha concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNF alpha was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNF alpha, each by approximately 50% (P < 0.05 for TNF alpha, P < 0.1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNF alpha and 36% for IL-6 (P = 0.14 for TNF alpha and P < 0.05 for IL-6). CONCLUSIONS: This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism.

Aged↗

PubMed1997

Screening for alcohol misuse in older people.

OBJECTIVES: To evaluate whether the CAGE, MAST-G or an abnormally high MCV are effective screening instruments for alcohol misuse and if not to devise a new instrument. DESIGN: Questionnaire survey of randomly selected patients. SETTING: Acute admission wards of two district general hospitals. PERIOD: 9 months. SUBJECTS: Randomly selected patients, aged 65 and over, admitted as emergencies. MAIN OUTCOME MEASURES: Excessive alcohol intake, alcohol dependence. RESULTS: The sensitivities of the CAGE, MAST-G and an abnormally high MCV for excess alcohol intake and alcohol abuse are low, ranging from 0.13 to 0.54. CONCLUSION: The results confirm previous UK studies which indicate that the CAGE and an abnormally high MCV are poor screening instruments for alcohol misuse in older patients and also indicate that the MAST-G is an insensitive screening instrument. A new two-step instrument with five questions in total was generated. This requires further validation.

Aged↗

PubMed1996

Bloodstream infections with vancomycin-resistant enterococci.

OBJECTIVES: To describe the population in whom bloodstream infections with vancomycin-resistant enterococci occur and the clinical and microbiologic features of infection. METHODS: From June 1, 1991, to January 31, 1994, 73 patients with bloodstream infections with vancomycin-resistant enterococci were identified by retrospective review of hospital charts and microbiology records. RESULTS: Fifty-two (73%) of 71 patients with evaluable data were hospitalized in an intensive care, unit, the adult oncology unit, or the acquired immunodeficiency syndrome unit. Before the development of the bloodstream infection with vancomycin-resistant enterococci, patients were hospitalized and received antibiotics for a median of 26 and 25.5 days, respectively. A hematologic malignancy, respiratory failure, or renal failure requiring dialysis was present in 59 patients (83%). Acute Physiology and Chronic Health Evaluation II scores of the patients ranged from 6 to 35 (median, 17). Forty-five (63%) of the patients died. Compared with 37 patients who had only a single positive blood culture, the 34 patients with 2 or more blood cultures positive for vancomycin-resistant enterococci more often were neutropenic or had acquired immunodeficiency syndrome (74% vs 35%; P = .002). CONCLUSIONS: Bloodstream infections with vancomycin-resistant enterococci predominantly affect severely ill patients who have received extensive antibiotic treatment during a prolonged hospitalization. Immunocompromised patients are more likely to have a persistent blood-stream infection with vancomycin-resistant enterococci.

Anti-Bacterial Agents↗

PubMed1996

C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.

OBJECTIVE: To test the hypothesis that minor chronic insults such as smoking, chronic bronchitis, and two persistent bacterial infections may be associated with increases in C reactive protein concentration within the normal range and that variations in the C reactive protein concentration in turn may be associated with levels of cardiovascular risk factors and chronic coronary heart disease. DESIGN: Population based cross sectional study. SETTING: General practices in Merton, Sutton, and Wandsworth. SUBJECTS: A random sample of 388 men aged 50-69 years from general practice registers. 612 men were invited to attend and 413 attended, of whom 25 non-white men were excluded. The first 303 of the remaining 388 men had full risk factor profiles determined. INTERVENTIONS: Measurements of serum C reactive protein concentrations by in house enzyme linked immunosorbent assay (ELISA); other determinations by standard methods. Coronary heart disease was sought by the Rose angina questionnaire and Minnesota coded electrocardiograms. MAIN OUTCOME MEASURES: Serum C reactive protein concentrations, cardiovascular risk factor levels, and the presence of coronary heart disease. RESULTS: Increasing age, smoking, symptoms of chronic bronchitis, Helicobacter pylori and Chlamydia pneumoniae infections, and body mass index were all associated with raised concentrations of C reactive protein. C Reactive protein concentration was associated with raised serum fibrinogen, sialic acid, total cholesterol, triglyceride, glucose, and apolipoprotein B values. C Reactive protein concentration was negatively associated with high density lipoprotein cholesterol concentration. There was a weaker positive relation with low density lipoprotein cholesterol concentration and no relation with apolipoprotein A I value. C Reactive protein concentration was also strongly associated with coronary heart disease. CONCLUSION: The body's response to inflammation may play an important part in influencing the progression of atherosclerosis. The association of C reactive protein concentration with coronary heart disease needs testing in prospective studies.

Aged↗

PubMed1996

Reading and spelling deficits among children attending a psychiatric day treatment program.

To investigate the specific behavioural and cognitive characteristics which may account for academic deficits in children with psychiatric disorders, 50 children admitted to a day treatment and school program were assessed using behaviour questionnaires for parents and teachers, and tests assessing intelligence (WISC-R), language (CELF-R) and academic performance (Kaufman Test of Educational Achievement). The academic measures Reading Decoding, Reading Comprehension and Spelling formed the dependent variables. Behaviour and cognitive measures which distinguished the sample from normative data constituted the independent variables. Hierarchical multiple regression analyses were performed in order to identify behaviour and cognitive measures accounting for the academic deficits. In the analyses, three measures (Digit Span, Sentence Assembly, Recalling Sentences), probably assessing overlapping cognitive/linguistic functions, accounted for a large proportion of variance for Reading Decoding (0.47), Reading Comprehension (0.63) and Spelling (0.29). None of the behaviour measures accounted for any variance of the academic variables. It is argued that linguistic dysfunction is a primary deficit which underlies problems in academic learning.

Adolescent↗

PubMed1996

Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia.

PURPOSE: This open-label pilot study was designed (1) to determine the effect of hydroxyurea on the hemoglobin level in children with sickle cell anemia, (2) to evaluate the toxicity of hydroxyurea, and (3) to assess any impact of hydroxyurea on the frequency of vaso-occlusive crises (VOCs). PATIENTS AND METHODS: Ten children (group 1) with three or more VOCs of the extremities or two or more VOCs of the lungs (acute chest syndrome) in the preceding 12 months, and five children (group 2) with hemoglobin levels less than 70 gm/L were treated with hydroxyurea in doses of 20 to 35 mg/kg per day. The frequency of VOCs before hydroxyurea therapy was compared with the frequency during therapy, and the peak hemoglobin levels during hydroxyurea therapy were compared with the pretreatment values. RESULTS: One patient in group 1 was removed from the study within 1 month because of nausea. Seven of the remaining nine patients in group 1 had a decrease in the frequency of VOCs. The number of VOCs per patient-year for all 14 patients decreased from 2.5 before hydroxyurea therapy to 0.87 during hydroxyurea therapy, a decrease of 65% (p < 0.00001). Two of five patients in group 2 had an increase in hemoglobin of 27 gm/L and 34 gm/L over the baseline. The median rise in hemoglobin was 19 gm/L (range, 7 to 37) for all 14 patients. Nine patients are still receiving hydroxyurea for a median period of 23 months (range, 18 to 59). CONCLUSIONS: Hydroxyurea decreases the severity of anemia in some patients, and it may decrease the frequency of VOC. Its short-term hematologic toxicity is minimal.

Adolescent↗

PubMed1996

Clinical and economic effects of mupirocin calcium on preventing Staphylococcus aureus infection in hemodialysis patients: a decision analysis.

This study was performed to determine the clinical and economic consequences of alternative strategies of preventing Staphylococcus aureus infection in chronic hemodialysis patients by use of intranasal mupirocin calcium to clear nasal carriage of S aureus. Decision analysis evaluated clinical outcomes and cost-effectiveness of three likely management strategies to address S aureus nasal carriage and prevent subsequent infection in chronic ambulatory hemodialysis patients: (1) screen for S aureus nasal carriage every 3 months and treat those with a positive test result with mupirocin calcium; (2) treat all patients weekly with mupirocin calcium; or (3) no prevention strategy, treat infection only. Rates of nasal carriage of S aureus, S aureus infection rates, proportion of infections attributable to nasal carriage, efficacy of mupirocin, natural history of infection, and patient management strategies were derived from the published literature and supplemented by a panel of experts. Actual payments for medical services were obtained from Medicare parts A and B. Incremental cost-effectiveness was calculated from the perspective of Medicare and subjected to sensitivity analyses. Assuming that 75% of S aureus infections are attributable to nasal carriage in hemodialysis patients, eliminating nasal carriage of S aureus with mupirocin calcium (with or without screening) markedly reduces the number of infections (45% to 55%) and also reduces health care expenditures relative to treating infections when they occur. Annual savings to Medicare are $784,000 to $1,117,000 per 1,000 hemodialysis patients, depending on the prevention strategy. Preventing S aureus infection by eradicating nasal carriage in chronic hemodialysis patients reduces morbidity while simultaneously reducing medical care costs. The decision to eliminate nasal carriage on a regular basis or use a screening test to guide antibiotic therapy is dependent on the tradeoff between improved short-term clinical and cost benefits and the potential for bacterial resistance that may arise from widespread use of mupirocin calcium.

Administration, Intranasal↗

PubMed1996

The effect of combined expression of interleukin 2 and interleukin 4 on the tumorigenicity and treatment of B16F10 melanoma.

The recent use of interleukin 2 (IL-2) and interleukin 4 (IL-4) single cytokine modified tumour cells in rodent models has demonstrated a potential use of these cytokines to produce autologous cancer cell vaccines. Here we compare the potential therapeutic benefit of transduction with IL-2 or IL-4 alone, and combined IL-2 + IL-4 in B16F10 cells, a murine malignant melanoma of poor immunogenicity. Transduction of B16F10 cells (MHC class I and II negative) to express either IL-2 or IL-4 alone delays the formation of tumours, IL-4 being more effective than IL-2. However, combined expression of IL-2 + IL-4 reduces tumorigenicity more than either cytokine alone. The eventual formation of tumours may result from loss of gene expression, and preliminary results suggest methylation of the retroviral long terminal repeat (LTR), rather than loss of the transduced DNA sequences. Histological examination of tumours expressing either IL-2 or IL-4 alone shows a non-specific inflammatory reaction with an increased tissue infiltrate of immune effectors (monocytes/macrophages, lymphocytes, granulocytes) localised around the tumour. In comparison, when cells expressing combined IL-2 + IL-4 were injected there were more granulocytes present, and perhaps more importantly, these were mainly localised within the tumour. The benefit of combined IL-2 + IL-4 expression results from a local rather than systemic effect as the growth of tumours from cells expressing IL-2 or IL-4 alone injected at distant sites was comparable with a single inoculation of cells expressing either cytokine alone. However, when cells expressing single cytokines IL-2 or IL-4 were mixed and injected at the same site, in comparison with the clonal population of cells expressing combined IL-2 + IL-4, tumour growth was characteristic of IL-4 alone rather than IL-2 + IL-4. Treatment of established tumours with a single injection of lethally irradiated tumour cells expressing IL-2 + IL-4 was sufficient to either reject tumours, or at least delay further tumour development. Furthermore, treatment stimulated an initial non-specific immune reaction that lead to a systemic immunity. Lethally irradiated wild-type cells were also successful in treating some established tumours, although this did not induce any systemic immunity. However, although successful in treatment studies, neither wild-type nor combined IL-2 + IL-4 expressing cells were able to vaccinate animals against a subsequent challenge with live wild-type tumour. These results indicate a potential therapeutic benefit with the use of combination IL-2 + IL-4 transduction of autologous cancer cells.

Animals↗