Soil microbial community response to land use change in an agricultural landscape of western Kenya.

Tropical agroecosystems are subject to degradation processes such as losses in soil carbon, nutrient depletion, and reduced water holding capacity that occur rapidly resulting in a reduction in soil fertility that can be difficult to reverse. In this research, a polyphasic methodology has been used to investigate changes in microbial community structure and function in a series of tropical soils in western Kenya. These soils have different land usage with both wooded and agricultural soils at Kakamega and Ochinga, whereas at Ochinga, Leuro, Teso, and Ugunja a replicated field experiment compared traditional continuous maize cropping against an improved N-fixing fallow system. For all sites, principal component analysis of 16S rRNA gene denaturing gradient gel electrophoresis (DGGE) profiles revealed that soil type was the key determinant of total bacterial community structure, with secondary variation found between wooded and agricultural soils. Similarly, phospholipid fatty acid (PLFA) analysis also separated wooded from agricultural soils, primarily on the basis of higher abundance of monounsaturated fatty acids, anteiso- and iso-branched fatty acids, and methyl-branched fatty acids in the wooded soils. At Kakamega and Ochinga wooded soils had between five 5 and 10-fold higher levels of soil carbon and microbial biomass carbon than agricultural soils from the same location, whereas total enzyme activities were also lower in the agricultural sites. Soils with woody vegetation had a lower percentage of phosphatase activity and higher cellulase and chitinase activities than the agricultural soils. BIOLOG analysis showed woodland soils to have the greatest substrate diversity. Throughout the study the two functional indicators (enzyme activity and BIOLOG), however, showed lower specificity with respect to soil type and land usage than did the compositional indicators (DGGE and PLFA). In the field experiment comparing two types of maize cropping, both the maize yields and total microbial biomass were found to increase with the fallow system. Moreover, 16S rRNA gene and PLFA analyses revealed shifts in the total microbial community in response to the different management regimes, indicating that deliberate management of soils can have considerable impact on microbial community structure and function in tropical soils.

A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy.

BACKGROUND: The role of chemotherapy in the treatment of patients with primary central nervous system lymphoma (PCL) remains unclear, with no randomized trials available to aid in the interpretation of the current data. The Medical Research Council therefore conducted the current randomized trial to assess the impact on survival of postradiotherapy chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in nonimmunocompromised adult patients with pathologically proven PCL. METHODS: After surgery, patients were randomized at a ratio of 1:2 to radiotherapy alone (RT: 40 grays [Gy] in 20 fractions to the whole brain followed by a 14-Gy boost to the tumor plus a 2-cm tumor margin) or to the same radiotherapy followed by six cycles of CHOP chemotherapy given at 3-week intervals (RT-CHOP). The target sample size was 90 patients, which allowed 90% power to detect a doubling of the median survival time. RESULTS: Between 1988 and 1995, 53 patients were randomized: Fifteen patients were randomized to RT, and 38 patients were randomized to RT-CHOP. The trial closed earlier than planned through poor accrual. The median patient age was 57 years, 57% of the patients were male, and 75% of the patients had unifocal disease. The median number of chemotherapy cycles received was 6 (mean, 4 cycles). Forty-three patients have died, and the median follow-up of survivors is 5 years (range, 1-9 years). There was no evidence of a benefit from RT-CHOP with respect to overall survival (hazard ratio [HR], 1.19; 95% confidence interval, 0.51-2.76) after adjustment for prognostic factors (patient age and neurologic performance status) in an analysis in which HR > 1 favored the control (RT) group. CONCLUSIONS: CHOP has no clear role in the postradiotherapy treatment of patients with PCL. Chemotherapy is poorly tolerated and largely palliative in older, less fit patients. In younger patients, initial chemotherapy designed to penetrate the blood-brain barrier warrants further investigation.

Northern region asplenia register--analysis of first two years.

OBJECTIVES: To assess the feasibility of setting up a register of patients with asplenia within a defined geographical area; to ensure that guidelines on best practice were implemented; to obtain information on antibody levels to pneumococcal capsular polysaccharides and Haemophilus influenzae type b capsular polysaccharide, before and after immunisation and annually thereafter; to raise awareness of risks among clinicians and to offer advice on management. DESIGN: Prospective recruitment using multiple sources of recruitment. Annual follow up reminders sent from Registration Centre. SUBJECTS: Population of (old, pre-1995) Northern Health Region: approximately 3.1 million. MAIN OUTCOME MEASURES: Data were obtained on reasons for asplenia, duration of asplenia, use of prophylactic antibiotics, Medic-Alert bracelets, immunisations, antibody levels, death. RESULTS: The register was initiated at the beginning of April 1995 and ran to the end of March 1997. After two years of operation, 1111 cases had been registered but the response from some health districts was poor. Major primary causes of asplenia were trauma (264), other surgical (198), lymphoproliferative disease (154), and idiopathic thrombocytopenic purpura (147). There were 664 patients on prophylactic antibiotics, of whom 498 were on continuous antibiotics. Only 18 had any type of warning bracelet. Antibody measurements were carried out at least once on 75% of patients; 306 patients had satisfactory antibody levels on first blood sample in year 1, rising to 405 in year 2; 43 patients failed to make any antibody response to Pneumovax despite multiple immunisations, and three patients failed to respond to Hib vaccine. Sixteen patients with satisfactory antibody levels in year 1 had low levels in year 2 requiring vaccine boosters. Sixteen deaths were reported, two of which were directly attributable to overwhelming sepsis. CONCLUSIONS: Registration has been successful and has raised awareness of the management of asplenia. Compliance with antibiotic prophylaxis and immunisation was initially poor. A potential high risk group of vaccine non-responders has been identified and poor persistence of pneumococcal antibodies has been identified which is likely to alter approaches to immunisation in asplenic patients.

Dose escalation with repeated intrathecal injections of 131I-labelled MAbs for the treatment of central nervous system malignancies.

We have previously demonstrated a 33% response rate in patients with primitive neurectodermal tumours after the direct injection of 131I-monoclonal antibodies (MAbs) into the cerebrospinal fluid (CSF). Dose-limiting toxicity is myelosuppression due to the passage of the radioimmunoconjugate from the CSF to the blood compartment. This occurs at doses of 2220 MBq of 131I-MAb and above, although this is not seen in all patients studied and appears to be related to the degree of prior therapy received. Rather than attempting to improve the efficacy of this approach to the treatment of disseminated disease within the CSF compartment by dose escalation and haemopoietic rescue, we have explored the possibility of repeatedly administering the radioimmunoconjugate. Eight patients were recruited to the study, two of whom received two and six of whom received three injections of 131I-MAb. After repeated administration of 131I-MAb pharmacokinetic data revealed that, with one exception, the radioimmunoconjugate cleared from the CSF compartment with similar kinetics, while its residence time in the blood decreased with each injection. This was due to the development of an anti-mouse Ig response in the blood. Clearance of 131I-MAb from the ventricular CSF appears to be independent of the presence of an anti-mouse Ig response in this compartment. The differential clearance of the radioimmunoconjugate from the ventricular CSF and from the blood results in a marked increase in the therapeutic index that can be achieved. Up to 5920 MBq of 131I-MAb was administered as the third injection of radioimmunoconjugate and combined doses of up to 12,500 MBq were given without either haematological or neurological toxicity. These data illustrate that dose escalation and thus an increase in the dose rate delivered to tumour cells within the CSF is possible if ways are found to reduce the residence time of the radioimmunoconjugate in the blood compartment. Suggestions as to how this can best be achieved are reviewed in detail.

Long-term results from the first UKCCSG Ewing's Tumour Study (ET-1). United Kingdom Children's Cancer Study Group (UKCCSG) and the Medical Research Council Bone Sarcoma Working Party.

The aim of this study was to evaluate multimodal chemotherapy and radiotherapy in patients with Ewing's sarcoma. 142 (74 male, 68 female) patients were entered into the ET-1 study between 1978 and 1986. They were treated with vincristine, doxorubicin, actinomycin D, and cyclophosphamide with radiotherapy plus or minus surgery to the primary tumour. Of the 120 who had no metastases at diagnosis, 45 remain alive with a median follow-up of 11.2 years. Only 2 of those with metastases at diagnosis remain alive. The major prognostic factor was site of disease, but age and serum lactic dehydrogenase at diagnosis also had an influence on outcome. 45 of the 61 patients who survived 4 years or more had late effects documented. The type and extent were dependent on tumour site, type of local therapy, volume and dose of radiotherapy. 4 patients had second malignancies. Prospects for long-term survival have improved in patients treated for Ewing's sarcoma. However, late sequelae are present in the majority of patients.

Involvement of the inferior vena cava by adrenal phaeochromocytoma--MRI findings.

Involvement of the inferior vena cava (IVC) by adrenal phaeochromocytoma is rare. Only angiographic and sonographic features have been described previously. We present a case with magnetic resonance demonstration of the IVC invasion.

A pilot study of the treatment of patients with recurrent malignant gliomas with intratumoral yttrium-90 radioimmunoconjugates.

A pilot study of the treatment of patients with relapsed malignant gliomas with direct intratumoral injections of yttrium-90 (90Y) radioimmunoconjugates has been completed. Patients were recruited following maximal tumour resection, and received 1-3 injections of 90Y conjugated to a monoclonal antibody designated ERIC-1, which binds the neural cell-adhesion molecule. Data were collected to establish clinical toxicity, pharmacokinetics and radiation doses to the cavity wall and critical body organs. Twenty-three injections were completed in 15 patients, with a mean injected activity of 675 MBq (range 399-921). Early toxicity manifested as cerebral oedema and was readily controlled with dexamethasone. Delayed myelosuppression was observed but no intervention was required. Pharmacokinetic analysis confirmed prolonged retention of isotope in the cavity with correspondingly low activity in the bloodstream. These data were translated into estimates of absorbed radiation dose using the Medical Internal Radiation Dosimetry (MIRD) scheme. Mean doses, and dose rates, to the wall of the cavity, i.e. 'tumour,' were very high in comparison to normal tissue doses, with a further advantage if targeting was achieved.

Treatment of recurrent and cystic malignant gliomas by a single intracavity injection of 131I monoclonal antibody: feasibility, pharmacokinetics and dosimetry.

A pilot study was undertaken to determine the feasibility of infusing 131I labelled monoclonal antibodies (MoAbs) into either the cavity remaining after resection of malignant glioma or into glioma cysts. Of the seven patients recruited into the study, two had cystic lesions and five resection cavities. Six of the seven were treated after relapse from primary therapy. All patients apart from one, were given a single injection of 131I conjugated to a MoAb (ERIC-1) recognising the human neural cell adhesion molecule (NCAM). One patient received a further injection of 131I-MoAb after regrowth of their disease. Pharmacokinetic studies revealed that the MoAb remained predominantly in the tumour cavity with little leakage into the systemic compartment. This resulted in a high calculated dose of radiation being delivered to the tumour cells either lining or within close proximity to the cavity/cyst wall. In such a small study, it is not possible to determine accurately response rates, but individual patient responses were observed. This, along with the low toxicity noted, demonstrates the feasibility of using 131I-MoAbs in this way. With 131I, radiation dose is deposited in tissue to a depth of 1 mm from the source. The possibility of applying isotopes such as 90Yttrium which will irradiate tumour/tissue to a greater depth (6 mm) is discussed in context with the biology of glioma infiltration into normal brain parenchyma.

Carcinomatous meningitis: antibody-guided therapy with I-131 HMFG1.

Seven patients with carcinomatous meningitis were administered intrathecal I-131 labelled monoclonal antibody HMFG1. Clinical responses were seen in two patients, with a long term survivor at 32 months. Aseptic meningitis occurred in 4/7 patients, but more serious toxicity was observed in the form of seizures (2/7 patients) and myelosuppression (3/7 patients). Partial obliteration of the subarachnoid space was identified as a potential problem in patients with advanced disease.

A new technique of brachytherapy for malignant gliomas with caesium-137: a new method utilizing a remote afterloading system.

Failure of conventional treatment to cure malignant gliomas has stimulated interest in various forms of brachytherapy. We describe a new method of using intracranial radiation utilizing a remotely-controlled afterloading system with a modified endotracheal tube as the applicator. The system used is the Selectron LDM/MDR (Nucleotron) which is a sophisticated machine widely available at radiotherapy centres and primarily used to treat gynaecological malignancies. It uses Caesium-137 in the form of spherical pellets in a linear source train within a sealed system. The applicator is implanted at the time of surgical resection. The inflated balloon stabilises the applicator and allows a suitable dose distribution at a distance from the source train to be achieved. Details of the implantation and radiation procedures as well as the dosimetry calculation are presented. The advantages are simplicity of use, the elimination of radiation risk to personnel and the combination of cytoreduction and applicator implantation in one surgical procedure.

Intrathecal administration of 131I radiolabelled monoclonal antibody as a treatment for neoplastic meningitis.

Fifteen patients with neoplastic meningitis received a single intrathecal injection of between 11 and 60 mCi of a 131I radiolabelled monoclonal antibody (MoAb), chosen for its immunoreactivity to tumour. Major toxicity was manifest as nausea, vomiting and headache (7/15 patients), reversible bone marrow suppression (3/8 patients) and seizures (2/15 patients). Nine patients were evaluable for either a tumour or clinical response. Six of these demonstrated an event-free response that was maintained for periods of between 7 and 26 months.

CT appearances of relapse of lymphoma in the lung.

The patterns of pulmonary relapse were studied in 15 patients with Hodgkin's disease and one patient with Non-Hodgkin's lymphoma. All the patients with Hodgkin's disease had mediastinal lymphadenopathy at initial diagnosis. For those patients with no prior episodes of relapse the mean time to pulmonary involvement was 2 years 11 months compared to over 8 years for those who first relapsed elsewhere. Thirteen patients are still alive; five have been followed up for more than 2 years. Pulmonary involvement consisted of: 1. nodules, either central (12 patients) or peripheral (10 patients), often with connection to the pleura or mediastinum, and sometimes with cavitation; 2. consolidation with or without cavitation (four patients); 3. mediastinal extension into the lung parenchyma (three patients). In seven patients there was evidence of newly enlarged mediastinal nodes. Pleural effusions or masses were seen in six patients and pericardial involvement in one. The chest wall was involved in five. A combination of three or more of these signs were present in 11 patients. The pattern of involvement seen in the patient with Non-Hodgkin's lymphoma was indistinguishable from that seen in Hodgkin's disease. This study has demonstrated a variety of CT appearances useful in establishing or suggesting the diagnosis of pulmonary relapse. Enlarged mediastinal nodes were not a prerequisite but had been present in all patients at some stage in the course of the disease.

Final report of the general clinical results of the British Institute of Radiology fractionation study of 3F/wk versus 5F/wk in radiotherapy of carcinoma of the laryngo-pharynx.

The 10 year follow-up of a clinical trial involving the comparison of 3F/wk versus 5F/wk in radiotherapy of squamous cell carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. The classification of all patients has been revised to conform with the latest TNM publication. A reduction in total dose was made for 3F/wk compared with 5F/wk. This varied between 13% and 11% in centres treating over 3 weeks and 6 weeks, respectively. No statistically significant differences have been found between the two arms (3F/wk versus 5F/wk) of the trial in any of the main group analyses. A number of sub-group analyses relating to survival, tumour-free and laryngectomy-free rates and to the comparison of acute or late normal-tissue radiation damage have also been performed. No differences have been found that could be considered to be statistically significant in relation to the particular sub-group. Previous interim reports suggested minor differences in sub-group analyses between the 3F/wk and 5F/wk regimes in this trial; these have diminished now that the full follow-up data are available. This trial has provided evidence on which clinicians may base their choice between either a 3F/wk fractionation regime or a conventional 5F/wk treatment protocol in the treatment of carcinoma of the laryngo-pharynx.

Pulmonary changes in breast cancer patients treated by three different radiotherapy techniques.

Twenty eight patients with breast cancer were studied by CT, perfusion scans and pulmonary function tests to assess the extent of post-irradiation changes. The patients had been treated by three treatment techniques using either two, three or four fields with different amounts of lung included in the target volume. The most extensive changes were seen in those patients who received treatment to the mediastinum.