Biomedical subjects
H Atkinson
Publications and source records attributed to H Atkinson.
A phase II study of the sequential administration of dacarbazine and fotemustine in the treatment of cerebral metastases from malignant melanoma.
34 patients with cerebral metastases from malignant melanoma received sequential dacarbazine at 250 mg/m2 followed 2 h later by fotemustine at 100 mg/m2; this was repeated on day 8. Maintenance therapy was given every 4 weeks to patients with radiological evidence of response or stable disease until a maximum response was achieved plus two more cycles. A 12% response rate was obtained for cerebral metastases, with 2 complete responses lasting 12 and 36+ months, and 2 partial responses lasting 2.5 and 3.75 months. Toxicity was mainly haematological with grade 3-4 leucopenia and thrombocytopenia in 23.5% of patients. No pulmonary toxicity was seen. This schedule of sequential dacarbazine and fotemustine has low activity against metastatic melanoma, and the response rate for cerebral metastases is not superior to that shown in other studies with single agent fotemustine, but the treatment was well tolerated and can be delivered on an outpatient basis.
The use of cisplatin plus 5-fluorouracil chemotherapy in an unselected group of patients with recurrent squamous cell carcinoma of the head and neck.
Cisplatin and infusional 5-fluorouracil (5-FU) has become regarded as the standard chemotherapy for squamous cell carcinoma (SCC) of the head and neck. Results of phase II studies vary widely and do not always reflect the activity of regimen in general clinical practice. We have treated 20 consecutive patients with cisplatin 100 mg/m2 and 5-FU given as a 4-day infusion at 1 g/m2 for 24 h. In order to reflect more accurately the activity of this regimen in everyday practice we have followed as many patients as possible to relapse and death and measured the duration of remissions from the end of treatment. 6 patients responded (30%, 95% CI: 10-48%) with 1 patient achieving a complete remission. Partial remission lasted for 3-18 months and the complete remission lasted for 7 months. Median survival of patients from the date of first treatment was 7 months (range 1 week-20.5 months). The regimen was well tolerated but required hospitalisation. We conclude that this regimen is well tolerated, active and a good choice for treating recurrent SCC of the head and neck in an unselected population of patients with recurrent disease in the context of everyday oncological practice.
An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gI or the putative gJ.
Mutants of herpes simplex virus type 1 (HSV-1) lacking glycoproteins gG, gE, gI or the putative gJ were constructed by inserting a lacZ expression cassette within the US4, US8, US7 and US5 genes respectively. Revertant viruses were then constructed by rescue with a wild-type DNA fragment. Each of these mutant viruses, by comparison with the parental virus HSV-1 SC16, exhibited normal particle to infectivity ratios, and had no discernible phenotypic abnormalities in baby hamster kidney-21 cells following high or low multiplicity infections. Infection of mice by scarification of the ear with these mutant viruses showed the following. (i) Interruption of the US5 (gJ) gene has no effect on the ability of HSV-1 to multiply at the inoculation site or its ability to enter or multiply in the peripheral or central nervous system (CNS). This shows that the US5 gene provides a convenient site for the insertion of foreign genes for both in vitro and in vivo studies. (ii) Disruption of the US4 (gG) gene results in marginal attenuation in the mouse ear model. (iii) Disruption of the US7 (gI) or US8 (gE) genes results in pronounced attenuation; virus was rapidly cleared from the inoculation site and was barely detectable in sensory ganglia or in the CNS. The failure of gI-negative or gE-negative viruses to replicate efficiently at the inoculation site in vivo led to the investigation of virus behaviour in epithelial cells in vitro. Viruses lacking gE or gI adsorbed to and entered these cells at normal rates compared with the parental virus, but formed minute plaques. This is consistent with a failure of cell-to-cell spread by the cell contact route. This was confirmed by measurement of the rate of increase in infectious centre numbers following low multiplicity infections. The view that gE and gI influence interactions between cells at the plasma membrane was reinforced by showing that the introduction of disrupted gE or gI genes into a syncytial, but otherwise syngeneic, background resulted in a non-syncytial phenotype. We conclude that the gE-gI complex plays a part, at least in some cell types, in the interactions at the cell surface that allow transmission of the virus from infected to uninfected cells by cell contact. In syncytial strains this leads to uncontrolled membrane fusion.(ABSTRACT TRUNCATED AT 400 WORDS)
Immunological parameters in peripheral blood of patients with renal cell carcinoma before and after nephrectomy.
OBJECTIVE: To determine the effects of nephrectomy on the immune response of patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Five patients with RCC were monitored before and over a period of up to 3 months after nephrectomy. The aspects measured were the phenotypic expression of markers on circulating lymphocytes, circulating concentrations of cytokines, markers of inflammatory and immune responses, and natural killer (NK) cell and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMC). The suppressive activity of patients' plasma on NK activity and ability to generate interleukin-2 (IL-2) induced LAK cells in PBMC of normal volunteers was also investigated. RESULTS: The results indicated that high CD4/8 ratios were present pre-nephrectomy with evidence of inflammatory responses and immune activation in some patients, particularly those with metastatic disease. CONCLUSION: The effect of nephrectomy was to decrease the inflammatory response and increase immune activation. Various defects in NK cell activity and LAK cell generation were demonstrated pre-surgery which slowly improved once the primary tumour had been removed and it is suggested that such defects could have contributed to tumour growth and development due to an ineffective immune response.
Benesh Movement Notation. A tool to record observational assessment.
This article describes the introduction into physiotherapy practice of Benesh Movement Notation, a method for recording observations of patients' posture and movement sequences. Assessments of the technique show it to be a reliable and practical tool for clinical use.
Concentrations of beta-blocking drugs in human milk.
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Assessment and management of the AIDS patient with neuropsychiatric disturbances.
The studies reviewed here and ongoing work indicate a primary role for psychiatry in treating patients with the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. Those patients often have neuropsychiatric disorders concurrent with the complications of physical disease. It is important to understand the diagnostic criteria for patients with HIV-related disorders to distinguish CNS disturbances caused by infections from those psychiatric problems exacerbated by the social consequences of the syndrome. Although treatment is difficult in immunocompromised patients and treatments may cause serious side effects, many of the CNS symptoms of AIDS patients can be treated in the same way as other diseases of the CNS. Psychostimulants are the most promising therapeutic agents for AIDS patients. In the treatment of psychotic episodes, high-potency neuroleptics at low dosages have been used successfully. In all therapies, careful consideration must be given to possible adverse reactions, which may be more serious in HIV-related diseases.
Chloroform use in oral medicines.
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Iota-carrageenan induced reaginic antibody production in the rat--I. Characterisation and kinetics of the response.
The intraperitoneal injection of graded amounts of ovalbumin into inbred PVG strain rats was found to produce a dose dependent anti-ovalbumin antibody response without eliciting the production of ovalbumin-specific reaginic antibodies. The injection of ovalbumin admixed with iota-carrageenan enhanced the anti-ovalbumin response and simultaneously elicited the de novo production of reaginic anti-ovalbumin antibodies. Isotype analysis of the anti-sera revealed the presence of both IgG and IgE class anti-ovalbumin antibodies and demonstrated that non-reaginic IgE anti-ovalbumin antibodies were also a feature of this reaction. The reaginic antibody phase of the response, although transient in nature, was re-elicited by secondary antigen challenge. The administration of ovalbumin prior to the ovalbumin-carrageenan preparation was shown to abrogate the reaginic antibody response without significantly influencing the non-reaginic component of the response. Conversely the injection of iota-carrageenan prior to antigen, significantly suppressed the normal agglutinating anti-ovalbumin response but did not prevent the induction of reaginic antibodies. These observations demonstrate that iota-carrageenan can, under specific conditions, function as an efficient adjuvant, and is capable of by-passing the normal mechanisms responsible for controlling antigen specific reaginic antibody production.
Evaluation of an enzyme linked-immunosorbent assay for the diagnosis of Brucella ovis infection in rams.
A simple enzyme linked immunosorbent assay (ELISA) was developed for the serological diagnosis of Brucella ovis infections in rams. Serums from brucellosis accredited-free flocks and flocks known to be infected with B. ovis were tested and the results correlated with warm complement fixation (CF) test and bacteriological examination of semen. Both the ELISA and the CF test detected 0.5% false positive reactions in rams from clinically negative flocks. However the ELISA detected significantly more positive reactors in infected flocks and the CF test failed to detect some rams excreting B. ovis. The ELISA proved to be a valuable test in eradicating brucellosis from infected flocks.
In vitro and in vivo responses of doxorubicin ion exchange microspheres to hyperthermia.
The utility of microspheres as targeted drug delivery agents is addressed with reference to using heat during formulation and to administration in combination with hyperthermia. It was demonstrated that rate of loading of the drug doxorubicin onto resin microspheres is enhanced under conditions of elevated temperature but this was shown to increase the incidence of microsphere aggregation. Total amount of drug loaded was related to time rather than temperature such that low temperature loading for up to 24 h produced optimum quality injectates. However, release of doxorubicin from microspheres was significantly increased during elevations of temperature to 43 degrees C. Thus, during hyperthermia doxorubicin release can be increased to provide periods of high drug availability targeted to tumour tissue for concomitant thermochemotherapy with microspheres. The therapeutic benefit derived from this combined therapy was assessed in 20 rabbits with VX2 carcinoma implanted in the liver. Hyperthermia was delivered by 2450 MHz microwave applicator to the exteriorized liver at 43 degrees C for 30 min, while chemotherapy was administered by intratumoural injection of doxorubicin microspheres (2.3 mg) into each tumour. Both hyperthermia and chemotherapy alone significantly reduced the size of tumours 10 days following treatment (p less than 0.01). However, in animals treated with both modalities, the size of tumours was significantly less than either treatment alone (p less than 0.05). These results provide a strong rationale for combining hyperthermia with targeted chemotherapy using microspheres.