Yttrium90 synovectomy in the management of chronic knee arthritis: a single institution experience.

Radiation synovectomy (RS) has been used to treat chronically inflamed joints refractory to treatment using conventional agents. In RS, the radioactive isotope is concentrated in the synovial membrane from the injected colloid suspension, where it exerts its activity. However, despite numerous reports confirming its safety and efficacy, this procedure is not widely practised. In the Singleton Hospital NHS Trust, yttrium(90) (Y(90)) RS has been practised since 1990 for refractory synovitis. In this study, we analyse the results of therapy and complications in 38 joints so treated. Doses of 10 mCi were used in the majority of patients. Most responses were apparent by 6 months following the procedure. Altogether, 68% of the treated joints showed satisfactory response at 3 years, with 29% having all symptoms under control beyond 3 years. In three patients, there was evidence of minor pigmentation at the injection site. Two patients had extravasation of the isotope and needle track ulcers, which were recorded as major toxicity. We find Y(90) radiosynovectomy to be safe, quick, and effective in the management of patients with refractory synovitis. The efficacy of RS should be tested in randomised clinical trials involving large numbers of patients.

Pulsed dye laser treatment of telangiectasia after radiotherapy for carcinoma of the breast.

BACKGROUND: Chronic radiodermatitis after radiotherapy for carcinoma of the breast is a common sequela of treatment and can be distressing for the patient. The skin is atrophic and shows prominent telangiectasia due to dilatation of a reduced or poorly supported skin vasculature. The pulsed dye laser (PDL) is an established treatment of cutaneous telangiectatic disorders including facial telangiectasia and spider naevi, and is safe and efficacious. OBJECTIVES: To study the efficacy of the PDL in the treatment of postradiation telangiectasia of the breast or chest wall. METHODS: Prospective open study of the treatment of eight females with the Candela SPTL1B PDL. Subjective assessments of vessel clearance, adverse effects and patient questionnaires. RESULTS: All treated patients showed complete clearance of vessels. Two patients developed hypopigmentation. All patients reported a high degree of satisfaction with the treatment. CONCLUSIONS: PDL therapy clears postirradiation telangiectasia of the breast and chest wall successfully with minimal adverse reactions, and can be recommended for patients distressed by this disorder.

Haemangiopericytoma diagnosed from a metastasis 11years after surgery for "atypical meningioma".

Meningeal haemangiopericytoma (HPC) is a rare tumour often mistakenly reported as "vascular meningioma". Unlike meningiomas, HPC has a high rate of local recurrence and distant metastases, which may occur several years after initial treatment. We report a patient in whom a HPC was misdiagnosed as benign vascular meningioma and the patient discharged from follow-up. HPC was diagnosed 11 years later from biopsy of a skeletal metastasis. Histological review of the meningeal tumour confirmed the diagnosis of meningeal HPC. Meningeal HPCs resemble meningiomas clinically, radiologically and even light microscopically. As a result, they can be reported as atypical meningioma, as in this case. HPC's are more aggressive than typical meningiomas, with a high rate of recurrence and distant metastasis, often late in the course of the disease. Management of meningeal HPC differs from that of typical meningioma, with a need for post-operative radiotherapy and long-term follow-up.

Total lymphoid irradiation in multiple sclerosis.

Following a report of the efficacy of total lymphoid irradiation (TLI) in the treatment of chronic progressive multiple sclerosis a further randomised double-blind placebo-controlled study was undertaken with the intention of entering 56 patients. In the event it was possible to recruit only 27 patients in a 2.5 year period. Three patients received active treatment openly and 24 were randomised to either active (14) or sham (10) treatment. Treatment was 1980 cGy to the lymphoid system and spleen or sham treatment after full simulation. The primary outcome measure was a comparison of the mean rates of change between treatment groups on the expanded Kurtzke disability scale (EDSS) over the two year follow up period. Patients were also assessed on other clinical outcome measures, psychometry, and serial MRI of the brain. Active treatment resulted in a profound and prolonged fall in T lymphocytes especially those with the CD4 marker and a reversal in CD4:CD8 ratio. No significant benefit was demonstrated on the rate of clinical disease progression (EDSS). A small but significant benefit was found on a score of bladder function. No significant benefit was demonstrated on other clinical or psychometric indices or on subjective visual analogue scales. There was a small but significant difference in the rate of accumulation of lesions on brain MRI favouring the treatment group. The treated group had a higher incidence of clinically relevant side effects, notably amenorrhoea and infections: three deaths (one in the TLI group, two in the sham treated group) occurred. A post hoc calculation indicates that the study had a possible 35% risk of a false negative result using the principal outcome measure. The study fails to confirm the previously reported clinical benefit of TLI although there may be a minor benefit on disease progression as indicated by MRI lesion counts. It is concluded that TLI cannot be recommended for the routine treatment of chronic progressive multiple sclerosis but the beneficial effect on MRI lesions, though modest, suggests that further research into immune modulation of this condition may be worthwhile.

Quinolone antibacterials containing the new 7-[3-(1-aminoethyl)-1- pyrrolidinyl] side chain: the effects of the 1-aminoethyl moiety and its stereochemical configurations on potency and in vivo efficacy.

A series of stereochemically pure 7-[3-(1-aminoethyl)-1-pyrrolidinyl]-1, 4-dihydro-4-oxoquinoline and 1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, were synthesized to study the effects of the 7-[3-(1-aminoethyl)-1- pyrrolidinyl] moiety on potency and in vivo efficacy relative to the known 7-[3-(aminomethyl)-1- pyrrolidinyl] derivatives. The antibacterial efficacies of the target compounds and their relevant reference agents were determined in vitro using an assortment of Gram-negative and Gram-positive organisms and in vivo using Escherichia coli and Streptococcus pyogenes mouse infection models. The effects of the 7-[3-(1-aminoethyl)-1-pyrrolidinyl] moiety were also examined at the level of the target enzyme by employing a DNA-gyrase supercoiling inhibition assay. Selected compounds were further evaluated for potential phototoxic and clastogenic liabilities using a phototoxicity mouse model and an in vitro mammalian cell cytotoxicity assay. It was found that the differences in in vitro antibacterial activity between the stereoisomers were significantly greater than previously reported for other optically pure 3-substituted pyrrolidinyl side chains. Relative to their 7-[3-(aminomethyl)-1-pyrrolidinyl] analogs, the (3R,1S)-3-(1-aminoethyl)pyrrolidines generally conferred a 2-4-fold increase in Gram-positive in vitro activity and an average of 10-fold improvement in oral efficacy. The level of phototoxicity and cytotoxicity of the product quinolones was ultimately determined by the combined influence of the 7-[3-(1-aminoethyl)-1-pyrrolidinyl] side chains and the other quinolone substituents. From this study, several compounds were identified with outstanding antibacterial activity and low degrees of phototoxicity and mammalian cell cytotoxicity. One such agent, 34F-R,S (PD 140248), showed the best overall blend of safety and efficacy.

Lymphangitis carcinomatosis arising from carcinoma of the cervix.

A case of lymphangitis carcinomatosis due to carcinoma of the cervix, and presenting clinically as pulmonary infarction, is described. The speed of progression of the disease is stressed and its protean manifestations are well exhibited by this case.

Hemibody irradiation in multiple myeloma.

Eighteen patients with multiple myeloma were treated by hemibody irradiation using large single fractions, usually to a dose of 10 Gy (lower half) and 7.5 Gy (upper half). All except one patient had previously been treated by multiple courses of conventional chemotherapy with melphalan and prednisone, and were considered to be resistant to further chemotherapy. In most cases, local field irradiation had also been given for symptomatic bone pain. Of the 13 patients who had symptoms at the start of hemibody irradiation, 11 improved sufficiently for their analgesia requirement to be reduced. In eight patients, there was a significant fall in circulating immunoglobulin but no patient with Bence-Jones proteinuria had complete resolution of this biochemical abnormality. Although thrombocytopenia and neutropenia were common, only two patients required platelet transfusion and the treatment was in general extremely well tolerated. Survival following hemibody irradiation was similar to the survival reported from the use of "second-line" chemotherapy and we feel that hemibody irradiation is a more acceptable alternative for most patients.

Radiation-induced lung fibrosis after treatment of small cell carcinoma of the lung with very high-dose cyclophosphamide.

Twenty-five previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide 160 to 200 mg/kg (with autologous bone marrow support) followed by radiotherapy (4000 cGy) to the primary site and mediastinum. No other treatment was given until relapse occurred. Nineteen patients were assessable at least 4 months after radiotherapy; of these, 15 (79%) developed radiologic evidence of fibrosis, which was symptomatic in 14 (74%). The time of onset of fibrosis was related to the volume of lung irradiated. A retrospective analysis was made of 20 consecutive patients treated with multiple-drug chemotherapy and an identical radiotherapy regimen as part of a randomized trial. Radiologic and symptomatic fibrosis was one half as frequent (35%) as in the high-dose cyclophosphamide group. Very high-dose cyclophosphamide appears to sensitize the lung to radiotherapy and promotes the production of fibrosis.