Vinorelbine and infusional 5-fluorouracil in anthracycline and taxane pre-treated metastatic breast cancer.

AIMS: To evaluate the efficacy and toxicity of a combination of intravenous vinorelbine and 5-fluorouracil (5-FU) given by continuous infusion in the treatment of metastatic breast cancer previously treated with anthracyclines and taxanes. MATERIALS AND METHODS: Sixty-one patients with metastatic breast cancer were treated with intravenous vinorelbine 30 mg/m2 on days 1 and 8 of each 21-day cycle together with 5-FU 200 mg/m2/day by continuous infusion. All had previously been treated with an anthracycline and 41% had also been previously treated with a taxane. All had normal haematological, renal and hepatic function and all but three had an Eastern Cooperative Oncology Group performance score of 2 or better. RESULTS: The overall response rate by World Health Organization criteria was 46% (28 patients); excluding nine non-evaluable patients gave a response rate of 54%. In patients who had previously been treated with both an anthracycline and a taxane, a response rate of 50% was observed (12 of 24 patients). Severe toxicity was uncommon, as was toxicity attributable to infusional 5-FU. Myelosuppression was rarely severe, but was common and led to delay or dose reduction in 38% of treatments. Eleven patients (18%) were admitted with fever and/or neutropenia and one patient died. The median received dose intensity was vinorelbine 16 mg/m2/week and 5-FU 143 mg/m2/day. CONCLUSIONS: The combination of vinorelbine and infusional 5-FU is active in metastatic breast cancer, including in patients previously treated with an anthracycline and a taxane. Toxicity is generally manageable, but myelosuppression is significant at this dose regimen. Recommended doses for routine clinical use are 5-FU 200 mg/m2/day and intravenous vinorelbine 30 mg/m2 days 1 and 15 on a 28-day cycle.

Differences in intramammary pathogenicity of four strains of Streptococcus dysgalactiae.

The intramammary pathogenicity of four strains of Streptococcus dysgalactiae was measured by infusion of small numbers of bacteria (8-16 colony-forming units) into the teat sinus after milking. Significant differences in the infectivity of strains were detected.

Recovery of fertility 14 years following radiotherapy and chemotherapy for testicular tumour.

We report a patient who developed a left-sided malignant teratoma with ipsilateral para-aortic nodes at the age of 20 years. Following treatment with left orchidectomy, abdominal and pelvic radiotherapy and chemotherapy, he was found to be azoospermic. More than 14 years after treatment, he regained his fertility. Similar prolonged iatrogenic depression of spermatogenesis has been reported in younger lymphoma patients; however, in post-pubertal patients with testicular tumour this has not been frequently reported.

Carcinoma of the penis: a retrospective review of treatment with iridium mould and external beam irradiation.

This paper is a retrospective review of the treatment of carcinoma of the penis with radiotherapy alone over a 30-year period from 1960-1990 at The Royal London Hospital. During that time, 44 patients aged 31-85 years (mean 63) underwent treatment in our department, all of whom had histologically proven squamous carcinoma. Patients initially treated by surgery and those treated with combined surgery and radiotherapy were excluded from analysis. Twenty-four patients were treated by an iridium mould, and 20 by external beam irradiation. There were 67% complete responses; 79% for the patients treated by an iridium mould, 53% for those treated by external beam irradiation, although this difference between the two treatment groups was due to a more favourable stage distribution in the iridium group. Actuarial 2-, 5- and 10-year overall survivals were 87.9%, 85.1% and 72.3% respectively, with no significant difference between the iridium and external beam groups. For Stage I patients, the response rates and actuarial penile disease free survivals were comparable for the iridium and external beam groups. Urethral stricture was recorded in 10% of those treated by external beam irradiation and 13% of those treated by iridium mould. These results confirm that conservative treatment of carcinoma of the penis with radical radiotherapy allows preservation of a functioning penis with acceptable morbidity and a high proportion of long term survivors when surgery is used for salvage of locoregional relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Disinfection properties of some bovine teat dips.

The efficacy of 18 disinfectant teat dips was tested on teats artificially contaminated with a milk suspension of Staphylococcus aureus. A solution of Na hypochlorite with 40 g/l available chlorine was significantly more bactericidal than one containing 1 g/1 available chlorine and than most other disinfectants tested. The method was not able to distinguish differences in efficacy between solution containing 40g/1 and 10g/1 available chlorine nor between these and some of the iodophors containing 5 g/1 available iodine. The additon of 190-416 g/1 (15-33% v/v) glycerol significantly reduced the bactericidal properties of 3 iodophors (5 g/1 available iodine), but soluble lanolin at approximately 20 g/1 did not appear to lower the efficiency of NaOC1 (45 g/1 available chlorine) or of an iodophor (5 g/1 available iodine).

Effect of vacuum fluctuation during milking on the development of intramammary infection from teat duct colonization by Staphylococcus aureus.

Twelve of twenty-one udder quarters with colonized teat ducts became infected within 13 d when milked with a machine producing large cyclic and irregular vacuum fluctuations in the teatcup; of 23 quarters milked under the same conditions, but with metal shields fitted inside the liners to protect the teat apex (Thiel, 1974), only 2 quarters became infected in the same period. The introduction of a post-milking teat disinfectant teat dip resulted in the elimination of orifice colonization from 15 teats dipped in Na hypochlorite solution (40 g/l available chlorine) and from all but 2 of 15 teats dipped in an iodophor solution (5 g/l available iodine).

Use of deflector shields to reduce intramammary infection by preventing impacts on the teat ends of cows during machine milking.

A series of short duration experiments has shown that infections caused by the milking machine or the way in which it is used can be controlled by fitting deflector shields in the teatcup liners. This not only provides a simple means of controlling such infections, but demonstrates that they result from penetration of the streak canal of the teat by contaminated milk particles impacting on the teat ends.

A method of diagnosing intramammary infection in dairy cows for large experiments.

Diagnosis of microbial infections in the udders of cows in commercial dairy farms for large experiments cannot be without error. Limitations of sampling method and routine prevent collection of the necessary information for sure diagnosis. However, with an organized method of repeated bacteriological examinations using consistent and proven methods of aseptic sampling the errors were shown to be very low. A method based on bacteriological tests on aseptic milk samples was used in 32 herds (approximately 2000 cows) for a 3-year period. This is described and examined in terms of other criteria to validate its use in experimental work. With this method it was not difficult to differentiate between those quarters which regularly shed pathogens and those which did not. Other evidence indicated that it was reasonable to assume that this classification accurately distinguished between infected and uninfected quarters. The errors using this method were quite small: when measuring the state of infection of all quarters in the herds the errors did not exceed 1%. Some small modifications to the method described are suggested to improve further its diagnostic accuracy.

Susceptibility of the bovine udder to bacterial infection in the dry period.

The teats of 18 cows were externally exposed to infection with mastitis organisms by dipping them daily for 1 or 2 weeks in a mixed suspension of Streptococcus dysgalactiae and Str. uberis at the start, the middle or the end of the dry period. The teat sinuses of quarters which remained uninfected after external exposure at the beginning or the middle of the dry period were then infused with the same strains of streptococci. Of the 9 quarters infected following external exposure 8 occurred in animals exposed at the start and one in the middle of the dry period. Thirty-six new infections occurred after infusion of bacteria into the teat sinuses of 38 quarters. In a further trial with 10 cows, Staphylococcus aureus and Str. zooepidemicus were inoculated into the distal 3 mm of the streak canals of 5 cows immediately after drying-off and into those of 5 cows which had been dry for 28 weeks. Animals were slaughtered 48 h later and infection determined by teat puncture. Five infections occurred in cows which were at the start of the dry period and only one in the cows dry for 28 weeks. It is suggested that these differences in the rates of new infection between the early dry period and a very extended dry period are due to differences in the ease with which bacteria can penetrate the teat canal. At the later stage bacterial growth through the teat canal appeared to be inhibited.

Effect of deflector shields fitted in the milking machine teatcup liner on bovine udder disease.

Deflector shields were inserted in the teatcup to prevent 'impacts' against the teat end, and their effect on the rate of new udder infections was studied on 15 commercial dairy farms in Britain and 16 in Australia. Small metal shields were fitted between the liner barrel and short milk tube of 2 teatcups in each cluster in a milking installation so that all cows in a herd always had the same 2 quarters shielded. Half-udder comparisons were made using 1039 cows in the British herds and 1268 in the Australian herds. Herds were quarter-sampled for cytological and bacteriological examination when shields were fitted at the start of the experiment and again after 6 months. The shield effects were similar in the 2 experiments. The combined results from the 31 farms showed that 10.5% fewer quarters became infected when protected by shields (P less than 0.05). In the 1287 cows that had no infected quarters at the start of the trial, 15% fewer quarters became infected when protected by shields (P less than 0.01). The shield effect was mainly confined to hind quarters in which 23% fewer shielded quarters became infected (P less than 0.001). The small reduction of 2% in forequarters was not significant. In the 16 herds in which post-milking disinfection of teats was practised, shielded quarters had 23.5% fewer new infections than unshielded quarters (P less than 0.01). In 6 British herds milked in installations classed as non-standard, shielded quarters had almost 50% fewer new infections than the unshielded quarters (0.05 less than P less than 0.10). The results provide evidence of a milking machine effect, at varying levels of intensity, to increase new infection rates on all or most farms. Control of this machine effect could lead to substantial reduction in new infections in some herds and a modest reduction in most.