Further experience of Corynebacterium parvum in malignant pleural effusion.

The outcome of drug induced pleurodesis has been evaluated in a non-randomised retrospective study of 67 patients with recurrent malignant pleural effusions treated during 1976-83. Fourteen died within 30 days of treatment. Of the remaining 53 patients, 26 studied during 1976-80 were treated with intrapleural mustine hydrochloride, while 27 studied during 1978-83 were treated with intrapleural Corynebacterium parvum. There was no significant difference between the groups in age, sex, or tumour type, most tumours being secondary to bronchial neoplasms. Corynebacterium parvum successfully prevented reaccumulation of the effusion in 24 (92%) patients, while mustine was effective in only 17 (65%) (p less than 0.05). Data on survival were obtained on 47 cases where a single agent was used to induce pleurodesis. In 25 patients treated with C parvum the mean survival was 251 (range 31-1143) days, compared with 119 (range 31-380) days for the 22 patients in whom mustine was used. Survival of the C parvum group was significantly greater (p less than 0.01). The difference was principally due to the greater number of long term survivors in the C parvum group, nine of this group living for more than 180 days (mean 574, range 180-1143 days) compared with only four such survivors in the mustine group (mean 263, range 193-380 days). This study confirms our initial impression that C parvum is highly effective in controlling recurrent malignant pleural effusions. The finding of unexpected long term survivors with C parvum treatment suggests that this treatment may have an additional effect on the progression of disease, a finding that merits further investigation.

Five-year results of a controlled study of BCG immunotherapy after surgical resection in bronchogenic carcinoma.

Ninety-two patients with histologically confirmed bronchogenic carcinoma treated by surgical resection of the tumour were subsequently given immunotherapy with BCG (Glaxo). The patients were randomly allocated into three groups. Twenty-nine patients received multipuncture BCG (50 to 250 X 10(6) viable units), and twenty-six patients intradermal BCG (0.4 to 0.9 X 10(6) viable units), treatment being given at 1, 2, 6, 9, 13, 26, and 52 weeks after operation. Thirty-seven control patients did not receive any BCG immunotherapy; two patients in the control group were lost to follow-up. The overall five-year survival in all groups was 37%. Favourable prognostic features were squamous carcinoma (45% five-year survival), the absence of involved mediastinal nodes at operation (46%), and lobectomy (45%), but even the presence of involved mediastinal nodes was associated with a 19% five-year survival. There were no statistically significant differences between the survival of the control group and either group treated by immunotherapy considered individually or in combination. The influence of the presence of positive mediastinal lymph nodes and the extent of surgical resection on survival was not affected by immunotherapy. No serious side-effects of immunotherapy were encountered.

The changing pattern of laryngeal tuberculosis.

Laryngeal tuberculosis is now an uncommon disease in the United Kingdom. A series of ten cases is reported. In contrast to the pre-chemotherapy era, when the disease was associated with advanced cavitated pulmonary tuberculosis and was highly infectious, it now presents in a manner similar to laryngeal carcinoma except that painful dysphagia is a prominent symptom. All such patients should have a chest X-ray carried out as part of their initial investigation. Sputum is almost always positive for tubercle bacilli on direct films. Direct laryngoscopy and biopsy are necessary if a carcinoma is suspected. The change of pattern of the disease may be due to the fact that the larynx now usually becomes involved by haematogenous spread rather than by direct spread along the airways. Laryngeal tuberculosis is now no more infectious than pulmonary tuberculosis, and responds well to antituberculous chemotherapy. Symptoms resolve completely within three weeks if corticosteroids are given in combination.

Intrapleural immunotherapy with Corynebacterium parvum in recurrent malignant pleural effusions.

Twenty-one patients with proven recurrent malignant pleural effusions were randomly allocated to treatment groups receiving either intrapleural Corynebacterium parvum in a dose of 7 mg or intrapleural mustine (20 mg). The designated intrapleural therapy was repeated on one occasion if further pleural aspiration was required. Corynebacterium parvum (nine patients) proved superior to mustine (12 patients) in suppressing the reaccumulation of pleural fluid, and was associated with only minimal side-effects of fever and nausea in two patients. Mustine caused marked nausea and vomiting in almost all patients. Three of the four patients who were deemed "failures" after mustine therapy had complete suppression of pleural fluid reaccumulation after a single dose of C parvum, the survival of the fourth being too short to assess a response adequately. There were no failures in the C parvum treated group. Corynebacterium parvum appears to be an effective, well-tolerated agent in the management of recurrent pleural effusions. The relative contribution of its potent immunological stimulant effect to its mode of action remains uncertain.

Rifampicin-induced porphyria cutanea tarda.

A patient who developed porphyria cutanea tarda and disturbed liver function tests following treatment with rifampicin and isoniazid for a tuberculous psoas abscess is reported. The patient had normal liver function tests prior to receiving anti-tuberculosis chemotherapy, but was subsequently demonstrated to have cholelithiasis. Challenge testing with both drugs incriminated rifampicin as the agent precipitating porphyria cutanea tarda and disturbance of the liver function tests particularly the serum bilirubin. The association between rifampicin and porphyria cutanea tarda has not previously been described but might be expected because of the ability of rifampicin to induce various liver enzyme systems including delta aminolevulinic acid synthetase activity. This further illustration of rifampicin hepatotoxicity emphasizes the need for regular monitoring of liver function when rifampicin is prescribed. Rifampicin should be used with extreme caution in any patient with a previous history of porphyria cutanea tarda.

Intralesional injection of BCG using the fibreoptic bronchoscope in the treatment of bronchogenic carcinoma.

Current evidence suggests that the most effective administration of BCG immunotherapy is by the intralesional route. The new technique and complications of BCG intralesional injection of bronchogenic carcinomas via the fibreoptic bronchoscope is described. Seventeen patients with irresectable bronchogenic carcinoma have been treated with chemotherapy and BCG intralesional immunotherapy. Side-effects observed with intralesional BCG injection are: fever, hypotension and transient mild disturbances of liver function tests, and a single episode of granulomatous hepatitis. Early clinical improvement (nine patients) and radiological regression of the tumour (six patients) have been observed. Cavitation of the tumour has also been observed in three patients. Long term results are not yet available.

Vulval tuberculosis.

A patient with chronic tuberculous ulceration of the vulva is reported. Tuberculosis of the external genitalia is unusual and primary infections are rare. Venereal transmission of the infection could not be proven in this patient, but appears the most likely origin of the disease. Complete healing of the vulval ulcer, with rapid relief of symptoms, followed antituberculosis chemotherapy. The importance of biopsy in the diagnosis of chronic genital ulcers is emphasised.

Tuberculosis in immunosuppressed patients.

11 patients who developed tuberculosis while on long-term immunosuppressive-drug therapy are described. The indications for immunosuppressive therapy were varied, but all patients received high doses of corticosteroids with azathioprine in addition in 2 cases and chlorambucil in a third. The diagnosis was delayed in all cases because of suppression of symptoms, so that 4 patients died, 3 directly as a result of tuberculosis. 3 of the remaining patients were critically ill at the time of diagnosis but recovered with antituberculosis chemotherapy; whereas the other 4, although not critically ill, had advanced cavitated pulmonary tuberculosis with miliary spread in one case. A clear policy of investigation and, if indicated, chemoprophylaxis is necessary for all patients in whom long-term immunosuppressive therapy, especially with prednisolone, is contemplated. A high index of suspicion for tuberculosis must be maintained with regular clinical and radiological review.

Spontaneous mid-oesophageal rupture.

The clinical presentation and management of spontaneous rupture of the middle third of the oesophagus is described in two patients. Early presentation and treatment in one case led to uncomplicated recovery. In the other patient late presentation and diagnosis resulted in delayed surgical intervention with an unsuccessful outcome. The nature of this rare lesion is discussed and nine previously described cases are reviewed.

An evaluation of the efficacy and acceptability of 'Slender' in refractory obesity.

A formula diet 'Slender' was assessed in 55 patients with refractory obesity. During the initial 12 weeks of the study, the subjects were instructed to take a carbohydrate restricted diet designed to provide 1000 kcal (4.2 MJ) per day. They were then advised to replace up to four meals a day with a packet of Slender. Of the 42 subjects completing the study, 21 stopped taking Slender after six weeks and 21 completed 12 weeks. During the pre-Slender treatment, the mean weight gain was 1.7 kg. This contrasts with a mean weight loss during the first six weeks of treatment with Slender of 1.9 kg. Those continuing to take Slender for 12 weeks lost 3.7 kg and subjects who said that they had adhered strictly throughout the trial period had a mean loss of 4.6 kg. The overall results are relatively disappointing but are similar to that which can be achieved with other forms of therapy in comparable patients. If there is use for Slender, and other similar products, it may be the prevention of obesity rather than in the management of the morbidly obese.

Comparison in leprosy patients of Fernandex and Mitsuda reactions using human and armadillo antigens. A double-blind study.

The Mitsuda and Fernandez reactions to bacilli prepared from lesions of human patients and bacilli from infected armadillos were studied in 112 leprosy patients. It was observed that there is no substantial difference when armadillo lepromin is used instead of human lepromin except that a larger induration occurs with the use of the armadillo lepromin in a majority of cases. The number of those reporting a burning sensation at the armadillo lepromin injection site was slightly higher in lepromatous patients; whereas the burning sensation was observed at the human lepromin injection site by the tuberculoid cases. With the significant information compiled in this study, it is concluded that lepromin prepared from bacilli obtained from infected armadillos is as effective as that prepared from bacilli obtained from the lesions of leprosy patients.