Expression of phage P4 integrase is regulated negatively by both Int and Vis.

Phage P4 int gene encodes the integrase responsible for phage integration into and excision from the Escherichia coli chromosome. Here, the data showing that P4 int expression is regulated in a complex manner at different levels are presented. First of all, the Pint promoter is regulated negatively by both Int and Vis, the P4 excisionase. The N-terminal portion of Int appears to be sufficient for such a negative autoregulation, suggesting that the Int N terminus is implicated in DNA binding. Second, full-length transcripts covering the entire int gene could be detected only upon P4 infection, whereas in P4 lysogens only short 5'-end covering transcripts were detectable. On the other hand, transcripts covering the 5'-end of int were also very abundant upon infection. It thus appears that premature transcription termination and/or mRNA degradation play a role in Int-negative regulation both on the basal prophage transcription and upon infection. Finally, comparison between Pint-lacZ transcriptional and translational fusions suggests that Vis regulates Int expression post-transcriptionally. The findings that Vis is also an RNA-binding protein and that Int may be translated from two different start codons have implications on possible regulation models of Int expression.

Recombinant bacterial cells as efficient biocatalysts for the production of nucleosides.

The preparation of nucleosides as well as their base-modified analogues using purified nucleoside phosphorylase enzymes or, more conveniently, using whole bacterial cells is described. The development of genetically modified strains of Escherichia coli, able to over-produce Uridine-phosphorylase and Purine-nucleoside-phosphorylase in the same cells, improves the specific biocatalytic activity and the consequent industrial scale approach.

Octreotide in relieving gastrointestinal symptoms due to bowel obstruction.

Gastrointestinal obstruction is a common problem in advanced malignant disease, but its management remains controversial. In those patients for whom surgery is not appropriate, medical intervention is the only remaining option. We present a series of 14 patients with intestinal obstruction who were managed with subcutaneous injections of octreotide, a somatostatin analogue which reduces the volume of gastrointestinal secretions. Good control of vomiting was achieved in 12 patients, and no major side effects were observed. Octreotide would appear to be a useful drug in this clinical situation.

Continuous subcutaneous infusion of hyoscine butylbromide reduces secretions in patients with gastrointestinal obstruction.

We describe the use of hyoscine butylbromide as a subcutaneous infusion in 3 patients with inoperable malignant bowel obstruction. An objective reduction of drainage from the gastrointestinal tract was observed with the hyoscine butylbromide infusion (60-120 mg/day). We suggest that this effect can be useful in the palliative treatment of vomiting in inoperable bowel obstruction.

Local toxicity with subcutaneous methadone. Experience of two centers.

We report on 8 patients treated with subcutaneous methadone for cancer-related pain at 2 institutions. The success of other subcutaneous agents for pain control has been well demonstrated. It was felt that methadone would be useful due to its low cost. Unfortunately, 7 of the 8 patients experienced adverse reactions at the subcutaneous sites requiring cessation of subcutaneous methadone.

The management of inoperable gastrointestinal obstruction in terminal cancer patients.

The aim of the study was to assess vomit and pain control in terminal cancer patients with inoperable gastrointestinal obstruction, using a pharmacologic symptomatic treatment which prevents recourse to nasogastric tube placement and intravenous hydration, in hospital and home care settings. Twenty-two symptomatic patients, who were judged as inoperable, were treated with a pharmacologic association of morphine hydrochloride and scopolamine butylbromide as analgesics and haloperidol as an antiemetic. The drugs were administered by continuous subcutaneous infusion via a syringe driver or intravenously only when a central venous catheter had been inserted previously. Daily recordings included assessment of pain, number of vomiting episodes, dry mouth, drowsiness, and thirst sensation. Data were examined before starting the treatment (T0), 2 days after (T2) and 2 days before death (T-2). They showed that there was a significant decrease in the pain score (p less than 0.001) on T2 and a further decrease on T-2 (p less than 0.05). Vomiting was controlled in all patients, with the exception of three patients with upper abdomen obstruction who required nasogastric tube placement. Dry mouth showed an upward trend throughout the observation period (p less than 0.05) but was successfully treated by administering liquids by mouth or ice-cubes to suck. Drowsiness too presented an upward trend from T0 to T-2 (p less than 0.001). Only one patient out of 16 who reported to be thirsty required intravenous hydration. We believe that in terminal cancer patients, vomit and pain resulting from inoperable intestinal obstruction, with the exception of obstruction of the upper abdomen, can be controlled through administration of analgesic and antiemetic drugs, in the hospital and at home, without recourse to nasogastric tube placement or intravenous hydration.

Intraspinal morphine for cancer pain.

From a survey of the recent literature on chronic intraspinal morphine administration for cancer pain concerning 412 cases, the present authors observe that: 1. data regarding follow-up on pain relief and complications are lacking; 2. continuous administration by closed systems shows more efficacy in long-term pain relief; 3. tolerance, although not reported by all authors, is present and becomes remarkable in prolonged administration; 4. serious side-effects are less frequent with the epidural administration technique. These data are confirmed by the present authors' clinical experience of 22 patients treated with epidural morphine administration and 53 patients treated with intrathecal morphine. The widespread use of these methods is limited not only by technical complications but also by the existence of certain types of pain which do not respond to morphine and which may develop, as part of the evolution of the neoplastic disease, even during treatment with intraspinal morphine.