Continuous versus intermittent subcutaneous infusion of octreotide in the treatment of acromegaly.

This review evaluates the efficacy, tolerability, and safety of continuous subcutaneous infusion (CSI) relative to intermittent subcutaneous injection (ISI) of the somatostatin analog, octreotide in the treatment of acromegaly. Data was extracted from five clinical series using CSI octreotide in acromegaly, six reports comparing CSI to ISI, and three studies comparing pulsatile subcutaneous infusion (PSI) to ISI. Effects of each drug regimen on the control of growth hormone (GH), insulin-like growth factor (IGF-1), clinical symptomatology, pituitary tumor size, and adverse effects were evaluated. Normalization of serum GH or IGF-1 levels, as well as improvement in clinical symptoms was reported in the majority of the patients studied. Cases in which pituitary adenomas decreased in size were also documented during the study period. When the effects of CSI were compared with ISI, a more pronounced control of GH and IGF-1 was observed. In addition, diurnal GH fluctuation during CSI was significantly reduced relative to ISI in two reports. Moreover, in two patients, CSI achieved similar clinical and biochemical effects at lower doses than when the drug was given by ISI. Finally, adverse effects with CSI may be less severe than with ISI. Continuous subcutaneous infusion of octreotide produced biochemical improvement in 67 of the 88 patients reviewed. When compared with ISI, CSI induced more pronounced biochemical control, often with less fluctuation in GH and IGF-1 levels. Because of a lack of data, definite conclusions regarding the differences between regimens on clinical symptomatology and tolerability could not be discerned. A large prospective, long-term randomized crossover study is recommended to make these determinations.

[Therapeutic applications of somatostatin and its analog, octreotide]. / Applications thérapeutiques de la somatostatine et de son analogue, l'octréotide.

Octreotide is routinely used in the treatment of acromegaly and gastroenteropancreatic tumours such as carcinoids and VIPomas. The most promising indications for octreotide appear, at present, to be as an adjunct therapy in the management of acute oesophageal variceal bleeding, AIDS-related refractory, diarrhoea, digestive fistulae and the prevention of postoperative pancreatic complications (e.g. pancreatitis, fistulae...). Its potential role in the treatment of carcinoma is being currently explored in prospective controlled trials.

In vitro flow phantom analysis and clot-capturing ability of incompletely opened Vena Tech-LGM vena caval filters.

It has been shown recently that Vena Tech-LGM (B. Braun Vena Tech, Evanston, IL) filters inserted into the inferior vena cava via the jugular route may be deployed sometimes in an incompletely opened (IO) position. The flow characteristics and clot capturing ability of IO Vena Tech-LGM filters are not clearly understood. Using a vena cava flow phantom, the clot-capturing abilities of the IO and opened Vena Tech-LGM filters were assessed. For 5 x 5-mm clots, the IO Vena Tech-LGM filter captured only 40% of thrombi compared with a 90% capture rate for the opened filter. The capture rates were 90 and 100% for the IO and opened filter, respectively, for larger 5 x 15-mm clots. It was found that the IO filter could capture 2-7 x 25 mm thrombi prior to the development of a turbulent bypass channel which prevented subsequent clot capture. Using 5 x 15 mm clots, this same phenomenon occurred with the capture of 6 and 11 thrombi by the IO and opened Vena Tech-LGM filters, respectively. Our results suggest a significantly reduced filtering efficiency for the IO Vena Tech-LGM device. However, there is a high rate of clot capture with the opened Vena Tech-LGM filter.

RAS enzyme-linked immunoblot assay discriminates p21 species: a technique to dissect gene family expression.

The members of the RAS gene family of protooncogenes are of implied biological significance in oncogenesis. The precise role of these genes is unclear. One difficulty has been the inability to discriminate the individual p21 protein products of various ras genes in cell lines, de novo human tumors, and related normal tissues. In this report, specific proteins of the human c-Ha-ras-1, c-Ki-ras-2, and c-N-ras genes have been detected and discriminated by the differential use of various antisera recognizing these p21s. This enzyme-linked immunoblot assay utilizes a double antibody system in which monoclonal antibodies are initially used to immunoprecipitate the p21ras proteins. Immunoprecipitates are then subjected to one-dimensional Western blot analysis utilizing other antibodies raised against p21s, coupled with nonradiolabeled enzyme-linked colorimetric detection. By direct detection, the specific products of the three human ras genes can be discriminated. In addition, we describe the generation and characterization of a new anti-p21c-N-ras-specific antibody. The simultaneous expression into protein of multiple ras genes is unequivocally demonstrated in both homogeneous cell lines and heterogeneous human tissues. This new technique is also applicable for discrimination of the protein products of other gene families.

Human bladder and colon carcinomas contain activated ras p21. Specific detection of twelfth codon mutants.

Members of the ras family of proto-oncogenes code for 21,000-dalton molecular weight protein products (p21s). Transformation of cells from the normal to the malignant phenotype in experimental studies has been associated with point mutations within the coding region for these ras proteins. Recent reports demonstrate that 40% of human colon cancers and 20% of acute leukemias contain ras mutations in the twelfth or thirteenth codon that can result in amino acid substitutions at these positions in the p21 products. Similarly, studies of ras mRNA detected 40% of human colon tumors with twelfth codon c-Ki-ras mutant mRNA. The authors previously developed a nonradioactive double-antibody enzyme-linked immunoblot assay (ELIBA) for detection of normal and mutant ras p21. They have adapted that technology to specifically detect twelfth codon activated ras p21 utilizing mutation-specific antisera. In this report the authors show that one of seven de novo human bladder cancers and four of seven colon cancers express a twelfth codon activated ras p21. These results document that mutations at both the DNA and mRNA levels are ultimately translated into an abnormal protein product present in human tumors.