Options for investigative postsurgical therapy for gastric cancer, and case report of using the option for combined immunotherapy and chemotherapy.

The investigative therapy for a senior patient after radical subtotal gastroesophagectomy for regional lymph node and proximal esophagus metastasized adenocarcinoma (stage IIIA, T3, N 1 M0) of the cardioesophageal junction is reported. The case has several unusual features: (1) the patient is the author and is not a physician; (2) in the absence of codified postsurgical treatment, he used his academic biomedical background, commercial associations, and international contacts to find and prioritize six clinically tested options for investigative postsurgical therapy; (3) after unsuccessful efforts to append ongoing clinical trials of new immunotherapies for breast adenocarcinoma (the first two therapy options), an innovative protocol was designed and gained allowance by the U.S. Food and Drug Administration for his use of combined nonspecific immunotherapy and chemotherapy based on extensive trials in South Korea that showed the synergistic effect of the two postsurgical therapies used together. A potent, new, nonspecific immunostimulant (DetoxPC) was injected subcutaneously in 10 diminishing doses during 105 weeks. Two standard chemotherapeutic drugs (5-fluorouracil and mitomycin-C) were injected intravenously in six equal doses during three weeks. Five years after the surgery, the patient enjoys good health without signs or symptoms of recurrence or metastasis. He discusses his perspectives on future clinical trials and on a patient actively pursuing investigative postsurgical therapy for a malignancy when otherwise poor survival is indicated.

Adenocarcinoma of the gastro-esophageal junction: CT for monitoring during neoadjuvant chemotherapy.

OBJECTIVE: A clinical study was performed to assess the diagnostic value of spiral CT for evaluation of response during neoadjuvant chemotherapy (CTx) in patients with adenocarcinoma of the gastro-esophageal-junction (GEJ). Results were compared to those of endoscopy. METHODS AND MATERIAL: Twenty-five patients with histologically proven adenocarcinoma of the GEJ scheduled to undergo neoadjuvant CTx were studied. Before CT examination, 1200 ml of a vanilla flavoured paraffin emulsion were applied orally to the fasting patients and 40 mg BuscopanR or 2 mg glucagon were injected i.v. for hypotonia. Iodine (100 ml) was injected automatically (3 ml/s) and the CT scan was started 10 s after complete administration of CM. For response evaluation to CTx, four standardized parameters were measured by two experienced, blinded radiologists. The results were categorized according to the WHO classification of 1981 and compared to those of endoscopy. RESULTS: In 24 of 25 patients endoscopic and computed tomographic response evaluation showed a close correlation (r = 0.96). CONCLUSION: Spiral CT with negative oral contrast agent is a suitable technique for monitoring of GEJ masses. In combination with standardized metric parameters it offers a quantitative response evaluation in patients with GEJ masses during neoadjuvant CTx.

Evidence for dose-dependent positively and negatively reinforcing effects of the substance P C-terminal analog DIME-C7.

Possible positive reinforcing and aversive effects of intraperitoneally (ip) administered substance P (SP) and its C-terminal heptapeptide analog [pGlu5, MePhe8, Sar9]-SP5-11 (DIME-C7) were investigated in rats. The 'conditioned corral preference and avoidance procedure' was used for assessing positive and negative reinforcement. Behavioural testing was conducted in a circular open field consisting of four uniform quadrants equally preferred by the rats prior to drug treatment. On 3 consecutive days, rats received an ip injection of either SP (37 nmol/kg), DIME-C7 (3.7, 7.4, 37, 185 nmol/kg) or vehicle (0.01 M acetic acid in saline) and were placed immediately into their assigned treatment corral. During the test for conditioned corral preference and avoidance, when provided a choice between the four quadrants, rats treated with SP and with the equimolar dose of DIME-C7 (37 nmol/kg) spent significant more time in the drug-paired corral, indicative of positive reinforcing effects. The doses of 3.7 and 7.4 nmol/kg DIME-C7 did not influence the preference behaviour. The high dose of 185 nmol/kg DIME-C7 led to a significant decrease in time spent in the previously drug-paired corral, suggestive of aversive effects of the treatment. Gross locomotor activity was not influenced by either treatment. These results are discussed in the framework of a structure/activity relationship for the reinforcing properties of peripheraly applied SP.

Antimicrobial actions of hexachlorophene: cytological manifestations.

Hexachlorophene is a soap-compatible bisphenol that has been widely used as an antiseptic, yet its mechanism of action is undefined. The relative threshold concentration for bactericidal effect on a susceptible test organism, Bacillus megaterium, was established to be about 10 mug/mg of cell dry weight. At this or at high (>/=100 mug/mg) concentration, adsorptive uptake by cells displayed saturation kinetics. At about 30 mug/mg, the time course of adsorption occurred in three distinct stages. The triphasic pattern was interpreted to represent successive penetration of and adsorption by the cell wall, the protoplast membrane, and the cytoplasm. This interpretation was substantiated by determinations of hexachlorophene adsorption by isolated cell components. Electron microscopy disclosed cytopathology, evidenced as gaps or discontinuities, in the protoplast membrane (but not in the cell wall or cytoplasm) at > 30 mug of hexachlorophene per mg of cell dry weight. Similarly, treatment with > 30 mug/mg allowed a fluorescigenic dye (tolyl-peri acid) to penetrate into the protoplast. However, no detectable cytological manifestations were discerned at the minimum lethal concentration of 10 mug/mg. Apparently, hexachlorophene is physically disruptive at intermediate or high relative concentrations but acts in a more subtle fashion at the minimal lethal concentration.

Chemical composition of exosporium from spores of Bacillus cereus.

Homogeneous fragments of exosporium were extricated in centigram amounts from dormant spores of Bacillus cereus and analyzed for intrinsic constituents. The membrane proved to be chemically complex but not unique, consisting mainly of protein (52%), amino and neutral polysaccharides (20%), lipids (18%), and ash (4%). Seventeen common amino acids were identified by chromatography, and were present in usual proportions except for low levels of cystine-cysteine, methionine, tyrosine, and histidine. Glucosamine was the only amino sugar, and glucose and rhamnose were the principal neutral sugars. The lipid fraction contained 5.5% cardiolipin as the only phospholipid, 12.5% neutral lipids, and at least 19 fatty acids, among which normal C(16) and C(18) ones predominated. Calcium and phosphorus occurred in the ash. Small amounts of teichoic, ribonucleic, and dipicolinic acids were believed to represent contamination.