Effect of age on the relationship between gastric cancer and Helicobacter pylori. Tokyo Research Group of Prevention for Gastric Cancer.

Helicobacter pylori is thought to be involved in the pathogenesis of gastric cancer, but the time point at which it produces its effects (critical time) is unknown. We measured the serum level of H. pylori antibody in 787 gastric cancer patients and 1007 controls aged 20 to 69. Odds ratios for different gastric cancer types and stages were determined for each 10-year age class. The overall odds ratio for gastric cancer decreased with age, being 7.0 for those aged 20 - 29, 14.5 for those aged 30 - 39, 9.1 for those aged 40 - 49, 3.5 for those aged 50 - 59, and 1.5 for those aged 60 - 69 (trend in odds ratios: P < 0.01). However, there was no such age-dependent trend for early diffuse-type cancer; the odds ratios were 12.6, 4.0, 7.2, 6.5, and 18.5 respectively (P = 0.29). Early cancer tended to show higher seroprevalence than advanced cancer, especially in older subjects. No significant difference in seroprevalence was observed between diffuse and intestinal cancers within each age-class. Seroreversion must have occurred in the time interval between the critical time and the diagnosis of the cancer, especially in older patients. The age-dependent relationship between H. pylori and gastric cancer may be due to seroreversion, which itself may be independent of age. This age-independence indicates that prolonged exposure to H. pylori does not increase the magnitude of its influence on gastric carcinogenesis. Possible mechanisms through which H. pylori exerts pathogenic effects are continuous inflammation in adulthood and / or irreversible damage to gastric mucosa in childhood or the teenage years.

[Interferon production in vitro].

Interferon production in vitro was induced by poly I: C and PHA in leukocytes obtained from patients with cancer, benign diseases and control subjects. The interferon response per lymphocyte was relatively constant in all groups. However, interferon production was slightly inhibited in patients receiving cancer chemotherapy. The peak response of interferon occurred at 48 hours after the initiation of the combined culture in each specimen. From our observations, it was suggested that interferon production in vitro seems to be useful marker for evaluation of effect of chemotherapy and or immunotherapy, and, furthermore, in the treatment of cancer patients with interferon inducers, there seems to be optimum BRM dose and optimum timing of administration.

[Host factors in cancer chemotherapy].

Cancer grows in interaction with the host, that is, a host-tumor relationship exists. Investigations of host factors in patients receiving cancer chemotherapy are important, as they reveal the conditions in which a tumor response can develop. Furthermore, reliable host factors, if present, will be useful for quantitative evaluation of the effects of treatment. We have investigated the following three categories of host factors in relation to the effects of cancer chemotherapy and/or immunotherapy. CBC, and blood chemistries (44 parameters). Tumor markers; sialic acid, RNase, lysozyme, ferritin, IAP (immunosuppressive acidic protein), elastase I, AFP, CEA, POA, CA 19-9, CA 125, etc. Immunological parameters; lymphocyte, active T cell, T cell, B cell, IgG Fc receptor-positive T cell, lymphocyte blastogenesis stimulated by PHA, or concanavalin-A, ADCC activity, interferon production in vitro induced by poly I: C, or PHA, PPD skin test, immune complex, immunoglobulin G, A, and M, OKT series 3, 4, 8, 11, 4/8 ratio, antihuman HLA-DR, Leu 11, NK cell activity, etc. From our clinical observations, there were no significant differences in the pretreatment levels of these parameters between responders and non-responders. In responders, there was a tendency for the host factors to show greater degrees of improvement following treatment than in non-responders, but none proved to be reasonably reliable parameters for evaluating therapeutic effects. On the other hand, from our clinical observations on the advanced gastric cancer cases, life span showed a close correlation with tumor regression induced by cancer chemotherapy. Because of these facts, it is only natural that the clinical effects of chemotherapy are currently determined by definite tumor regression.

[A case of jaw opening phenomenon associated with basilar artery thrombosis].

We describe a 74 year old man who showed the jaw opening phenomenon by painful stimuli from two months after the onset of basilar artery thrombosis. He was admitted to our hospital because of consciousness disturbance and paralysis of all extremities. Soon after admission, he was in a state of impending herniation but with conservative therapy he recovered slightly, and then fell into an akinetic and mute state. Two months after the onset of the stroke, he began to open his mouth in response to painful stimuli, and five months after the stroke palatal myoclonus also appeared. Neurological signs and symptoms five months after admission were as follows; he was akinetic, mute and always kept his eyes closed because of complete blepharoptosis due to oculomotor nerve palsy. Pupils were dilated and adducted. Bilateral light reflexes were absent and the oculocepharic reflex could not adduct the eyes inwardly. Bilateral corneal reflexes were present, facial reflexes were exaggerated and jaw reflexes were also active. All limbs were spastic and paralyzed, and no voluntary movement was observed. Deep tendon reflexes were active in all extremities, and bilateral plantar responses were extensor. Palatal myoclonus was recognized in his soft palate, lips, sternocleidomastoid and diaphragm. Its frequency was about 150 cycles per minute. CT scan revealed severe low density areas in the midbrain and bilateral posterior lobes. In cerebral angiography, the upper part of the basilar artery was completely occluded.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacokinetics of human interferons].

Interferon in the blood was rapidly cleared from the circulation after intravenous injection. Intramuscular injection of alpha-interferon caused low but stable interferon levels in the blood. However, in the case of beta-interferon, interferon was never detected consistently in the blood after intramuscular or subcutaneous administration. Intraarterial administration of beta-interferon also caused low but stable interferon levels in the blood. Our studies suggest that beta-interferon should be given intravenously to see clinical beneficial. No difference in pharmacokinetics was seen between natural interferon and recombinant interferon. No difference was also noted between partially purified interferon and highly purified interferon.

[Phase II clinical trial of MCNU].

MCNU is a new derivative of nitrosourea and experimental studies have shown equal or superior activity to known nitrosourea compounds. Twenty one cases were entered into our clinical studies with a phase II study. Nineteen cases have had a several courses of prior chemotherapy. Four out of 21 cases achieved a partial response (each one of lymphoepithelioma, parotid gland cancer, recurrent uterine cancer and recurrent breast cancer). The major toxicity encountered during treatment was myelosuppression. Full recovery of myelosuppression was delayed and was seen six to eight weeks after each injections. These initial results justify further clinical investigations with MCNU.