Combination of consecutive low-dose cisplatin with bleomycin, vincristine, and mitomycin for recurrent cervical carcinoma.

PURPOSE: To evaluate the efficacy and toxicity of combination chemotherapy with bleomycin, vincristine, mitomycin, and consecutive low-dose (CLD) administration of cisplatin (CLD-BOMP) for patients with recurrent cervical carcinoma. PATIENTS AND METHODS: Ninety patients with recurrent cervical carcinoma and no prior chemotherapy were enrolled onto this study. The median age was 56 years. Eighty-seven of the 90 patients had received prior radiotherapy. The CLD-BOMP regimen was bleomycin 5 mg infused continuously days 1 through 7; vincristine 0.7 mg/m2 bolus day 7; mitomycin 7 mg/m2 bolus day 7; and cisplatin 10 mg/m2 infused over 4 hours days 1 through 7. The treatment was repeated at 3-week intervals. RESULTS: All 90 patients were assessable for response, toxicity, and survival. After a median of four cycles (range, two to 10 cycles), we observed objective responses in 68 patients (76%), with 25 (28%) complete responses (CRs) and 43 (48%) partial responses (PRs; 95% confidence interval (CI), 66 to 85; 18 to 38; 37 to 59, respectively). Median survival for all 90 patients was 24.3 months (range, 2.3 to 100 months). The median survival for patients who achieved CR, PR, no change (NC), and progressive disease (PD) were not reached (NR), 23.6, 8.2, and 6.4 months, respectively. The median progression-free survival for patients who achieved CR and PR were NR and 12.3 months, respectively. There was no significant nausea or vomiting, nephrotoxicity, or pulmonary toxicity, which was attributable to the CLD-cisplatin and the adequate dosing schedule of bleomycin. The reduced toxicities allowed this regimen to be administered at the projected dose-intensities. CONCLUSION: The CLD-BOMP regimen has significant antitumor activity with markedly reduced toxicity.

Response of adrenal efferent nerve activity to non-noxious mechanical stimulation of the skin in rats.

The effects of brushing various segmental skin areas (neck, lower chest, abdomen and thigh) on adrenal sympathetic efferent nerve activity were examined in anesthetized rats. In the CNS intact rats, brushing of all areas produced a large reflex decrease in the efferent nerve activity, whereas, in the spinalized rats, brushing the lower chest or abdominal skin area produced an increased response while brushing the neck or thigh skin area produced no significant changes in the efferent nerve activity. It is suggested that the segmental excitatory organization of the adrenal nerve reflex caused by brushing within the spinal cord is modified into a non-segmental or generalized inhibitory organization by the supraspinal structure.

Effect of human urinary macrophage colony-stimulating factor on the immune functions and the blood cell counts in patients with ovarian carcinoma receiving cytotoxic chemotherapy.

The present study investigated the effect of macrophage colony-stimulating factor (M-CSF) on the immune functions and blood cell counts of patients with ovarian carcinoma receiving cytotoxic chemotherapy (CTX). Seventy-five consecutive patients with white blood cell counts less than 3,000/microl after CTX were randomly assigned to receive either M-CSF (human urinary macrophage colony-stimulating factor: hM-CSF, 8x106 U as 7-day intravenous infusions) or no treatment. Immune assays in addition to routine peripheral blood examinations were performed on these patients at various time points. hM-CSF dosing significantly increased monocyte, lymphocyte, granulocyte, and platelet counts that were decreased by CTX. hM-CSF also significantly enhanced lymphokine-activated killer and natural killer activities, which was accompanied by a significantly augmented interleukin (IL)-2 production. Interestingly, IL-2 production was enhanced by hM-CSF dosing in 24 of the 27 patients with a pre-hM-CSF level of IL-2 below 10 U/ml, but such an effect was not observed in nine of the 10 patients having a basal value of 10 U/ml or higher. Thus, hM-CSF is considered to be a cytokine that can augment or regulate immune functions impaired by CTX and increase blood cell counts that are decreased by CTX.

Primary lymphocutaneous nocardiosis due to Nocardia otitidiscaviarum: the first case report from Japan.

We report a case of lymphocutaneous syndrome caused by Nocardia otitidiscaviarum (formerly known as N. caviae) in a 78-year-old woman who underwent long-term therapy with prednisolone for bronchial asthma. Histological examination showed granulomatous reaction with multiple polymorphonuclear leukocytes and revealed a Gram positive filament in the dermis. Gram-positive, slightly acid-fast branched filaments were also found in the smear of the purulent material. The cell wall constituents of the isolate were meso-diaminopimelic acid, arabinose, and galactose; the mycolic acid pattern of the isolate was Nocardia type. The organism decomposed xanthine and hypoxanthine, but not tyrosine or casein, which distinguished it from N. asteroides and N. brasiliensis. The skin lesions responded to minocycline and later to a combination of doxycycline and ofloxacin. This primary lymphocutaneous nocardiosis due to N. otitidiseaviarum is the first in Japan.

Influences of everninomicin, vancomycin and teicoplanin on chemical mediator release from rat peritoneal mast cells.

We examined influences of certain antibiotics on the release of chemical mediators from isolated rat peritoneal mast cells in vitro. Isolated peritoneal mast cells were obtained from male Wistar strain rats. Everninomicin (0.06-1.2 mg/ml), vancomycin (0.05-1.0 mg/ml), teicoplanin (0.07-1.4 mg/ml) and concanavalin A (0.01 mg/ml) were used. Isolated mast cells were incubated in the presence of various concentrations of the test compound at 37 degrees C for 10 min. Histamine contents of the supernatant and cell pellet were measured by an automated fluorometric method. Prostaglandin D2 (PGD2) contents of the supernatant were determined by enzyme immunoassay. Everninomicin (0.06-1.2 mg/ml) had no influence on histamine and PGD2 release from mast cells. On the other hand, vancomycin significantly released both histamine (0.5 and 1.0 mg/ml) and PGD2 (1.0 mg/ml) from mast cells, but vancomycin did not affect concanavalin A-induced histamine and PGD2 release. Teicoplanin (more than 0.07 mg/ml) significantly stimulated histamine and PGD2 release from mast cells and it also significantly potentiated concanavalin A-induced histamine and PGD2 release. These results suggest that everninomicin causes no chemical mediator release from mast cells, different from vancomycin and teicoplanin.

Is the invasion depth in millimeters valid to determine the prognosis of early invasive cervical adenocarcinoma? A case of recurrent FIGO stage IA1 cervical adenocarcinoma.

BACKGROUND: Recurrence of FIGO stage IA1 cervical adenocarcinoma is extremely rare. We herein report a patient with early invasive cervical adenocarcinoma who developed a recurrence in the vaginal stump. CASE: A 52-year-old female complained of contact bleeding. Biopsy of the uterine cervix verified cervical adenocarcinoma, and the patient underwent Okabayashi hysterectomy with pelvic lymphadnectomy and bilateral adnectomy. Histopathologic examination of the uterus revealed an invasive cancer 3 mm in depth. Neither lymph node metastasis nor lymph-vascular space invasion was observed. However, the depth of her normal cervical gland area was 2 mm only, and the cancer invasion involved an area which was deeper than the normal cervical gland area. The vaginal stump recurrence developed 4 years after surgery. CONCLUSION: The depth of invasion with reference to that of normal cervical glands may become a possible prognostic factor for early invasive cervical adenocarcinoma.

Effects of diethyldithiocarbamate, a metabolite of disulfiram, on the pharmacokinetics of alcohol and acetaldehyde in the rat.

The effects of diethyldithiocarbamate (DDC), a metabolite of disulfiram which is known as Antabuse, on the blood concentrations of alcohol and acetaldehyde were determined simultaneously by head space gas chromatography in rats. After an intravenous injection of alcohol, the blood concentration of acetaldehyde was much lower than that of the alcohol. A pharmacokinetic model featuring the liver compartment for acetaldehyde was used to estimate pharmacokinetic parameters on the assumption that the distribution volumes of the central compartments were same for alcohol and acetaldehyde, and that the elimination rate of acetaldehyde from liver was large enough to isolate the liver compartment from the central compartment. The results showed that the clearance of alcohol was 0.0226 l/min/kg and the elimination rate constant of acetaldehyde from the liver compartment was very large and 35 min-1. The administration of DDC decreased the above significantly to 0.0132 l/min/kg and 20 min-1, respectively. After intravenous infusion of acetaldehyde, the time course of the blood concentration of acetaldehyde was analyzed by the one compartment model. The estimated elimination rate constants from blood and the distribution volume were in good agreement with those calculated from alcohol injection, indicating the appropriateness of the method used in this study. DDC had no effect on the elimination of infused acetaldehyde from blood indicating that the elimination may be due to the loss from lungs into breath, from skin surfaces and/or from the kidney but not by metabolism in the liver.

Utility of the monoclonal antibody HIK1083 in the diagnosis of adenoma malignum of the uterine cervix.

OBJECTIVES: The aim of this study was to qualify a staining technique for the diagnosis of adenoma malignum. METHODS: The gastric mucin expression of adenoma malignum, ordinary endocervical adenocarcinoma, and normal cervical glands was immunohistochemically compared using the monoclonal antibody HIK1083. RESULTS: The three categories were clearly distinguished, with 90% (9/10) of cases with positive adenoma malignum, 30% (3/10) of cases with weakly positive ordinary cervical adenocarcinoma, and no (0/10) cases of positive normal cervical glands. CONCLUSIONS: This preliminary report indicates that the use of HIK1083 is valuable in the diagnosis of adenoma malignum.