Febrile seizures after 2010-2011 influenza vaccine in young children, United States: a vaccine safety signal from the vaccine adverse event reporting system.

During the 2010-2011 influenza season, the Centers for Disease Control and Prevention and the Food and Drug Administration conducted enhanced vaccine safety monitoring for possible febrile seizures in all trivalent influenza vaccine (TIV) products in the United States using the Vaccine Adverse Event Reporting System (VAERS). We used Empirical Bayesian data mining techniques to assess disproportionate reporting after TIV and reviewed febrile seizure reports in children aged <5 years. On November 23, 2010, the combination of the coding term "febrile convulsion" and the Fluzone(®) TIV product exceeded a predetermined threshold in the VAERS database. By December 10, we confirmed 43 reports of febrile seizure following TIV in children aged 6-23 months. Clinical features of most reports were consistent with typical uncomplicated febrile seizures, and all children recovered. Further epidemiologic assessment of a possible association between TIV and febrile seizures was undertaken in a separate, population-based vaccine safety monitoring system.

Distinct effects of pitavastatin and atorvastatin on lipoprotein subclasses in patients with Type 2 diabetes mellitus.

AIMS: Effects of pitavastatin and atorvastatin on the lipid profile and lipoprotein subclasses were compared in patients with Type 2 diabetes with dyslipidaemia. METHODS: Patients with Type 2 diabetes with hypercholesterolaemia and/or hypertriglyceridaemia were randomized to receive pitavastatin 2 mg (n = 16) or atorvastatin 10 mg (n = 15) for 6 months, and blood lipid and lipoprotein profiles and cholesterol and triglyceride contents of 20 lipoprotein subclasses, determined by high-performance liquid chromatography, were compared. RESULTS: At baseline, cholesterol in VLDL and LDL subclasses were increased equally in two groups of patients with diabetes as compared with normolipidaemic control subjects. As compared with baseline, serum levels of total cholesterol, LDL cholesterol, non-HDL cholesterol, LDL cholesterol:HDL cholesterol ratio and apolipoprotein B were decreased after 1, 3 and 6 months of treatment with atorvastatin and pitavastatin. Serum triglyceride levels were decreased after 1, 3 and 6 months of atorvastatin, but only at 3 months of pitavastatin. Serum HDL cholesterol was increased after 1, 3 and 6 months of pitavastatin, whereas HDL cholesterol was even decreased after 6 months of atorvastatin. Cholesterol levels of most VLDL and LDL subclasses were decreased equally in both groups. However, only pitavastatin increased cholesterol of medium HDL subclass. Serum triglyceride and triglyceride contents in VLDL and LDL subclasses were decreased only by atorvastatin. CONCLUSIONS: The impact on lipoprotein subclass profiles was different between pitavastatin and atorvastatin. It may be beneficial to determine lipoprotein subclass profile and select the appropriate statin for each profile in patients with diabetes with an additional cardiovascular risk such as low HDL cholesterol or hypertriglyceridaemia.

St. Jude Medical prosthetic aortic valve malfunction due to pannus formation.

According to the literature, the incidence of pannus formation with the St. Jude Medical prosthetic aortic valve has been reported at 0.03% and 0.14% (per patient-year), with no case report of St. Jude Medical prosthetic aortic valve malfunction due to pannus formation. Between 1980 and 1999, 1,186 patients underwent aortic valve replacement at our institute. We encountered 2 aortic valve malfunctions due to pannus formation, including the case of a 53-year-old woman who suffered a St. Jude medical aortic valve malfunction 13 years after the initial operation. A second aortic valve replacement was successful and the postoperative course was uneventful. The possibility of pannus formation on St. Jude Medical aortic valves must thus be considered and its mechanism clarified.

A comparison between low-flow leak test and oxygen flush leak test.

PURPOSE: The clinical efficacy of two methods of preanesthetic leak test,namely the oxygen flush leak test (OFLT) and the low-flow leak test (LFLT), was compared regarding their ability to detect leakage in the anesthesia circuit and their accuracy. METHODS: Examinees comprised 16 staff anesthesiologists and 7 physicians undergoing anesthesia training at our institution. They performed the two leak tests on anesthesia machines with some intentional leaks (0.1-1.0 l.min(-1)). The leakage detection rates (LDR) were analyzed by the chi(2)-test. The ability to detect leaks was measured by recording how many leaks were detected by 50% (LDR(50)) and 95% (LDR(95)) of the examinees. RESULTS: The LDRs in the two tests were significantly different (chi(2)- analysis, P < 0.0001). Both LDR(50) and LDR(95) for the LFLT (0.23 and 0.41 l.min(-1), respectively) were smaller than the values for the OFLT (0.37 and 0.82 l.min(-1), respectively). The sensitivity and specificity of the LFLT (0.97 and 0.84, respectively) were higher than those of the OFLT (0.78 and 0.80, respectively). CONCLUSION: The LFLT was found to be superior to the OFLT regarding leak detection and reliability. We therefore recommend the LFLT for preanesthetic leak testing.

Appropriate method of administration of propofol, fentanyl, and ketamine for patient-controlled sedation and analgesia during extracorporeal shock-wave lithotripsy.

PURPOSE: The aim of this study was to identify the appropriate method for administering propofol, fentanyl, and ketamine (PFK) for patient-controlled sedation and analgesia (PCSA) during extracorporeal shock-wave lithotripsy (ESWL). METHODS: Twenty-one unpremedicated patients were randomly assigned to three groups that received different drug administration regimens. (group 1: low loading dose and high demand bolus, group 2: high loading dose and demand bolus, group 3: high loading dose and low demand bolus). RESULTS: The patients in all groups were hemodynamically stable during ESWL. Oxygen desaturation was recognized in all groups, but was avoided by 2 l.min(-1) of oxygen supply via a nasal prong. The total administration dose of the drugs was significantly higher ( P < 0.05) in group 2 than in groups 1 and 3. The median level of sedation was the same, but the episodes of oversedation were not recognized in group 3 ( P < 0.05). A significant difference in the frequency of episodes of oversedation was found between groups 2 and 3 ( P < 0.05). The results were good or excellent for almost all patients, and were assessed as fair by only one patient in group 2. CONCLUSION: We concluded that the method used for group 3 is the most appropriate for administering PFK for PCSA during ESWL.

[Differential epidural block for definitive diagnosis of snapping hip joint].

Snapping hip joint syndrome is defined as snapping phenomenon accompanied by motion of the hip joint. It occurs from various causes, and its diagnosis and treatment are often difficult. We gave anesthesia for surgery against snapping hip joint under patient's active motion for definitive regional diagnosis. Differential epidural block, which precludes pain while maintaining motor function, was performed by 0.25% bupivacaine, 0.5% lidocaine, and additional administration of fentanyl by 25 micrograms. Although the mechanism of differential nerve block remains to be unknown, the case suggests that effective pain block preserving motor function may be achieved by differential epidural block in combination with low concentration of local anesthetics and small dose of opioid.

[Patient-controlled sedation using propofol for a patient with von Gierke disease].

Patient-controlled sedation (PCS) using propofol under spinal anesthesia in transurethral lithotripsy was carried out in a 44 year old patient with von Gierke disease accompanied with liver dysfunction, chronic renal failure, hypoglycemia and metabolic acidosis. After administering spinal anesthesia PCS was started (0.2 mg.kg-1 intravenous bolus dose of propofol; infusion at 2 mg.kg-1.h-1; a three-minute lockout time interval following an initial doses of 0.4 mg.kg-1). PCS with propofol, throughout the operation, brought about adequate sedation level for this patient with 2 or 3 on Wilson's sedation score, and the sedative effect by propofol diminished quickly within 15 minutes after the end of PCS. In addition, respiratory depression due to this sedation which would be worse in acidotic condition was not seen using PCS during the operation. This patient was much satisfied with this sedation in an interview during the postoperative period. PCS using propofol is a useful method without respiratory depression for a patient with von Gierke disease.

[Efficacy and safety of a single oral dose of pilsicainide in supraventricular arrhythmia after coronary artery bypass grafting].

We evaluated the efficacy and safety of administration of a single oral dose of Pilsicainide, a class Ic antiarrhythmic agent, in 34 patients (26 men, 8 women, age from 48 to 81, mean age 66 +/- 8 years) who developed supraventricular arrhythmia after coronary artery bypass grafting (CABG). A total of 42 episodes of postoperative supraventricular arrhythmia, with the majority occurring 2-4 days after CABG, were classified as follows: paroxysmal atrial fibrillation, 34; paroxysmal atrial flutter, 6; and sinus tachycardia, 2. Sinus rhythm was restored in 32 episodes (78%) by treatment with oral pilsicainide given in a single dose of 50 ro 100 mg. Successful conversion was obtained within 90 minutes in 44% and 3 hours in 56% of episodes, with a mean conversion time of 119.2 +/- 107.5 minutes after the administration of pilsicainide. The mean conversion times tended t highlight the difference between the 50 mg and 100 mg doses, but this difference was not statistically significant (p = 0.053). The ventricular rate was significantly reduced from 123.3 +/- 29.5 beats/min to 85.6 +/- 19.9 beats/min (p < 0.0001), however no significant changes in blood pressure or no significant side effects were observed. The results of the present study suggest that a single oral dose of pilsicainide, administered for its favorable pharmacokinetic profile and lack of hemodynamic side effects, is a valuable drug for converting supraventricular arrhythmia to sinus rhythm in most patients after CABG.

Induction of heat shock response: effect on the rat liver with carbon tetrachloride-induced fibrosis from ischemia-reperfusion injury.

The role of heat shock pretreatment in the induction of tolerance for ischemia-reperfusion injury was investigated in rat livers with fibrosis produced by carbon tetrachloride (CCI4) injected subcutaneously. The control group (group C, n = 56) received no pretreatment except anesthesia, and the heat shock group (group HS, n = 56) were exposed to heat shock (42 degrees C) for 15 minutes. After a 48-hour recovery all rats were subjected to 30 minutes of warm ischemia. Western blotting analysis was employed for heat shock protein (HSP) 72 detection. The adenine nucleotide levels in liver tissue and the liver enzyme levels in serum were measured before and after ischemic intervention (seven animals were used at each of six time point measurements in both groups). HSP72 was induced in group HS at greater intensity than in group C. The survival rate on postoperative day 7 in group C (3/14) was significantly poorer than that in group HS (14/14) (p < 0.01). The higher survival rate in group HS was accompanied by more rapid recovery of the adenosine triphosphate level and lower serum levels of liver enzymes after reperfusion (p < 0.01 vs. group C). Heat shock preconditioning induces HSP72 in the rat liver with fibrosis and provides significantly increased tolerance of warm-ischemia reperfusion injury.

[Hemodynamic evaluations of patients with small aortic annulus with St. Jude Medical prosthetic heart valve].

As the elderly population in Japan increases, senile degenerative aortic valvular disease also tends to increase. These patients often have a small aortic annulus. The problem of "valve-patient-mismatch" occurs when a small prosthesis is inserted into a patient with a small aortic annulus. To avoid annular enlargement after aortic valve replacement (AVR), we tried to use a small-sized St. Jude Medical (SJM) valve. From September 1988 through November 1996, 110 AVR were performed in our institution. In these cases, 30 underwent AVR with a small sized SJM valve (male < or = 21 mm, female < or = 19 mm). Dobutamine stress echocardiography was performed in 19 patients who had undergone AVR with a small-sized SJM valve. Surgical results were also compared between patients with small aortic annulus and those with normal-sized aortic annulus. Using Doppler echocardiography, pressure gradients (PG), cardiac index (CI), effective orifice area (EOA), and performance index (PI) were calculated at rest and during stress. The mean body surface area (BSA) of patient who had undergone AVR with SJM19A, 19HP and 21A was 1.40, 1.42 and 1.56 m2, respectively. With dobutamine stress, heart rates, PG and CI increased significantly. Mean and maximum PG of patients with 19HP (8.0 and 15.4 mmHg at rest, 12.9 and 28.0 mmHg under stress, respectively) and 21A (9.5 and 19.1 mmHg at rest, 16.5 and 35.3 mmHg under stress, respectively) were relatively low. EOA index (EOAI) of patient with 19HP showed the highest values mean 0.93 cm2/m2. PIs tended to be higher with HP models than with standard models. The tests were completed without significant side effects such as frequent ventricular arrhythmias. Among the cases with small aortic annulus, there were no operative deaths or hospital deaths. There were also no late deaths, episodes of hemorrhage or thrombosis. Conclusions. In our institution, AVR was performed safely without any aortic annular enlargement with a small aortic anulus in small BSA patients. Postoperative hemodynamic data obtained by echocardiography were satisfactory for all patients at rest and even during maximum dobutamine stress test.

[Femoral to radial artery pressure gradient in the patients undergoing coronary artery bypass graft under normothermic cardiopulmonary bypass].

Femoral to radial artery pressure gradient was evaluated in 14 patients undergoing coronary artery bypass graft under normothermic cardiopulmonary bypass (CPB). CPB was instituted at a flow rate of 2.6 l.min-1.m-2, using non-pulsatile pump and blood temperature of pump arterial line was controlled to maintain bladder temperature between 36 and 37 degrees C. Pressure gradients occurred 30 min after commencement of CPB and the mean gradients of systolic, diastolic and mean artery pressure were maximum all at the end of CPB (38 +/- 7 mmHg, 4 +/- 1 mmHg and 10 +/- 2 mmHg). These pressure gradients remained until the end of the surgery. Throughout the operation, nasopharyngeal and blood temperature remained unchanged, while mean palm temperature increased from 31.8 degrees C (after induction) to 34.6 degrees C (30 min after commencement of CPB) and thereafter remained between 33.3 and 33.9 degrees C. This increase in peripheral temperature might indicate that normothermic CPB was accompanied by peripheral vasodilatation. These results indicate that the magnitude of femoral to radial pressure gradient during normothermic CPB is similar to that during mild hypothermic CPB.

High prevalence of GAD65 (and IA-2) antibodies in Japanese IDDM patients by a new immunoprecipitation assay based on recombinant human GAD65.

Marked differences have been reported in the prevalence of glutamic acid decarboxylase (GAD) antibodies between Caucasian (63-84%) and Japanese (30-50%) or Asian (5-50%) IDDM patients. Using a new immunoprecipitation assay based on 125I-labelled recombinant human GAD65 we have reassessed prevalence of GAD65 antibodies in Japanese patients. We also assessed prevalence of IA-2 antibodies. GAD65 antibodies were detected in 83.3% of sera taken within 1 year of onset, comparable to the prevalence reported in Caucasian patients. Positivity decreased to 66.7% after 2 to 3 years and to 54.3% after 3 years from onset, still higher than previously reported Asian prevalence. Except in one patient, high antibody levels persisted chronically, up to 12 years. There was no difference in the prevalence of GAD65 antibodies between Japanese IDDM patients with and without autoimmune thyroid disease (AITD). IA-2 antibodies were detected in 64.7% of sera taken within 1 year of onset. Prevalence of IA-2 antibodies was lower than that of GAD65 antibodies. The difference in positivity in Asian IDDM patients between present and previous reports arose from the sensitivity of our assay for GAD65 antibodies. Additionally, the patients we studied had classic IDDM with a well-defined onset. We conclude that prevalence of GAD65 antibodies in Japanese IDDM patients is comparable to that in Western studies. There was no relationship of GAD65 antibody positivity to coexistence of AITD. Our results suggest that autoimmunity is the most significant cause of Japanese IDDM.

Cytokine-mediated antitumor effect of OK-432 on urinary bladder tumor cells in vitro.

Fatal complications from the intravesical instillation of bacillus Calmette-Guérin (BCG) for the treatment of superficial urinary bladder tumors have been reported. OK-432, an immunomodulating agent like BCG, may be an effective and safe agent for the treatment of urinary bladder tumors. We investigated the cytokine-mediated antitumor effect of OK-432 on established human bladder cancer cell lines (T24 and KK-47) in vitro. Peripheral blood mononuclear cells (PBMCs) from a healthy volunteer were cultured with OK-432 for various periods, and the culture supernatants were used as conditioned media. Cytokines in the culture supernatants were quantified. The antitumor effect of OK-432 was evaluated by colony-forming assays, using the conditioned media as the culture media. The colony survival of T24 and KK-47 cells was significantly inhibited by conditioned media from 24-h cultures of PBMCs incubated with OK-432 at concentrations of 0.05 and 0.1 Klinische Einheit (KE)/ml. Conditioned media from PBMCs cultivated with OK-432 for 7 days at 0.01 and 0.05 KE/ml also significantly inhibited the colony survival of both cell lines. Higher concentrations of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) were detected in conditioned media cultivated with OK-432 for 24 h than in media from PBMCs alone. However, higher concentrations of interferon gamma (IFN gamma) were detected in conditioned media cultivated with OK-432 for 7 days. Approximately 90% of the inhibition of KK-47 cells by the 24-h conditioned media was neutralized by an anti-TNF monoclonal antibody. The inhibition of T24 cells was neutralized approximately 50% by the same antibody. The inhibition of T24 and KK-47 cells by 7-day conditioned media was completely neutralized by an anti-IFN gamma monoclonal antibody. The cultivation of PBMCs with OK-432 inhibited the production of granulocyte-colony-stimulating factor (G-CSF) by PBMCs. The inhibition may play a role in the mechanism of the antitumor effect of OK-432. Urinary bladder tumor cell lines have different sensitivities to cytokines. The cytokines induced by OK-432 vary with the concentration of OK-432 and the culture period. It is suggested that in intravesical instillation of OK-432 for treatment of urinary bladder tumor, the optimal dose and interval of instillation should be considered.

Ischemic preconditioning of the liver in rats: implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury.

It has been reported that ischemic preconditioning of the heart or brain has a possible relevance to heat shock protein (HSP). It is still unknown, however, whether HSP induced by means of ischemic preconditioning of the liver is a direct factor in the acquisition of tolerance to succeeding ischemia-reperfusion injury. In the present study we used ischemic preconditioning of the liver to verify the effects of induced HSP72 in the liver on the subsequent longer warm ischemia and reperfusion. Rats preconditioned with short-term (15-minute) ischemia were compared with rats preconditioned by heat exposure or with control rats. After a 48-hour recovery from the sublethal stress for preconditioning, all rats were exposed to longer (30-minute) warm ischemia and reperfusion. Forty-eight hours after ischemic preconditioning, HSP72 was clearly induced in the liver, as well as in the liver preconditioned with heat shock, but not in the kidney or heart. This ischemic preconditioning also attenuated the liver damage in the subsequent ischemia-reperfusion injury, improving the restoration of hepatic function during reperfusion and resulting in higher postischemic rat survival. According to the proposed model of tolerance acquisition for ischemia-reperfusion injury by stress preconditioning, these observations support the speculation that the induced HSP72 plays some beneficial role in this protection mechanism.

Difference in onset of warm ischemia and reperfusion injury between parenchymal and endothelial cells of the liver. Evaluation by purine nucleoside phosphorylase and hyaluronic acid.

The onset of warm ischemia and reperfusion injury in the liver was investigated in a canine model through changes in parenchymal markers [isozyme class V of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT)], endothelial markers [purine nucleoside phosphorylase (PNP) and hyaluronic acid clearance], and the liver metabolism (ketone body ratio) in warm ischemia induced by inflow occlusion using Pringle's maneuver and subsequent reperfusion. In this in vivo model, a PNP assay system and a model were designed so as to exclude the influence of wide localization of PNP possibly originating in erythrocytes or the intestine, and to discriminate between PNP of endothelial cells and that of parenchymal cells in the liver. After 45 min of warm ischemia, reperfusion resulted in damage only to endothelial cells, as seen by significant increase in PNP alone (3.6 +/- 0.1 U/liter at the end of warm ischemia to 6.8 +/- 0.5 U/liter at 5 min after reperfusion, P < 0.01) and significant decrease in hyaluronic acid clearance compared to the 30-min warm ischemia group in which no increase in either marker for parenchymal and endothelial cells was noted. By contrast, after 60 min of warm ischemia, reperfusion resulted in damage to parenchymal cells along with damage to endothelial cells, as seen by significant increases in LDH(V) and ALT (93 +/- 4 U/liter and 32 +/- 2 IU/liter at the end of warm ischemia to 239 +/- 17 U/liter and 165 +/- 27 IU/liter at 5 min after reperfusion, respectively), as well as a marked increase in PNP and deterioration of hyaluronic acid clearance compared to the 45-min warm ischemia group. Reperfusion after 120 min of warm ischemia did not show recovery of metabolic function of the liver as evaluated by hepatic mitochondrial redox state. It is suggested that a time lag occurs in the onset of injury between parenchymal cells and endothelial cells and that endothelial cells are temporally earlier in failing than parenchymal cells when the liver is exposed to short-term warm ischemia and subsequent reperfusion.

Expression of proliferating cell nuclear antigen and deoxyribonucleic acid value in renal cell carcinoma: correlation with different histopathological parameters and patient survival.

Forty-six human renal cell carcinoma tissues obtained from radical nephrectomy, fixed in 10% formaldehyde solution and embedded in paraffin for histopathological examination were used for immunohistochemical staining of proliferating cell nuclear antigen (PCNA) using a monoclonal antibody PC10, and 37 of the 46 were also used for flow cytometric DNA ploidy analysis. PCNA-positive rates were compared with different histopathological parameters and patient survival. The relationships between the DNA ploidy and PCNA-positive rates and patient survival were also determined. Statistically significant differences in PCNA-positive rates were observed in different histopathological grades and stages of renal cell carcinoma. No relationship was observed between the PCNA-positive rate and DNA ploidy. For all cases analyzed, patients whose tumors had PCNA-positive rates of less than 10% survived statistically longer than those with tumors with PCNA-positive rates of 10% or more (p < 0.02). When patients were stratified by histopathological stage-I and grade-1 tumors, however, there was no significant difference between the PCNA-positive rate and survival. No difference in survival was observed according to DNA ploidy. The PCNA-positive rates showed a close relation to the different histopathological grades and stages of renal cell carcinoma. For all cases analyzed, high PCNA-positive rates showed poor prognosis. But for patients with histopathological stage-I and grade-1 tumors, the PCNA-positive rates and DNA ploidy did not provide independent prognostic information.

Prognostic implications of the response of arterial ketone body ratio and insulin secretion to glucose load in major hepatectomy.

Impaired glucose tolerance is a serious obstacle to major hepatic resection. To assess the predictability of surgical risk in major hepatectomy for patients with chronic liver diseases from the viewpoint of glucose metabolism, we evaluated the insulinogenic index (II) and redox tolerance index (RTI) in 48 patients who underwent major hepatectomy at our university hospital due to hepatocellular carcinoma. Patients with low II and low RTI fell into the high risk group. Based on this finding, the Z score was developed as an index of patient risk for major hepatectomy: Z = 3.11 x [II] + 1.43 x [RTI] - 2.27. When the Z score was negative, mortality reached 33.3%, but when it was positive the mortality was only 3.2%. Intraportal insulin supplementation after hepatectomy to patients with a negative Z score could reduce mortality. Preoperative evaluation of surgical risk by Z score seems to be useful for predicting patient prognosis after hepatectomy.

Prevalence of intestinal parasitic infection in five farms in Holambra, São Paulo, Brazil.

A parasitological survey was carried out on 222 inhabitants of five farms in Holambra, located 30 km north of Campinas, São Paulo, Brazil, on October 1992. Approximately 70% of the inhabitants were found to be infected with at least one species of intestinal parasite. The positive rates of 6 helminths and 7 protozoan species detected are as follows: 5.4% Ascaris lumbricoides; 8.6% Trichuris trichiura; 19.8% Necator americanus; 10.4% Strongyloides stercoralis; 1.4% Enterobius vermicularis; 0.9% Hymenolepis nana; 3.2% Entamoeba histolytica; 2.7% E. hartmanni; 9.9% E. coli; 14.0% Endolimax nana; 2.3% Iodamoeba butschlii; 10.4% Giardia lamblia; 37.8% Blastocystis hominis. The positive rates of helminth infection were generaly higher in the younger-group under 16 years-old than those in the elder group aged 16 or more, whereas the infection rates of protozoan species were higher in the elder group. The infection rate of Strongyloides was found to be 10.4% by a newly developed sensitive method (an agarplate culture methods).

Cytokine-mediated antitumor effect of bacillus Calmette-Guérin on tumor cells in vitro.

Intravesical instillation therapy of bacillus Calmette-Guérin (BCG) is a useful modality for recurrent superficial transitional-cell carcinoma (TCC) of the urinary bladder. The mechanism of BCG effect has not yet been well characterized. BCG was tested in vitro for cytokine-mediated antiproliferative activity against T24 and KK47 cells (cell lines established from human TCC of the urinary bladder), and ACHN cells (cell line established from human renal cell carcinoma) using a modified human tumor clonogenic assay. Continuous exposure of cells to BCG at concentrations of more than 5 micrograms/ml in the presence of peripheral blood mononuclear cells (PBMC) consisting of a mixture of 5 x 10(4) monocytes/dish and 5 x 10(5) lymphocytes/dish, obtained from healthy donors, significantly inhibited colony formation of T24 and ACHN cells in comparison with growth inhibition in the absence of PBMC (P < 0.05). Slightly inhibited colony formation was observed with KK47 cells under the same conditions. At the same time various cytokines were measured in supernatants when BCG and the same conditioned PBMC were co-cultured. Tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) were detected at markedly high levels at 24 h, and interferon gamma (IFN gamma) was detected at 120 h. IL-2 and macrophage-colony-stimulating factor were not detected. Neutralizing anti-TNF alpha monoclonal antibody significantly reduced the anti-proliferative activity of ACHN cells, and anti-IFN gamma antibody reduced that of T24 cells. The results obtained suggest that cytokines mediated by BCG play an important role in the antitumor activity of BCG and that the sensitivity of bladder cancer cells to the cytokines induced by BCG may differ considerably.