Pharmacokinetic imaging of 11C ethanol with PET in eight patients with hepatocellular carcinomas who were scheduled for treatment with percutaneous ethanol injection.

PURPOSE: To evaluate the carbon 11 ethanol kinetics with positron emission tomography after intratumoral injection of the tracer and assess its redistribution and dilution in patients who have hepatocellular carcinomas and who were scheduled for treatment with percutaneous ethanol injection. MATERIALS AND METHODS: The study included eight patients with hepatocellular carcinomas. 11C ethanol was administered via a puncture needle positioned with ultrasonographic guidance. Parametric images based on the Fourier transformation were created for further analysis of the local distribution patterns of the tracer. The ratio of the 45-minute postinjection standardized uptake value to the 5-minute postinjection standardized uptake value was used for the evaluation of ethanol dilution. RESULTS: Five of eight tumors demonstrated almost constant uptake values after the initial distribution phase. In contrast, a rapid elimination of the 11C ethanol from the tumor was documented in three of eight tumors. The 45 minute-to-5 minute ratio was 0.18-0.67 (median value, 0.56) in the tumors. The time-activity curves of the normal liver parenchyma increased slowly but steadily with time owing to a low ethanol elimination from the tumor. Fourier transformation demonstrated inhomogeneous parts on the amplitude images in seven of eight tumors and random redistribution on the phase images in six of eight tumors. CONCLUSION: Inhomogeneous drug distribution and drug dilution in the target area are likely to be the major limiting parameters for therapy response.

18F-labeled fluorouracil positron emission tomography and the prognoses of colorectal carcinoma patients with metastases to the liver treated with 5-fluorouracil.

BACKGROUND: Although many factors have been investigated in connection with the prognoses of colorectal carcinoma patients with metastases to the liver, a means for evaluating response and prognosis prior to the administration of standard chemotherapy has not been available. Positron emission tomography (PET) is a noninvasive means of measuring the distribution of radiolabeled cytostatic agents in tumor regions. METHODS: Prior to the administration of 5-fluorouracil chemotherapy, the authors examined 14 colorectal carcinoma patients with unresectable liver metastases using a single PET scan and 18F-labeled fluorouracil (18F-FU). Clinical response and survival time were correlated with 18F-FU uptake values (SUV) measured in liver metastases 120 minutes after tracer infusion. RESULTS: Trapping of 18F-FU varied even among different metastases in the same patient. The range of SUV was 0.9-4.3 (mean, 2.20). Four patients with SUV exceeding 2.8 had stable disease for longer than 12 months and survived longer than 21 months. Three patients with SUV less than 1.2 had progressive disease and survived less than 12 months. The 6 patients with partial remission or stable disease had a mean SUV of 2.96 and a mean survival of 31.6 months. Eight patients with progressive disease had a mean SUV of 1.59 and a mean survival of 14.5 months (Student's t-test, P < 0.012). In scatterplot analysis, there was a statistically significant correlation between SUV and survival time. CONCLUSIONS: Patients with high 18F-FU uptake values are more likely to achieve at least stabilization of disease with planned chemotherapy. 18F-FU PET may be a valuable new tool for determining, prior to 5-FU-based chemotherapy, which patients are likely to have good responses and prolonged survival.

Primary hepatic high-grade non-Hodgkin's lymphoma and chronic hepatitis C infection.

Little is known about the coincidence of hepatitis C virus infection (HCV) and non-Hodgkin's lymphoma, although there is an increased incidence of chronic HCV infection with cryoglobulinemia type II and, interestingly, low-grade non-Hodgkin's lymphoma (NHL) in a few patients. We therefore report on a 74-year-old white male with known chronic hepatitis C virus infection who was admitted to the clinic due to weight loss and pain in the right upper quadrant. Ultrasound examination was performed for suspected hepatocellular carcinoma since a lesion in the left lobe of the liver was seen. X-ray of the lungs showed a few scattered lesions, suggestive of metastases. The ultrasound-guided fine-needle puncture revealed a high-grade malignant B-cell NHL While alpha-fetoprotein was normal, both cryoglobulin type II and the polymerase chain reaction (PCR) for HCV were positive. After six cycles of chemotherapy consisting of CHOP, the patient showed complete remission over three years. Ultimately, he died due to a sudden myeloic blast crisis. In summary, we discuss the possible etiopathologic role of the hepatitis viruses in the occurrence of non-Hodgkin's lymphoma. As we and others showed that HCV infects peripheral mononuclear blood cells (PBML), the infected PBML not only may be a source for reinfection after orthotopic liver transplantation, but also could be the cause for transformation and monoclonal propagation of lymphomatous tissue.

[PET studies with C-11 ethanol in intratumoral therapy of hepatocellular carcinomas]. / PET-Studien mit C-11-Athanol bei der intratumoralen Therapie von hepatozellulären Karzinomen.

Positron emission tomography (PET) is a noninvasive functional method for the study of solid tumor perfusion, metabolism and interaction with different therapeutic agents. The aim of the study was the investigation of the metabolism of hepatocellular carcinomas (HCC) and the kinetics during a treatment with intratumoral ethanol by PET. The ongoing study includes seven patients with child. A cirrhosis and HCC (UICC stage III-IVA; tumor size 3-6 cm). Dynamic PET studies (60 min) with 18F-fluordeoxyglucose (FDG) were performed prior to therapy to assess tumor viability. The evaluation of the FDG data demonstrated a liver-equivalent uptake in six of the tumors (well and moderately differentiated HCC), which were poorly delineated against the normal liver parenchyma. One moderately differentiated HCC showed an increased FDG metabolism, indicating no correlation between histology and metabolism. A dose of 37-80 MBq 11C-ethanol was applied together with a nonlabelled therapeutic dose of the drug via a puncture needle positioned under sonography. Five out of seven tumors demonstrated a high 11C uptake shortly after the end of the ethanol injection followed by constant 11C-ethanol concentration during the whole study period of 45 min. The PET data demonstrated no significant elimination of the 11C-ethanol from the tumor and no accumulation in the surrounding liver tissue. One case showed a decrease of the intra-tumoral 11C-ethanol concentration due to a punkture of a tumor vein, and in another case the surrounding liver parenchyma demonstrated significant 11C uptake in the early phase following paratumoral injection of the drug. In conclusion, PET is a useful tool for the study of the mechanism and the kinetics of percutaneous intratumoral ethanol injection of HCC.

Tissue concentrations of ofloxacin in necrotic foot lesions of diabetic and non-diabetic patients with peripheral arterial occlusive disease.

Six diabetic patients with infected foot lesions (mean age 64 years) and six male patients (mean age 71 years) with ischemic acral ulceration due to advanced peripheral arterial occlusive disease were treated with 200 mg ofloxacin b.i.d. The necrotic margin tissue concentrations of ofloxacin determined by HPLC and confirmed by microbiological assay were in the same range (1.6 to 6.4 mg/kg) as plasma levels (1.6 to 5.9 mg/l). No difference of plasma and tissue concentrations was found between patients with peripheral vascular disease and diabetics, respectively. After three weeks treatment bacterial wound pathogens disappeared in 7 subjects, changed in 4 patients and were resistant in one patient. Clinical improvement appeared in 9 of 12 patients after three weeks of therapy. Satisfactory tissue levels of orally administered ofloxacin were achieved in the infected necrotic tissue area of diabetic and non-diabetic patients with impaired peripheral arterial circulation.

[Guillain-Barré polyneuropathy in Wegener's granulomatosis with pulmonary-renal syndrome]. / Guillain-Barré-Polyneuropathie bei Wegenerscher Granulomatose mit pulmorenalem Syndrom.

A 49-year-old female patient suffering from severe necrotising respiratory granulomatosis (Wegener's granulomatosis) had acute renal failure, nearly uncontrollable haemoptyses and severe deterioration of pulmonary function. Haemodialysis had to be performed; immuno-suppressive therapy was effected by administration of high doses of methylprednisolone (100-500 mg/d) and cyclophosphamide (initially with single doses of 500-1000 mg) and plasmaphereses. Artificial ventilation by positive-negative pressure breathing became necessary because pulmonary function became consistently poorer. Glucocorticoid therapy led to the development of several duodenal ulcers resulting in profuse gastrointestinal bleedings requiring transfusions; on the whole, 20 erythrocyte concentrates had to be substituted. These transfusions, in turn, caused a non-A, non-B hepatitis. In the further course of the illness, a Guillain-Barré polyneuropathy developed. Biopsy and electrophysiological tests excluded granulomatous involvement of the nerves as a cause of the latter. But it is likely that there was a pathogenetic connection between the hepatitis and the polyneuropathy.

Ciprofloxacin and norfloxacin for selective decontamination in patients with severe granulocytopenia.

In a randomized multicenter study, ciprofloxacin and norfloxacin, each in two different dose regimens and in combination with non-absorbable antimycotics, were administered to 51 patients with acute leukaemia undergoing aggressive remission induction chemotherapy for infection prevention. Both drugs showed an effective elimination of gram-negative potential pathogens and Staphylococcus aureus not affecting the anaerobic flora of the gastrointestinal tract. A low incidence of side effects and a satisfactory patient compliance could be observed. A daily dosage of 1,000 mg ciprofloxacin or 800 mg norfloxacin is recommended for infection prevention in severely granulocytopenic patients.

Clinical and practitioners' reports on adverse effects of co-trimoxazole.

This study concerns the incidence of side effects occurring in connection with the prescription of co-trimoxazole which, according to the observations of medical practitioners, were suspected of being drug related. It is based on reports from 260 doctors in the Nordbaden/Rheinlandpfalz area between 1981 and 1984, as well as on those from hospital doctors concerning 33,300 in-patients at the Department of Internal Medicine at the University Hospital of Heidelberg from 1980 to 1983. General practitioners' reports: Of 3,739 side effects reported over a three and a half year period, 180 were related to drugs containing co-trimoxazole. Side effects were 3.3 times as frequent with the "forte" dosage as compared to the 80 mg trimethoprim/400 mg sulfamethoxazole preparation. The most frequently cited unwanted reactions concerned the skin (n = 63, of which two were Quincke oedema and three were urticarious reactions) and the gastrointestinal tract (n = 52), as well as disturbance of well being (n = 30). Gastro-intestinal disturbances appeared to occur more frequently after a higher than after a lower dosage. Clinicians' reports: During the period of observation an average of 12.6% of all in-patients were treated with drugs containing co-trimoxazole. The total number of cases of side effects due to this drug amounted to 255. Serious reactions included: two anaphylactic reactions; two thrombocytopenias below 80,000/mm3; and two cases of Lyell's syndrome (one of which could not be confirmed beyond all doubt). Side effects occurred more often after i.v. than after oral application.(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue concentrations of ofloxacin in necrotic lesions in patients with peripheral vascular disease and in diabetics.

In a pilot study six patients (three diabetics with gangrenous lesions of the lower limbs, mean age 74 years, three patients with peripheral vascular disease stage IV according to Fontaine, mean age 70 years) were treated with 200 mg ofloxacin orally b.i.d. The tissue concentrations of ofloxacin in the necrotic material (1.6 to 6.4 mg/kg) were in the same range as the plasma levels (2.3 to 5.9 mg/l) or even higher. In conclusion, besides local therapy, ofloxacin seems to be effective in the systemic treatment of infected necrotic and gangrenous lesions.

In vitro activity, pharmacokinetics, clinical safety and therapeutic efficacy of enoxacin in the treatment of patients with complicated urinary tract infections.

Minimal inhibitory concentrations (MIC) of enoxacin, nalidixic acid, pipemidic acid, norfloxacin, ciprofloxacin, ofloxacin and pefloxacin against isolates from 400 urological in-patients with complicated urinary tract infections (UTI) were determined by means of an agar dilution technique (10(4) cfu, multipointer). 28 patients (21 male, seven female) aged 36 to 84 years with complicated UTI due to sensitive bacteria were treated orally with 200 mg enoxacin b.i.d. for six to 14 days. Plasma and urine samples were collected from 19 patients, at intervals prior to and following a 400 mg dose of enoxacin, and enoxacin concentrations were determined by a high pressure liquid chromatography (HPLC) method. The MICs of enoxacin against all but one of the gram-negative isolates cultured from 265 urological patients were between 0.03 and 4 mg/l. The MICs against 134 gram-positive isolates were between 0.25 and 16 mg/l except two strains of streptococci. At a concentration of 4 mg/l (8 mg/l), 90.3% (98%) of the total spectrum of isolates were inhibited by enoxacin. Of the quinolones tested, ciprofloxacin appeared to be the most active compound in vitro and cinoxacin the least active antimicrobial agent. The in vitro activity of enoxacin was comparable to that of norfloxacin, ofloxacin and pefloxacin. Oral administration of 400 mg enoxacin to elderly patients resulted in peak serum concentrations between 0.7 and 6.3 mg/l (mean 3.6 mg/l) attained between 1.0 and 6.0 h following drug ingestion. The mean urinary recovery of parent drug within 24 h was 31.2% of the administered dose. 25 of 28 patients treated orally with enoxacin could be followed-up for five to 14 days after the end of treatment. Enoxacin therapy in these patients resulted in 18 cures, one failure and six relapses (same species). The drug was well tolerated and there was no evidence of renal, hepatic or haematological toxicity. Enoxacin appears to be well suited for the treatment of complicated UTI.

In vitro activity, pharmacokinetics, clinical safety and therapeutic efficacy of enoxacin in the treatment of patients with complicated urinary tract infections.

Minimal inhibitory concentrations (MIC) of enoxacin, nalidixic acid, pipemidic acid, norfloxacin, ciprofloxacin, ofloxacin and pefloxacin against isolates from 400 urological in-patients with complicated urinary tract infections (UTI) were determined by means of an agar dilution technique (10(4) cfu, multipointer). 28 patients (21 male, seven female) aged 36 to 84 years with complicated UTI due to sensitive bacteria were treated orally with 200 mg enoxacin b.i.d. for six to 14 days. Plasma and urine samples were collected from 19 patients, at intervals prior to and following a 400 mg dose of enoxacin, and enoxacin concentrations were determined by a high pressure liquid chromatography (HPLC) method. The MICs of enoxacin against all but one of the gram-negative isolates cultured from 265 urological patients were between 0.03 and 4 mg/l. The MICs against 134 gram-positive isolates were between 0.25 and 16 mg/l except for two strains of streptococci. At a concentration of 4 mg/l (8 mg/l), 90.3% (98%) of the total spectrum of isolates were inhibited by enoxacin. Of the quinolones tested, ciprofloxacin appeared to be the most active compound in vitro and cinoxacin the least active antimicrobial agent. The in vivo activity of enoxacin was comparable to that of norfloxacin, ofloxacin and pefloxacin. Oral administration of 400 mg of enoxacin to elderly patients resulted in peak serum concentrations between 0.7 and 6.3 mg/l (mean 3.6 mg/l) attained between 1.0 and 6.0 h following drug ingestion. The mean urinary recovery of parent drug within 24 h was 31.2% of the administered dose. 25 of 28 patients treated orally with enoxacin could be followed-up for five to 14 days after the end of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)