Epidural fentanyl improves the onset and spread of epidural mepivacaine analgesia

Purpose

To determine the extent of enhanced blockade by the combined use of epidural fentanyl and mepivacaine. We compared the onset of hypoalgesia, analgesia and the threshold of pressure pain.

Methods

Thirty patients were randomly divided into three groups. The fentanyl group received 10 ml saline containing 0.1 mg fentanyl, mepivacaine group received 10 ml mepivacaine 1% and a mixed group received 10 ml mepivacaine 1% with 0.1 mg fentanyl. All solutions, without epinephrine, were injected through an epidural catheter at T_5–6 to T_6–7. The change in sensation, loss of pin-prick and pain threshold sensation, measured by pressure algometer, were assessed at 2.5-min intervals for 15 min at the T₄ dermatome. Spread of analgesia was determined at 15 min.

Results

Loss of pinprick was more rapid in the mixed, 11.0 ± 2.7 (SD) min, than in the mepivacaine group, 15.0 ± 2.9 min, (P < 0.05), although there was no difference in change of sensation. Pressure pain threshold increased with time in the mepivacaine (P < 0.05) and mixed (P < 0.05) groups. It was higher in the mixed than in the fentanyl and mepivacaine groups at 5, 7.5 and 10 min (P < 0.05). The lower level of analgesia was lower in the mixed than in the mepivacaine groups (P < 0.05). Blood pressure was unchanged in the three groups, but heart rate decreased at 7.5, 10, 12.5, and 15 min in the mepivacaine and mixed groups (P < 0.05).

Conclusions

The addition of fentanyl to mepivacaine accelerates the onset of analgesia and enhances the analgesic effect of epidural block.     

In vitro metabolism of fenthion and fenthion sulfoxide by liver preparations of sea bream, goldfish, and rats.

The in vitro metabolism of fenthion and its sulfoxide (fenthion sulfoxide) in sea bream (Pagrus major) and goldfish (Carassius auratus) was investigated and compared with that in rats. Fenthion was oxidized to fenthion sulfoxide and the oxon derivative, but not to its sulfone, in the presence of NADPH by liver microsomes of sea bream, goldfish, and rats. These liver microsomal activities of the fish were lower than those of rats but were of the same order of magnitude. The NADPH-linked oxon- and sulfoxide-forming activities of liver microsomes of the fish and rats were inhibited by SKF 525-A, metyrapone, alpha-naphthoflavone, and carbon monoxide. The oxidizing activity to fenthion sulfoxide was also inhibited by alpha-naphthylthiourea. Several cytochrome P450 isoforms and flavin-containing monooxygenase 1 exhibited these oxidase activities. Fenthion sulfoxide was reduced to fenthion with liver cytosol of the fish and rats upon addition of 2-hydroxypyrimidine, N(1)-methylnicotinamide, or butyraldehyde, each of which is an electron donor of aldehyde oxidase, under anaerobic conditions. The activity was inhibited by menadione, beta-estradiol, and chlorpromazine, which are inhibitors of aldehyde oxidase. The activities in the fish livers were similar to those of rat liver. Aldehyde oxidase purified from the livers of sea bream and rats exhibited the reducing activity. Thus, fenthion and fenthion sulfoxide are interconvertible in fish and rats through the activities of cytochrome P450, flavin-containing monooxygenase, and aldehyde oxidase.     

Prediction of nodal metastasis by comparative genomic hybridization in biopsy specimens from patients with superficial esophageal squamous cell carcinoma.

PURPOSE: Selection of appropriate protocols for treatment of superficial esophageal squamous cell carcinoma (SESCC) is dependent on lymph node metastasis status. Therefore, it is important to know whether lymph node metastasis is present before treatment. EXPERIMENTAL DESIGN: In this study, we examined the relation between DNA sequence copy number aberrations detected by comparative genomic hybridization and lymph node metastasis in 26 surgically resected SESCCs (training samples). We then assessed whether the genetic information is predictive for nodal status in biopsy specimens from eight newly enrolled patients with SESCC (blinded samples). RESULTS: Pathological examination revealed that 17 of 26 training samples (65.4%) did not have associated lymph node metastasis. Gains of 8q24 and/or 20q12-qter were observed in 12, including all (nine of nine) with nodal metastasis. Fourteen training samples did not have gain of either 8q24 or 20q12-qter. Of the blinded samples, two showed no gain of 8q24 or 20q12-qter, and as anticipated the postoperative pathological examination revealed no nodal metastasis. The remaining six blinded samples had gains of 8q24 and/or 20q12-qter, and lymph node metastasis was detected by postoperative examination in four of these tumors. CONCLUSIONS: Absence of gains of 8q24 and/or 20q12-qter appears to be associated with absence of lymph node metastasis in patients with SESCC; therefore, less invasive surgery can be chosen.     

Ischial hypoplasia, tibial hypoplasia and facial abnormalities: a new syndrome?

A child with facial abnormalities, short stature and a variety of skeletal alterations is reported. The facial abnormalities comprised low-set ears, short nose with a long philtrum, micrognathia and cleft palate. The skeletal alterations included ischial hypoplasia, malformations of the cervical spine, hypoplasia of the lesser trochanters, tibial hypoplasia with bowing of the lower legs, tibio-fibular diastasis with malformed distal tibial epiphyses, clubfeet and brachymesophalangy. The constellation of clinical and radiological findings in the present patient do not fit any known malformation syndrome. Received: 14 February 1998 Accepted: 15 June 1998     

Increased Sensitivity to Long-term 5-Fluorouracil Exposure of Human Colon Cancer HT-29 Cells Resistant to Short-term Exposure

A 5-fluorouracil (5-FU)-resistant subline of human colon cancer HT-29 cells was developed by repeated 1-h exposure in vitro to 5-FU. This subline (HT-29/5-FU/S) had 8-fold resistance to 5-FU in a 1-h exposure assay. However, it had rather increased sensitivity to 5-FU when assayed after a continuous 96-h exposure to it. Significantly less 5-fluorouridine-5'-triphosphate was produced in the resistant cells, leading to a lower level of 5-FU incorporation into the cellular RNA. The reduced activity of orotate phosphoribosyltransferase might explain these results. In contrast, the HT-29/5-FU/S cells were more sensitive to the inhibition of in situ thymidylate synthase (TS) by 5-FU than were the parent cells. The lower in situ TS activity may have made HT-29/5-FU/S cells more sensitive to TS inhibition by 5-FU as compared with the parent cells. The fact that HT-29/5-FU/S was more resistant to short-term 5-FU exposure but more sensitive to long-term exposure than the parent line confirmed the existence of different modes of action of 5-FU, depending on the exposure time.     

Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women

The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P<0.01). Liver dysfunction (n=5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (<10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view. Received: 2 May 1997 / Accepted: 13 October 1997     

Effects of Interleukin-12 on the Induction of Cytotoxic T Lymphocytes from the Regional Lymph Node Lymphocytes of Patients with Lung Adenocarcinoma

Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA-A-locus-matched tumor cells. To investigate the effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL from HLA A24 / adenocarcinoma patients with either autologous tumor cells or HLA A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL-12, or the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and the cytokine production (IFN-γ, GM-CSF) of the CTL as compared with IL-2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti-MHC-class I monoclonal antibody. The CTL thus induced by IL-12 had a higher proportion of CD3⁺/CD56⁺ cells than the CTL induced with IL-2 alone. The positively selected CD8⁺/CD56^– lymphocytes showed PC-9-specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA-A26/A30). However, the CD3⁺/CD56⁺ lymphocytes were cytotoxic to both PC-9 and K562. In conclusion, IL-12 is considered to be a useful cytokine for both the induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL.     

Improved PCR amplification for molecular analysis using DNA from long-term preserved formalin-fixed,paraffin-embedded lung cancer tissue specimens

Archival tissue specimens are valuable resources of materials for molecular biological analyses in retrospective studies, especially for rare diseases or those associated with exposure to uncommon environmental events. Although successful amplification with PCR is essential for analysis of DNA extracted from archival formalin-fixed, paraffin-embedded (FFPE) tissue specimens, we have often encountered problems with poor PCR amplification of target fragments. To overcome this, we examined whether heat treatment in alkaline solution could efficiently restore the PCR template activity of DNA that had already been extracted from FFPE lung cancer tissue specimens. The effect of the heat treatment was assessed by PCR for the TP53 gene and other lung cancer-related gene loci. The heat treatment of DNA samples in borate buffer resulted in successful PCR amplification of DNA fragments ranging from 91 to 152 bp. This technique for restoration of template activity of DNA for PCR amplification is very simple and economical, and requires no special apparatus, so it may be applicable for molecular analysis of DNA samples from FFPE tissue specimens at various laboratories.     

Occupational Factors and Problem Drinking among a Japanese Working Population

Problem drinking is a serious public health problem in the workplace. However, few Japanese epidemiological studies have investigated the occupational characteristics of problem drinking. The purpose of this study is to clarify the occupational risk factors for problem drinking among a Japanese working population. We used data from a random-sampling survey about mental health and suicide, conducted among Hamamatsu City residents aged 15 to 79 yr old during May and June in 2008. The relation between occupational factors and problem drinking was analyzed with multiple logistic regression models stratified by gender. CAGE questionnaire was used to assess problem drinking. With regard to employment types, problem drinkers were more prevalent among self-employed women. With regard to occupational types, clerical and service professions had more problem drinkers of either sex, while administrative/managerial and sales professions had more women with such problem. With regard to company size, male problem drinkers were more prevalent in smaller companies than in larger ones. These results indicate that the prevalence of problem drinkers in the workplace depends on where one works. It is necessary to consider these characteristics to provide effective measures to address problem drinking in the workplace.