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Biomedical subjects

J C Arnold

Publications and source records attributed to J C Arnold.

At least 19 recordsLinked to original sources
PubMed2006

The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells.

Cannabis is the most widely used illicit drug in the world. Cannabinoids are used therapeutically by some patients as they have analgesic, anti-emetic and appetite stimulant properties which palliate adverse symptoms. Use of these agents in an oncology setting raises the question of whether they act to modulate the effectiveness of concurrently administered anti-cancer drugs. The transporter, P-glycoprotein (P-gp) confers multiple drug resistance (MDR) by effluxing a diverse array of anti-cancer agents. This study was undertaken to examine the effect of cannabinoids on P-gp. Unlike the known P-gp inhibitor, PSC833, short 1h exposure to three plant-derived cannabinoids, cannabinol (CBN), cannabidiol (CBD) and Delta(9)-tetrahydrocannabinol (THC) and the synthetic cannabinoid receptor agonist, WIN55, 212-2 (WIN) did not inhibit the efflux of the P-gp substrate Rhodamine 123 (Rh123) in either a drug-selected human T lymphoblastoid leukaemia cell line (CEM/VLB(100)) or in a mouse fibroblast MDR1 transfected cell line (77.1). However, in CEM/VLB(100) cells, prolonged 72 h exposure to the cannabinoids, THC and CBD, decreased P-gp expression to a similar extent as the flavonoid, curcumin (turmeric). This correlated with an increase in intracellular accumulation of Rh123 and enhanced sensitivity of the cells to the cytotoxic actions of the P-gp substrate, vinblastine. Taken together, these results provide preliminary evidence that cannabinoids do not exacerbate P-gp mediated MDR. Further, plant-derived cannabinoids are moderately effective in reversing MDR in CEM/VLB(100) cells by decreasing P-gp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Staging of abdominal metastases in pancreatic carcinoma by diagnostic laparoscopy and magnetic resonance imaging.

BACKGROUND: Different noninvasive and invasive techniques are available for the detection of abdominal metastases in pancreatic carcinoma. Since small hepatic or peritoneal metastases are a crucial problem which precludes resection, accurate detection is mandatory. We compared laparoscopic staging of abdominal metastases in adenocarcinoma of the pancreas with MRI. METHODS: 55 patients with pancreatic adenocarcinoma had been screened and 49 entered the retrospective study. All patients had undergone MRI of the upper abdomen with concomitant MR-cholangiopancreatography (MRCP) and diagnostic laparoscopy under conscious sedation. Patients without histologic proof of abdominal metastases underwent laparotomy. RESULTS: In 6/10 patients, metastases were correctly detected by laparoscopy, yielding a sensitivity of 60% and a specificity of 92%.MRI predicted metastases in 6/10 patients with 60% sensitivity and 100% specificity. Laparoscopy showed metastases in 3 patients that were missed by MRI, but failed to identify metastases in 3 of 6 patients with metastases on MRI. Though only one patient showed previously undetected metastases during laparotomy, 3 patients with abdominal metastases underwent unnecessary laparotomy due to a lack of histologic proof of malignancy. CONCLUSIONS: Whereas diagnostic laparoscopy is sensitive for the detection of small metastases and offers histologic verification, intrahepatic alterations are not detectable by sole visual inspection.MRI may compensate for this deficiency, but histologic proof of malignancy may be problematic. To date, no definite decision in favor of one of the presented procedures for the staging of abdominal metastases can be given.

Adenocarcinoma↗
PubMed2002

Feasibility and diagnostic impact of fluorescence-based diagnostic laparoscopy in hepatocellular carcinoma: a case report.

Fluorescence-based diagnostic techniques are an evolving field in the staging of hepatologic and gastroenterologic malignancies. The method aims at improved accuracy in the detection of locoregional and distant metastases. In hepatocellular carcinoma, detection of metastases is of utmost importance, because advanced tumors preclude curative surgical therapy. We present here our first experience of fluorescence-based diagnostic laparoscopy in a patient with hepatocellular carcinoma. We performed diagnostic laparoscopy in a 76-year-old woman who presented with a tumor of the liver and increased serum levels of alpha-fetoprotein. For photosensitization, 5-aminolevulinic acid (20 mg/kg bodyweight, p.o.) was used 6 hours prior to laparoscopy, which was performed with a prograde 0 degree telescope suitable for fluorescence-based laparoscopy. The D-Light AF system was used as a light source. Laparoscopy was carried out according to common guidelines in the white-light as in the blue-light mode. The main tumor and the satellite metastases clearly showed intense fluorescence compared with unaffected liver parenchyma and other abdominal organs. Fluorescence-based laparoscopy identified several small metastases which had been missed during conventional white-light illumination. Hepatocellular carcinoma was confirmed by the histological examination of several biopsies drawn from suspicious areas. Fluorescence-based laparoscopy provided additional information in the staging of hepatocellular carcinoma. The technique can further improve diagnostic accuracy in the staging of hepatocellular carcinoma, particularly in patients potentially suitable for partial liver resection or transplantation.

Aged↗
PubMed2001

The distribution of cannabinoid-induced Fos expression in rat brain: differences between the Lewis and Wistar strain.

Previous studies have suggested that cannabis-like drugs produce mainly aversive and anxiogenic effects in Wistar strain rats, but rewarding effects in Lewis strain rats. In the present study we compared Fos expression, body temperature effects and behavioral effects elicited by the cannabinoid CB(1) receptor agonist CP 55,940 in Lewis and Wistar rats. Both a moderate (50 microg/kg) and a high (250 microg/kg) dose level were used. The 250 microg/kg dose caused locomotor suppression, hypothermia and catalepsy in both strains, but with a significantly greater effect in Wistar rats. The 50 microg/kg dose provoked moderate hypothermia and locomotor suppression but in Wistar rats only. CP 55,940 caused significant Fos immunoreactivity in 24 out of 33 brain regions examined. The most dense expression was seen in the paraventricular nucleus of the hypothalamus, the islands of Calleja, the lateral septum (ventral), the central nucleus of the amygdala, the bed nucleus of the stria terminalis (lateral division) and the ventrolateral periaqueductal gray. Despite having a similar distribution of CP 55,940-induced Fos expression, Lewis rats showed less overall Fos expression than Wistars in nearly every brain region counted. This held equally true for anxiety-related brain structures (e.g. central nucleus of the amygdala, periaqueductal gray and the paraventricular nucleus of the hypothalamus) and reward-related sites (nucleus accumbens and pedunculopontine tegmental nucleus). In a further experiment, Wistar rats and Lewis rats did not differ in the amount of Fos immunoreactivity produced by cocaine (15 mg/kg). These results indicate that Lewis rats are less sensitive to the behavioral, physiological and neural effects of cannabinoids. The exact mechanism underlying this subsensitivity requires further investigation.

Analgesics↗
PubMed2001

Effects of the cannabinoid receptor agonist CP 55,940 and the cannabinoid receptor antagonist SR 141716 on intracranial self-stimulation in Lewis rats.

Lewis rats were trained to self-stimulate the medial forebrain bundle (MFB) using a rate-frequency paradigm. They were then tested for the effects of the cannabinoid receptor agonist CP 55,940, the selective cannabinoid receptor antagonist SR 141716 and the dopamine D1 receptor antagonist SCH 23390. CP 55,940 (0, 10, 25 and 50 microg/kg i.p.) had no effect on MFB self-stimulation behaviour as assessed by the M50, the stimulation frequency at which half-maximal response rates were obtained. With SR 141716, only a very high dose (20 mg/kg i.p.) caused a significant inhibition of the rewarding efficacy of the stimulation. This was seen as an increase in the M50. All other doses of SR 141716 (0, 1, 3, 10 mg/kg i.p.) were ineffective in modulating the M50. By comparison, a relatively low dose (0.06 mg/kg i.p.) of SCH 23390 caused a large increase in M50. These results indicate a relatively modest influence, if any at all, of exogenous or endogenous cannabinoids on reward-relevant neurotransmission.

Animals↗
PubMed2001

[Hepatocellular adenoma confirmed by Doppler ultrasonography and laparoscopy].

CASE REPORT: A 46-year-old female patient presented for further investigation of an isolated liver lesion that was diagnosed by her physician by abdominal ultrasound and computertomography. The Doppler ultrasound (including a signal amplifier) could not differentiate the lesion so that a laparoscopy was performed. A hepatic adenoma was found which was confirmed by the histological examination of a directed liver biopsy. CONCLUSION: Signs and symptoms, diagnostic procedures and differential diagnostic options of a hepatic adenoma are discussed.

Adenoma, Liver Cell↗
PubMed2001

[Phenprocoumon-induced necrotizing hepatitis].

CLINICAL PRESENTATION: A 52-year-old female patient presented at our hospital with right upper abdominal pain and impaired general condition. During the previous 7 months, the patient had received anticoagulation treatment with phenprocoumon due to a prosthetic aortic valve replacement. TESTS: Serological tests for virologic, autoimmune or metabolic causes of hepatitis were negative. The histologic examination of liver biopsies showed necrotizing hepatocellular injury in zone 3 of the acinus without relevant fibrosis. Initially, a lymphocyte transformation test with phenprocoumon was negative. A second test after one week turned out to be positive. DIAGNOSIS AND CLINICAL COURSE: After withdrawal from phenprocoumon therapy and switching to anticoagulation with a low molecular weight heparin, liver tests gradually became normal. Aminotransferase levels rapidly increased when phenprocoumon treatment was resumed. Phenprocoumon-associated necrotizing hepatitis was diagnosed by clinical course, liver histology and the positive lymphocyte transformation test. After immunosuppressive treatment with prednisolone was started again, liver enzymes gradually normalized. Anticoagulation was further performed with low molecular weight heparin. CONCLUSION: This case stresses the fact that an adequate and detailed history on concomitant medication is mandatory in patients who present with cryptic hepatitis. Though severe hepatic adverse effects of phenprocoumon are rare, physicians should consider coumarin derivatives as a potential source of hepatitis.

Anti-Inflammatory Agents↗
PubMed2001

[Photodynamic therapy of dysplasias and early carcinomas in Barrett esophagus with a diode laser system--a pilot study].

BACKGROUND: Photodynamic therapy (PDT) of dysplasia and early cancer of the esophagus could show good results in the potential of ablation. Unfortunately, the existing expensive and temperamental dye laser systems foiled a broad clinical use. In this pilot study, we investigated the feasibility of an inexpensive and maintenance-free diode laser system for PDT of dysplasia and early cancer in Barrett's esophagus. PATIENTS AND METHODS: Eight patients with Barrett's esophagus and/or early cancer were treated. As light source we used a diode laser system with a maximum power output of 2 W and a wavelength of 633 +/- 3 nm. One patient was treated initially with Photosan-3, seven patients received 5-aminolevulinic acid. RESULTS: In all patients we could achieve reduction in length and/or histologically proven downgrading. In three quarters of the patients, complete eradication of adenocarcinoma could be attained. Columnar-lined metaplastic epithelium could also be completely eradicated. CONCLUSION: PDT using a diode laser system is comparably effective in Barrett's esophagus/early cancer as PDT with dye laser systems. PDT is a gentle and effective technique with little side effects.

Adenocarcinoma↗
PubMed2001

Effects of environment on the creep properties of a poly(ethylmethacrylate) based bone cement.

The effect of test environment on the creep behavior of a poly(ethylmethacrylate) bone cement was investigated. The aim of the study was to assess the influence of environment on the inherent material behavior, and so it was convenient to perform tests in tension on well-prepared samples. In addition to control tests in air, the liquid environments studied were water, Ringer's solution and Intralipid. Creep tests were performed in each of these environments with a range of aging times, test temperatures and applied stresses. In order to compare the effects of the environments, the creep curves were fitted to a generalized form, from which a creep rate was determined. The ratio of these creep rates between different environments at each testing condition was then used as a basis for a comparison of the detailed effects of environment. It was found that in all cases the water-based environments (water and Ringer's) had similar effects and gave the largest creep rates. Intralipid was then intermediate and air gave the lowest creep rates. These effects are mainly due to plasticization by water, although with Intralipid, some increased monomer leaching occurred, which served to reduce the creep rates. The influence of environment on the effects of aging time, temperature and stress were complex, although in general any conditions which increased water plasticization (longer aging, higher temperature and to a lesser extent, higher stress) gave an increase in creep rate. The major exception to this was at temperatures of 40 degrees C and above, where the effects of water plasticization were diminished, due to the inherent increase in molecular mobility of the material.

Journal Article↗
PubMed2001

Diagnostic laparoscopy.

The value of surgical laparoscopy for various therapeutic interventions has been well established. In recent years, the interest of gastroenterologists in this method has revived, since laparoscopy can provide additional information for the staging of oncological and liver diseases. The introduction of miniature lenses may have contributed to this process, and an increasing number of physicians are using minilaparoscopy due to its safety and easy handling. Surgical studies have mainly focused on the evaluation of laparoscopic ultrasound for the detection of liver and lymph-node metastases. In specialized centers, laparoscopic ultrasound is also used for the estimation of locoregional pancreatic tumor spread, but the diagnostic impact of the method, particularly in colorectal carcinoma, still remains to be determined. Remarkably, the number of publications from gastroenterology departments has tended to increase in comparison with last year's review.

Endosonography↗
PubMed2001

Endoscopic papillary balloon dilation vs. sphincterotomy for removal of common bile duct stones: a prospective randomized pilot study.

BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy (EST) is the standard procedure for gaining access to the common bile duct for removal of bile duct stones. However, the procedure is associated with both short-term and long-term complications. Recent reports have described the use of endoscopic papillary balloon dilation (EBD) as an effective and safe alternative to EST. We conducted a prospective randomized pilot study to compare the efficacy and short-term complication rates of these two established methods for removing uncomplicated bile duct stones. PATIENTS AND METHODS: Sixty patients were randomly assigned to receive either EST (n = 30) or EBD (n = 30) prior to removal of bile duct stones (maximum size 20 mm, maximum number five). The patient groups were comparable with regard to sex and age ratios, the size of the stones (EST: mean 10 +/- 4.7 mm; EBD: mean 7 +/- 3.5 min; not significant) and the numbers of stones (EST: mean 1.8 +/- 1.5 mm; EBD: mean 1.6 +/- 1.1 mm; not significant). EBD was carried out using a balloon-tipped biliary catheter (Maxforce, Microvasive, Boston, Massachusetts, USA) with a maximum diameter of 24 Fr for 45-60 s. Bile duct stones were removed using Dormia baskets or retrieval balloons, or both. RESULTS: The two methods were successful in all patients studied. Subsequent stone removal was possible in all 30 patients after EST (100%) and in 23 of the 30 who underwent EBD (77%), respectively (P<0.01). After conversion to EST, complete bile duct clearance was also achieved in the remaining seven EBD patients. The mean duration for the whole procedure was 17 +/- 12 min for EST and 29 +/- 15 min for EBD (not significant). Complications (WHO grades 2-4) were observed in five of the 30 EST patients (three cases of mild pancreatitis, two of hemorrhage) and in nine of the 30 EBD patients (three cases of cholangitis, four of mild pancreatitis, and two of severe pancreatitis), showing a trend toward higher complication rates in the EBD group. Postintervention hyperamylasemia was observed in six patients (three in each group). CONCLUSIONS: The results of this prospective randomized pilot study indicate that EST is superior to EBD in terms of stone removal, duration of the procedure, and complication rates. EST will therefore continue to be the standard procedure for stone removal in the near future. Further studies will be needed in order to compare the longer-term results with EST and EBD.

Adult↗
PubMed2001

Hepatosplenomegaly and progressive neurological symptoms - Late manifestation of Niemann-Pick disease type C - a case report -.

Niemann-Pick disease type C is an inborn error of metabolism that affects lipid degradation and storage. Hepatosplenomegaly and progressive neurological symptoms are the main clinical features. We present a case of an adult-onset type of Niemann-Pick disease in a 33-year-old woman who initially presented with dysarthria. At first, laboratory findings suggested Wilson's disease. Laparoscopy showed macroscopic signs of liver cirrhosis and histology did not confirm Wilson's disease. After bone marrow biopsy showed characteristic sea-blue histiocytes, Niemann-Pick disease was suspected and confirmed by filipin stain of cultured fibroblasts. Though rarely encountered, lipid storage disease should be suspected especially in younger patients with organomegaly and progressive signs of neurologic disease.

Adult↗
PubMed2001

Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases.

BACKGROUND: Minilaparoscopy (ML) is being used increasingly in the diagnosis of liver disease. This is a prospective study of the accuracy and safety of ML compared with conventional laparoscopy (CL) in the diagnostic workup of liver disease. METHODS: One hundred four patients with suspected liver disease were randomized either to undergo CL (n = 50) or ML (n = 54). CL was performed with a standard Storz laparoscope (Ø 11 mm, Storz GmbH, Tuttlingen, Germany) according to accepted guidelines. For ML a 1.9-mm small-diameter optical telescope was used (Richard Wolf GmbH, Knittlingen, Germany). In all cases, an attempt was made to obtain a liver biopsy specimen. RESULTS: Laparoscopy could successfully be performed in 100 of 104 (96%) patients with simultaneous procurement of biopsy specimens of the liver. In 4 cases, postoperative adhesions prevented sufficient inspection of the liver and in another patient the technique was switched from CL to ML for the same reason. Minor self-limiting bleeding at the biopsy site was observed in 20% of CL and 15% of ML examinations. One patient in each group required surgery for uncontrollable bleeding from the biopsy site. The patients' subjective perception of the examination was comparable in both groups. Compared with CL, ML could be performed in a significantly shorter time (27 vs. 22 min, p < 0.05). Liver cirrhosis diagnosed during laparoscopy was histologically confirmed in 77%, independent of the method of examination. Cirrhosis was diagnosed by histology in 1 of 14 (7%) and 1 of 21 (5%) patients without macroscopic signs of cirrhosis. CONCLUSIONS: Laparoscopy with a small diameter telescope in the workup of liver disease is comparable in terms of results to CL. Possible advantages of ML are a shorter examination time and a subjective impression of lower degree of invasiveness.

Adult↗
PubMed2001

The relationship between juxtapapillary duodenal diverticula and disorders of the biliopancreatic system: analysis of 350 patients.

BACKGROUND: Data concerning the association of juxtapapillary duodenal diverticula (JPDD) with biliopancreatic disorders are inconsistent, but an association between bile duct stones and JPDD is widely accepted. The aim of this study was to investigate the frequency of JPDD and its association with biliopancreatic disorders in patients undergoing ERCP. METHODS: A retrospective analysis was conducted of 5497 consecutive ERCP procedures performed in 2925 patients. Matched-pair analysis yielded 350 pairs of patients with and without JPDD, matched for definite risk criteria such as age, gender, and indication for ERCP. RESULT: The incidence of JPDD was 12%. Patients with JPDD were significantly older than patients without JPDD (71 vs. 62 years; p < 0.0019) and had a significantly higher bleeding rate after endoscopic sphincterotomy (8.8% vs. 4.8%; p = 0.039). The presence of JPDD correlated with gallbladder stones (29.4% vs. 20.8%; p = 0.039), bile duct stones (46% vs. 33.1%; p < 0.001), and recurrence of bile duct stones (6.6% vs. 1.4%; p = 0.002). There were no significant differences in frequency of acute and chronic pancreatitis as well as pancreas divisum. After multivariate logistic regression analysis, technically difficult ERCP, bleeding after endoscopic sphincterotomy, and bile duct stones remained as independent risk factors. CONCLUSION: JPDD appears to be a risk factor for complications of endoscopic sphincterotomy and for gallbladder stones, bile duct stones, and their recurrence.

Adult↗
PubMed2001

Photodynamic therapy with 5-aminolevulinic acid is not effective in bile duct cancer.

BACKGROUND: The results of preliminary studies of photodynamic therapy (PDT) for palliation of patients with bile duct cancer with hematoporphyrin derivative have been good. Rapid elimination of a photosensitizer could potentially shorten the time requirement for shielding from light. This would enhance the benefit of this form of palliative treatment. Therefore the feasibility of PDT was investigated for nonresectable bile duct cancer by using 5-aminolevulinic acid. METHODS: Four patients with nonresectable bile duct cancer underwent cholangiography, cholangioscopy, and intraductal US before PDT. Light activation was performed 5 to 7 hours after oral administration of 5-aminolevulinic acid. All patients had an endoprosthesis placed in the bile duct after PDT. RESULTS: Cholangioscopy 72 hours after PDT revealed superficial fibrinoid necrosis. However, 4 weeks after PDT there was no significant reduction in bile duct stenoses. Two patients had infectious complications develop, but phototoxicity was not observed. CONCLUSIONS: Although superficial tumor necrosis was evident, PDT with 5-aminolevulinic acid failed to significantly reduce malignant bile duct obstruction. Therefore 5-aminolevulinic acid-PDT cannot be recommended for the palliative treatment of bile duct cancer.

Administration, Oral↗