Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: A phase I study

Background: We performed a phase I study of a novel system of complete hepatic venous isolation and extracorporeal chemofiltration in patients with unresectable hepatocellular carcinoma (HCC) to determine (a) whether systemic exposure to doxorubicin could be limited after high-dose hepatic arterial infusion (HAI), and (b) the hepatic maximum tolerated dose (MTD) of doxorubicin. Methods: Ten patients with biopsy-proven HCC were treated with 20-min HAI of doxorubicin (17 total treatments). Two patients were treated with doxorubicin 60 mg/m², three patients were treated at 90 mg/m², and five patients received 120 mg/m². A newly developed dual-balloon vena cava catheter was advanced from the femoral vein, and the balloons were inflated to isolate and capture total hepatic venous outflow. The hepatic venous blood was pumped through extracorporeal carbon chemofilters before return of the blood to the systemic circulation. Results: Peak systemic doxorubicin levels were an average 85.6% lower than were peak prefilter levels (p<0.01). Because all catheters were placed percutaneously and because the chemofiltration markedly limited systemic chemotherapy exposure, patients were discharged 1 day after 16 of the 17 treatments. The hepatic and systemic MTD of doxorubicin in this treatment protocol was 120 mg/m². Conclusions: This novel system of complete hepatic venous isolation and chemofiltration limits systemic chemotherapy toxicity and will allow use of higher doses of chemotherapeutic agents to treat HCC. The results of this study were presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.     

A diagnostic algorithm for male genital oedema

Male genital oedema can be defined as swelling or the appearance of swelling of the scrotum and/or the penile shaft and prepuce. Despite the various causes of genital oedema reported in the published work, a concise approach to the evaluation and management has not been sufficiently addressed.     

Effects of purine analogues on spontaneous alternation in mice

The Y-maze was used to examine the effects of purines acting at A₁ and A₂ adenosine receptors upon spontaneous alternation, a model of working memory, in mice. In support of previous work, scopolamine produced a loss of spontaneous alternation behaviour to the 0.5 chance level. The A₁ receptor selective agonist N6-cyclopentyladenosine (CPA) did not change spontaneous alternation behaviour alone, but it prevented the decrease of spontaneous alternation scores produced by scopolamine. The A₁ receptor selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (CPX) blocked the effect of CPA in combination with scopolamine but had no effect alone. The A₂ receptor selective agonist (N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA), and the A₂ receptor selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) had no effect of alternation behaviour alone and did not modify the effect of scopolamine. The results indicate the ability of A₁ but not A₂ receptor activation to modify working memory deficits induced by scopolamine, but suggest that endogenous adenosine does not normally participate in working memory processes.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Reflex sympathetic dystrophy in brain-injured patients.

One-hundred consecutive patients were prospectively evaluated on admission to our Brain Injury Unit for signs and symptoms of reflex sympathetic dystrophy (RSD) in the upper extremity. Patients averaged 4 months postinjury and had an average age of 29 years. Thirteen patients had clinical signs and symptoms of RSD and were then evaluated with standard radiographs and 3-phase radionuclide scintigraphy. Twelve of 13 patients had 3-phase bone scans (TPBS) consistent with RSD (12% overall incidence). RSD was present exclusively in the spastic upper extremity. There were 9 patients with hemiparesis and 3 with quadraparesis. There was a significantly higher (P < 0.01) incidence of associated upper extremity injury in the group with RSD (75%). All patients had a mean Rancho Cognitive Level of V and initial Glasgow Coma Scores less than 8. Patients who developed RSD had lower Glasgow Coma Scores than the non-RSD patients. Brain-injured patients often display agitation, hyperalgesia, disuse or neglect of the RSD-involved extremity. In addition, these patients are often cognitively unable to vocalize complaints of pain. Undiagnosed RSD in these patients can result in a significant delay in rehabilitation and possible loss of the use of an otherwise functional upper extremity.