Basiliximab decreases the incidence of acute rejection after intestinal transplantation.
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Acute Disease↗
Biomedical subjects
I Fox
Publications and source records attributed to I Fox.
Intestinal transplantation at the University of Nebraska Medical Center: 1990 to 2001.
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Adult↗
Long-term results of intestinal transplantation for pseudo-obstruction in children.
PURPOSE: The aim of this study was to determine long-term results of intestinal transplantation in children with pseudo-obstruction, particularly when stomach and colon are not part of the allograft. METHODS: The authors conducted a case-record review of all children who underwent transplantation at our center for a primary diagnosis of pseudo-obstruction. Supplementary information was obtained from outpatient charts, computerized database, and telephone survey of parents. RESULTS: Six small bowel and 3 liver-small bowel transplants were carried out in 8 patients between 1993 and 1999. Median follow-up is 40 months (range, 13 to 73 months). Median age at transplantation was 2.7 years (range, 0.7 to 12.8 years). Median graft survival in this series is 15 months (range, 1 day to 71 months). Stomach and colon were excluded from all allografts. Two children died 5 and 368 days after transplant and 2 graft losses occurred in 1 patient. Two children had lymphoproliferative disease; both are alive with functioning grafts. Five survivors with functioning grafts receive full enteral feedings at home. Four of the 5 have had ileostomies closed, and 3 have normal bowel movements. CONCLUSIONS: Intestinal transplantation without stomach or colon provides children with chronic intestinal pseudo-obstruction with a good quality of life. The underlying disease poses special challenges in management.
Child↗
Incidence, timing, and histologic grade of acute rejection in small bowel transplant recipients.
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Adolescent↗
Intestinal transplantation: a single-center experience.
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Adult↗
Immediate free TRAM reconstruction in lumpectomy and radiation failure patients.
Local recurrence after lumpectomy and radiation therapy indicates failed breast conservation surgery. These patients often proceed to mastectomy and are candidates for autogenous breast reconstruction. Free transverse rectus abdominus muscle (TRAM) reconstruction in these patients is complicated by repeated axillary dissection and the use of irradiated tissue. Complication rates for pedicled TRAMs have been reported at 33 percent when used in irradiated tissue beds. We report our results using the free TRAM for breast reconstruction after lumpectomy and radiation failure. All patients within this study developed a local recurrence after lumpectomy and radiation therapy. All patients had undergone axillary dissection for staging at the time of their lumpectomy. Patient records were reviewed for patient age, total radiation dose, associated risk factors for TRAM failure, operative time, donor vessels used for anastomosis, status of the native thoracodorsal vessels at the time of surgery, and postoperative complications. Over a 7-year period, 16 TRAM patients had undergone previous breast conservation surgery. Of these 16 patients, 14 underwent reconstruction with a planned free TRAM after simple mastectomy. Average operating room time was 7 hours. There were no partial or total flap losses. Complications were seen in 14 percent of the overall group. Overall, we found that the free TRAM provided an excellent aesthetic result with a lower complication rate than previously reported for pedicled TRAM flaps in irradiated beds. The thoracodorsal vessels provided an adequate donor vessel in 93 percent of the cases. The free TRAM provides a superior alternative in immediate reconstruction in patients who have failed breast conservative surgery.
Age Factors↗
Thoracodorsal vessels as recipient vessels for the free TRAM flap in delayed breast reconstruction.
The internal mammary vessels have been recommended as the first choice recipient vessels for delayed breast reconstruction with the free TRAM flap. This approach has avoided surgery in the previously operated axilla, has required a shorter pedicle length, and has allowed for more medial placement of the TRAM tissue. Frequency of nonusable axillary vessels has been reported at 11 percent, with a 6 percent incidence of flap loss in the delayed reconstructive setting. We reviewed our experience with the thoracodorsal vessels as recipient vessels in delayed free TRAM breast reconstruction to assess more accurately the adequacy of these potential recipient vessels. All patients undergoing delayed TRAM reconstruction were reviewed. Forty-seven of 300 consecutive TRAM procedures were for planned delayed free reconstruction. In seven of the patients (15 percent), the thoracodorsal vessels were found to be inadequate for free reconstruction. A supercharged pedicled TRAM was used for reconstruction in each of these seven patients. Average operating room time was 7 hours. Mean follow-up time was 38 months. Nineteen percent of all patients developed at least one complication. Twelve percent of free TRAM patients developed a complication, whereas 57 percent of supercharged patients developed a postoperative complication. The difference in complication rates was statistically significant. The thoracodorsal vessels have provided an adequate recipient vessel in 85 percent of delayed free TRAM reconstructions, comparable to previous reports. Pedicling and supercharging the flap, in those situations in which the thoracodorsal vessels were inadequate, were associated with an increased incidence of postoperative complications. This suggests that in the delayed reconstructive setting, higher-risk patients benefit from free reconstruction over supercharged reconstructions. A second recipient vessel should be used when the thoracodorsal vessels are inadequate for planned free TRAM reconstruction. In these circumstances, we would recommend the use of the internal mammary vessels followed by the thoracoacromial vessels as reliable alternative recipient sites for delayed free TRAM reconstruction.
Adult↗
Predation on Aedes aegypti (Diptera: Culicidae) by Theridion rufipes (Araneae: Theridiidae) in Puerto Rico.
Theridion rufipes Lucas was found in rearing cages of Aedes aegypti (L.) in the School of Medicine, San Juan, PR. From the 1970s to the 1990s, the spiders had a continuous existence in the cages and in the room outside the cages. A single spider eventually could eliminate all the mosquitoes in a cage. The behavior of the mosquitoes in the web was observed by isolating spiders individually in glass or plastic flasks. When a mosquito comes in contact with the beads of sticky silk on the web, it is immediately paralyzed before the spider approaches it. The instant immobilization without a struggle as well as other aspects of prey behavior suggest that there is a compound in the sticky webs that causes the paralysis. Analysis of this material might lead to the discovery of a new insecticide. Efforts to control dengue in Puerto Rico should not interfere with the natural enemies of the vector.
Aedes↗
Phase I study of high-dose, intravenous rsCD4 in subjects with advanced HIV-1 infection.
In vitro, recombinant soluble CD4 (rsCD4) attaches to and inactivates human immunodeficiency virus (HIV). To determine if prolonged therapy with high-dose intravenous rsCD4 provides an in vivo benefit, we gave three HIV-1-infected patients with AIDS, whose isolates were susceptible in vitro to rsCD4, 10 mg/kg of rsCD4 for 4 weeks, 5 mg/kg for 4 weeks, and 1 mg/kg for 2 weeks. Single-dose pharmacokinetic studies performed prior to this showed transient in vivo decreases of HIV-1 plasma viremia in all three subjects. Surrogate markers of HIV activity, clinical status, HIV-1 p24 antigen, plasma HIV-1 titers, and peripheral blood mononuclear cell (PBMC) intracellular titers of virus were measured at entry, and every other week after onset of therapy. All subjects demonstrated rsCD4 concentration-dependent reduction in plasma viremia, with two subjects having complete neutralization of cell-free virus. The third subject's isolate was relatively resistant to the in vivo effects of rsCD4 and only partial reduction in plasma virus titers was obtained, even at the highest dose of 10 mg/kg. There was no change in the PBMC intracellular viral titer or surrogate markers of HIV-1 activity (including CD4 cell count and beta 2-microglobulin). There was subjective improvement in clinical symptoms, and all subjects gained weight with the highest doses of rsCD4. rsCD4 exhibited linear pharmacokinetics over the dose range studied. We conclude that high-dose intravenous rsCD4 can be safely given for up to 10 weeks and that it has a stable pharmacokinetic profile.(ABSTRACT TRUNCATED AT 250 WORDS)
Acquired Immunodeficiency Syndrome↗
The effects of high-dose recombinant soluble CD4 on human immunodeficiency virus type 1 viremia.
In vitro, low-passage clinical human immunodeficiency virus type 1 (HIV-1) isolates require up to 1000 times greater serum levels of recombinant soluble CD4 (rsCD4) than have ever been given. To determine if sufficient serum levels of rsCD4 provide in vivo inhibition of HIV-1, 4 HIV-1 plasma-viremic subjects were given single-dose boluses of 2, 4, 6, 8, and 10 mg/kg intravenous rsCD4. Plasma HIV-1 cultures were done after infusion. Three subjects demonstrated a dose-dependent reduction in plasma HIV-1 viremia. The inhibitory effect of rsCD4 on plasma HIV-1 viremia was associated with the in vitro ID90-95 of the isolate, not the ID50. These data demonstrate that extremely high doses of rsCD4 inactivate cell-free HIV-1 in vivo and suggest that high doses of rsCD4 may have some short-term therapeutic utility, such as with accidental or occupational HIV-1 exposure.
CD4 Antigens↗
Nefazodone and imipramine in major depression: a placebo-controlled trial.
Nefazodone is a phenylpiperazine antidepressant with 5-HT2 antagonism and 5-HT reuptake inhibition. Two hundred and eighty-three out-patients with a diagnosis of DSM-III-R major depression of at least one-month duration (65% ill for over 6 months), and a mean score of 24 on the 17-item Hamilton Rating Scale for Depression (HRSD), were randomised to treatment with nefazodone, imipramine, or placebo. The double-blind treatment period was 8 weeks in duration. Nefazodone's antidepressant efficacy was comparable with imipramine's, with both drug treatments significantly better than placebo in a variety of outcome measures. For example, after 8 weeks of therapy, 78% of nefazodone and 83% of imipramine but only 55% of placebo patients (P < 0.01) were globally much or very much improved. Nefazodone was better tolerated than imipramine, with fewer drop-outs and a lower incidence of side-effects during treatment.
Adult↗
Anticoagulant effects of hirulog, a novel thrombin inhibitor, in patients with coronary artery disease.
Selective thrombin inhibitors are a new class of antithrombotic drugs that, unlike heparin, can effectively inhibit clot-bound thrombin and escape neutralization by activated platelets. Hirulog is a 20 amino acid hirudin-based synthetic peptide that has shown promise in experimental models of thrombosis. Little information is available about the effects of hirulog in patients with coronary artery disease. Forty-five patients undergoing cardiac catheterization, who were taking aspirin, were randomized to receive either (1) hirulog, 0.05 mg/kg intravenous bolus followed by 0.2 mg/kg/hour intravenous infusion until the end of the catheterization; (2) hirulog, 0.15 mg/kg intravenous bolus followed by 0.6 mg/kg/hour intravenous infusion; or (3) heparin; 5,000 U intravenous bolus. Serial activated partial thromboplastin time (APTT), prothrombin time, activated clotting time and fibrinopeptide A were measured. Hirulog produced a dose-dependent prolongation of all coagulation parameters; the 0.6 mg/kg/hour dose prolonged the APTT to 218 +/- 50% of baseline after 2 minutes and 248 +/- 50% of baseline after 15 minutes. The half-life of the effect on APTT was 40 minutes. The hirulog blood level correlated well with the APTT, prothrombin time and activated clotting time (r = 0.77, 0.73, and 0.82 respectively, all p < 0.001). Both doses of hirulog potently suppressed the generation of fibrinopeptide A (p < 0.05). There were no major hemorrhagic, thrombotic or allergic complications in patients treated with hirulog or heparin. Thus, hirulog, a direct thrombin inhibitor, provides a predictable level of anticoagulation and appears to have a potent yet well-tolerated anticoagulant profile in patients with coronary artery disease.
Amino Acid Sequence↗
Anticoagulant activity of Hirulog, a direct thrombin inhibitor, in humans.
Hirulog (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095-101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers. In a randomized, placebo-controlled study (n = .54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 l kg-1 h-1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p < 0.001) and subcutaneous administration (r = 0.7, p = 0.002). To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide's activity. At the administered dose of 0.6 mg kg-1 h-1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Neurofilament immunoreactivity in Merkel-cell tumors: a differentiating feature from small-cell carcinoma.
To differentiate Merkel-cell tumor (MCT) from other neuroendocrine (NE) carcinomas, we immunostained (using avidin-biotin-peroxidase method) nine MCT and 37 NE (including 28 small-cell) carcinomas for NE markers (neuron-specific enolase and chromogranin), cytokeratin, neurofilament, vimentin, and a number of other markers. Cytokeratin was positive in 100% of MCT and in 85% of small-cell carcinomas; neurofilament and vimentin were positive in respectively 100% and 22% of MCT and 0% of NE carcinomas. Our data suggest that the coexpression of cytokeratin and neurofilament by an undifferentiated dermal or visceral tumor is of significant help in diagnosing MCT and differentiating it from small-cell carcinomas. The vimentin reactivity is a weak and insignificant discriminant.
Adult↗
The efficacy and safety of paroxetine compared with placebo in outpatients with major depression.
Paroxetine, a phenylpiperidine derivative, is an antidepressant that selectively inhibits serotonin reuptake. In this study 111 outpatients with major depression diagnosed by DSM-III criteria were treated with either paroxetine or placebo in a 6-week, randomized, double-blind study. Paroxetine was significantly superior to placebo on six of the seven major efficacy variables. Significant differences in favor of paroxetine were apparent by Week 2. Paroxetine was also well tolerated. These results support the efficacy and safety of paroxetine as a treatment for patients with major depression.
Adult↗
Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study.
In summary, the clinical results of this double-blind study clearly show that imipramine, as expected, demonstrated significant antidepressive properties in outpatients suffering from major depressive disorders. In contrast, adinazolam showed rather mild and weak antidepressive properties, and in no measures did its response differ significantly from that of diazepam. These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam (Rickels et al., 1987) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo, while diazepam was not. While the rather high dropout rate may well be considered a limitation of the study, the dropout rate is equally distributed between all four treatments. And since both decreasing sample size and endpoint analyses which include all patients with at least one week data, provide rather similar results, the findings can be considered as robust despite the high dropout rate. While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar, when high dropout rates occur, endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice. The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam (Covi et al., 1974) and chlordiazepoxide (Lipman et al., 1986). The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Placebo-controlled trial of venlafaxine for the treatment of major depression.
Results are presented of the first double-blind, placebo-controlled trial of a novel antidepressant venlafaxine, which preclinically has demonstrated serotonin, norepinephrine, and dopamine reuptake inhibiting effects. Sixty outpatients meeting DSM-III-R criteria for major depression were randomized to receive 6 weeks of treatment with one of three fixed doses of venlafaxine--25 mg three times a day, 75 mg three times a day, or 125 mg three times a day--or placebo. Significant improvement was observed in depression scores at all doses, with the high dose resulting in earlier improvement, by week 2. For the combined venlafaxine treatment groups, 68% achieved a moderate or marked improvement on the Clinical Global Impression scale, compared with only 31% for the placebo group. Venlafaxine was well tolerated, and nervousness, sweating, and nausea were the only adverse effects observed more frequently with drug compared with placebo.
Adult↗
Lorazepam vs. alprazolam in the treatment of panic disorder.
Sixty-seven patients with panic disorder were treated with single-blind placebo for one week before being randomized to 6 weeks of double-blind treatment with either lorazepam or alprazolam. Both drugs showed significant and comparable antipanic efficacy throughout the course of the study. With the exception of sedative effects, both drugs were well-tolerated at a mean daily dose of 7 mg for lorazepam and 3 mg for alprazolam. Lorazepam appeared to be as effective as alprazolam in the acute treatment of panic disorder.
Adult↗