A randomized, controlled, safety study using imiquimod for the topical treatment of anogenital warts in HIV-infected patients. Imiquimod Study Group.

OBJECTIVE: To assess the safety of imiquimod, an immune response modifier, in the topical treatment of external anogenital warts in HIV-infected patients. SETTING: Clinical sites in the United Kingdom (eight) and the United States (five). DESIGN: A prospective, randomized, double-blind, vehicle-controlled study of imiquimod 5% cream or vehicle applied for 8+/-2 h three times per week for a maximum of 16 weeks in HIV-seropositive males (n = 97) and females (n = 3) aged 18 years or more with clinically diagnosed external anogenital warts, CD4 T lymphocyte count of > or = 100 x 10(6) cells/l and Karnofsky score > or = 70. MAIN OUTCOME MEASURES: Safety was assessed through the incidence and severity of local skin reactions and other adverse events, and through clinical laboratory tests. Wart clearance was documented by two-dimensional measurements of warts and by photography. RESULTS: Among the patients treated with imiquimod (n = 65) and vehicle (n = 35), the most common local skin reaction was erythema, (41.9 and 26.7%, respectively) and the incidence of patients reporting at least one adverse event was 69.2 and 65.7%, respectively. No clinically meaningful differences or changes in laboratory values were observed between treatment groups, nor were drug-related adverse effects observed in regard to HIV disease. While there was no significant difference between treatment groups in the number of patients who totally cleared their baseline warts (imiquimod 11% versus vehicle 6%, P = 0.488), more imiquimod-treated patients experienced a > or = 50% reduction in baseline wart area (38% versus 14%, P = 0.013). CONCLUSION: Most local skin reactions were mild and no adverse effects on HIV disease were observed. Topically applied imiquimod 5% cream reduced wart area and may have clinical utility in treating external anogenital warts in some HIV-infected patients.

Psoas weakness and femoral neuropathy: neglected signs of retroperitoneal hemorrhage from ruptured aneurysm.

Femoral neuropathy may occur with aortic aneurysm more commonly than reports in the literature indicate. The combination of an aortic aneurysm and femoral neuropathy indicates rupture. The presence of abdominal pain and neuropathy should suggest ruptured aneurysm and exclude other commonly considered diagnoses. Preoperative recognition of femoral neuropathy provides the opportunity for intraoperative nerve decompression and assures the surgeon that the operation itself was not causative. The literature is reviewed, and the preoperative occurrence of femoral neuropathy in two patients with ruptured aortic aneurysms is described.

Inhibition by colchicine of phospholipid secretion induced by lung distension.

The effect of colchicine, a microtubule disruptor, on phospholipid secretion stimulated by distension of fetal rabbit lungs was investigated. After colchicine injection and breathing for 45 min, pups were killed and their lungs were lavaged with colchicine. Controls were injected and lavaged with saline. All lungs were given static air inflation and a final lavage, and the returns were analyzed for phospholipid DNA, and lactate dehydrogenase. The first lavage after breathing yielded 33% less phospholipid with colchicine, 3.83 compared with 5.72 mg/g dry lung wt (P less than 0.05). The postinflation phospholipid yield was also significantly reduced with colchicine from 1.04 to 0.70 mg/g dry lung wt (P less than 0.05). The postinflation DNA was significantly reduced with colchicine, from 1.26 to 0.44 micrograms (P less than 0.01), suggesting reduced alveolar macrophages. Colchicine did not change the recovery by lavage of exogenous radioactive phospholipid. As reflected by ATP and lactate levels, tissue metabolism was well maintained. The results are interpreted to mean that colchicine reduced simultaneously lavage-associated phospholipid secretion, inflation-produced phospholipid secretion, and macrophage migration.

Prevention of neurologic complications of carotid endarterectomy.

We studied the neurologic complications after carotid endarterectomy to develop recommendations for prevention. From 1973 through June 1981, 195 carotid endarterectomies were performed on 184 patients. Carotid endarterectomy was performed using general anesthesia with routine use of a Javid shunt. There were no postoperative deaths. Three major, disabling strokes (1.5%) and four (2%) minor, permanent neurologic deficits occurred. The neurologic deficits were analyzed according to cause: (1) inadequate cranial inflow in four patients, (2) fluctuation in blood pressure requiring treatment in one third (61) of our patients, and (3) embolic complications, usually a single, transient ischemic episode, in 17 patients during the first postoperative week. This was not observed in patients receiving postoperative antiplatelet therapy. Inadequate collateral cerebral inflow accounts for most permanent postoperative neurologic deficits. Postoperative hypotension is now more dangerous than hypertension. Postoperative embolization is largely preventable with antiplatelet agents.

Aortic grafting procedures: tailoring the options.

Records from 165 patients who had received aortoiliac or aortofemoral bypass grafts were reviewed. The overall five-year patency rate was 88%. There was no significant difference in operative duration, amount of blood transfused, postoperative complications, and life table patency rates when comparisons were made of unilateral and bilateral grafts, of patients who underwent sympathectomy and those who did not, or of aortofemoral and aortoiliac grafts. When bypass grafting included an additional procedure, the amount of blood transfused and the number of postoperative complications increased significantly. We conclude that (1) the decision to operate should be based on symptoms, (2) the site of anastomosis should be chosen from anatomic characteristics, and (3) other procedures should not be performed except to achieve obvious therapeutic goals and to assure graft patency.

Gastrointestinal complications after renal transplantation: predictive factors and morbidity.

In a ten-year study involving 109 renal transplant patients, 37 (34%) developed gastrointestinal complications. The immediate mortality from these complications was 27%. Three of four patients with erosive gastritis died. Five deaths occurred among 17 patients who developed ulcers after transplantation. Emergency surgery for ulcers resulted in two deaths. Patients with peptic ulcer disease, esophagitis, or bleeding before transplantation were much more likely to develop recurrences that patients not so affected. Peptic ulcer occurred notably more often in recipients whose kidneys came from cadavers than from related donors. Experience with gastrointestinal bleeding or its absence during a first transplant is a useful predictor of the results after a second transplant. The high recurrence rate and high mortality suggest that patients with ulcer disease demonstrated before kidney transplantation should either undergo elective surgery for ulcer disease or not be accepted for transplantation. Patients in whom ulcer disease develops after a kidney transplant shoud undergo early elective surgery.

Discontinuance of immunosuprression in renal transplant patients.

Immunosuppressive therapy was discontinued in six patients for an average of 27 months. In these six patients, only two rejections have occurred. A survey of other transplant centers showed that in such patients rejection was often delayed weeks or months after therapy was stopped. Once immunosuppressive therapy has been stopped, for whatever reason, and rejection has not occurred, consideration should be given to not resuming therapy unless signs of rejection appear.

Recurrent transient ischemic attacks after carotid endarterectomy.

The postoperative courses of 113 patients undergoing 121 carotid endarterectomies between 1974 and 1979 were analyzed for recurrent transient ischemic attacks (TIAs). The TIAs were the indication for the original operation in all patients; 31 patients had a stable neurologic deficit prior to operation. Two patients sustained major strokes and three had nondisabling minor strokes. Three patients had late strokes. Recurrent TIAs occurred during follow-up in 28 patients, and these were classified into four distinct categories: (1) Ten patients had single TIAs in the distribution of the carotid artery operated on in the early postoperative days. (2) Four patients had late, repetitive TIAs related to the operated side. (3) Five patients had late TIAs in the distribution of the contralateral artery. (4) Nine patients had single or multiple TIAs owing to recurrent vertebrobasilar insufficiency. Close, long-term follow-up of postendarterectomy patients is recommended to locate those who will have surgically correctable lesions.

Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus.

OBJECTIVE: To compare the safety and effectiveness of 5% and 1% imiquimod cream with vehicle cream in the treatment of external anogenital warts. DESIGN: Randomized, double-blind, placebo-controlled comparison that evaluated patients for total clearance of their warts. Patients who experienced total clearance were evaluated for recurrence in a 12-week follow-up. SETTING: Eleven ambulatory offices, including both private physician offices and referral medical centers. PATIENTS: Three hundred eleven healthy men and women aged 18 years or older with 2 to 50 external anogenital warts were recruited from the practices of investigators, referring physicians, and advertisements. Eighty-two additional patients were screened but did not qualify. Four patients discontinued use of the medication because of adverse effects. INTERVENTIONS: Five percent imiquimod (Aldara) cream, 1% imiquimod cream, or vehicle cream was applied to all external warts overnight 3 times each week for 16 weeks, or until all treated warts disappeared, whichever occurred first. MAIN OUTCOME MEASUREMENTS: The number of patients experiencing the elimination of all baseline warts and the recurrence rate of these warts. In addition, the reduction in baseline wart area the duration of therapy required to eliminate warts, and the frequency and severity of adverse reactions were principal measurements. RESULTS: In the intent-to-treat analysis, 54 (50%) of 109 patients who received 5% imiquimod cream, 21 (21%) of 102 of those who received 1% imiquimod cream, and 11 (11%) of 100 patients treated with vehicle cream experienced eradication of all treated baseline warts. The difference between the effectiveness of 5% imiquimod cream and the vehicle cream was statistically significant (P < .001). Of those patients whose warts cleared during therapy, 13% of patients who received 5% imiquimod experienced a recurrence of at least 1 wart. Recurrences occurred in none of the patients who used 1% imiquimod cream and in 10% of patients who used the vehicle cream. Local erythema was the most common adverse reaction, but the majority of patients in each group experienced no or only mild local inflammatory reactions. There were no differences in incidences of flulike symptoms among treatment groups. CONCLUSIONS: Five percent imiquimod cream is an effective and safe self-administered therapy for external anogenital warts when applied 3 times a week overnight for up to 16 weeks. The recurrence rate is low.

Hypothermic renal preservation during vascular anastomosis.

During the vascular anastomotic portion of renal transplantation, handling is facilitated, the kidney is cushioned, and deep hypothermia is maintained while the kidney is held in a simple sling made of polyethylene foam.

Femoral neuropathy complicating anticoagulant therapy.

A twenty-six year old white male on long-term sodium warfarin (Coumadin therapy for recurrent thrombophlebitis had sudden onset of severe groin pain, right iliac hematoma, and a femoral nerve palsy. A review of the twelve previously reported cases of this hemorrhagic complication indicates that immediate surgical decompression may be necessary to prevent residual disability.

Convenient oxidation of phenothiazine salts to their sulfoxides with aqueous nitrous acid.

A simple method is reported for the preparation of gram quantities of phenothiazine sulfoxides by aqueous nitrous acid oxidation of phenothiazines at room temperature. The chiral levomepromazine gave rise to diastereoisomeric products analogous to those reported for thioridazine sulfoxidation.

The effect of unilateral carotid endarterectomy on neuropsychological test performance in 53 patients.

Six psychomotor tests (Ravens matrices, finger tapping, spatial orientation, arithmetic, vocabulary, and short-term memory) were administered preoperatively, at 3-7 days and 3 months postoperatively to 53 patients undergoing unilateral carotid endarterectomy between 1978 and 1982. Standard operative technique included general anesthesia and Javid shunt. None of the patients experienced postoperative neurological deficit or significant complications. Individual and cumulative test scores were correlated with prior CVA, neurological examination, cerebral angiography, pre and postoperative computerized cerebral tomograms and intraoperative carotid flow measurements. Psychometric scores did not change postoperatively in 18 patients with prior CVA's. Forty-five patients operated upon for high grade stenosis (75% reduction in cross sectional diameter) had a significant increase in early post-endarterectomy test scores which returned to preoperative levels by three months postoperatively. Increase in intra-operative carotid artery blood flow correlated with improved test performance. We conclude that carotid endarterectomy of flow restrictive stenosis initially augments psychometric test performance but the improvement is not sustained at the third postoperative month.

Aortocolic fistula, a lethal cause of lower gastrointestinal bleeding: report of a case.

Aortocolic fistula occurs with spontaneous rupture of aortic and iliac aneurysms into the sigmoid colon, or due to involvement of the aneurysmal wall by acute diverticulitis. In the eight cases reviewed, this complication proved uniformly lethal, although sufficient clinical findings were present for diagnosis, and adequate time was available for a planned therapeutic approach. Lower gastrointestinal bleeding in the patient who has an aortic aneurysm and left-lower-quadrant inflammation suggests the presence of an aortocolic fistual. Angiography should be performed during a bleeding episode to confirm the diagnosis. Surgical correction consists of an axillofemoral by pass graft, excision of the aortic aneurysm, and a Hartmann procedure.

Inotropes inhibit endothelial cell surface adhesion molecules induced by interleukin-1beta.

OBJECTIVES: Leukocyte-endothelial cell interactions play a critical role in sepsis-induced multiple organ system failure and acute respiratory distress syndrome. Increased cyclic adenosine 3',5'-monophosphate (cAMP) has been previously reported to inhibit expression of the cytokine-stimulated endothelial cell adhesion molecules, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). We hypothesized that clinically relevant concentrations of inotropes, such as amrinone and dopamine, which increase cAMP, could inhibit cytokine-stimulated upregulation of endothelial adhesion proteins. DESIGN: Prospective, controlled in vitro study. SETTING: Leukocyte biology laboratory. SUBJECTS: Human umbilical vein endothelial cells isolated from neonatal umbilical cord specimens and whole blood obtained from normal human adult volunteers were used in this study. INTERVENTIONS: Endothelial cell monolayers were pretreated with increasing concentrations of amrinone or dopamine, or left untreated as controls, followed by exposure to recombinant human interleukin (IL)-1beta for 6 hrs. Monolayers were then incubated with monoclonal antibodies to E-selectin, VCAM-1, and intercellular adhesion molecule-1 (ICAM-1), fluorescence labeled, and assessed for mean fluorescence intensity by flow cytometry as a measure of surface adhesion molecule concentrations. Whole blood neutrophils were pretreated with or without inotropes, then stimulated with n-formyl methyl leucine phenylalanine. Stimulated neutrophils were incubated with antibodies against the neutrophil adherence protein CD11b and assessed by flow cytometry. MEASUREMENTS AND MAIN RESULTS: IL-1beta markedly increased E-selectin (p = .01), VCAM-1 (p < .01), and ICAM-1 (p < .001) concentrations (n = 6). Pretreatment with amrinone significantly decreased endothelial E-selectin surface values at all concentrations (p < .001 by analysis of variance, n = 5), including therapeutic concentration ranges. Amrinone also inhibited upregulation of ICAM-1 (p < .001) at therapeutic concentrations, and VCAM-1 (p < .001) at higher concentrations. Dopamine inhibited only E-selectin at relevant concentrations. Neutrophil pretreatment with inotropes did not prevent CD11b upregulation. CONCLUSIONS: Pretreatment with amrinone, and to a lesser degree, with dopamine, at clinically relevant concentrations inhibits in vitro IL-1alpha-induced increases in human umbilical vein endothelial cell adhesion molecule concentrations. Future studies are necessary to investigate the mechanisms of these effects and to determine in vivo efficacy of inotropes as anti-inflammatory agents.