Randomized controlled trial comparing the controlled rehabilitation with early ambulation and diet pathway versus the controlled rehabilitation with early ambulation and diet with preemptive epidural anesthesia/analgesia after laparotomy and intestinal resection

BACKGROUND: Multimodal postoperative care regimens accelerate recovery after abdominal surgery. The benefit of thoracic epidural (TE) analgesia over patient-controlled analgesia (PCA) remains unproven when used with a fast-track postoperative care plan. METHODS: Fifty-six patients undergoing major intestinal resection, and on a fast-track postoperative care plan, were randomized to preemptive TE or PCA. Patients were evaluated at standard time points for pain score, quality of life (Short Form-36), and complications. Oral analgesia was substituted for TE and PCA on the second postoperative day. Discharge criteria were identical for both groups. RESULTS: Six patients (20.6%) had a failed epidural. There was no difference in length of stay (5.8 versus 6.2 days, TE versus PCA, P = .55), total length of stay (including readmissions), pain scores, quality of life, complications, or hospital costs at any time point. CONCLUSION: TE offers no advantage over PCA for patients undergoing major intestinal resections who are on a fast-track postoperative care plan using PCA.     

Significance of tumor spread in adenocarcinoma of the ampulla of Vater

Twenty-eight patients with ampullary carcinoma were treated between 1965 and 1988: 22 underwent pancreaticoduodenectomy with 1 operative death (5 percent), 1 had local excision, 3 had bypass, and 2 were not explored. Of the 21 patients who survived pancreaticoduodenectomy, 4 had tumor confined to the ampulla, 7 had tumor extending into the duodenum, and 10 had tumor invasion beyond the duodenum. Nine of these patients had positive lymph nodes and 12 had negative lymph nodes. The patient who had local excision was disease-free at last follow-up 104 months postoperatively. Each of the three bypassed patients died of tumor progression within 15 months. The estimated 5-year survival rate for resected patients was 60 percent and was independently related to lymph node metastases (p = 0.031) and to tumor size (p = 0.039). This experience suggests that long-term survival is possible in patients with lymph node metastases or invasive tumors extending beyond the duodenal wall and that curative pancreaticoduodenectomy can be performed with a low operative mortality; therefore, aggressive surgical resection is recommended for all patients with ampullary carcinoma.     

The selective retention of lutein, meso-zeaxanthin and zeaxanthin in the retina of chicks fed a xanthophyll-free diet

Lutein and zeaxanthin are pigmented oxygenated carotenoids, or xanthophylls, derived from plants and concentrated in the retina of primates and birds. We investigated the transport, distribution and depletion of lutein and zeaxanthin in the plasma and tissues of newly hatched chicks fed xanthophyll-free diets. One-day-old Leghorn chicks were randomly divided into two groups. A control group was fed a diet containing lutein and zeaxanthin (5.2 and 1.7 mg/kg diet, respectively) for 28 days. An experimental group was fed a diet containing no lutein and zeaxanthin for 28 days. Plasma and tissues were analyzed for lutein and zeaxanthin at 28 days (control) and on days 1, 14 and 28 (experimental). At hatching, lutein and zeaxanthin were the predominant carotenoids present in the blood and tissues. As indicated by their similar mass contents, there was complete transfer of these carotenoids from egg yolk to chick. Lutein and zeaxanthin concentrations in the plasma and tissues of chicks fed the xanthophyll-free diet decreased rapidly to almost zero (with a depletion time of seven days [t(1/2)]). In contrast, the retina retained its initial concentrations of lutein and zeaxanthin similar to the control group. meso-Zeaxanthin and cis-zeaxanthin were identified only in the retina. The retina concentrated zeaxanthin over lutein. Lutein and zeaxanthin were selectively retained in the retinas of chicks fed a xanthophyll-free diet. In contrast, the plasma and other tissues lost up to 90% of their original content of xanthophylls. These data emphasize the relative stability of lutein and zeaxanthin in the cone-rich retina where they are present as esters in oil droplets. The tissue depletion suggests the need for a regular dietary intake of lutein and zeaxanthin because of rapid depletion in the body. It is clear that these xanthophylls may have an essential role in the cone-rich retina of the chick as evidenced by their selective retention.     

The prime role of HDL to transport lutein into the retina: evidence from HDL-deficient WHAM chicks having a mutant ABCA1 transporter

PURPOSE: Lutein and zeaxanthin are largely transported in plasma by high-density lipoprotein (HDL). The Wisconsin hypoalpha mutant (WHAM) chicken has a recessive sex-linked mutation in the ABCA1 transporter gene that results in a severe deficiency of HDL. In this study, the transport and tissue distribution of lutein and zeaxanthin were examined in newly hatched and 28-day-old WHAM chicks compared with control chicks. METHODS: One-day-old WHAM and control chicks were randomized to be fed a high-lutein or a control diet for 28 days. The plasma and tissues were analyzed for lutein, zeaxanthin, and lipoproteins on days 1 and 28. RESULTS: The WHAM chicks had very low plasma levels of HDL cholesterol (5.3% of normal). They also had very low concentrations of lutein in the plasma and all other tissues compared with control chicks. The plasma and retina were only 9% and 6% of control levels (P < 0.01), respectively. Zeaxanthin levels were similarly low (9% of control, P < 0.01). The high-lutein diet increased the content of lutein in the plasma and tissues of control chicks (P < 0.01). In contrast, in WHAM chicks, lutein increased greatly in the plasma, liver, and heart, but little in the retina (6% of control). CONCLUSIONS: HDL deficiency in the WHAM chicks was associated with a deficiency of lutein and zeaxanthin in the tissues, especially in the retina. The high-lutein diet increased the lutein content of some tissues via LDL and VLDL transport, but retinal lutein remained very low. These data support the prime role of HDL as the specific transporter of lutein and zeaxanthin into the retina. The WHAM chick provides an excellent model for the study of the role of HDL in the retinal uptake of lutein and zeaxanthin.     

Early and late results of coronary artery bypass after failed angioplasty. Actuarial analysis of late cardiac events and comparison with initially successful angioplasty

We reviewed the results of early (less than 24 hours) coronary artery bypass after unsuccessful percutaneous coronary artery angioplasty in 146 patients treated between October 1979 and July 1986. Overall operative mortality was 2.7%, and risk was significantly increased among patients with hemodynamic instability and new occlusion or further narrowing of the dilated vessel (3.8 versus 0%, p less than 0.05). Actuarial analysis was used to compute the rates of cardiac events during the follow-up interval, and event rates were also estimated in a comparison group of 776 patients who had successful first-time PTCA during the same time period. At a follow-up interval of 5 years, the cumulative risks of recurrence of angina and need for an additional procedure (bypass or angioplasty) were significantly (p less than 0.05) lower for patients who had undergone bypass than for those who had successful angioplasty (angina 21% versus 56%, PTCA 2% versus 21%, CAB 6% versus 16%). Cumulative risks of myocardial infarction and death were 4% versus 9% and 6% versus 9% in the two groups. The differences between late outcomes in the bypass and angioplasty groups persisted when patients were stratified into cohorts with single-vessel and multivessel disease, and the highest late event rate occurred in patients in the angioplasty group who had incomplete revascularization. The difference in late events after bypass or angioplasty was greatest during the first year. These late data should be considered when the mode of revascularization (bypass or angioplasty) is selected for symptomatic patients, especially those with multivessel disease.     

Clinical Evaluation of the Cook Advance Enforcer 35 Focal-Force PTA Balloon Catheter for Treatment of Hemodialysis Fistula Stenoses: A Feasibility Study

Purpose

A prospective, single-center, single-arm feasibility study evaluated procedural and short-term performance of the Advance Enforcer 35 focal-force percutaneous transluminal angioplasty (PTA) balloon catheter in treating stenoses of mature native arteriovenous (AV) hemodialysis access circuits.

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).